II

Merci aussi à tous mes collègues doctorantsavec qui j'ai travaillé au cours de mes trois années au labo. Merci également à Rachid NAITALEB et Dr Rémi BEAULIEU avec qui j'ai partagé les labos 18 et 19, merci pour votre aide et votre dynamisme au labo. C'est un vrai plaisir de travailler à vos côtés. Merci également au Dr Mehdi OMRI pour ta bonne humeur, tes blagues et ton aide. Je n'oublie pas les doctorants Thibaut CHARTREL, Lucas FONTAINE, Meriem ALOUI qui apportent une bonne ambiance dans le

List of Figures

List of Tables

 28. Esterification of D-ribose derivative (16) with phosphonate derivative (18) ...........

Abbreviations and Symbols

C:

Carbon-13 1 H: Proton μ:

Micro J:

J-coupling AA:

Asymmetric aminohydroxylation AAS:

Atomic absorbtion spectroscopy Ab:

Antibody AEPH 2 : 2-aminoethyl dihydrogen phosphate AHBA:

3-amino-5-hydroxybenzoic acid APPA:

(3-aminopropyl) phosphonic acid APTES:

(3-aminopropyl) tri-ethoxysilane BAIB:

Iodobenzene diacetate bp:

Boiling point CH:

Conventional heating Co(TPP):

Cobalt(II) Tetraphenylporphyrin CPPA:

3-phosphonopropionic acid DAHP:

D-arabino-heptulosonic acid-7-phosphate DCM:

Dichloromethane DHS:

3-dehydroshikimate DHQ:

3-dehydroquinate DLS:

Dynamic light scattering DMAP 4-(Dimethylamino)pyridine DMF:

Dimethylformamide DMP:

Dess-martin periodinane DNA:

Deoxyribonucleic acid Dopa: Dopamine DPPA Diphenyl phosphoryl azide E4P:

Erythrose 4-phosphate EDA:

Ethyl diazoacetate EDX:

Energy-dispersive X-ray spectroscopy ee Enantiomeric excess EG:

Ethylene glycol eq: Equivalent EWG:

Electron withdrawing group FTIR:

Fourier-transform infrared spectroscopy Glu:

Glutamic acid HAS:

Human serum albumin HAP Hydroxyapatite HRFAB-MS: High resolution fast-atom bombardment mass spectrometry HRMS:

High resolution mass spectrometry Hz: Hertz L-Dopa:

L-3,4-dihydroxyphenylalanine LSS:

Liquid-solid-solution Polyvinylpyrolidone SAXS:

Small-angle X-ray scattering SEM:

Scanning electron microscopy SES:

β-(trimethylsilyl)ethanesulfonyl SPCe:

Screen-printed carbon electrodes SPIO:

Super paramagnetic iron oxide SQUID:

Superconducting quantum interference device TBAF:

Tetra-n-butylammonium fluoride TBS:

Tert-butyldimethylsilyl ether TEA:

Triethylamine TEM:

Transmission electron microscopy TGA:

Thermogravimetric analysis TLC:

Thin layer chromatography TMSD:

Trimethylsilyldiazomethane THF:

Tetrahydrofuran Thr:

Threonine Ts:

Toluenesulfonyl XPS:

X-ray photoelectron spectroscopy XRD:

X-ray diffraction Val:

Valine VSM:

Vibrating sample magnetometer 13 C:

Carbon-13 1 H: Proton μ: Micro

Résumé de thèse en français

Les résultats presentés dans cette thèse portent sur la synthèse et la caractérisation de nano catalyseurs magnétiques puis de leur application à la réaction d'aziridination d'alcènes.

Le projet de cette thèse est inspiré des travaux antérieurs d'Evans et Jacobsen portant sur la réaction d'aziridination en catalyse homogène au cuivre. Sur cette base, nous avons étudié la possibilité d'introduire un catalyseur hétérogène durable pour une approche plus verte de la réaction d'aziridination. Une aziridine est une fonction organique composée d'un cycle à trois membres et contenant un atome d'azote endocyclique. Ce motif présente un intérêt synthètique qui, par ouverture du cycle, peut intervenir comme précurseur de fonction aminées. Il est également impliqué dans l'activité biologique de plusieurs composés notamment des antibiotiques et antitumoraux.

A. Aziridines dans les produits naturels

Le motif aziridine est présent dans certains produits naturels ayant une activité biologique bénéfique connue (anticancéreux, antileucémique, antibiotique). Par exemple, la Miraziridine A (Figure A, 1) agit comme inhibiteur de l'action de la cathepsine B avec une valeur d'IC50 de 1,4 mg/ml (2,1 μM), alors que le Persistol (2), et la Mitomycine A (3) agissent comme anticancéreux.

B. Aziridine en synthèse organique

Des méthodes classiques de préparation des aziridines ont été développées et sont divisibles en deux grandes classes : les réactions par cyclisation intramoléculaire d'une amine via le départ d'un groupe partant ou alors des réactions d'addition sur un alcène ou sur une imine. Pour cette deuxième classe, la réaction d'addition peut impliquer le transfert de nitrène sur un alcène catalysé par un métal de transition. Ce type de réaction a été rapporté indépendamment par Evans et Jacobsen. Par exemple, Evans a développé l'aziridination avec le N-(ptolylsulfonyl)imino]phényliodinane (PhI=NTs) comme source de nitrène avec un complexe de cuivre (I) et un ligand bis-oxazoline pour la version asymétrique (Schéma A). Le transfert de nitrene par utilisation de catalyseur métallique dans les réactions d'aziridination, est une technique d'intérêt pour obtenir des synthèses plus directes et donc plus courtes. Cependant, l'extraction, le recyclage et la toxicité des métaux sont souvent des sujets peu discutés. Ainsi, nous proposons la préparation de Nano-Catalyseur Magnétique (NCM) recyclable afin de corriger cette lacune mais aussi afin d'accroitre le potentiel de cette reaction en s'orientant vers une chimie plus durable et respectueuse de l'environement.

C. L'aziridination en utilisant un nano-catalyseur magnétique (NCM)

Les nanoparticules magnétiques sont aujourd'hui considérées comme une solution pour valoriser les systèmes catalytiques hétérogènes et atteindre des vitesses de réaction proches de celles des réactions effectuées en catalyse homogène. De nombreuses méthodes ont été mises au point pour synthétiser des nanoparticules de magnétite. Elles peuvent être obtenues selon différentes voies de synthèse comme la co-précipitation, la micro-émulsion, la décomposition thermique, l'irradiation par ultrason, l'encapsulation à l'échelle micrométrique ou la méthode sol-gel. En raison de sa facilité de mise en oeuvre, la méthode par coprécipitation a été retenue par a synthèse de Fe 3 O 4 (schéma B). Afin d'améliorer la stabilité des nanoparticules magnétiques, une modification de la surface est envisageable notamment via le greffage d'agents de couplage pour permettre la chélation du cuivre. Par exemple, nous avons utilisé différents linkers tels que la dopamine pour modifier la surface de Fe 3 O 4 . Les linkers utilisés possèdent 2 fonctions : Le groupe fonctionnel de chélation et le groupe fonctionnel d'ancrage. La chélation permet d'interagir avec des métaux catalyseurs (par exemple le Cu) via une complexation métal-ligand. Ces groupes sont typiquement des fonctions carboxylates, thiols ou encore amines. D'autre part, l'ancrage du linker à la nanoparticule permet la formation d'une liaison forte avec Fe 3 O 4 . Ainsi, les molécules qui contiennent des groupements tels que des fonctions catéchol, silanol, et phosphonate ont été utilisées comme ancrage.

Nous avons évalué notre catalyseur sur la réaction d'aziridination classique, c'est-à-dire sur le styrène et en utilisant différents oxydants et précurseurs de nitrène. Puis, nous avons optimisé les conditions et fixé les paramètres de réaction pour cette réaction d'aziridination. Ensuite, nous avons étudié la recyclabilité du catalyseur (turnover) puis nous avons évalué la tolérance et la diversité des substrats pour laquelle cette méthodologie est applicable. Enfin, les limitations du catalyseur dans la réaction d'aziridination seront discutées ce qui conduira à la synthèse de nouveaux nanocatalyseurs magnétiques proposés pour la réaction d'aziridination.

D. Mise au point des conditions réactionnelles

Une série d'expériences a permis de déterminer les meilleures conditions d'aziridination catalysée par un complexe de cuivre dans le cas d'une catalyse homogène. Le but ici, était de trouver des conditions de références pour comparer à la version hétérogène (Schéma C). Notre première expérience a été réalisée à l'aide d'un équivalent du styrène et de 1,4 équivalents d'oxydant (PhI(OAc) 2 ou PhI=O) en présence de 10 mol % de Cu(OTf) 2 . Avec le PhI(OAc) 2 l'aziridine n'a finalement pas été obtenue de facon satisfaisante (tableau A, entrées 1-3). Les réactions effectuées avec de l'iodosylbenzène (PhI=O) ont en revanche, montré de bien meilleurs resultats (tableau A, entrées 4 et 6). Il est à noter que dans ce cas, la température a un effet très néfaste (tableau A, entrée 5). Après avoir trouvé les conditions réactionnelles optimales pour l'aziridination, un catalyseur de cuivre magnétiquement recyclable a été synthétisé pour remplacer le Cu(OTf) 2 .

E. Première utilisation d'un nano catalyseur magnétique récupérable (NCM) pour la réaction d'aziridination.

En s'inspirant des travaux de Varma, un catalyseur de Cu supporté par des nanoparticules magnétiques a été facilement préparé avec le procédé de co-précipitation. La première étape consiste en la précipitation de Fe Finalement, l'addition du complexe de cuivre (schéma E) a permis d'immobiliser le cuivre sur la nanoparticule fonctionnalisée par la dopamine. La spectrométrie d'absorption atomique a permis de déterminer les teneurs en cuivre avant et après réaction. Dans le cas de cuivre après cinq réactions, le résultat a révélé que le pourcentage de cuivre dans le catalyseur (10 wt %) a diminué jusqu'à 4,4 wt %. L'irradiation micro-ondes (MW) n'a pas montré de nette différence par rapport à l'utilisation du bain d'huile et le leaching reste à des valeurs similaires, mais qui ne limitent pas l'efficacité de la reaction.

H 3 C 70 >95 6

General introduction

Thesis work is a research on the synthesis of environmentally benign and sustainable heterogeneous catalyst for greener synthetic approaches of aziridine product which is done in research group of Axe Chimie pour le Développement Durable (C2D) at LG2A laboratory (Laboratoire de Glycochimie des Antimicrobiens et des Agroressources) at University of Picardie-Jules Verne (UPJV) under the Kouh Shekan SA Co. financial support.

Because of the overabundance of amino-compound in nature, introduction of nitrogen atom has arisen as a fundamental step in organic synthesis. To do so, valuable tools, such as nitren insertion, had been developed to introduce such atom onto Csp 3 -H bond via direct C-H amination or on alkene through aziridination. For the latter, the resulting aziridine ring has a great interest in biological area as potential therapeutic and cytotoxic agents, which make them attractive synthetic targets to design new antibiotic and antitumor drugs. However, this often needs many steps to control the configuration and obtaining desired product. Discovery of the copper catalyst in aziridination reaction was a hopeful procedure to orient the reaction towards direct and shorter steps. Using metal catalysts always have some limitations such as toxicity or requirement for filtration or extraction after completion of the reaction. In this way, for an environmentally benign, sustainability, and economic point of view, the preparation magnetic nano catalyst (MNC) is highly desirable. Thus, for the first time we propose a Cu-MNC for aziridination reaction. Synthesis of aziridine and MNC is done at LG2A laboratory. Classic aziridination reaction was successfully reproduced in present of Cu(I) or Cu(II) complex. Then, copper complex in aziridination reaction was replaced with copper loaded magnetic nano particles (MNPs). This magnetic nano catalyst was used to easily recover copper from reaction and examine its reusability for more than 5 runs. The catalytic characterization such as XRD, TEM, SEM, TGA, and Atomic Absorption Spectroscopy (AAS) is done at LRCS laboratory (Laboratoire de Réactivité et Chimie des Solides) at University of Picardie-Jules Verne (UPJV). NMR and HRMS analysis is done at plateforme analytique at UPJV. FT-IR and mass analysis of organic products were done at LG2A laboratory at UPJV. This thesis contains two general parts. The first part (bibliography) contains two chapters which the first chapter is a review of aziridination such as its historical background, natural product that incorporate aziridine and different aziridination synthetic methods. Chapter two is a review of magnetic nano particles and magnetic nano catalysts. In this chapter different methods for synthesis of magnetic nanoparticles and its modification with organic linker is discussed. Also, application of magnetic nano catalyst in organic reaction such as hydrogenation, oxidation and C-C coupling reaction is discussed in this chapter.

In the second part (results and discussion) we discussed the objective of aziridination reaction with the aim of magnetic nanocatalyst (chapter 3). We discussed the methodology and results of aziridination reaction with MNC. We optimized the conditions and expand the scope of aziridination. Also, we discussed about limitation in aziridination with MNC and propose different possibilities to pass the barriers. Finally, after a general conclusion (chapter 4) we presented all synthesis methods and analysis spectra such as NMR, FT-IR and HMRS for all obtained aziridine compounds and XRD, FTIR and AAS for all obtained magnetic nanocatalysts in experimental part ( chapter 5).

Chapter 1: Review of aziridination

In this chapter, we reviewed important features of aziridine rings such as bonding in aziridine, N-inversion and activated or non-activated aziridine. In each section, a general feature of the topic is talked and then it is discussed precisely. In continue the biological feature of the natural product containing aziridine ring (section 4) and the challenge of biological synthesis of aziridine products are discussed which led us to the next section. In following (section 5), the main organic synthesis of aziridine ring such as cyclization and addition reactions are discussed precisely. Transition metal catalyzed aziridination which is one of the main parts of the topic of this thesis is talked in this section. Finally, the last part of this chapter is devoted to intramolecular aziridination and mechanism of aziridination reaction with the copper catalyst.

1.1.Aziridines -historical background

Aziridines, also known as ethyleneimine, is the class of three-membered heterocyclic containing one nitrogen atom. The aziridine discovery dates back to the nineteenth century when Gabriel unknowingly synthesized "aziridine" while attempting to prepare vinylamine by treatment of 2-bromoethylamine with base (Scheme 1). 1 Later, Marckwald explained and suggested this cyclic structure as aziridine. 2 It is noted that the intramolecular displacement of a leaving group by a nitrogen atom, was later known as a general method to form this 3membered ring system.

1.2.Aziridine features 1.2.1. Bonding in aziridine ring

Aziridine ring is a highly strained heterocycle, the strain energy is calculated at 26.7 kcal/mol, compared with 27.5 and 26.3 kcal/mol for cyclopropane and oxirane, respectively. The internal ring bond angle of aziridine is 60° that causes a large divergence from natural angles between sp 3 -hybridized bonds. For minimizing this strain, aziridine rings adopt a change in hybridization of the ring atoms. Thus the bonds are not made up of sp 3 hybrids orbitals but show more a p-character, and overlap outside the axes joining the center of the nuclei that can be assumed as "banana" or bent bond (Figure 6). Also, the bonding feature of aziridine ring can influence its chemical features. For example, the higher "s" character in aziridine ring causes decreasing of the basicity (pH=8.04) compared to diethylamine (pH=10.7) and ammonia (pH=9.5).

N-inversion in aziridine ring

Generally, the process of nitrogen inversion involves an intermediate in which the nitrogen has a sp 2 hybridization. In aziridine ring, the strain makes N-inversion difficult to occur. The inversion barrier is influenced by the angle strain and the electronic structure of molecules which involve an incompatible decrease in the "p" character of the N-C ring bonds (Figure 7). 5

N N N H H H X X
Nitrogen tetrahedral (sp 3 )

Nitrogen trigonal planar (sp 2 )

Nitrogen tetrahedral (sp 3 )

Figure 7. Strain prevents nitrogen inversion.

On the other hand, the activation energy for inversion depends on the nature of the substituent on nitrogen. For substituents conjugated to the lone pair of the nitrogen, the rate is high. For other groups, the inversion is substantially slower because of the increased angle strain in the sp 2 hybridized intermediate (Figure 8). 6 The electron withdrawing substituents enhance the barrier to inversion. As an example, in case of the sulfonyl group (Figure 8), the electron pair on the nitrogen cannot accommodate aziridine ring to N-inversion. The electron withdrawal effect of the N-substituent increased the "p" character of the nitrogen-substituent bond, while the inversion process involves a decrease in "p" character. On the other hand for -CO 2 Me substituent, the electrons lone pairs is completely delocalized with the C=O bonds. This is the reason why the energy barrier is so low at 5 (kcal/mol). 6

1.3.Reactivity of activated and non-activated aziridine toward nucleophiles.

According to the properties of the N-substituent, aziridines may be broadly divided into two groups, named "activated aziridines" or "non-activated aziridines". In the activated group, aziridine is capable to conjugate with the partial negative charge on nitrogen and reduce the activation energy needed to undergo reaction. 7 Such activated aziridines exhibit sulfonyl, sulfinyl, phosphoryl, phosphinyl or carbonyl functional groups at the nitrogen atom (Scheme 2, a).

On the contrary, "non-activated" aziridines contain alkyl, aryl or just hydrogen (Scheme 2, b). It can be attributed to a more pronounced "s" character of the nitrogen lone pair which results in lower basicity and reduced π-donor ability. In terms of ring-opening reaction, nonactivated aziridine undergo ring-opening after protonation or action of a Lewis acid

N C O + X - H 2 C N C O X d - d - (a) (b) HN + X -

Activated aziridine

Aziridines activated by N-sulfonyl and N-phosphoryl substitutions are the most widelyemployed class used in ring-cleavage reactions. In addition, these derivatives have been demonstrated with pharmaceutical and other important synthetic applications. 8 In the following section, these two classes of N-substituent are discussed.

1.3.1.1.N-sulfonyl aziridines

The sulfonyl derivation is normally used to stabilize the negative charge of nitrogen in aziridine ring. Aziridines containing N-sulfonyl substituent can easily be prepared and easily crystallized. N-sulfonyl derivative can include 2-mesitylenesulfonyl (Figure 9, a), β-(trimethylsilyl)ethylsulfonyl (Ses) groups (Figure 9, b), nitrobenzene sulfonamides (Figure 9,c) , tosyl (Figure 9, d) and 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Figure 9, e). 9 These derivatives have been developed to improve the ring opening of aziridine and liberates the amine product. For example, Ooi research group 10 reported diastereoselective ring opening of N-sulfonyl aziridine using 3-substituted oxindoles as nucleophiles. It was observed that the stereoselectivity of the ring opening product depended on N-sulfonyl substituent of the aziridines and highly stereocontrol alkylation reaction was achieved by using N-mesitylsulfonyl aziridine in 98 % yield with 99 % ee.

1.3.1.2.N-phosphoryl aziridines

Phosphonoaziridines are another family of aziridine that contains phosphoryl functional group at the nitrogen atom and can be synthesized from common organic azides such as phosphoryl azides. 11 Phosphorylated aziridines and their derivatives (Figure 10) can be introduced as the key intermediates in the enantioselective synthesis of biologically active agents, such as anti-bacterial, and enzyme inhibitors. Several groups have investigated the use of phosphorus activating groups in the ringopening reactions of aziridines. Thus, N-diphenylphosphoryl aziridines (N-DPP aziridine) have been shown to undergo a range of ring-opening reactions (Scheme 4) with heteroatom and carbon-centred nucleophiles to give N-DPP amines in good yield (68 %). 12 .

Non-activated aziridine

The reactivity of non-activated aziridines appears to be different as compared to activated aziridines. This aziridinium intermediate represents a valuable feature to understand the regioselectivity of the ring opening of C-substituted aziridines (Scheme 5). 13

N R 2 R 1 E N R 2 a b Nu E R Nu R 2 N E R 1 N Nu R 2 E R 1 a b R 1 =Alkyl R 2
= 1-alkenyl, aryl, acyl, alkyl E=Lewis acid, H, acyl, alkyl, silyl Scheme 5. Activation and ring opening of non-activated aziridine.

Non-activated aziridines constitute a large variety of functionalized nitrogen-containing target compounds. For example, aminolactam which has unique properties as constituents of biologically active molecules was prepared by azidolysis of a non-activated aziridine followed by the catalytic hydrogenation of the resulting β-amino-γ-azido ester (Figure 11). The ring-opening reactions of different types of non-activated aziridines such as vinylaziridine 15 , arylaziridines 16 , acylaziridines 17 , and alkylaziridines 18 were widely studied. For example, the successful synthesis of trans-isoxazolidin-3-ones from 1-alkyl-3-arylaziridine-2-carboxylates was conducted by Besbes (Scheme 6). 19 Attack of a hydroxylamine anion as the nucleophile at position 3 of the aziridine ring in 1-alkyl-3-arylaziridine2-carboxylate provided an aziridine ring opening as an intermediate which underwent spontaneous ring closure.

1.4.Natural products incorporating aziridines and biosynthesis

Aziridine ring can play a versatile role in the construction of bioactive agents. However, there is not a vast number of naturally occurring aziridine. Also, the biochemical reaction used for the formation of aziridine ring remains unclear. [START_REF] Yudin | Aziridines and Epoxides in Organic Synthesis[END_REF] In contrast with epoxide natural products for which enzymatic formation occurs by insertion of an oxygen atom from O 2 into an alkene, it doesn't seem that the aziridines are formed in a similar manner using N 2 . Some natural molecules were studied to define the role of aziridine functional group in their bioactivity. [START_REF] Konno | [END_REF] For example, Miraziridine (Figure 12), that contains aziridine ring, is a pentapeptide isolated from the marine sponge. It inhibits the action of cathepsin B with an IC 50 value of 1.4 mg/ml (2.1 μM). [START_REF] Konno | [END_REF] The analog lacking the aziridine site showed remarkably weak inhibitory activity for cathepsin B. The azinomycin (Figure 13) is an antitumor agent isolated from fermentation broths of Streptomyces griseofuscus. The electrophilic nature of the aziridine ring has been shown to play a key role in DNA interaction. 22 Another natural product containing an aziridine ring system is Maduropeptin. This protein contains a chromophore moiety holding an aziridine ring (Figure 14). It is isolated from the Actinomadura and exhibits antitumor and antibacterial activities. The aziridine ring in the structure of Maduropeptin chromophore plays a useful and versatile role in the design and construction of bioactive agents. Perhaps the best-known compound that shows the biological importance of aziridine ring is mitosane, a family of compounds which is extracted from Streptomyces verticillatus. These compounds possess a wide range of activity against various cancers, including gastric cancer, cervical cancer, prostate cancer or bladder cancer. The five members of this class are mitomycin A, B and C, porfiromycin, and mitiromycin (Figure 15). These first classes of bioactive compounds, which can undergo a nucleophilic ring opening of aziridine inhibit DNA synthesis. 24 In the first step of the postulated mechanism of action (step 1, Scheme 7), the natural products are metabolically activated by reduction of the quinone form to give the hydroquinone. In general, the drug requires chemical or enzymatic reductive activation to the hydroquinone form, to bind DNA by mono-or bifunctional alkylation. Then, the formation of indoloaziridine (step 3) occurs. The aziridine ring is next cleaved (step 4) and DNA is first alkylated (step 5) and then a cross-linking occurs (step 6). Finally, the interaction of mitomycin and DNA cause crosslinking of strands of double helical DNA. Step 1

Step 2

Step 3

Step 4

Step 5

Step 6 DNA Cross-linking

X = NH 2 Y = CH 3 Z = H Scheme 7.
Aziridine ring opening of mitosane and DNA alkylation.

Studies on the mode of action of mitomycins (Figure 15) showed that the aziridine ring is essential for antitumor/antimicrobial activities of these compounds. In fact, experiments with Mitomycin isotope-tracer indicated that all mitomycins proceed via a combination of 3-amino-5hydroxybenzoic acid (AHBA), D-glucosamine derivatives, and carbamoyl phosphate, to form the mitosane core, followed by specific tailoring steps (Scheme 8). 26 Scheme 8. Mitomycins and their hypothetical biosynthetic pathway.

The biosynthesis of azicemicin is not well-known, but an obvious possibility is the use of serine as a starter unit for an aromatic polyketide synthase, with cyclization through a S N 2 reaction occurring at some step (Scheme 9).

1.5.Aziridines in organic synthesis

Organic synthesis methods for the preparation of aziridines can be grouped into two broad classes: cyclization and addition processes and each of these categories can be further divided.

Cyclization processes (Scheme 10) involve ring-closure of amino alcohols (1) (Wenker synthesis), cyclization of 1,2-aminohalides from halide alkene (2), N-cyclization of primary amines with diols (3) and from oxirane (4). In amino alcohols cyclization, hydroxy group must be first converted into a good leaving group. In the next step, aziridine is formed in presence of a base. 28 In oxirane case, the process involving a ring-opening of the oxirane with sodium azide is followed by the organic reduction of the azide with triphenylphosphine (Scheme 10). 29

N R 3 R 1 R 2 Br R 2 R 1 H 2 NR 3 R 1 NHR 3 R 2 HO H + , SOCl 2 OH R 1 HO R 2 O R 1 R 2 (1) (2)
(3) (4)

NaN 3 , PPh 3 SOCl 2 , [O] H 2 NR 3 R 4 P + X - R 3 =H

Scheme 10. Aziridination via cyclization processes

Addition processes can proceed through the addition of nitrenes (or nitrenoids) to alkenes. They are classified as C 2 +N 1 reactions (Scheme 11a). It also could proceed via the addition of carbenes (or carbenoids) to imines. They are classified as

C 1 N 1 +C 1 reactions (Scheme 11b). 30 R 1 C 2 C 2 R 2 R 3 N 3 Y-I=N-R 3 R 3 NHOAc, Cat R 1 C 1 N 1 R 2 R 3 C 2 ML n R 3 YR 2 a) b) N 1 R 1 R 2 R 3 N 1 R 1 R 2 R 3 R1=R2=R3= Alkyl, Aryl Y= Aryl
Scheme 11. a) C 2 +N 1 reaction: addition of nitrenes to alkenes. b) C 1 N 1 +C 1 reaction: addition of carbenes to imines.

Cyclization reaction

Cyclization reaction is the oldest and the simplest classes of reaction leading to aziridines. The most obvious cyclization reaction precursors for aziridines are probably the amino alcohols. The reaction can be readily achieved when the hydroxyl functional group is converted to a nucleofuge. Intramolecular nucleophilic displacement reaction by either the amide anion or the amine lone pair then yields the aziridine ring. Wenker subsequently reported that heating of 600 g of ethanolamine with more than 1 kg of 96 % sulfuric acid at high temperature produced 282 g of β-aminoethyl sulphuric acid. After distillation under KOH, 23g aziridine was obtained (Scheme 12). This method is efficient for simple amino alcohols but unsatisfactory for tertiary alcohols where elimination preferentially occurs to produce the corresponding alkenes. Also, this method cannot be extrapolated to the synthesis of N-acyl or N-carbamoyl aziridines.

Another cyclization procedure is the obtaining of aziridine from oxirane (Scheme 13). In this case, oxirane is opened by azide ion. Then, reduction of the azide moiety with triphenylphosphine in the Staudinger reaction yields an imino phosphorane. [START_REF] Gololobov | [END_REF] Aziridine was obtained through the oxazaphospholine intermediate (generally not isolated) by thermallyinduced cyclization. Phosphine-mediated ring-closures of azidoalcohols, obtained from epoxides opening have been widely investigated. For example, the method has been applied to the synthesis of aziridine (2S,3S)-dicarboxylic ester (Scheme 14). 32 In this strategy, the key aziridine-forming reaction involves the treatment of azides functional groups with trialkyl-or triphenylphosphine, producing oxazaphospholidine, which is rapidly formed but slowly converted into Nunsubstituted aziridines upon heating in the organic solvent. The reaction has been applied in a wide range of chiral and achiral epoxides and when enantiomerically-pure epoxides are used, access to non-racemic aziridines is feasible.

Addition reaction

Addition reaction is a title for a broad area of methods used for the synthesis of aziridines. Along this line, ylide and carbene addition to imines or nitrene addition to olefins are parts of the most common addition methods for aziridine formation. 33 Ylides such as phosphonium, sulfonium ylides, and ylides of other heteroatoms have also been used to perform aziridinations. The generally accepted mechanism for aziridine formation from sulfur ylides and imines involves two key steps (Scheme 15). The first one is an addition of the ylide to the imine to form a betaine intermediate. Two isomeric betaines can be formed during this step: an anti and a syn diastereoisomer. The transoid conformer (aza and sulfonium groups antiperiplanar to each other) of each of these betaines can then ring close to yield a trans and a cis aziridine, respectively. 34 Another addition method for formation of aziridine is carbene addition to imines in the presence of a metal complex as the catalyst. The first mechanism contains a metal-carbene intermediate (Ia) which reacts with imine in the next step leading to the aziridine (Scheme 17, a). The second mechanism involves coordination of the imine to the metal complex leading to an imine-metal complex (Ib), which reacts with the diazo compound leading to the elimination of N 2 (Scheme 17, b). 35 Many attempts have been devoted to developing catalytic aziridination of imines, and there has been some success using copper, iron or lanthanide -carbene intermediate. Other important addition reaction method is nitrene addition to olefins involves metalonitrenes species. The nitrene sources can come from imino iodinanes, sulfonyl azides, aryl azides, tosyloxy carbamates or Chloramine-t. The aziridination usually occurs in presence of a catalytic amount of metals such as ruthenium, copper, cobalt, rhodium silver, gold or iron leading to metal-nitrenoid intermediate. It plays a pivotal role in catalytic nitrogen transfer to the olefin. (Scheme 18). 36 As previously described, transition metal-catalyzed aziridination reactions are the main method that is used in this thesis. This method generally involves nitrene transfer to alkenes. Among the various metal catalysts reported in the literature, copper or rhodium catalyst in presence of PhI=NTs caused selective, and efficient aziridination of olefins. In the following section, we are going to discuss metal catalyzed aziridination in present of Cu or Rh as the most transition metal for catalytic aziridination reaction.

S

LM + N 2 CHR' -N 2 LM H R' N R R R' LM H N R R N R R R -LM N R R + LM N R R LM N 2 CHR' N 2 R' H N R R LM N 2 H N R R R' N R R' R -N 2 -LM

Cu-catalyzed aziridination

Copper catalyst is to date the most studied transition metal for aziridination reaction. Evans 37 , as the pioneers in this research area, disclosed that aziridination of a number of olefins can be achieved using Cu(I) or Cu(II) with PhI=NTs (Scheme 19). His reseaches showed that copper is superior to other metal complexes such as Mn(TPP)Cl and Fe(TPP)Cl. Also, he examined different olefins in the presence of different copper sources with a 5-fold excess of the substrates and 5-10 % of the catalyst. Under this condition, the catalyzed aziridination reaction proceeds in good yields with both aromatic and aliphatic olefins (table 1). Series of considerable attention has been devoted to developing copper catalyzed aziridination with representing Cu in presence of different kinds of ligands. For example, Halfen et al. introduced Cu-1-(2-pyridylmethyl)-5-methyl-1,5-diazacyclooctane trifluoroacetate complex (Figure 16, a) and Cu-1,4,7-triisopropyl-1,4,7-triazacyclononane-bis(trifluoroacetate) ( Figure 16,b) as catalysts that exhibited remarkable efficiency in aziridination of styrene. However, these catalysts are not efficient catalysts for the aziridination of activated olefins such as 1-hexene and cyclooctene that caused only 35 % and 23 % yield, respectively. Most of the effort for modifying copper catalyst with ligands proceeds to introduce a chiral copper catalyst. In this way, bisoxazoline ligands have been successfully applied to the copper-catalyzed asymmetric aziridination which was pioneered by Evans 39 and Jacobsen 40 . As a recent example, Lebel et al. 41 reported the synthesis of an asymmetric aziridine using a chiral gem-dimethyl-phenylglycine-derived bisoxazoline ligand. The bis(oxazoline) ligand bring stereodifferentiation in cooperation leading to efficient diastereoselectivities. The corresponding aziridine was obtained with electron-deficient styrenes, such as nitro-substituted styrenes, with yields up to 84 % and diastereoselectivities up to 86 % (Scheme 20).

Rh-catalyzed aziridination

Subsequent investigations showed that rhodium catalysts can induce aziridinations, but with a higher propensity to generate C-H insertion products. 42 One of the first rhodium-catalyzed aziridinations was reported by Müller. 42 In this experiment, PhI=NNs {(4nitrophenylsulfonyl)imino}phenyliodane was used as nitrene precursor in presence of [Rh 2 (OAc) 4 catalyst that the proceeds in yields up to 85 % when the olefin is used in large excess (Scheme 21). Bidentate chiral ligands were also vastly used to develop Rhodium-mediated aziridination. 43 For example, Che's group reported different chiral rhodium (II) dimers (Figure 17) and obtained aziridine products up to 68 % yield. The Rh-catalyzed aziridination with PhI=NNs exhibits many similarities to Cu-catalyzed reactions with PhI=NTs. In this way, rhodium catalyst was modified with ligands to introduce a chiral rhodium catalyst. As an example, styrene and cis-β-methylstyrene were aziridinated with PhI=NNs in the presence of the Rh 2 (R-BNP) 4 catalyst. The chemical yields of the reaction were satisfactory, and enantioselectivity of β-methylstyrene observed 73 % (Scheme 22). 42 In general, the experimental results showed that chemical yields of the reaction with rhodium catalysts for aziridination reaction were usually satisfactory, but enantioselectivity can't reach a useful level for synthetic applications.

1.6.Intramolecular aziridination

The benefit of intramolecular aziridination is that the reaction happens faster in compare of intermolecular reaction which takes place in two separate molecules. In this way, transitionmetal complexes provide a convenient access to bicyclic aziridines through intramolecular C-N bond formation reactions. Many of these procedures involve iodine (III) compounds PhI=NTs, PhI=O, or commercially available PhI(OAc) 2 . The mechanism involves the intramolecular transfer of unsaturated sulfonamides and sulfamate ester to alkene double bonds in presence of metal catalysts like a copper and ruthenium.

The intramolecular synthetic potential of the aziridination was markedly improved by Dauban and Dodd. 45 They introduced unsaturated sulfonamides/sulfamate esters as starting material and obtained the expected product in the range of 20-80 % using copper catalysts. (Table 2). 2. Intramolecular copper-catalyzed reaction. 45 Also, Liu developed a stereocontrolled intramolecular aziridination procedure based on glycal derived sulfamates and using rhodium catalyst. Intramolecular nitrogen atom transfer to πbonds of sulfamate glycals can form semistable aziridines, which is subjected to various nucleophiles to give cyclic sulfamate containing aminosugar derivatives (Table 3). 46 Table 3. Stereoselective aziridination of sulfamate glycal. 46 This intramolecular reaction mechanism involves firstly the generation of a Rh-nitrene complex and then, an elimination of the PhI moiety from iminoiodinane which is followed by catalyst bound aziridine formation. Finally, a nucleophilic attack on the aziridine intermediate can cause ring opening. 46

1.7.Mechanism of the metal-catalyzed aziridination

To date, there is a lot of reports in the literature that give information on the mechanism of aziridination reaction from different methodologies. However, since the 1990s, synthetic attention has been directed more towards the use of metal-stabilized nitrenes as synthetic effectors of alkene aziridination. This synthetic method was dominated by different researchers such as Evans 37 and Jacobsen 68 and was investigated from the different point of view. One important question in this specific method is the mechanism of nitrene transfer to olefins. However, behind the general issues and rules in metal-catalyzed nitrene transfer to olefin, the mechanism may be more system dependent and each researcher tries to put more details on their case study. Here is, we tried to report a general mechanism for the copper-catalyzed olefin aziridinations according to the copper catalyst.

Experimental and computational results support the idea of the formation of highly active nitrene intermediate using copper (I) or (II). 47 If copper (II) is used, it is proposed to be reduced to Cu (I) in the first step of the catalytic cycle.

In the first step, nitrene source (PhI=NR, R = alkyl, aryl, sulfonyl, carbonyl, phosphoryl ) generate a reactive free nitrene intermediate able to react with Cu catalyst. The copper-nitrene intermediate plays a crucial role in the subsequent catalytic steps. Two electronic states, singlet, and triplet are possible for the "Cu=NR" species (Figure 18 shows a deceptively simple representation of both). The triplet species has been usually associated with a stepwise mechanism, whereas a concerted pathway has been frequently assigned as a consequence of the singlet state (Figure 18). The presence of the radical or the concerted paths was established on the basis of a series of model experiments, from which a typical behavior is expected depending on the nature of the nitrene intermediate. In the next step, the reaction between the alkene and an electrophilic radical species causes carbon-nitrogen bond formation and finally at the end of reaction copper catalyst come back to the catalytic cycle (Figure 18). 48 (Figure 18) and the works of Jacobsen. He used the hybrid density functional theory (DFT) for calculating oxidation state of copper and suggested a possible potential free energy surface for diimine system.

He mentioned that at the beginning, the catalytic cycle initiate with the formation of a Cu-alkene complex (Figure 19-a). By addition of PhI=NTs to the Cu-alkene mixture, decomplexation of the alkene and coordination of PhI=NTs to the catalyst appear (Figure 19-b). It should be noted at this point, the N-I bond is very weak. According to DFT calculation, the Cu-PhI=NTs complex could not be the resting state for the catalytic cycle. Excitation of this species to the triplet state results in immediate dissociation of iodobenzene forming triplet Cunitrene (Figure 19-c). As it discussed before, the singlet or triplet states depended on the nature of nitrene intermediate. In continue, the nitrogen-carbon bond is formed. The triplet state of this intermediate has one unpaired electron at Cu and one at the terminal carbon of the alkene ( Figure 19-d). Also, according to DFT analysis, it is possible to calculate the energy of the transition state for ring closure and forming the final aziridine product (Figure 19-TS2). The DFT analysis showed 1.2 kcal/mol activated energy is needed for the formation of aziridine in this case. Finally, the formation of the aziridine is accomplished without loss of coordination of copper, leading to complex e.

Chapter 2: Review of magnetic nanocatalyst

In this chapter different type of catalyst such as homogeneous and heterogeneous catalysts is reviewed. Different aspects of these catalysts are discussed at the beginning of this chapter. The drawbacks and limitations of using homogeneous and heterogeneous catalysts led us to talk about nanocatalysts. As the aim of this thesis for the synthesis of magnetic nanocatalyst, the benefit of magnetic nanoparticles (MNPs) and magnetic nanocatalysts (MNCs) are discussed (section 2.3). In continue, different synthesis methods of MNPs and their modifications with organic compounds are discussed precisely (section 2.4 and 2.5). In following, the application of modified MNPs for chelating metals is discussed. Different possibilities and examples are counts to show the importance of MNCs in the field of organic chemistry. Also, we count the examples of using MNCs in hydrogenation, oxidation, C-C coupling, and epoxidation reactions. In our point of view, the use of MNCs for aziridination reaction is not reported until now which is the subject of our work in chapter 3. Finally, the importance of characterization of MNCs and the feature of each characterization method is talked in the following section (2.7).

Green and sustainable catalysis

Catalysis is a key field of science because it can represent a way to achieve the objectives of sustainable (green) chemistry. In this way, the main concerns of the global vision are: design the chemical products and procedure more environmentally acceptable. This progress in all areas of chemistry for designing a sustainable catalyst has become a fundamental part of research.

Green chemistry strives to design sustainable catalyst for minimizing the waste generated by the use of stoichiometric reagents. This involves the use of the full breadth of catalyst: heterogeneous, homogeneous, supported, and organocatalyst. 50 In this chapter, the search for environmentally benign, sustainable, and efficiently reusable alternative catalytic systems and historical view of catalysis development is discussed.

Homogeneous and heterogeneous catalysis

Catalysis can be divided into two types, homogeneous and heterogeneous. By definition, homogeneous catalysis refers to a type of catalytic system in which the catalyst operates in the same phase as the substrates. Homogeneous catalysts can be used in the chemical reaction to carry out the reaction with high selectivities, of catalytic activity. Different reactions such as C-C coupling reaction, 51 aziridination 52 or hydrogenation 53 have been reported in homogeneous condition.

Despite their advantages, these catalysts are used in less than 20 % of the industrially relevant processes. 54 It is often because of a high-priced noble metal or ligand, generally difficult to isolate and separate from the final product at the end of the reaction. Thus, recycling of homogeneous catalysts is an important issue in the sustainable and large-scale production of fine chemicals. 54 On the other hand, heterogeneous catalysis is widely used in industrial applications because of the facile separation, which often results in lower operating costs. Heterogeneous catalysts can promote different chemical reactions such as hydrogenation 55 and oxidation 56 reactions. In this way, some transition metal complexes have shown high selectivity, efficiency, and reproducibility to catalyze the reaction under mild condition. 57 However, when they are used in the homogeneous catalytic processes, huge waste materials are produced. Heterogeneous catalysts are considered to be a better choice when environmental safety is under attention. Heterogenization of transition metals can be achieved by grafting on the surface of a solid support, like silica, zeolite, metal oxide polymers, and alumina. 58 This grafting can be achieved by adsorption or by covalent binding of active catalytic molecules. For example, silica is used to achieve this aim. 59 This support (Figure 20) is made via a sol gel template of organosilica precursors in four steps to give materials with organic moieties inside the pore walls. At first, the solution of precursors that consist of metal alkoxides is hydrolyzed to metal hydroxide in the presence of water (sol). Then, in next step, condensation of the sol result polymer network (gel) and finally supercritical drying cause the product. In this case, the organic moiety is located in the pore wall of the material and can be used to post-functionalization of the support such as graft/anchor metal sites. The benefit of using support is the recyclability of the catalyst at the end of the reaction. The covalent binding between support and catalyst is generally chosen to survive in harsh reaction conditions. This binding minimizes the catalyst leaching and allows the catalyst to be reused several times. 60 However, the active sites in heterogeneous catalysts are not as accessible as in a homogeneous system. There are often different active sites in the bulk material of a heterogeneous catalyst, which causes a decrease in the overall reactivity of the catalyst system. 61 One way to overcome the drawbacks of homogeneous and heterogeneous systems is bridging the gap between homogeneous and heterogeneous catalysis. This system should show not only high activity and selectivity (like a homogeneous system), but also possess easy recovery and reuse of catalysts (like a heterogeneous system). That is to say, this sustainable and green catalyst must possess specific features including high activity and recyclability. These goals can be achieved using nanocatalysis. 62

Magnetic nanoparticles (MNPs) and magnetic nanocatalysts (MNCs)

Nanocatalysts emerged as efficient alternatives for enabling a heterogeneous catalytic system to achieve reaction rates close to its homogeneous counterpart. 63 Nano size of the particle brings a large specific surface area, i.e. high loadings of catalytically active sites and enhances the contact between reactants and catalyst. Investigating such small-sized particles will also assist in understanding the relationships between homogeneous and heterogeneous catalysis, and could efficiently bridge the gap between these two traditional processes. The smaller object causes the higher surface area-to-volume ratio and experience close to a homogeneous. When materials are produced at the nanoscale size, tuning material properties such as size, shape, and morphology is possible. In this way, in nanoscales, catalysts exhibit novel properties which would often be difficult to find in their macroscopic counterparts. 64 The most common difficulty associated with the nanocatalyst is its tedious recovering process. Different approaches have been suggested to circumvent difficulties in catalyst separation, such as nanofiltration and separation techniques based on liquid-liquid phase separation, including ionic liquids, fluorous phases, supercritical solvents, and polymeric supports. 65 Each separation method has its own limitations of cost, efficiency, or generation of secondary waste. Additionally, nanoparticles often undergo agglomeration without the addition of stabilizers, thereby diminishing their activity. 66 Therefore, the focus during the past decade has been on stabilizing nanoparticles by immobilization on different solid supports such as silica, alumina, polymer, and carbon, among others. 67 However, many of these supports have serious limitations including the difficulty of their synthesis, along with their tiresome recovery using centrifugation or time-consuming filtration. 68 To overcome these issues, use of magnetic nanoparticles (MNPs) appears to be a logical solution. Magnetic nanoparticles can be simply and efficiently removed from reaction mixtures with an external magnet (Figure 21). MNPs can be used in two different ways: they can directly be used as a catalyst in the reaction or can be modified to support active molecules or transition metals. As an example, Fe 2 O 3 MNPs have found application in several oxidation and coupling reactions. Beller used Fe 2 O 3 MNPs to catalyze the oxidation of olefin and alcohols in presence of O 2 or hydrogen peroxide with great result. 70 Later Fe 2 O 3 MNPs were used for the catalysis of borylation with bis(pinacolato)diboron. Also, spinel ferrite nanoparticles such as CoFe 2 O 4 MNPs were exploited for different reactions like Knoevenagel reaction between various aldehydes and ethyl cyanoacetate. 71 These examples were a showcase of the unique catalytic activity of magnetic particles for different kind of reactions and their great potential for replacing homogenous and some heterogeneous catalysts (Scheme 23).

R 2 R 1 OH R 2 R 1 O Fe 2 O 3 MNPs [O] R R O Fe 2 O 3 MNPs [O] R + O B O B O O Fe 2 O 3 MNPs [O] B O O R O R + CN O O CoFe 2 O 4 NP H 2 O:EtOH O R CN O Scheme 23.
Selected reactions catalyzed by magnetic nanoparticles. 71

Synthesis of magnetic nanoparticles

Magnetic nanoparticles have been synthesized following several protocols and can consist of different compositions. Thus, they can be divided into three different categories: 1/ carbonaceous magnetic materials, 2/ metal oxide magnetic materials and 3/ polymer divided magnetic materials. The main compositions of magnetic nanoparticles can be pure metals, such as Fe, Co, iron oxide (Fe 3 O 4 and γ-Fe 2 O 3 ), 72 or spinel-type ferromagnets (MnFe 2 O 4 73 and CoFe 2 O 4 74 ). In the last decades, numerous studies have been devoted to describing efficient synthetic routes to shape-controlled, highly stable, and monodisperse magnetic nanoparticles. These aims can be achieved by using different synthetic methods such as precipitation, thermal decomposition and/or reduction, micelle synthesis, hydrothermal synthesis, and laser pyrolysis which some of them are discussed below. It is important to note that the practicality and costeffectiveness of these processes have a direct effect on the sustainability of the protocols based on the materials used. 75 In continue, some common synthesis of magnetic nanoparticles will be discussed.

Precipitation

Among all existing methods, precipitation is a facile and convenient way to synthesize magnetic nanoparticles especially Fe 3 O 4 (Scheme 24). In a typical procedure, the size, shape, and composition of the magnetic nanoparticles very much depend on the alkaline source (NaOH or NH 4 OH), the ferrous/ferric ratio, the type of metal salts, the reaction temperature, and the pH value. With this method, particles with diameter inferior to 50 nm are generally obtained. 76 On the other hand, even if the method is fast with high yield and low cost of the precursors, it is reported that as-synthesized magnetite nanoparticles (Fe 3 O 4 ) are poorly stable under ambient conditions, and are easily oxidized to maghemite (Fe 2 O 3 ).

Thermal decomposition

This method is inspired by the synthesis of semiconductor nanocrystals. 78 It involves the chemical decomposition of substance at an elevated temperature. 79 In this method, various parameters including organometallic compounds (metallic precursors), surfactant, and solvent as well as reaction time and temperature are decisive to control the final size and morphology of magnetic nanostructures. 80 When the thermal decomposition method is used, iron oxide nanoparticles are obtained with excellent control of size, morphology and good crystallinity. Recently, Nogues and co-workers demonstrated that the ratio of precursors and the thermal decomposition time can be used to achieve size-and morphology-controlled nanocrystals. They showed that short decomposition duration (2-4 h) resulted in spherical nanoparticles whereas longer reaction time (10-12h) resulted in cubic morphology (Figure 22). 81

Microemulsion

Microemulsion consists of two immiscible liquids which are stabilized by surfactant molecules. 82 In this method, the aqueous phase is dispersed as microdroplets (typically 1-50 nm in diameter) surrounded by a monolayer of surfactant molecules. 83 By mixing two identical water-in-oil microemulsions containing the desired reactants, the microdroplets will continuously collide, coalesce, and break again, and finally will form a precipitate in the micelles. 84 For the synthesis of MNPs, nanoemulsion containing iron source and sodium hydroxide are mixed together. After microemulsion, the product is precipitated with acetone or ethanol to remove the surfactant and washed with ethanol. Then the precipitate can be extracted by filtering or centrifuging. The colloidal MNPs exhibit superparamagnetic behavior with high magnetization values. 85 This method can be applied to the synthesis of various nanoparticles. For example, spinel ferrites such as MnFe 2 O 4 nanoparticles with controlled sizes from about 4-15 nm were synthesized through the formation of water-in-toluene inverse micelles from Mn(NO 3 ) 2 and Fe(NO 3 ) 3 in aqueous solution. 86 However, it must be mentioned that one of the main disadvantages of this method is adverse effects of residual surfactants on the properties of the particles and difficulty in scale-up procedures.

Hydrothermal

Hydrothermal synthesis can be defined as a method for the synthesis of single crystals. It is based on the ability of water and aqueous solutions to dilute minerals at high temperature and pressure. The temperature and the pressure of this method depend on the solubility of minerals in hot water which is practically insoluble under normal conditions. 87 It is a unique method for fabrication of special shape and size of metal, metal oxide and metal oxide magnetic nanoparticles. 88 As an example, Li 89 used this method for synthesis of different nanocrystals (such as Fe 3 O 4 and CoFe 2 O 4 ). The reaction in the preparation of metal nanocrystal involves adding an aqueous solution of metal ions, sodium linoleate (or another sodium stearate) and the mixture of linoleic acid (or another fatty acid) and ethanol into the vessel that cause the formation of the three phases. As it is shown in Figure 23, these three phases involve: the reduction of metal ions by ethanol at the interfaces of metal linoleate (solid), ethanol-linoleic acid liquid phase (liquid) and water-ethanol solutions (solution). In this method, linoleic acid is used to absorb on the surface of the metal nanocrystals with the alkyl chains on the outside of the surface for producing a hydrophobic surface. Finally, phase-separation process can occur from the hydrophilic solution because of the hydrophobic feature and weight of the metal nanocrystals. Recently, Wu and co-workers have synthesized Fe 3 O 4 @C core-shell nanorings (NR) which involved a hydrothermal process. 90 The procedure of formation of the Fe 3 O 4 @C Core-Shell nanoparticles with loop and truncated morphology is given below (Scheme 25). The morphological evolution of the nanoparticles from the plates shape/scaffold (a) to the nanoring shape/scaffold (d), is achieved by surface Polyvinylpyrrolidone (PVP) adsorption and followed by glucose reduction. 90 The Ostwald ripening through a hydrothermal reaction at 160-220 °C gave the nanorings. Also, TEM images of NR showed that it possesses a wall thickness of 25 nm, lengths of about 150 nm with 2-4 nm coated carbon shell. In general, Fe 3 O 4 /C NRs formed under hydrothermal conditions displayed better features (such as better electromagnetic wave absorption), than Fe 3 O 4 /C obtained via high temperature carbonization. These nanorings show potential use in various fields, such as density data storage technology, nanocatalysis, biosensing, microwave absorption, and MRI contrast agents. The advantages and disadvantages of the as-discussed chemical methods (precipitation, thermal decomposition, microemulsion, and hydrothermal methods) for the synthesis of magnetic nanostructures are briefly summarized in Table 4. In general, thermal decomposition and hydrothermal approaches provide better results in terms of size and morphology in comparison with other synthetic routes. In terms of simplicity of the synthesis, precipitation which involved the precipitation of nanoparticles from the solution in mild conditions is the preferred route.

Liquid

Synthetic method

Synthesis observation

Temp.

( o C) To date, magnetic nanoparticles prepared from co-precipitation and thermal decomposition was more studied and can be prepared on a large scale. The microemulsion can be another alternative for synthesizing monodispersed nanoparticles with various morphologies but needs a large amount of organic solvent. Hydrothermal methods are a relatively useful method to synthesize high quality magnetic nanoparticles controlling the shape, and some complicated or hard achieving morphology such as nanorings can be obtained with this method. 91

Modification of magnetic nanoparticles

This part describes a general strategy using anchors to present functional molecules on the surface of iron oxide nanostructures. The successful synthesis of monodispersed magnetic nanoparticles, particularly iron oxide nanoparticles (Fe 3 O 4 , γ-Fe 2 O 3 ) pave the way to broad applications of magnetic nanoparticles in different domains of research. 92 But, these applications usually require particular molecules which should be immobilized on the surfaces of the magnetic nanoparticles. Several alternatives have been developed to modify magnetic nanoparticles depending on the functional group used in anchoring molecule: organosilicon, phosphonic or catechol functional group. 64 Thank these grafting groups, new molecules (metal ions or drugs) can be easily introduced on the surface of magnetic nanoparticles. Here we summarize some of these robust anchors and their preparation for chelating different metal catalysis.

Silane and silica

Introduction

Silica is the most often used coating agent for metal oxide surfaces, because of biocompatibility and resistance to biodegradation in biological environments. Moreover, a secondary modification can be easily performed on a silica shell. 93 Organosilicon compounds used for modification of magnetic nanoparticles, such as silane have two different functional groups: one reacts with organic materials and the other one with inorganic materials. 94 In the general formula of silane (X-(CH 2 ) n -Si-R 3 ) the X group can be amino, cyano, carboxylic acid, epoxy group, etc. able to react with an organic moiety, and the silane function (SiR 3 , where R represents generally methoxy or ethoxy is able to graft onto the surface of the metal oxides nanostructures (Scheme 26). [95][96] Scheme 26. A) example of some commercial organosilanes, B) Surface functionalization of MNPs.

Applications

A great number of studies deal with the surface modification of MNPs with silane and its potential applications in many areas, such as biology, medicine, and environment. As an example, Saint-Cricq et al. 97 modified the surface of superparamagnetic iron oxide (SPIO) with silica and functionalized it with a thermodegradable polymer for a drug delivery targeting (Figure 24). In this study, they physical encapsulated a high amount of drug (rhodamine 6G) in porous silica and used the azo-modified polymer as caps for the nanochannels within the silica matrix. Various properties such as grafting efficiency, surface composition, zeta potential, particle size and drug loading were investigated to determine this thermoresponsible MNP. 1 The obtained sized of MNPs with TEM were approximately 70 nm in diameter and TGA analysis showed that the density of grafted polymer on the surface of MNPs is 7 wt % to 13 wt %. Drug loading was monitored by UV-visible spectroscopy and the loading capacity of the drug in MNPs was calculated 18 wt %. Then, the drug release can be activated on demand upon exposure to a magnetic field thanks to magnetic heating and degradation of the polymer. 97 Also, they showed that responsible polymer cap is not cytotoxic after examination the ability of MNPs used for NIH 3T3 fibroblast cells.

Organophosphorus

Introduction

Organophosphorus molecules appear to be complementary to organosilicon modifier molecules as they show an excellent tendency towards metals oxide supports such as Fe 3 O 4 and γ-Fe 2 O 3 . Organophosphorus compounds like phosphonic acid, alkylphosphoric acid, and their salts, form a stable metal-oxygene-phosphorus (M-O-P) bond via heterocondensation and coordination. 99 Phosphonic acids and phosphonates can adsorb on the surface of metal oxide in a mono-, bi-or tridentate mode that can bring a stable organic shell (Figure 25). 100 These molecules react with hydroxyl groups on the surface of metal oxide leading to monolayers and ultrathin hybrids. 101 Subsequently, organophosphorus coupling agent as like as silane can be used to derivative the metal oxide surfaces with active functional groups such as -COOH or -NH 2 .

Applications

Muthukumaran and his co-worker reported the modification of MNPs with orthophosphate moiety. In this work, phosphate coated iron oxide nanoparticles were synthesized by a one-pot reaction over magnetite nanoparticles. This work was done with the aim to synthesize monodispersed magnetic nanoparticles able to produce stable ferrofluids. The nanoparticles were characterized by TGA-DSC, FTIR, XRD, small-angle X-ray scattering (SAXS), TEM, vibrating sample magnetometer (VSM), DLS and showed a good stability in pH range of 6-10. Suitable hydrophilic biomolecules like peptides, proteins or nucleotides can be linked to the MNP and offer various applications in biochemistry and biological field. 103 Organophosphorus ligands are low cost for surface functionalization of superparamagnetic nanoparticles. Sahoo et al. reported coated magnetic nanoparticles with phosphonomethyl iminodiacetic acid for immobilization of urease enzyme. Magnetic nanoparticles were prepared by simple precipitation method in an aqueous medium and then subsequently coated with organophosphorus. This study is an example of immobilization of enzyme on the surface of modified MNPs and a comparison with a free enzyme in solution. Also, immobilization of enzyme on magnetic nanoparticle support offers several advantages in compare of other conventional supports such as polymer membranes or zeolites. The magnetic nanoparticles allow an easy isolation of product from the solution, recovering the enzyme at the end of the reaction and simultaneously reduce the cost of the procedure. In this study, different factors such as optimum pH, temperature, the thermal stability of the enzyme (urease) were investigated. The key step in this process lies in the stability of enzyme on the magnetic nanoparticle. Scheme 28 shows the detail synthetic procedure for functionalized magnetic nanoparticles and immobilization of urease. 104 After the formation of MNP and adsorption of carboxylic acid derivative, the surface was modified by "ammonium salt". Finally, urease was loaded on the scaffold through a carbodiimide reaction for obtaining a magnetic enzyme. The stability of enzyme on magnetic nanoparticle was determined by checking its catalytic activity through the hydrolysis experiment of urea measured in UV-Vis spectrometer. It was observed that the immobilized enzyme shows up to 70 % of relative activity after six times reuse. This immobilized enzyme can retain its catalytic activity for repeated use while free enzyme cannot be reused and recycled for next subsequent catalytic experiment.

Catechol derivatives 2.5.3.1. Introduction

The needs of modified magnetic nanoparticles, particularly iron oxide nanoparticles (Fe 3 O 4 , γ-Fe 2 O 3 ) in specific applications led researchers to design and develop new surface modifiers for magnetic nanoparticles. The catechol moiety creates a tight binding with the surface of iron oxide leading to a stabilized complex. 105 The spectroscopic study (X-ray absorption spectroscopy) of these bidentate enediol ligands showed that catechol converts the octahedral bulk structure of the surface of MNP to an under-coordinated Fe surface which makes it able to form a covalent bond with the dopamine (Figure 26). 106 Octahedral bulk Undercoordinated surface states Octahedral surface states after modification Also, catechol derivatives such as dopamine and L-Dopa serve as versatile and robust chelators to link the functional molecules on the surface of magnetic nanoparticles.

Applications

Several groups developed magnetic nanoparticles modified by catechol ligands, where the pending functionality was used as a catalyst. Amstad et al. built catechol-derivative on superparamagnetic iron oxide nanoparticles under physiologic conditions and studied the influence of the anchor groups on nanoparticle stability. In particular, the stability of modified nanoparticles at 37 °C or higher is important when these particles are used for in vivo applications such as cell tracking and stimulated drug release. They selected nine different catechol derivatives to design the surface of iron oxide nanoparticles and coupled poly(ethylene glycol) (PEG) to each anchor groups (Figure 27). They observed that the presence of PEG in catechol building block greatly enhances the stability of iron oxide. Iron oxide nanoparticle stability was investigated with TGA and XPS equipment. TGA analysis measured between 200 and 400 o C showed that iron oxide with PEG-nitroDopa is the most stable one. 107 The striking difference in binding affinities of these different anchor groups might be related to different pK a values. PEG-nitroDOPA have its pK a values around 6.5, close to the point of zero charges (PZC) of iron oxide nanoparticles (6.7). But, PEG-DOPA, PEG-dopamine, and PEGhydroxydopamine have pK a > 9. Also, the lower stability of iron oxide nanoparticles coated with PEG-dopamine compared to PEG-nitroDOPA might partially be because PEG-dopamine is prone to oxidation especially in the presence of iron. Another example using catechol functional group is shown in Figure 28, where Fe 3 O 4 was coated by poly(dopamine) and been employed in electrochemical biosensors as solid supports for the immobilization of biomolecules. Martín et al. 108 described the combination of modified magnetic nanoparticles with poly(dopamine) (MNPs@pDopa) and screen-printed in carbon electrodes (SPCe) as a sensitive and selective detector for monitoring L. pneumophila bacterium in water. In this study, poly(dopamine) (pDopa) was demonstrated to be a useful functional group to create interactions with bio-molecules and immobilize them on the surface of MNPs. The initial step in this research was the synthesis of MNPs by precipitation of Fe 2+ /Fe 3+ salts and after obtaining the MNPs were coated with poly(dopamine) under stirring during 6 h. Then, MNPs@pDopa have suspended in a specific capture antibody (Ab) solution. Subsequently, MNPs@pDopa-Ab were washed with PBS-Tween buffer solution to block the remaining active sites on MNPs@pDopa. After washing, the MNPs@pDopa-Ab were resuspended in target bacteria solution in PBST. Then MNPs@pDopa-Ab-bacteria were immersed in the antibody labeled with horseradish peroxidase (Ab-HRP) solution to obtain the final MNPs@pDopa-Ab-bacteria-Ab-HRP conjugates (MBs). This conjugate was placed on a magnet holding block and the biorecognition event was monitored by amperometric measurement of the reduction current generated with the Hydroquinone/Water (HQ/H 2 O 2 ) system (Figure 28). 108 In this work, they made a specific detector for detecting lipoproteine. As mentioned before, MNPs and MNCs take place in different field of research. Also, the use of magnetic nanoparticles as efficient supports for catalysts has become a subject of organic chemistry. This is because MNPs can be well dispersed in reaction mixtures without a magnetic field, providing a large surface area that is readily accessible to substrate molecules. In this way, chelating metal catalysts such as Cobalt, nickel, copper, palladium, ferrites, as well as gold, silver, rhodium on the surface of MNPs become an interesting subject in organic chemistry. This section deals with immobilization of metal catalyst on MNPs and its application in different organic reactions.

One of the early examples involved a palladium catalyst coordinated magnetic nanoparticle via a chelating compound such as dopamine. For example, Pollshettiwar and his collaborators report a simple and inexpensive synthesis of a magnetically recyclable Pd catalyst and its application in oxidation reactions. 77 The catalyst was prepared by sonicating magnetic nano-ferrites with dopamine and followed by addition of sodium palladium chloride at basic pH (Scheme 29). After synthesis, the nano-ferrite-supported Pd catalyst (0.025 mol %) was successfully used for oxidation of alcohols and olefins (95 % selectivity). At the end of the reaction, catalyst was magnetically separated from the reaction mixture with an external magnet without any loss of catalyst, for at least 5 times turn over. Catalysts based on magnetic nanoparticles have been used for a very wide range of organic transformations, including oxidations, epoxidation, hydrogenation, C-H functionalization, C-C coupling and click chemistry. They are vitally important for this purpose because they provide green and sustainable reaction conditions to convert raw materials into valuable chemicals. In following, the advantages of using magnetic nanoparticles catalysts for different kind of reactions are discussed.

NH 2 HO HO Sonication rt, H 2 O NH 2 H 2 N H 2 N NH 2 NH 2 H 2 N H 2 N NH 2 H 2 N NH 2 NH 2 NH 2 NH 2 NH 2 NH 2 H 2 N NH 2 H 2 N H 2 N

Pd

Hydrogenation reactions

Recently, immobilized magnetically recoverable nanocatalysts, that containing transition metals (Pd, Rh, Ru, Pt…), were used in various hydrogenation processes including the hydrogenation of carbon-carbon double or triple multiple bonds and carbonyl reaction. 109 Ying et al. reported the preparation of a series of catalyst where Pd is supported on the surface Fe 2 O 3 @SiO 2 . Atomic Pd was directly immobilized on the surface of amine-or thiolfunctionalized MNPs and the catalyst was employed in the hydrogenation of nitrobenzene (Scheme 30). The obtained Pd/HS-SiO 2 /Fe 2 O 3 and Pd/H 2 NSiO 2 /Fe 2 O 3 catalysts exhibited high conversion and activities relative to those obtained with commercial Pd/C catalyst. After 14 cycles, These Pd/SiO 2 /Fe 2 O 3 were found stable and no agglomeration in the catalytic efficiency was detected.

Oxidation reaction

Conventional oxidation is generally achieved with the excess amount of oxidants using metal oxides (Cr, Mn, Co, Os, Ru) which are expensive and caused serious environmental problems and toxic waste. Because of the growth of environmental concerns, transition metal catalysts immobilized on modified MNPs have received considerable attention for developing oxidation protocols. 111 Oxidation of alcohol is one of the primary examples of oxidation reaction using magnetic nanocatalyst. Mori et al. developed a new magnetically recoverable apatite catalyst that exhibits catalytic activity for the oxidation of various alcohols to corresponding carbonyl compounds. 112 They reported the accommodation of γ-Fe 2 O 3 (maghemite) into the HAP (hydroxyapatite) matrix and fixing Ru cation species containing Ru(IV) species on the outer HAP surface. The RuHAPγ-Fe 2 O 3 offered a simple and highly efficient recoverable and reusable catalyst system for selective oxidation of benzylic alcohols using molecular oxygen. In this study various allylic and benzylic alcohols were converted into carbonyl compound as well as sterically bulky alcohols with high yield and selectivity ( Finally, it is mentioned that recovery of the catalyst was accomplished by external magnet and catalyst was used several times without loss of activity. There is hope that this kind of catalyst is extendable to biomedical fields such as biomolecular separation and targeted drug delivery. 112

C-C Coupling

Various catalytic systems based on transition metal have been developed to create carbon-carbon bonds and the technology involved has been widely explored and welldeveloped. However, despite the remarkable emergence of transition metal in this area, the efficient separation and recycling of these catalysts still remain a challenge. In this way, utilization of MNP-supported transition metal catalysts for construction of C-C bonds via Heck, Suzuki or Sonogashira coupling has received considerable attention.

Li et al. reported a highly efficient Pd MNPs catalyst that could be stable in air and moisture environment. 113 A wide range of Suzuki, Sonogashira and Heck reaction has been successfully tested with this catalyst and good yields of the desired products were obtained. The supported catalyst was easily dispersed in both aqueous and organic solvent. It was easily recycled and used eight times without significant loss of its catalytic activity. For example, they investigated the Suzuki coupling reaction with the optimized condition of 0.5 mol % loading of palladium, K 3 PO 4 , MeOH, during 1.5 h in 60 o C. Series of aryl bromides and chlorides with phenylboronic acid lead to the corresponding products in excellent yields (table 6). 113

B(OH) 2 + X R 2 R 1 SiO 2 @Fe 3 O 4 -Pd (0.5 mol% Pd) K 3 PO 4 , MeOH 60 o C R 1 R 2
Arylbronic acid Aryl halide Yield (%)

B(OH)

Epoxidation reaction

Epoxides are important intermediates in the synthesis of many fine chemicals and pharmaceuticals products. Various heterogeneous catalysts containing Ag, Mn, Co, and Ru have been employed to achieve epoxides compounds like ethylene and propylene oxide. However, considering the economic importance of epoxidation reaction, new sustainable methods are needed. In this regard, Shylesh and co-workers demonstrated that organic-inorganic hybrid heterogeneous nanocatalysts prepared via covalent grafting of oxodiperoxomolybdenum complexes onto silica-coated Fe 3 O 4 were efficient and magnetically separable for alkene epoxidation (Scheme 31). 60 The catalyst activity was tested with several substrates such as cyclooctene, cycloheptene, cyclohexene, and styrene in a series of different solvents like choloroform, toluene, acetonitrile and different oxidizing agent such as tert-butylhydroperoxide (t-BuOOH) under reflux condition. For practical applications of heterogeneous catalyst systems, the stability and reusability were examined six times in the epoxidation of cyclooctene without any change of conversion and selectivity. This stability of catalyst system can be attributed to the uniform dispersion of the catalytically active sites on the surface and the strong interaction between the chelating ligand and the oxodiperoxomolybdenum center.

Characterization of magnetic nanocatalysts

Various physico-chemical techniques can be employed for the characterization of the synthesized catalysts. Analyses can be targeted to evaluate the crystalline nature, the phase purity, the magnetic behavior or the morphology of the nanoparticles, but also the presence or absence of functional group on the surface and the amount of metal loaded on the nanoparticle support. To characterize the magnetic nanocatalyst, different techniques such as X-ray diffraction (XRD), transition electron microscopy (TEM), FT-IR, atomic absorption spectroscopy (AAS) are used routinely. In this way, some of the important characteristic techniques are discussed below.

X-ray diffraction (XRD)

The diffraction pattern is a rapid analytical technique that shows information about the crystal structure and phase. This technique is used to quantify the proportion of iron oxide formed in a mixture by comparing the peak intensities in the experimental and reference diffractograms. In addition, XRD can be used to calculate the crystal size according to the Scherrer equation (eq. 1).

(eq. 1)

Where d is the crystal size, β is full width at half maximum (FWHM), θ corresponded to Bragg angle, K is a dimensionless shape factor and λ is X-ray wavelength. As an example, the crystalline structure of Fe 3 O 4 which was modified with L-lysine and copper anchored on the surface of Fe 3 O 4 (Fe 3 O 4 @Cu) were analyzed (Figure 29). 116 It was observed that the samples have the same shift peaks that corresponding to the spinal structure of Fe 3 O 4 and matched well with the standard XRD data. The XRD results showed that there is no change in the topological structure before and after surface modification. However, for Fe 3 O 4 @Cu there is an additional peak at 50.40 o which can present a lattice plane of metallic Cu nanoparticles. 116

Electron microscopy

Scanning electron microscope (SEM) and transmission electron microscopy (TEM) are the most versatile instruments available for examination and analysis of the morphology and chemical composition characterization. Transmission electron microscopy (TEM) and its correlation with energy-dispersive X-ray analysis (EDX) are a unique technique for measuring the size uniformity, the real-space image of magnetic nanoparticles, as well as the elemental composition of core-shell structure. Alternatively, high-resolution TEM (HR-TEM) is also a powerful tool for providing electron diffraction patterns from single nanoparticle of 1 nm and revealing atom distributions on nanocrystal surface. 114 For example, Polshettiwar showed that with the same synthetic protocol and just simply changing in the iron precursor, it's possible to obtain six different shaped of iron oxides which were proofed with SEM (Figure 30). This observation was important because each small change in the arrangement of atom and shape of the nanostructure can affect its various properties and can have an important effect on the performance of nanocatalyst. 115

Superconducting quantum interference device (SQUID) magnetization measurements and Mössbauer spectroscopy

Superconducting quantum interference device (SQUID) magnetometer is used to study the net magnetization of the magnetic nanoparticles. This magnetization is described by Equation 2(eq. 2) where T is the temperature, B the external field, μ i the magnetic moments and υ i the volume contribution. 116

(

) ∑ ( ) (eq. 2)

On the other hand, Mössbauer spectroscopy is used to identify the different iron (oxide) phase, such as magnetite and maghemite iron oxides which are difficult to characterize. As both systems possess an inverse spinel structure, X-ray technique is unable to distinguish them. Then Mössbauer spectroscopy can be a good candidate for phase recognition.

As an example, Daou et al reported the influence of the coupling agent (carboxylate and phosphonate) at nanoscale on magnetic properties of functionalized magnetite. 117 Understanding the effect of surface (inorganic-organic) interaction are necessary to develop efficient magnetic functionalized nanoparticles. In this case, SQUID measurement and Mossbauer spectroscopy can demonstrate the feature of the magnetite core and the surrounded oxidized layer. The presence of carboxylate function on the surface of magnetite causes a spin canting and leads to a decrease of net magnetization of oxide nanoparticle, unlike the phosphonate ones. This decrease in saturation magnetization of the oxidized layer can cause magnetically dead surface layer (Figure 31) which was demonstrated with SQUID and Mossbauer spectroscopy.

FT-IR

Some physico-chemical techniques, such as Fourier-Transform InfraRed spectroscopy (FT-IR) are used to investigate the surface properties of functionalized iron oxide nanoparticles. While other chemical analysis methods such as ATR-IR and NMR have attracted much attention for characterization of the surface of nanoparticles, they can't be used for magnetic nanoparticles because of magnetic field interaction of MNPs with the magnetic field of these types of equipments. 118 Fourier transform infrared spectroscopy (FT-IR) is used to monitor and confirm the functionalization of magnetic catalysts and provide information on the nature of functional groups. For example, Zarghani and her co-workers prepared and modified Fe 3 O 4 MNP with a short-chained organic molecule that had both a phosphate group and an amino group. 119 The FT-IR analysis was used to confirm the existence of the bonded species and defining the catalyst structure. The spectra of Fe 3 O 4 NPs and Fe 3 O 4 modified with 2-aminoethyl dihydrogen phosphate (Fe 3 O 4 @AEPH 2 ) are illustrated in Figure 32. The identical bonds of Fe 3 O 4 can be observed in fingerprint area that shows the vibrational frequency of Fe-O and asymmetric or symmetric stretching of Fe-O bond (400-1500 Cm -1 ). Then, adding organic molecules on the surface of MNPs can cause shifting, appearance or disappearance of some peaks. In this example, the characteristic band of Fe 3 O 4 @AEPH 2 appears at 1153 cm -1 due to stretching vibration of P=O bond. The presence of the P-O-Fe bond was confirmed by two absorption bands at 1012 and 987 cm -1 . Absorption bands at 3457 and 3415 cm -1 confirmed that NH 2 is not grafted on the surface of Fe 3 O 4 and remained an active functional group on the surface of MNPs.

Inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and atomic absorption spectroscopy (AAS)

In addition to size, phase, and site occupancy, the catalytic activity of magnetic nanoparticles depends on the quantity of metal that is presented on the surface of MNPs. Several techniques can be used for determining this parameter. Inductively coupled plasma-atomic emission spectroscopy (ICP-AES) is widely used because of its sensitivity, wide applicability, and ease of use. In this technique, a plasma torch is used to atomise, ionise, and excite the atoms in a solution to the sample, which are then quantified by the intensity of their characteristic emissions. The sensitivity of the technique varies considerably between elements but is generally accurate to better than 2 % for the main constituents of magnetic nanoparticles. This technique can be used to determine the stoichiometry of the samples. Understanding the stoichiometry can help to reduce the number of free parameters related to site occupancy and cause better and more precise results. As an example, Nasir Baig and Varma used inductively coupled plasma-atomic emission spectroscopy (ICP-AES) to detect the weight percentage of copper on the surface of nanoferrite-Dopamine-copper catalyst before and after the reaction. This analysis helped to study the leaching of copper from the support to the reaction and study the strength of dopamine to anchor the copper on the surface of the support. Thus, the catalyst was recovered and reused more than 3 times for coupling thiophenols with aryl halides without any leaching of copper. 120 On the other hand, atomic absorption spectroscopy (AAS) can be also used to estimate the total metal content. In this analysis, a standard solution of the targeted metal must be prepared in various concentration ranges. Then, the absorbance of these solutions is measured at a specific wavelength of targeted metal using a background correction technique. After that, the calibration graph will be plotted for a metal solution. Finally, the concentration of an unknown solution can be calculated from its respective absorbance by using the standard values. As an example, Sharma and his co-workers used AAS for assaying of copper metal quantity in the magnetically separable Fe 3 O 4 @silica core-shell supported catalyst. After the reaction, the catalyst was recovered from the reaction with an external magnet and AAS analysis was conducted. Results revealed that there was barely any change in the metal amount in contrast to the fresh catalyst. 121

Chapter 3: Results and discussions

In this chapter, we reproduced classic aziridination reaction and synthesized MNCs according to literature studies. The initial part of our work was focused on reproducing aziridination reaction with styrene in presence of different oxidation agents (BAIB and PhI=O) and H 2 NTs in the presence of "free copper" sources to obtain the best conditions of reaction. Then the copper complex of aziridination reaction was replaced with MNCs. The primary result of the catalytic test with MNCs was not satisfactory and led us to discover another reagent (PhI=NTs). After optimizing the reaction condition, our secondary catalytic test with PhI=NTs and MNCs caused high yield of styrene aziridination. In continue, we have shown that the catalysts could be reused for 5 times with total conversion of styrene and good yields, even after 5 runs. However, some limitation of the use of MNCs in aziridination reaction such as copper leaching from support to the reaction environment appeared. In continues, we tried better condition of reaction such as MW radiation. As it is discussed in section 8, MW radiation causes a time decrease of reaction, but not an obvious decrease in copper leaching during the turn over reaction. As the next part of our work, we have examined MNCs for serious of olefin substrates with successful extrapolation of this methodology to electron-poor or electron-rich substituted styrene derivatives as well as the aziridination of long-chain olefins. In continues, after examination of MNCs in aziridination reaction with the different conditions and observing satisfactory results, we examine different linker of MNCs for tolerating limitation of aziridination using MNCs. In section 3.10, we talked about the effect of Cu-chelating function and MNPs-anchoring groups of different linkers. We proposed different kind of MNCs for decreasing of copper leaching from support to reaction environment. Finally, in the last section (section 3.12) after selecting the best linker of MNCs, we developed our methodology and have proposed a new MNCs with carbohydrate chiral linker to introduce enantioselective synthesis using chiral heterogeneous catalysts. We design, synthesize, purified and characterized this organic linker to may be possible to turn it into an interesting alternative for enantioselective aziridination. This new linker is under examination as the perspective of our work for feature studies.

Reproducing classic aziridination reactions

We started the experiments with reproducing classic aziridination reaction of styrene following the Evans works 37,39 under different conditions (Scheme 32).

Scheme 32. Styrene aziridination

We investigated different parameters such as temperature, time and the effect of copper oxidation state on conversion and yield. In these attempts, styrene was initially chosen as a substrate to establish the reaction conditions and find the best conditions, which are discussed below.

Aziridination reaction with PhI(OAc) 2 and H 2 NTs

In general, hypervalent iodine is used as an oxidant and aryl amines (RNH 2 ) where R can be p-MeC 6 H 6 SO 2 or p-NO 2 C 6 H 6 SO 2 are one of the alternatives as nitrogen sources in metalcatalyzed aziridination. In our initial investigation, iodobenzene diacetate (BAIB) and ptoluenesulfonamide (H 2 NTs) were used as potential reagents for the aziridination of styrene. Different parameters of reaction were investigated with these two reagents.

The effect of time, temperature and oxidation state of copper

Our first experiment of aziridination was inspired by Evans condition with copper catalyst. As he mentioned, both Cu(I) and Cu(II) complexes are the most efficient catalysts yet discovered for olefin aziridination. Copper catalyst in compare of other metal complexes, such as SmI(OTf) 2 , Mg(OTf) 2 or Zn(OTf) 2 , in the presence of different nitrogen atom sources can provide a high yield of aziridine. In our preliminary studies, a reaction was carried out with 0.1 equivalent of Cu(OTf) 2 as a catalyst in the presence of styrene (1 eq.) and BAIB (1.4 eq.). The active species is the iminoiodinane (PhI=NTs) in the reaction media which should display a high capacity of aziridination of olefins (Scheme 33). Also, the only by-products of this process are PhI and acetic acid that are trapped by the base MgO. According to Table 7, different reactions were carried out at different times to obtain the corresponding aziridine. However, from the initial experiments, it was found that the isolated yield of the aziridine is too much lowering than those of obtained by Evans and coll. Also, the reaction was not complete even after 24 hours (monitored by TLC). After stopping the reaction, then extraction, low yields of aziridine were obtained after column chromatography purification. Also, conversion of starting material was determined by NMR of the crude mixture. After applying different times, maximum of 21 % aziridine were reached (Table 7, entry 3) at 0 ○ C for 18 hours. The low yield of aziridine is presumably due to the weak ability of oxidant to form the PhI=NTs intermediate. In continue, an increase of the temperature was done to boost the conversion, but it didn't cause any efficient effect in terms of conversion and yield. As it is illustrated in Table 7 (entry 4 and 5), increasing the temperature cause a decrease in the yield and higher temperature (40 o C) caused no reaction. To investigate the effect of copper oxidation state in the reaction, other sources of copper (CuPF 6 ) were studied to observe the change in the yield and conversion. However, the oxidation state of copper does not play a crucial role (Table 7 entry 6). Since all attempts to achieve high yield percent with primary reagents (H 2 NTs, PhI(OAc) 2 ) were unsatisfactory, we explored other hypervalent iodine -(III) reagents. Next reactions were carried out with iodosylbenzene (PhI=O) which is easily accessible in large quantity and high purity by KOH treatment of commercially available PhI(OAc) 2 . 122

Entry

Aziridination reaction with PhI=O and H 2 NTs

First, experiments were run with styrene as stoichiometrically limiting component in the presence of a catalytic amount of Cu(OTf) 2 or CuPF 6 and a slight excess of PhI=O and H 2 NTs (1.4 eq.). It is noted that these two reagents fit the same active species (PhI=NTs), as well as PhI(OAc) 2 and H 2 NTs which is mentioned before. Results are shown in Table 8 and generally, yields are comparable to those obtained in aziridinations using PhI(OAc) 2 reagents. Therefore, in addition to its practical interest, this nitrene transfer appeared to be better than the classical procedure. In this reaction, both Cu(I) and Cu(II) act as adequate catalysts (entries 1,2) and this observation indicate that it is possible that a common oxidation state exists in both cases. However, Jacobsen 40 , Pérez 47 and Norrby 49 discussed that the active catalyst can be in the +III, +II or +I oxidation state and general mechanism may be system dependent. In continues, studies were carried out at different temperatures such as 25 and 40 °C (entries 3, 4) with Cu(OTf) 2 catalyst. It was also observed that increasing temperature up to 40 o C had a negative influence in reaction. This effect can be attributed probably to the catalyst deactivation at high temperature (40 o C) and the possibility of not withstand the high temperature applied. 123 Deactivation is a complex phenomenon and increasing the temperature might cause poisoning the catalyst or probably deactivating the triflic counterion of copper and totally inhibited the aziridination reaction promoted by Cu(OTf) 2 . 124 Other parameters were optimized. As it is shown in Table 8, a shorter time (entries 5, 6) aziridination with PhI=O and H 2 NTs gave similar results. The best yield is obtained in 6 h reaction time. However, still some trace of styrene can be observed on TLC for this reaction. It is noteworthy that portion-wise addition of PhI=O into the reaction media allowed isolation of aziridines in better yields and molecular sieves (4Å) are used to trap water molecules in aziridine reaction when PhI=O is used as a reagent.

Entry

After finding optimum conditions of temperature, time and oxidant, a magnetically recoverable copper catalyst was synthesized for primary experimental design to replace copper complex (Cu(OTf) 2 ). The details of this investigation are discussed below.

Replacing copper complex with recoverable magnetic nanocatalyst (MNC)

Synthesis of magnetic nano ferrites

There are several protocols reported in the literature for the preparation of catalytic magnetic materials. As it was mentioned, the practicality and cost-effectiveness of processes have a direct effect on the sustainability of the catalytic protocols. Herein, inspired by work of Varma, 125 a magnetic nanoparticle-supported Cu catalyst was readily prepared from an inexpensive starting material in the aim of recovering it with an external magnet. The first step in the accomplishment of this goal was the synthesis of magnetic nanoparticles (Scheme 34). Iron(II) and iron (III) were precipitated in the presence of ammonium hydroxide and adjusted pH to 10. Then, the precipitated nanoparticles were separated magnetically, washed with water until the pH reached 7, and then dried under a vacuum at 60 °C. Nanoferrites (Fe 3 O 4 ) were characterized by X-ray diffraction (XRD) (Figure 33) and transmission electron microscopy (TEM) (Figure 34). As displayed in Figure 33, diffraction peaks at around 30.1 ○ , 35.4 ○ , 43.1 ○ , 53.5 ○ , 57.02 ○ , and 62.6 ○ 2θ, correspond to the spinel structure of Fe 3 O 4 , 77 and which can be assigned to the diffractions of the ( 220), ( 311), ( 400), ( 422), (511), and (440) faces of the crystals, respectively. 77 TEM analysis shows that Fe 3 O 4 nanoparticles are deposited on the surface of amorphous carbon. From Figure 34, it can be seen that particles have a narrow size distribution with an average diameter of 11 nm that can form a large surface area. These magnetic nanoferrites (Fe 3 O 4 ) were then used for further chemical modifications.

Surface modification of nanoferrites

In the next step magnetic nanoparticles (MNPs) were modified with dopamine under ultrasonic irradiation (Scheme 35) and their stability analyzed with FTIR.

The FT-IR spectra of the Fe 3 O 4 , dopamine and dopamine supported on Fe 3 O 4 were recorded to confirm the modification of the magnetite surface with the dopamine. According to Figure 35, the IR spectra of dopamine showed a large peak around 3250 cm -1 , due to the O-H stretching vibrations of catechol. It is also clear that the strong O-H stretching vibrations of catechol, which are generally present at 3250 cm -1 , are absent in the spectrum of Fe 3 O 4 -dopamine. The presence of magnetite nanoparticles in Fe 3 O 4 -Dopamine is observable by the strong absorption band at a range of 1012 cm -1 to 1078 cm -1 , corresponding to the Fe-O vibrations. Also, according to the above Figures, the successful Fe 3 O 4 surface modification with dopamine can be verified with 2 peaks at 1257 cm -1 and 1487 cm -1 . According to Rajh spectroscopic study, 106 bidentate enediol ligands convert the under-coordinated iron surface sites back to a bulk-like lattice structure with an octahedral geometry for oxygen-coordinated iron, which may result in tight binding of catechol functional group of dopamine to Fe 3 O 4 . Also, thermogravimetric analysis (TGA) was realized for measuring the content of the approximate quantity of dopamine on the surface of the Fe 3 O 4 -dopamine. Fe 3 O 4 -dopamine displayed an abrupt weight loss from 251 o C, indicating a rapid decomposition of the dopamine at that temperature. According to the abrupt weight loss, the calculated content of the dopamine was approximately 18.8 % of the whole weight of the sample.

Synthesis of Fe 3 O 4 -Dopa-Cu catalyst

The last preparing step of the catalyst was followed by addition of copper complex (Scheme 36). Amine-functionalized nano-Fe 3 O 4 were dispersed in water and Cu(OTf) 2 solution in water was added to the mixture to get 10 wt % of Cu. Hydrazine monohydrate and NaBH 4 were used to increase the pH of this mixture to 9 and reducing copper salt to the copper nanoparticle, respectively. Also, it is mentioned that hydrazine monohydrate has an impact on the size and shape of Cu nanoparticles either in the presence of inert atmosphere or in nonaqueous medium to prevent oxidation. 126 Scheme 36. Copper anchoring on the surface of modified Fe 3 O 4 .

According to a paper of MacNaughton, 127 Cu (II) can be reduced to Cu(I) in presence of hydrazine (Eq. 1). Sodium borohydride also reduces Cu(I) to Cu(0) and in general, there is a possibility of the presence of Cu(I)/Cu(0) on the surface of Fe 3 O 4 -Dopamine.

        H Cu H N Cu H N o 3 2 2 4 2
(Equation 1)

o HO Cu H O Cu 2 2 2         (Equation 2)
Catalyst characterization by X-ray diffraction (XRD) (Figure 36) and transmission electron microscopy (TEM) (Figure 37) confirm that magnetic nanoparticles were formed after copper chelating. Also, FT-IR and atomic absorption spectroscopy (AAS) confirmed the anchoring of copper on the surface of nanoferrites. AAS showed that the weight percentage of Cu in the catalyst can be found to be more than 10.0 %.

Primary catalytic test with PhI=O and magnetic nanocatalyst

To evaluate the potential of the new catalyst for aziridination reaction, magnetic targeting experiments have been performed with 0.1 equivalent of catalyst that contained 10 wt % copper loaded. The reaction with magnetic nanoparticle (MNP) was evaluated under the obtained optimization conditions (6 h, 0 o C and under an inert atmosphere). As the result of the preliminary experiment, the observation indicates that the magnetic properties of the functionalized nanoparticles are not retained and that they accumulate in the solution that makes them hard to collecting with an external magnet. Also, the result of the catalytic test was low; the yield percent of aziridine of only 27 % of product was obtained after celite filtration and flash chromatography (Table 9). After a hardly recovering process, catalyst was washed several times with acetonitrile and dried for 2 h at 60 o C under argon atmosphere. We found that the weight of the recovered material after the reaction increased and AAS analysis showed that an acceptable amount of copper was lost from the catalyst. As a reason, according to a paper of Kolotilov et al. 128 there is a possibility that the molecular sieves (MS), which are used in the reaction in the presence of magnetic nanoparticles, cover Fe 3 O 4 nanoparticles. The combination of MS and MNPs may cause poisoning and deactivating the magnetic properties of the catalyst (Figure 38). The issue with molecular sieve lead us to use the aza-analogue of PhI=O, N-(ptolylsulfonyl)imino]phenyliodinane (PhI=NTs). In this regard, PhI=NTs was synthesized according to the method of Yamada et al. 129 by reaction of PhI(OAc) 2 with H 2 NTs and KOH in MeOH. At the end of the reaction, PhI=NTs precipitates upon the addition of water and can be isolated by filtration, and stored for several weeks.

Catalyst

Aziridination reaction with PhI=NTs

Motivated by the research work of Evan et al. 130 PhI=NTs was employed as a nitrogen precursor replacing PhI=O. The benefit of PhI=NTs is the omission of molecular sieves from the reaction and simplifying the reaction protocol.

The primary result of the formation of the desired aziridine product with PhI=NTs at 0 o C was only 18 % yield (Table 10, entry 1). In this case, the result is discussable with the Evans's work which used 5 equivalents of styrene to obtain more than 89 % yield. 130 However, our aim was to reduce the amount of substrates to present a protocol more practical with better sustainability. In our next effort, increasing the temperature up to 40 o C offered a slightly improved yield up to 55 % (Table 10, entry 3). Lastly, further increasing of the reaction temperature (60 °C), as already observed previously, had a negative effect on yield and caused decreasing of the product to 4 % yield (Table 10, entry 4). While there is no clear reason of the negative effect of the higher temperature on aziridination, there is a possibility of copper to be poisoned at a higher temperature because it is realized that copper catalyst stability is depended upon its counterion. 37 Evans et al. 37 showed that the copper catalysts gave high yield of aziridine in excess of alkene (5 eq.) at the temperature range of -20 to 25 o C. However, in our experiment with just 1 eq. of styrene, a higher temperature is required (40 o C) to afford the expected product in a high yield too. In this way, different experiments have been designed to optimize the reaction. We supposed that such copper-catalyzed aziridination could be performed in a shorter time. Sequential addition of reagent in acetonitrile after 4 h (Table 10, entry 5) gave rise to aziridine in 64 % yield. Then, application of the same procedure at shorter times 2 h and 1 h led to the expected product in 64 % and 72 % yield respectively (Table 10, entries 6 and 7). Finally, we decided to run the reaction in 30 min and to our surprise, aziridine was isolated with nearly 82 % yield (Table 10, entry 8), while no by-product was detected. It is noteworthy that this result was achieved with portionwise addition of PhI=NTs in acetonitrile. Also, we tried to add all of the reagents at once at the beginning of the reaction with different time and temperature. In most of the cases we obtained a very low yield of aziridine or the reaction didn't proceed at all.

3.5.Secondary catalytic test with PhI=NTs and magnetic nanocatalyst

A postulated mechanism reaction for copper-catalyzed aziridination with MNC is shown in Scheme 37. Reaction start by the formation of the highly active copper-nitrene species with the reduction of PhI=NTs to iodobenzene. In the next step, nitrene is directly added to the double bond and aziridine is produced. In our new investigation, the previous synthesized magnetic nanocatalyst was assessed for a range of aziridination reaction with PhI=NTs. The choice of conditions used, for the first set of experiments with magnetic nanocatalysts is based on those employed for similar reactions with Cu(OTf) 2 that contained PhI=NTs (1.4 eq.), styrene (1 eq.) and the catalyst (0.1 eq.).

Under these conditions, only 18 % yield of product was obtained (Table 11). The product was characterized by 1 H and 13 C NMR. Also, the NMR spectrum of the crude reaction showed a single product without any by-product or didn't show the interaction of Fe 3 O 4 with NMR magnetic field. In general, the catalysts could be simply recycled without loss in amount with an external magnet which was not typically accomplished in our previous trials. Low conversion and yield can be attributed to the influence of the nature of the support on catalyst activity. The Fe 3 O 4 supported copper catalyst may be more effective at the higher temperature. Thus, the effect of the nature of the carrier on the catalyst performance has been investigated with different researchers. 131 132 The authors observed, during the decreasing of the temperature from 150 o C to 120 o C, a diminution of the conversion from 99 to 36 % respectively. In order to optimize the reaction conditions and obtain the best catalytic activity, different reaction parameters, such as temperature, time, the equivalent of reagent and the amount of catalyst were investigated. It is noteworthy that in all the reactions, PhI=NTs has been added portionwise.

Effect of temperature and time on conversion and yield with MNC

Influence of reaction temperature on catalyst activity was investigated at different temperature (Table 12). As described above, the activity of catalyst significantly increased at a higher temperature. When the temperature increase from 40 ○ C to 70 ○ C, the reaction yield increase from 18 % to 70 %. These results were estimated for 30 min reaction time. Because the reaction did not show complete conversion at this time, a range of reactions were done at different times to achieve higher conversion and yield. In this reaction step, conversion of the styrene to aziridine was investigated over 240 min periods. The yield was proportional with the time increment while styrene conversion attained an optimum value of 86 % at 120 min reaction time. Table 12 (entries 4-6) presents the effect of reaction time on conversion and yield.

Entry

Effect of equivalent of PhI=NTs on conversion and yield with MNC

Other experiments were carried out with the aim of decreasing reagent loading to 1 equivalent. Table 13 shown a comparable yield of 90 % which was obtained in an optimum amount of PhI=NTs (1.2 eq.), but slightly lower product yields 64 % was afforded on decreasing PhI=NTs to 1 equivalent. Conditions: For entry 1-3: Styrene (1eq.), MNC (0.1 eq.). For entry 4: Styrene (1.5 eq.) a: Yield is calculated according to PhI=NTs conversion Table 13. Effect of PhI=NTs equivalent on conversion and yield with MNC.

Entry

Also, one experiment (Table 13, entry 4) was run with PhI=NTs as the stoichiometrically limiting reagent and a notable result is observed when 1.5 equivalent of styrene was used in the presence of only 1 equivalent of PhI=NTs. The result showed in a shorter time (30 min) at 70 o C, 99 % of the PhI=NTs was converted into aziridine. This is comparable with previous works while it was needed to add more than 5 equivalents of starting material to obtain a complete conversion. 133

Effect of Fe 3 O 4 and Fe 3 O 4 -Dopamine on aziridination reaction

After different experimentation, two reactions were done in absence of copper to investigate the involvement effect of Fe 3 O 4 and Fe 3 O 4 -dopamine in aziridination reaction. To the mixture of styrene and Fe 3 O 4 or Fe 3 O 4 -dopamine was added PhI=NTs (portionwise) and the mixture was stirred at 70 • C (Scheme 38). The reactions were followed by thin-layer chromatography (TLC). After 2 hours, the reaction mixtures were stopped then diluted and Fe 3 O 4 (or Fe 3 O 4 -dopamine) was removed by using a magnetic field and then the resulting solution was evaporated. The residue was concentrated and analyzed by NMR. No conversion of styrene was observed and the starting material remained unchanged. It clearly proves that the Fe 3 O 4 or Fe 3 O 4 -dopamine particles have no catalytic effect in aziridination reaction and clearly showed that only copper is effective for this transformation.

Scheme 38. Aziridination reaction in absence of copper

Effect of copper loaded in MNC and amount of MNC on conversion and yield

In these investigations, different Fe 3 O 4 -Dopa-Cu catalysts with 1, 5 and 10 wt % loading of copper were prepared and their activities tested in aziridination reaction. Our initial studies began with the reaction of Fe 3 O 4 -Dopa-Cu (10 wt %) (Table 14, entry 1). This catalyst can perform aziridination of styrene in high yield. A decrease in copper amount, from 10 to 5 wt %, enabled to obtain 76 % of aziridine (Table 14, entry 2). Similar yields were also obtained when diminishing the copper load to 1 wt % (Table 14, entry 3). It is mentioned that from Table 14 (entries 1-3) still add 4 % of the catalyst in the reaction. The scopes of these reactions are minimizing the amount of copper that is used in aziridination reaction while in previous works a higher copper loading (5-10 %) was usually needed for the copper-based catalytic reaction. Conditions: Styrene (1 eq.), PhI=NTs (1.2 eq.).

Table 14. Effect of copper loading and amount of MNC on conversion and yield.

The effect of MNC amount on aziridination with styrene is reported in Table 14 (entry 4). The copper amount with respect to MNC was varied 0.04 and 0.02 mmol % for reaction conducted at 70 o C temperature, and reaction time of 2 h. Styrene conversion getting worse from 90 to 60 % as MNC amount decreased to half. A decrease in catalyst amount resulted in a decrease in yield of aziridine. This can result from less availability of active catalyst in the reaction media that doesn't allow the substrate tobe transformed into the final product. 134

3.6.Turn over reactions

This part focus is examining the ability of catalyst for turnover numbers (TONs). Separation and recovery of the catalyst is generally performed by filtration, but in our catalytic system, because of the paramagnetic property of the magnetic nanocatalyst, it can be recovered by simply using external magnets. After completion of each reaction, within 2 h, the reaction mixture turned clear and the catalyst was deposited on the magnetic bar (Figure 39), which was easily washed and removed from the reaction mixture using an external magnet. With a set of conditions in hand, the scope of reusability of catalyst was examined with a series of reaction. After the first reaction, the catalyst is isolated with a simple magnet then washed with acetonitrile and dried at 60 o C under vacuum. The Fe 3 O 4 -Dopa-Cu recovered was reused for five runs in styrene aziridination. As depicted in Figure 40, it is observed that the yield of the product decreased mainly after the third run. The results observed for the fifth reuse showed that the catalyst was still active (Figure 40). It could be suggested that the magnetically recoverable copper nanocatalyst was deactivated or poisoned during the catalytic or separation processes. The characterization of the Fe 3 O 4 before and after reuse five times showed the same particle size by transmission electron microscopy and the same crystal structure by XRD (Figure 41). The only difference was visible from FT-IR, which showed higher peak intensity after the fifth use (Figure 42). This is due to the decrease copper content of the surface. According to Figure 42, in terms of Fe 3 O 4 -dopa-Cu (after reaction), the peaks appeared at 788 cm -1 , 885 cm -1 , 1072 cm -1 , 1149 cm -1 and 1199 cm -1 attributed to dopamine identification peaks which were disappeared or shifted in fresh Fe 3 O 4 -Dopa-Cu. Higher intensity of these peaks after reaction can be probably because of leaching of copper during the reaction. Also, increasing of intensity at 1529 cm -1 probably is the result of low interaction between amine functional group of dopamine and the metal ions. Also, AAS showed copper ratio drop from 10.0 wt % in the fresh catalyst to 5.3 wt % after the fifth use in aziridination. We believed that this is also the possible reason for the low activity of the catalyst. Also, another possibility could be linked to the oxidation state of copper changing during the process. To investigated the influence of the oxidation state of copper on catalyst deactivation, we synthesized fresh catalysts with Cu(I) or Cu(II) and without the reducing treatment with NaBH 4 . 135 The two catalysts were prepared by sonication of Fe 3 O 4 with dopamine hydrochloride (Dopa) in water for 2 h, followed by addition of Cu(OTf) 2 or CuPF 6 at a basic pH. Then, we obtained Fe 3 O 4 -Dopa-Cu(II) named catA and Fe 3 O 4 -Dopa-Cu(I) named catB, respectively. First, the reactions were explored using catA in MeCN using PhI=NTs as the reagent. The activity of catA decreased linearly with each repeated use Figure 43 (a). Under the same Fe3O4-Dopamine-Cu (after reaction) conditions as described above, reaction cycle with catB showed the same behavior but deactivation seems to proceed faster. Indeed, immediately after the first run, more than 50 % of activity was lost (Figure 43(b)). Those two turnover experiments suggest that MNCs with Cu(I) or Cu(II), are unstable under the reaction condition and/or during the catalyst retrieval. This could be linked to the oxidation of copper (to CuO or Cu 2 O) in presence of air or by solvent effect (moisture, acidity). [136][137] Indeed, compared with other metal catalysts, copper catalysts usually are less competitive in reactions, and often can provide desirable selectivity, but they are sensitive towards a variety of processes such as air that cause it to be deactivated. To confirm our hypothesis, we tried to retrieve our used catalyst. To do so, we reduced the final recovered catalyst after 5 runs with NaBH 4 . In this way, to the spent MNC was added the equivalent amount of NaBH 4 and let stir for 24 h at room temperature (Scheme 39). Scheme 39. Catalyst treatment processes with NaBH 4 .

The catalyst was allowed to settle, washed several times with methanol, and dried under vacuum at 60 o C for 2 h. The result obtained in studying the activity of the catalyst is presented in Figure 44. It indicates that the NaBH 4 treatment has a significant effect on the restoration of catalysts activity and outcome in yield percent. According to Figure 44, we compared the results of the catalytic activity of the catalyst after 5 runs (deactivated catalyst) with the regenerated catalyst (reactivated catalyst) with NaBH 4 as a reducing agent. The results clearly support the hypothesis for an oxidation of the catalyst and the positive effect of NaBH 4 for regenerating it. Finally, we exposed our catalyst under air after aziridination reaction for 24 h. Then the catalyst was reused for the second run and only 4 % of product was observed under this condition.

Under this observation, in next series of turnover reactions, the catalyst was kept in the reaction flask under argon which is essential to keep the catalyst effectivity for the next run. At each run, the aziridine was removed from the reactor with a syringe under argon and catalyst was stirred and washed with dried acetonitrile for 10 min and directly used for next run. Figure 45 shows that the catalyst can be reused for five times without any significant reduction in product yield. These results indicate that magnetic nanocatalyst have excellent recyclability for aziridination reaction, but extra care should be taken to store or handle the catalyst in the recovery process because of its air sensitive nature. In continue, AAS analysis of the catalyst after separation was conducted and the results revealed that the concentration of copper on the magnetic support decreased corresponding to copper leaching. AAS analysis before and after the five reactions showed Cu concentration is approximately 10.0 wt % before the reaction and 4.4 wt % after the run 5. In order to overcome this major drawback, the reaction mixture was re-optimized under different parameters such as heating method, 139 temperature, reaction time, solvent, and the ability of linker to chelate copper.

3.7.Aziridination reaction in microwave

Microwave irradiation (MW) replaced conventional heating (CH) to investigate the effect of MW radiation on the catalyst. In our case, reactions ran in sealed vessels of small volumes and under pressure. We investigated different factors such as temperature, reaction time and solvent under this situation. Also, the reusability of the catalyst was examined by turnover reactions in the best condition.

Effect of temperature and time of reaction with MW

A set of temperature was examined by microwave heating in acetonitrile (bp 82 °C) are presented in Table 15. Microwave heating of closed reaction vessels is a very energy efficient heating technique since the heat is transferred directly into the reaction mixture and not the reaction vessel. The heating procedure is also highly controlled since the energy input starts and stops immediately when the power is turned on or off, respectively. 140 As illustrated in Table 15, the reaction temperature to achieve the formation of the aziridine started from at 60 °C with 20 % yield and achieved to high yield of 87 % at 70 o C. High purity of products observed at this temperature can probably be largely attributed to catalyst activation with the homogeneous and smooth in-situ heating of microwave irradiation. By using closed microwave vessels, which can sustain higher pressures, the superheating effects were substantially examined to maintain acetonitrile at temperatures much above its reflux temperature. At the boiling temperature of MeCN and higher temperature, no efficient effects were observed. Also, increasing the temperature up to 120 o C resulted in a slight decrease in yield (Table 15, entry 5). Then, metal leaching was studied by AAS analysis of the catalyst before and after the reaction. Metal leaching during the recycling procedure still reminds as a major problem. In fact, to date, there is not more than 23 % leaching metal catalyst. In this area, settle the leaching issue needs to optimize each parameter individually. Then, the effect of the time of reaction for exploring copper leaching has been studied.

In this case, it has been demonstrated that the use of MW irradiation can dramatically decrease reaction times. As illustrated in Table 15 (entries 6-10), the reaction time to achieve the formation of the aziridine started from 3 h at 70 °C (Table 15, entry 6). It can be decreased to 30 min with 87 % yield of product (Table 15, entry 9). When reaction time was set to 10 min, 66 % of product was obtained but upon which the TLC monitoring revealed incomplete conversion.

Atomic absorption spectroscopy of recycled catalyst after each reaction showed that the copper leaching into the solution doesn't have a correlation to time of reaction. Table 15 revealed that the dissolved (leached) amount of copper in the solvent is the same during different times of reaction from 30 min to 3 h, excepted when a reaction ran for 10 minutes (Table 15, entry 10) that showed 11 % leaching of copper after stopping the reaction. However, in this case, lower yield of product was observed in comparision of other times.

Effect of solvent on conversion and copper leaching under MW irradiation

To appraise the effects of media in leaching of copper, we carried out the reaction in various organic solvents by using MNC under MW irradiation conditions (Table 16). It should be noted that MNC in different solvent has different activity. The reaction was conducted in acetonitrile (entry 1) as a reaction medium at 70 o C and more than 87 % yield was observed. Decreasing solvent polarity and using a solvent such as acetone provided no significant results in conversion and leaching (entry 3). Based on the copper leaching alone, the best result was observed when the reaction was performed in dichloromethane (entry 4). Nevertheless, the reaction in dichloromethane provided poor conversion and yield of product. In continue, when the reaction was carried out in water or tetrahydrofurane, no conversion was observed (entries 2, 5). In addition, PhI=NTs was not active in water. Also, we carried out the reaction in dried methanol; no conversion was achieved in 2 h at 70 o C under MW irradiation (entry 6). It was observed that the best product yield was obtained when the reaction was conducted under acetonitrile.

Entry

Effect of catalyst amount on conversion and copper leaching in MW

The copper loading effect on the magnetic nanoparticle in MW was also explored from 10 wt % copper to 5 wt % or 1 wt % (Table 17). Reducing the amount of catalyst (entry 2) to half (0.02 mmol %) can reduce the activity of the catalyst and only 60 % yield was obtained after 2 h reaction. Using the catalyst with 5 wt % copper (entries 3, 4) loading indicated the high yield of product and decreasing the amount of catalyst to 0.02 mmol % (entry 4) gave the same result. In continue, different amounts of catalyst that contained 1 wt % of copper (entries 5-7) were examined. Copper in catalyst at 1 wt % and half amount (0.02 mmol) showed a complete conversion and 97 % yield (entry 6). In our point of view, this experiment demonstrated that 110 MNC is very active for aziridination, which performs well at 1 wt % loading when 1:1.2 Styrene/PhI=NTs is used. In continue, to measure Cu leaching after the reactions, the catalysts were examined with AAS. It was determined that leaching trend doesn't depend on the amount of catalyst or amount of copper loaded on the catalyst. Two last column of Table 17 Also, Atomic absorption spectroscopy was used to determine the copper amount in the crude solution. From this point of view, after an aziridination reaction and catalyst removal, the crude product was dried and dissolved in 1 mL of Aqua Regia solution and diluted with 1 % HNO 3 in a volumetric flask. The results showed that approximately 20 % of homogeneous copper is present in the solution. In continues, to measure the effect of this free copper (homogeneous copper) in the reaction and its catalytic activity, a series of experiments were designed. For this aim, to a solution of styrene and MNC (0.04 mmol) in dried MeCN, portion wise of PhI=NTs (1.2 eq.) was added. The reaction was stirred under the argon atmosphere in the microwave and after 10 min, MNC was removed from the reaction flask. The reaction was then stirred for another 50 min without MNC (monitored by TLC). The crude was analyzed by NMR and purified with flash chromatography. The result showed only 9 % of product was observed when MNC were removed after 10 min and when PhI=NTs was added in one pot at the beginning of reaction (Scheme 40). Here we had proved that the residual homogeneous copper in the media (coming from the leaching) is not able to precede aziridination, as well as the MNC, do. We hypothesized that it could be copper metals. This was investigated with another aziridination reaction in the presence of copper metal powder. The corresponding aziridine was obtained in only 20 % yield using 1 equivalent of styrene and 1.2 equivalents of PhI=NTs and 0.1 equivalent of copper powder. This experimental finding suggests that deactivated leached copper in the reaction can include copper zero (copper metal) which has poor catalytic activity.

The effect of pH on copper leaching was also investigated. Indeed, according to pH of the solution under our regular condition (pH= 4), the amino functional group of dopamine (catalyst linker) can be protonated and causes faster leaching of copper into solution. Magnesium oxide was then added in the media to regulate the pH of the reaction. To do so, aziridination of styrene was carried out using PhI=NTs as nitrene donor and MNC in the presence of 1 equivalent of MgO. However, the result showed that MgO doesn't have a specific effect on avoiding the leaching of copper or improving the yield of product and the same AAS result is observed for this experiment. Also, we have carried out a reaction without styrene to study interactions between MNC and PhI=NTs in the leaching process. According to the mechanism of the reaction (section 4), this is clear that a discrete Cu=NTs intermediate occurs before nitrene addition to olefin. 40 This test under our optimized reaction conditions demonstrated that 68.7 % of copper was removed from Fe 3 O 4 in 2 h. This experiment showed that metal-nitrene species (Cu=NTs) which is formed during the catalytic reaction is strong enough to cause leaching of copper from the surface of Fe 3 O 4 -dopamine. In continuation of our efforts to understanding the leaching behavior of copper, we synthesized a magnetic nanocatalyst without the dopamine linker (Fe 3 O 4 -Cu). 141 The stability and activity of this catalyst were tested in aziridination reaction of styrene. The result showed a high yield of aziridine (92 %), but AAS analysis showed 60 % leaching of copper from the surface of the support after 1 time use of this catalyst.

3.8.Turnover reaction in MW

The final step after modification of the condition within microwave assistance is turnover reactions (Figure 46). By monitoring the conversion and yield of the product during turnover, it is shown that the microwave heating can be as efficient as conventional heating and even better because it is possible to decrease the time of reaction to 30 min with this activating technique. Noteworthy, 82 % yield is still maintained even when the catalyst is reused for 5 times. However, metal leaching, as measured by AAS analysis after 5 reactions showed copper weight percent in catalyst decreased from 10 % to 5.3 % after 5 runs. Also, this result was confirmed by ICP-AES analysis. Copper leaching behavior illustrated that modifying the condition of reaction and changing heating method doesn't affect this leaching and there is a slight difference between leaching behavior of conventional heating method (CH) and microwave assistance (MW). The catalytic activity with different loading of copper on MNC was also tested 5 wt % and 1 wt %) was evaluated. Reactions showed that the catalysts with 5 wt % and 1 wt % were still active for the aziridination under our classical conditions. However, the catalytic activity decreased after the first run and the yield of the reaction with these two catalysts was low. Furthermore, leaching study showed, Cu content after four times reaction is 1.3 and 0.3 wt % for a catalyst with 5 wt % and 1 wt % copper, respectively.

In continues, for expanding the scopes of aziridination using MNP, a range of commercially available or synthesized olefins were tested toward aziridination with Fe 3 O 4 -Dopa-Cu catalyst. Furthermore, this work presents also an investigation of the leaching of copper using different ligands. The influences of different organic linkers on copper chelating or anchoring to Fe 3 O 4 will be discussed later in this chapter.

3.9.Scope and limitation of aziridination using MNC

Encouraged by the positive aziridination results with styrene, we investigated different substrates to form aziridine ring on a variety of olefins. To date, there are no examples of catalytic reaction based on magnetic nanocatalyst that convert olefins into aziridine. We satisfy our method by running our developed catalyst on a series of olefins that contain functional groups such as alkyls, halogens, alcohols, or amines. A variety of electron rich or poor substrates could be readily converted to the desired products with modest to excellent yields with magnetic nanocatalyst. As an example, three different vinyl toluene derivatives with alkyl group in ortho, meta and para position were investigated (Table 18).

Entry

<95

Conditions: Substrate (1 eq.), PhI=NTs (1.2 eq.), inert atmosphere (Ar), 2h, MNC (0.1 eq.)

Table 18. Aziridination of vinyl toluene derivatives.

Using the conditions for optimal aziridination reaction, the alkyl group in ortho position was well tolerated, maintaining very good results about 83 % of yield. Also, when the substituent was introduced in the meta and para-positions, 78 and 70 % of the corresponding aziridine were obtained, respectively. The structures of the resulting aziridines were determined by 1 H and 13 C NMR spectroscopy (see experimental section).

Our observation continued using electron-withdrawing groups. Results are summarized in Table 19. In the case of chloro-or nitro styrene derivatives, it did not affect the olefin conversion and provided the corresponding aziridine in excellent yields, 96 and 91 % respectively. Styrene with electron-withdrawing substituents showed a better reactivity than unsubstituted styrene.

Entry

Substrate Product Yield (%) Conversion (%)

1 5 96 100
2 6

<95

Conditions: Substrate (1 eq.), PhI=NTs (1.2 eq.), inert atmosphere (Ar), 2h, MNC (0.1 eq.)

Table 19. Aziridination of electron-withdrawing groups.

Amino styrene was also investigated as a substrate. Unfortunately, the 4-aminostyrene couldn't give aziridine (Scheme 41). Our hypothesis is that, the amino function undergoes an interaction with the catalyst. The resulting chelation of copper prevents aziridination and generates leaching of metal from the MNC. We succeeded in the formation of the aziridine by the protection of the amine group with an acetyl group to avoid the chelating effect on the catalyst (Scheme 42). Acylation of amines is done according to a procedure of Yang et al. 142 and experimental procedures and characterization data of thus reaction is available in the experimental part. Our next examination involved the aziridination of N-(4-vinylphenyl)acetamide 7 with MNC applying the optimized condition (Scheme 43). The corresponding aziridine was obtained in 78 % yield. No deactivation of catalyst was observed with this substrate. Although aziridine was stable enough and didn't undergo ring opening. We also examined the effect of the methoxy group in aziridination reaction with MNC. We tested the activity of MNC toward the electron-rich 4-methoxystyrene (Scheme 44). After 1 hour reaction time, two products were observed on TLC. The desired product was obtained with 41 % yield but also with an amino-alcohol as a by-product. It resulting from the ring opening and appeared with 58 % yield. Controlled experiments showed that the desired aziridine product decomposes during long time reaction conditions and turned to the corresponding aminoalcohol after 2 h. The opening of the aziridine ring can be possible from secondary (C 8 ) or tertiary carbon (C 7 ). Also, the NMR analysis didn't clearly show which product is obtained. Proof of the exact structure of by-product (degraded aziridine) has been investigated with oxidation reaction with Dess-Martin periodinane (DMP) reagent (Scheme 45). The NMR analysis of the product after oxidation clearly showed that ring opening happened at tertiary carbon (C 7 ). A shift at δ 4.32 ppm (J ~ 4.5 Hz) indicated the presence of two hydrogen atoms (positioned on C 7 ).

MNC, PhI=NTs

The DEPT spectra for side-product before (10) and after (11) oxidation is shown in Figure 48. It is clear that there is a CH 2 -peaks (50.34 and 48.34 ppm for 1 and 11, respectively) which appear in antiphase for both compounds. The presence of a methylene is incompatible with the structure of compound 10ˈ. Furthermore, oxidation of hydroxyl at C 7 position lead to the disappearance of the signal at 72.34 ppm in the starting material and confirm the formation of byproduct 10 after aziridination (Figure 47). We also tested aziridination of more functionalized starting material such as cinnamic derivatives, the products which may allow access to phenylalanine analogs. 143 Different substrates were used to obtain aziridine products (Scheme 46). We tested the aldehyde, the carboxylic acid, and the ester derivative. Significantly, no product was observed; the reaction only led to a low conversion or product degradation in comparison to those with the functionalized systems above. These results are in contrast with Evans observation for cinnamate substrates. 39 Those limitations could be attributed to the presence of chelating groups like carbonyl from aldehyde our ester or hydroxyl on the substrate that could have a negative effect on MNC activity. In continues, under the same reaction conditions, stilbene and chalcone were used in subsequent studies (Table 20). As an example, chalcone was aziridinated with PhI=NTs under catalysis of MNC (Table 20, entry 1) with 40 % yield and 80 % of conversion. Also, transstilbene reacted very slightly with nitrene reagent and 32 % of aziridine was observed with approximately 40 % conversion of the substrate. Interestingly, in the case of cis-stilbene, no product was formed. We consider that this can be probably due to the relatively steric hindrance of bulky cis-substrate. We also explored the scope of aziridination using a range of unactivated olefins (Table 21). Both cyclic and acyclic aliphatic alkenes undergo smooth aziridination. Methyl oleate gave promising results since 32 % yield (entry 1) which was observed with only 40 % conversion (80 % based on recovered starting material). This observation demonstrated the potential utility of MNC for the modification of bio-sourced substrate such as fatty acids. However, for terminal alkenes that contain halide group, no aziridination was observed (entry 2). In continues, we were curious to see whether aziridination reaction can happen for substrates containing both arene and alkene moieties. Reaction with cyclohexene in the microwave caused 12 % yield of aziridine which can be improved up to 40 % with the conventional heating method for a longer time (entry 3). We further examined aziridination with different sugar derivatives, but no reaction was observed with these attempts (Table 22). We considered that these results can be attributed to the bulky structure of substrate or electronic nature of it that effect aziridination reaction, irrespective of the location of the double bond. Also, heterocycle containing electron-rich (oxygen atoms) such as 5-(hydroxymethyl)-2(5H)-furanone was examined in aziridination reaction, but no aziridine product was observed with this substrate (entry 4).

R 2 R 1 O R 2 R 1 O MeCN, Ar PhI=NTs, MNC R 1 = H, OH, OCH 2 CH 3 R 2 =

Entry

Entry

Entry

Substrate Yield (%) Conversion (%) 1 0 0 Generally, yields of aziridination reaction with MNC are comparable to those obtained using a homogeneous copper catalyst. Therefore, in addition to its practical interest, this new aziridination procedure with magnetically recoverable copper appears to be at least as effective as the classical procedure. Maybe catalytic activity of MNC is not sufficient for polyfonctionalized substrates, but it is active for a range of olefins with EWG, EDG and long chain olefin with good to excellent yields and high conversions which typically are obtained in 30-120 min. Aziridination reaction with magnetic nanocatalyst can be under influence of different parameters. Not only the electronic nature of substrate which can affect the final result, but also the linker of the catalyst and leaching of the copper which influence the performance of the catalytic system and yield of product. Thus, in continues we concentrated on the development of new catalysts which can strongly chelate the copper on the surface of MNP.

2 0 0 3 0 0 4 0 0

Linker optimization

Following our experiments, in the next step, we examined different organic linkers for catalysts in order to evaluate the effect of different chelating and anchoring groups on the leaching. We functionalized magnetic nanoparticles with several different MNP-anchoring (phosphonic compounds, catechol) holding various Cu-chelating functions (-COOH, -NH 2 ) (Figure 48).

Effect of Cu-chelating functions

First, attention has been devoted to the effect of Cu chelating groups in the functionalization process of Fe 3 O 4 with catechol anchoring (Figure 49). The chelating modes of two carboxylic acids and an amino function have been studied to evaluate the role on the surface binding group and the leaching behavior of copper. 144 In order to have reliable references, the grafting process of linkers on Fe 3 O 4 MNPs and chelating copper on the surface of modified MNPs were similar to Fe 3 O 4 -Dopa-Cu. The obtained monolayers were characterized by XRD and FT-IR spectroscopy. Then, the new catalysts were tested in aziridination reaction to investigate their performance (Table 23). Also, the leaching of the copper has been analyzed by AAS (last columns). According to Table 23, these three catalysts exhibited good activity in aziridination reaction. In all cases, 5 wt % of copper was expected to be loaded on MNP, except the catalyst with L-Dopa (entry 3) where 1.35 wt % of copper was loaded in MNP. This low loading of copper can be attributed to the amino functional group that its basic feature could deprotonate the carboxylic acid to form an unreactive ammonium carboxylate salt for chelating copper. Furthermore, the copper leaching observation showed a high amount of leaching with L-Dopamine linker to the level of 41 % of the initial amount (entry 3), that showed this linker is not applicable for copper chelating.

Entry

Effect of MNP-anchoring groups

In continues, we investigated the effect of anchor functional group by replacing catechol. Our aim was to prepare a functionalized Fe 3 O 4 nanoparticle carrier, using linkers with a phosphonic group as anchoring function and amino or carboxylic acid as copper chelating groups (Figure 50). Because of the high affinity between phosphonic and hydrated oxide particles, in particular, iron (III) oxides, the phosphonic group has covalent interaction with Fe 3 O 4 . 145 In this way, three different catalysts were synthesized in the same condition of preparation. The catalytic activity of new magnetically recoverable heterogeneous catalysts was studied in on styrene to form aziridine (Table 24). 123

Entry

Under the same reaction conditions, the linkers have different behavior in aziridination. Fe 3 O 4 -APPA (Table 24, entry 1) showed low potential for chelating copper and gave a low aziridination yield. According to AAS studied 57 % of copper were leached in the reaction media. The presence of amino function didn't show a good compatibility with phosphonate anchoring functional group and not be strong enough to keep the copper on the surface of MNC during the reaction. FTIR-ATR spectroscopy of Fe 3 O 4 -APPA-Cu (Figure 51) may confirm this result. According to FTIR the presence of the APPA ligand at the surface of the Fe 3 O 4 can be proofed with two bands at 795 and 887 cm -1 and a broad band from 939 to 1193 cm -1 which is attributed to Fe-O-P bonds and other bonds from 2947 to 3248 cm -1 in Fe 3 O 4 -APPA related to amino functional group. 146 Also, spectra of Fe 3 O 4 -APPA clearly shows the absence of OH bonds which is observable in APPA spectra from 2300 to 2899 cm -1 and shows APPA is correctly anchored from its OH groups to Fe 3 O 4 . For all spectra (Figure 51) the band that presents Fe-O-P is visible except for Fe 3 O 4 -APPA-Cu (fresh) which shows the lower intensity compared to APPA and Fe 3 O 4 -APPA. This can be attributed to the presence of copper on the surface of MNC which causes decreasing of intensity. On the other hand, after reaction and 56 % leaching of copper, the peaks related to Fe-O-P (Fe 3 O 4 -APPA-Cu (1 run)) are observed with better intensity. This change in intensity (fresh and run1) may proof that this leaching is more related to week ability of amino functional group to chelate the copper on the surface of the support and it is not attributed to phosphonate anchoring group. Another case, Fe 3 O 4 -CPPA with the presence of carboxylic groups (Table 24, entry 2) showed the better result in catalyst reactivity and probably a better chelating ability for copper. As it is shown in Table 24, only 18 % leaching of copper is observed when carbocyclic acid is used. Also, comparing the results (Table 23 andTable 24) showed -COOH group has better compatibility with phosphonic compound and catechol group in compare of amine functional group. To test the copper stability with two carboxylic groups, we used commercially available bi-dentate ligands that containing a pair of -COOH group (Table 24, entry 3). However, an additional amount of -COOH group does not lead to complete conversion after 2 h of reaction. That may be attributed to the donation of the extra pairs of electrons to a metal atom in presece of secondary -COOH group and influence of non-bonding electron pairs of nitrogen that these three functional groups strongly stabiles the copper on the surface of MNC, but caused deactivation of copper. From this result, both Fe 3 O 4 -hydrocaffeic acid (Figure 49) and Fe 3 O 4 -CPPA (Figure 50) are good candidates for the next studies and developing the performance of magnetic nanocatalyst. In continues, with the intention of appraisal of the optimized conditions for Fe 3 O 4 -CPPA-Cu reaction, parameters such as heating method, copper loading in Fe 3 O 4 -CPPA-Cu, amount of catalyst and the time of reaction were explored systematically by choosing the styrene aziridination reaction as the model. The results are in the next section.

Aziridination reaction with new Fe 3 O 4 -CPPA-Cu catalyst

On the basis of the optimized reaction conditions, aziridination reactions were explored using different heating method (CH, MW). The results are summarized in Table 25. In this catalytic system, both MW and CH proceed well and readily gave the corresponding aziridine in good yields. CH compared with MW probably requires longer reaction times for a complete conversion of styrene. It is discovered that MW causes faster reaction rates than CH, which is a result of the high reactivity of catalyst and lower leaching of copper. Moreover, the yield and reaction rate with MW were higher than those of CH. In continues, the model reaction was explored with the amount of copper loaded in Fe 3 O 4 -CPPA-Cu ranging from 1 wt % to 10 wt % of Cu (Table 26). The reaction could proceed efficiently even with a low amount of catalyst (1 wt % of Cu) in 94 % product yield (entry 1). With the increase in the amount of catalyst from 1 wt % to 10 wt %, the yields decreased from 94 % to 46 %, correspondingly (entries 1-3). Notably, changing the linker from dopamine to CPPA has shown the positive effect for catalyst activity and stability. The present catalyst was further examined with a higher or lower amount in the reaction (Table 26, entries 4-5). According to these observations, the minimum of 0.04 mmol of catalyst needed for the reaction to obtain the acceptable yield of product. Also, the higher amount of catalyst (0.06 mmol) under similar conditions caused the higher yield of aziridine with the same copper leaching during the reaction (Table 26, entry 4).

Entry

Reaction time was optimized for Fe 3 O 4 -CPPA-Cu as catalyst (Table 27). It shows the repetition of optimum aziridination procedure for a reaction time of 15 min, 30 min, 1 h and 2 h. As can be seen, no significant loss of activity of the catalyst is observed. AAS analysis shows that freshly prepared Fe 3 O 4 -CPPA-Cu contains 5 wt % of copper, while Fe 3 O 4 -CPPA-Cu after five cycles contains 3.4 wt % of Copper. In spite of leaching of Cu during the recovery process of the catalyst, CPPA linker worked better than dopamine to chelating copper on the surface of MNC. The result showed 32 % of copper lost from the surface of Fe 3 O 4 -CPPA-Cu which showed a better result in comparison to the previous result with Fe 3 O 4 -Dopa-Cu that caused 47 % leaching of copper (Figure 53).

Entry

Sugar based linker

A key challenge for MNCs applications is the development of linkers that provide a versatile and stable interface between MNPs and the metal catalyst and bring the desired activity and selectivity in the reaction. This section deal with synthetic routes for developing CPPA linker and introducing carbohydrates to the structure of CPPA linker (Figure 54). As it was mentioned previously, MNPs prefunctionalization with phosphonic group forms a stable coating. Also, phosphonic-based MNCs were proven to possess excellent thermal and hydrolytic stability. 102 Carbohydrates are the interesting alternatives because they are easily accessible from biosourcces, can be prepared in few steps and bearing a second functional group such as carboxylic group (-COOH) which is more favored to chelate copper. Also, the linkers based on carbohydrate can be an interesting alternative for replacing conventional Pybox or box linkers which are not accessible from natural sources. 147 This linker later can be anchored on the surface of MNC for the aim of recovering.

As the beginning, we proceeded from commercially available D-ribose (Scheme 47). The aim of this choice is using inexpensive carbohydrate precursor for introducing chirality to the scaffold of the new linker and may be possible to turn it into an interesting alternative for enantioselective aziridination.

The first step was the protection of hydroxyls on C2 and C3 of the D-ribose with an isopropylidene group to form 17 with an overall yield of 30 % after treatment with a catalytic amount of I 2 in acetone solution for 18 h. 148 Compound 17 was then silylated with tertbutyldiphenylsilyl chloride at the primary hydroxyl group under standard conditions to give compound 18 as colorless crystals in 80 % yield (Scheme 47). In this process, thionyl chloride was used for this esterification (table 28, entry 1). 150 But, no product was observed. For the next, we tried 4-(dimethylamino) pyridine (DMAP) in presence of triethylamine (TEA) (table 28, entry 2). 151 However, after 48 h no product was observed. For the next, the esterification of 18 with 20 by DCC in CH 2 Cl 2 gave desired product 21 as a mixture of α/β-isomers in a 5:95 ratio and in 80 % yield (table 28, entry 3). 152 Finally, after obtaining the desired product we scale up the product from 50 mg to 200 mg, but the yield of the product did not exceed 50 %. For the next step, we tried to remove the silyl group of 21 for a later oxidation of the primary alcohol. As it's mentioned in literature, 153 we used tetra-n-butylammonium fluoride (TBAF) for the cleavage of the silyl group to form compound 22 in 63 % yield. This reaction was followed by the oxidation of the primary alcohol to give the corresponding carboxylic acid 23 (Scheme 50). Different methods such as the TEMPO-BAIB oxidation 154 or TEMPO-Fe 3 (NO 3 ) 3 .9H 2 O 155 system was utilized to oxidized primary alcohol. TEMPO is a mild procedure for the oxidation of 2ˈ,3ˈ-isopropylidene protected ribose. It's mentioned that this method gives high yields and has a very simple isolation procedure. But to our surprise, NMR analysis did not show the presence of the oxidized primary alcohol. Indeed, in presence of catalytic amount of TEMPO, the anomeric position was oxidized and compound 23ˈ was obtained instead of 23 (Scheme 50). This unexpected result was due to the migration of the phosphonate group from the aglycone part to the primary alcohol during or after the cleavage of the silyl group to give compound 22ˈ (Figure 55).

Entry

The structure of compound 22ˈ was determined by 1 H NMR analysis (Figure 56). As a comparison, chemical shift for anomeric proton of compound 18 is at 5.37 ppm and after esterification its deshielded to 6.11 ppm. We expected to observe the same chemical shift for compound 22 after silyl group deprotection. But, 1 H NMR analysis of compound 22 showed a lower chemical shift. A signal at 5. To overcome the migration of phosphonate group, we used bulkier protecting group to protect the primary alcohol of ribose. It is assumed that bulkier substitute can help to avoid acetyl migration. 156 There is no evidence of acetyl migration during deprotection when TBDMSCl is used as the protecting group. Thus, ribose part was treated with tert-Butyldimethylsilyl (Scheme 51) to protect the primary alcohol and then with an esterification reaction phosphonate part was linked to the ribose (25). Then, we removed silyl protecting group from hydroxyl function with TBAF/THF for 1 h. After purification, we observed the same product as compound 22 (Scheme 52). However, according to Migaud research, acetyl migration in furanosides such as riboside takes place even using mild desilylating conditions. As our try to avoid this intermolecular migration failed, we used a direct method involving desilylation followed by oxidation of primary alcohol of compound 25 in a one-pot reaction. According to Vatèle research, 158 Bi(OTf) 3 allows a mild deprotection of primary silyl ethers followed by TEMPO/BAIB oxidation of primary alcohol. Application of this procedure to a onepot reaction allowed the conversion of silyl ether 25 into the acid 27, in a pleasing 70 % yield (Scheme 53). Regard to achieve a chiral copper catalyst supported on magnetic nanoparticles, a new linker was prepared from an inexpensive carbohydrate precursor in six steps with an overall yield of 12 %. Also, it is possible to turn this linker into an interesting alternative to conventional ligands such as pybox which are not accessible from natural sources. For this purpose, the selectivity and also the activity of a system with Fe 3 O 4 -linker ( 27)-Cu has to be examined by anchoring the linker ( 27) on the surface of MNP. However, because of the limitation of time for this doctoral study, the investigations to this end as a perspective and feature of our work will be in progress in our laboratory.

Chapter 4: General conclusion

In the light of the results exposed in this thesis, some general considerations can be made on the aziridination reaction with magnetic nano catalyst. The project of this thesis started from the previous work of Evan and Jacobsen for homogeneous aziridination reaction with copper catalysts. On this basis, we investigated the possibility to introduce an environmentally benign and sustainable heterogeneous catalyst for greener synthetic approaches of aziridination reactions (Scheme 54). This catalyst was successfully prepared via co-precipitation procedure. This route was a three steps synthetic approach in which an aqueous solution of both ferric and ferrous salts was used to prepare iron oxide MNPs. Analysis with HRTEM showed that particles of between approximately 11 nm in size were obtained. Then, MNPs were modified with dopamine and the effect of the surface modification of MNPs with dopamine was investigated with XRD and FT-IR. The last step of preparing of the catalyst was followed by addition of copper complex. Chelated copper on the surface of modified MNPs then was investigated with AAS and the result was confirmed by ICP-AES analysis. Therefore, we tested an approach, which involves the use of PhI=O reagent. Whereas the classic aziridination via PhI=O and H 2 NTs turned out to be a very successful reaction, the alternative approach via magnetic nano catalyst (Fe 3 O 4 -Dopa-Cu) showed a limited success. In particular, our investigation showed the negative influence of 4Å MS on magnetic nano particle (Fe 3 O 4 ) which caused deactivation and poisoning of the catalyst. Our observation led us to directly synthesis PhI=NTs for avoiding the side effect of molecular sieves and simplifying the reaction protocol. Secondary catalytic tests didn't give a high yield of aziridine, but catalysts could be simply recycled without loss in amount with an external magnet which was not typically accomplished when PhI=O and H 2 NTs was used. Eventually, improved aziridine yield (90 %) was obtained after optimizing the conditions includes different temperature, solvents, time and type of radiation.

In order to expand the scope of aziridination, a range of commercially available olefin had been tested toward aziridination with Fe 3 O 4 -Dopa-Cu catalyst. The results demonstrate the effect of electron-donating or withdrawing group, the position of substitution and long chain olefin in aziridination reaction with magnetic nano catalyst. When the electron withdrawing group, such as Chloro-or Nitro-, are added to styrene, it did not affect the olefin conversion and provided the corresponding aziridine in excellent yields, 96 and 91 % respectively. Also, Vinyl toluene derivatives gave very good results, especially for the ortho substituted. Interestingly, in the case of 4-aminostyrene, aziridination did not undergo, probably due to interaction with the catalyst. The reaction of protected amine group, however, proceeded sluggishly and required time for completion. More functionalized starting material like cinnamic derivatives led to low conversion or product degradation. Finally, unactivated olefins, such as Methyl oleate gave promising results since 32 % yield was observed with only 40 % conversion (80 % Based on Recovered Starting Materials).

Later, the reusability of the catalyst was examined by turn over reactions in the best condition. The results show that the Fe 3 O 4 -Dopa-Cu magnetic catalyst could be reused up to five times with still full conversion of styrene, very good yield and no significant loss of activity. Also, it should be mentioned that after five runs, no loss of magnetic responsiveness or morphological change was detectable and the catalyst still exhibited high activity even after five recycles (Figure 57). The metal leaching has been measured by atomic absorption spectroscopy (AAS) analysis after all experience and finally after 5 runs. Analysis showed there was leaching of 23 % copper from support to the reaction. To investigate the stability of copper on the support we examined different organic linker as a copper chelator to decrease copper leaching during the reaction. MNPs coated with phosphonic acids have been proved to be suitable for the preparation of functional materials for copper chelating. Fe 3 O 4 -CPPA has been further functionalized with copper, and the ability of catalyst has been demonstrated in aziridination reaction. In particular, AAS tests proved a lower leaching of the copper, but still, 18 % of leaching appeared at the end of the reaction.

In summary, the data collected so far indicates that these magnetic nano particles have great potential for application in the C-H bond insertion and can be good candidates for developing an environmentally-friendly protocol from the viewpoint of simplicity and versatility for aziridination reaction. Some work remains to fully improve the MNPs system described in this work for future investigation. This work proposes further investigation on the scope of aziridination with cinnamic derivative and carbohydrate such as galacto glycosylglycerol 159 derivatives for finding the aziridine limitations and possibilities with these substrates. Also, studying the effect of pH on the copper leaching seems essential. As an example, Lei et. al. reported the positive effect of bicarbonate ion for CuO-Fe 3 O 4 due to the suppression of copper leaching in phenol degradation reaction. 160 The next proposed for this work is studying the intramolecular aziridination reactions of sulfonamides and developing an intramolecular version of the MNC aziridination. 45 Also, the potential of the catalyst to transfer nitrene to double bond can be examed in presence of other nitrene sources such as azide compound which gives nitrene species by releasing nitrogen gas and is environmentally friendly nitrene precursors. 161 There is still more study on the catalyst to fully understanding copper behavior on the surface of magnetic nano particles which can be part of long term future study. These investigations contain Extended X-Ray Absorption Fine Structure (EXAFS) to reveal the atomic dispersion or cluster accumulation of copper on the surface of the support. In order to provide further evidence of copper oxidation state the X-ray photoelectron spectroscopy (XPS) can bring a comparable result for the synthesized catalysts. A serious of elemental analysis needs to calculate the exact amount of linker before and after the reaction. Also, Brunauer Emmett Teller (BET) analysis to help to determine the surface area of a MNC and vibrating sample magnetometry (VSM) to be used to investigate the magnetic properties of the synthesized MNPs and MNC. Finally, one of the feature perspectives of this work will be introducing an asymmetric version of this catalyst and testing the ability of MNC in enantioselective aziridination reaction. The support of this catalyst can be a developed form of Fe 3 O 4 -CPPA that will contain an inexpensive carbohydrate precursor. Also, new sugar base linker can be an interesting alternative to conventional Pybox or box linker which are not accessible from natural sources. For this purpose, the selectivity and also the activity of the MNC has to be improved by modification of the linker structure. Investigations to this end will progress in our laboratories.

J. PHI=NTs

Tosyl-substituted [N-(phenylsulfonyl)imino]phenyliodinane as a nitrogen precursors synthesized according to a protocol of Evans. 37

K. PhI=O

Iodosylbenzene as an oxidant was synthesized according to Philippe Dauban protocol. 122

L. Substrates description

In the characterization of styrene derivatives aziridination, the carbon atoms of aziridine ring are named as C A and C B and the substitutes are identified as R.

M. General Synthesis protocol

To a mixture of Olefin substrates (0.4 mmol), catalyst (0.04 mmol) in dry acetonitrile, was added PhI=NTs (0.48 mmol) portion wise in 5 times in Microwave at 70 o C under argon atmosphere and the whole mixture was stirred between 10 minutes to 3h. After, the catalyst was removed with an external magnet and washed with extra dried MeCN. The solvent was evaporated with evaporator and crude was analyzed with TLC, NMR, Mass spectroscopy. The crude was purified by flash chromatography on silica gel eluted with 20 % EtOAc in cyclohexane to afford the product. 4-Vinylaniline (96 mg, 0.8 mmol, 1 eq.) was added to a round-bottom flask via syringe. The flask was purged with argon and dry DCM (2 ml) was added. Acetic anhydride (96 μl, 0.96 mmol, 1.2 eq.) was added and the reaction was stirred at room temperature and monitored by TLC. Upon completion, the reaction mixture was washed with a saturated solution of sodium carbonate, the organic layers dried with MgSO 4 and the solvent removed under reduced pressure. The crude product was purified by chromatography on silica gel (cyclohexane/AcOEt = 1/2) to give the product as a yellow solid (110 mg, 89 %). All the charactirization analysis are liteartury reported followed by Yang et al . D-ribose (6.6 mmol, 1g) was stirred with dry acetone under atmosphere of argon. When the mixture was homogenized, I 2 (1 mmol, 250 mg) was added. The solution stirred at room temperature for 24h and monitored by TLC (silica gel, eluent ethyl acetate -cyclohexane, 1:1 v/v). The end of reaction, the I -3 was neutralized by aqueous Na 2 S 2 O 3 . After solvent evaporation crude was purified with chromatography (7/3= hexane-EtOAc). To a magnetically stirred solution of 15 (0.65 mmol, 123 mg) and imidazole (2.6 mmol, 177 mg) in DMF at 0°C, was added dropwise TBDPSCl (0.68 mmol, 186 mg ) over 10 min. The mixture be allowed to reach room temperature and stirred for 1 hour. TBME and water be added to the mixture, and the organic layer be separated and washed with water (20 ml×2) and brine (20 ml). After drying over Na 2 SO 4 and evaporation, purification was done with cyclohexane/EtOAc (9/1). To the mixture of 18 and 20 in dried DCM, were added DCC and 4-(Dimethylamino) pyridine at 0 o C and the whole mixture was stirred for 20h at room temperature. After DCM was added, the precipitate was filtered off through a celite and then washed with DCM. The filtrate was washed with 5 % aqueous Na 2 CO 3 solution and water, dried over MgSO 4 , and concentrated to dryness. The residual oil was purified by flash chromatography on silica gel( EtOAc/Cyclohexane 2:8) to afford the product. Exposure of 21 to Tetra-n-butammonium fluoride (2eq.) in THF at 0 o C to room temperature regenerated product 22ˈ. The crude was extracted with EtOAc and water then the aqueouse layer is acidified with ammonium chloride and extracted with EtOAc. The combined organic layer is dried, filtered, evaporated and was purified by flash chromatography on silica gel ( EtOAc / cyclohexane 1:1). To the mixture of Km 22 in MeCN/H 2 O (1:1), were added 0.2 eq. of TEMPO and 2.2 eq. of BAIB. The mixture is stirred at room temperature until the most starting material is consumed. At the end of reaction the solvent was evaporated and the crude was extracted with water and EtOAc. To the the stirred solution of 17in dry DCM was added imidazole and TBDMSCl at room temperature and mixed stirred for 3h. The solvent was removed and residue partitioned between EtOAc and H 2 O. The organic layer washed with brine, dried over anhydrous Na 2 SO 4 , and evaporated. The residue was purified by silica gel column chromatography (Cyclohexane/EtOAc 9/1) to give the product. To the mixture of 20 and 24 in DCM were added DCC and 4-(Dimethylamino) pyridine at 0 o C and the whole mixture was stirred for 20h at room temperature. After that DCM was added, the precipitate was filtered off through a celite pad and then washed with DCM. The filtrate was washed with 5 % aqueous Na 2 CO 3 solution and water, dried over MgSO 4 , and concentrated to dryness. The residual oil was purified by flash chromatography on silica gel eluted with 20 % EtOAc in cyclohexane to afford the product. Exposure of 25 to Tetra-n-butammonium fluoride (2eq.) in THF at 0 o C to room temperature regenerated produced 26. The crude was extracted with EtOAc and water then the aqueouse layer is acidified with ammonium chloride and extracted with EtOAc. The combined organic layer is dried, filtered, evaporated and was purified by flash chromatography on silica gel ( EtOAc / cyclohexane 1:1). 1 H NMR (400 MHz, Chloroform-d) δ 7.32 (p, J = 3.7 Hz, 10H), 5.44 (s, 1H, H-1), 5.08 -4.86 (m, 4H), 4.72 -4.47 (m, 2H, H-2 and H-3), 4.17 -4.00 (m, 1H, H-4), 2.55 (ddd, J = 15.6, 8.5, 2.4 Hz, 2H, H-5), 2.14 -2.02 (m, 2H), 1.46 (s, 2H), 1.30 (d, J = 1.9 Hz, 3H). To 25 (1 eq. 0.08 mmol) in dried MeCN were added H 2 O and Bi(OTf) 3 (0.01eq. 8×10 -4 mmol). The reaction mixture was stirred for 18h (monitored by TLC, Cyclohexane-EtOAc, 1:1) and NaHCO 3 (3 eq. 0.24 mmol), TEMPO (0.05 eq. 4×10 -3 mmol) and PhI(OAc) 2 (2.2 eq. 0.176 mmol) were successively added. The suspension was stirred for 4h from 0 o C to r.t in vacuo. Finally, crude was worked up with NaHCO 3 and HCl(1M). Fe3O4-Dopamine (400 mg) was dispersed in water-Ethanol mixture (1:1). CuCl 2 (54 mg) solution in water was added to the reaction mixture. Hydrazine monohydrate solution in water was added drop wise to bring the pH of this mixture to 9, followed by the addition of 13 mg of NaBH 4 . The reaction mixture was then stirred for 24 h at room temperature. The product was allowed to settle, washed several times with acetone, and dried under vacuum at 60 • C for 2 h.

5.2.Aziridines and organic linker molecules 1. 1-[(4-methylphenyl)sulfonyl]-2-phenylaziridine

3-Benzoyl-1-[(4-methylphenyl)sulfonyl]-2-phenyl-aziridine phenyl(3-phenyl-

Figure A .

 A Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 6 .

 6 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 7 .Figure 9 .Figure 10 .Figure 11 .Figure 14 .Figure 15 .

 7910111415 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 16 .

 16 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 17 .

 17 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 18 .

 18 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 19 .

 19 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 20 .

 20 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 21 .

 21 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 22 .Figure 23 .Figure 24 .

 222324 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 25 .

 25 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 26 .Figure 27 .

 2627 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 28 .

 28 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 29 .

 29 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 30 .

 30 Figure A. Quelques produits naturels contenant la fonction aziridine ......................................... Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) ......................... Figure C. Expériences de turnover avec NCM. ........................................................................... Figure D. Optimisation de NCM avec différents ligands. ........................................................... Figure E. NCM à base de sucre ...................................................................................................Figure 6. Hybridization in aziridine. ............................................................................................Figure 7. Strain prevents nitrogen inversion. ............................................................................... Figure 8. Calculated N-inversion energies of substituted aziridines. 6 .........................................Figure 9. The sulfonamide groups. .............................................................................................. Figure 10. The phosphoryl groups. .............................................................................................. Figure 11. Aminolactam synthesis from non-activated aziridine. ............................................... Figure 12. Miraziridine. ............................................................................................................... Figure 13. Azinomycin. ............................................................................................................... Figure 14. Maduropeptin chromophore. ...................................................................................... Figure 15. Five members of mitosane family. ............................................................................. Figure 16. Halfen catalytic system for olefin aziridination. ........................................................Figure 17. Chiral dirhodium(II,II) catalysts used by Che. ........................................................... Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48 .........................Figure 19. Potential free energy surface of Norrby's system. 49 ...................................................Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59 .................................................................................... Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B. .......................................................................................................................... Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3 nanoparticles. 81 ................................................................................................................ Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy. ............................ Figure 24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating. 97 ...................................................................................................Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker. ....................................Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106 ........................................................................................... Figure 27. Chemical structures of catechol stabilizer with PEG. 107 ............................................Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 108 .........................................Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu. ......................................................................Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers. .......................

Figure 31 .Figure 33 .Figure 34 .

 313334 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 35 .

 35 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 36 .Figure 37 .Figure 39 .Figure 40 .

 36373940 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 42 .

 42 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 43 .

 43 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 44 .

 44 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 46 .

 46 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 47 .Figure 49 .Figure 51 .Figure 52 .Figure 53 .

 4749515253 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 54 .

 54 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 55 .

 55 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 56 .

 56 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

Figure 57 .

 57 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K. ...................................................................................................... Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2 .......................................................... Figure 33. XRD patterns of iron oxide nanoparticles. ................................................................ Figure 34. TEM images of Fe 3 O 4 .................................................................................................Figure 35. FT-IR spectra of modified Fe 3 O 4 . ...............................................................................Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper. .........................................Figure 37. TEM of Fe 3 O 4 -Dop-Cu. .............................................................................................. Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS). ................. Figure 39. Catalyst recovering with external magnet. ............................................................... Figure 40. First turnover experiments with MNC. ..................................................................... Figure 41. XRD pattern of MNC before and after reaction. ......................................................Figure 42. FT-IR of MNC before and after reaction.................................................................. Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I). ....... Figure 44. Comparing styrene aziridination with activated and deactivated catalyst. ............... Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere. ............Figure 46. Turnover reactions with microwave assistance. .......................................................Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material ..................................................................................................................................................... Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction. ................ Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups. ..................................................................................................................................................... Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups. ......................................................................................................................................... Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction. ............................................... Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu. ............................................................... Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction. .................................................................................................................Figure 54. Sugar based linker ....................................................................................................Figure 55. Silyl group deprotection of 19. .................................................................................Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23. .......Figure 57. aziridination and catalyst recovering with external magnet .....................................

  ................................................................. Table 19. Aziridination of electron-withdrawing groups. .......................................................... Table 20. Aziridination of chalcone and stilbene. ...................................................................... Table 21. Aziridination of unactivated olefin. ........................................................................... Table 22. Aziridination of the sugar derivatives. ....................................................................... Table 23. Aziridination with catechol anchor and different chelating groups ........................... Table 24. Aziridination with phosphonic anchor and different chelating group. ...................... Table 25. Aziridination reaction with Fe 3 O 4 -CPPA-Cu in MW versus CHM. .......................... Table 26. Aziridination reaction with different loading and amounts of copper in Fe 3 O 4 -CPPA-Cu. ............................................................................................................................................... Table 27. Effect of the time on copper leaching in aziridination reaction with Fe 3 O 4 -CPPA-Cu. ..................................................................................................................................................... Table

Figure A .

 A Figure A. Quelques produits naturels contenant la fonction aziridine

  Aziridination d'oléfines catalysée au cuivre avec le catalyseur d'Evans.

FeSO 4 . 4 Fe 3 O 4 Ar, 60

 443460 7H 2 O + Fe 2 (SO) o C 1h, NH 4 OH Schéma B. Formation de nano particules de Fe 3 O 4 par co-précipitation.

H 2

 2 NTs , [O], MgO, MeCN Cu(I) or Cu(II) Styrene Aziridine NTs [O]: BAIB, PhI=NTs, PhI=O KM1 Schéma C. Aziridination de styrene.

  3 O 4 avec du fer (II) et du fer (III) en présence d'hydroxyde d'ammonium à un pH ajusté à 10 (Schéma B). Ensuite Fe 3 O 4 les NPs ont été modifiées avec de la dopamine grâce à une activation par sonication (Schéma D). La structure du matériau a été analysée par spectroscopie infrarouge à transformée de Fourier. Elle est conforme aux résultats obtenus dans la littérature. Schéma D. Modification de Fe 3 O 4 avec dopamine.

Fe

  Figure B. Désactivation de Fe 3 O 4 avec le tamis moléculaire (hexagone = MS) Pour contourner ce problème, nous avons synthétisé le N-(p-tolylsulfonyl)imino]phényliodinane (PhI = NTs) qui ne génère pas d'eau et évite l'utilisation de tamis moléculaire dans la réaction. La deuxième optimisation est faite avec PhI=NTs.

  Le scope de l'aziridination avec NCM.

  de NCM La relargage du cuivre peut influencer les performances du système catalytique et le rendement du produit d'une réaction à la suivante. Nous avons donc cherché à stabiliser notre NCM afin de limiter la perte de cuivre. L'effet de différents groupes de chélation et d'ancrage sur l'activité du catalyseur et le relargage du cuivre ont été particulièrement examinées (Figure D).

Figure D .

 D Figure D. Optimisation de NCM avec différents ligands.Nous avons fonctionnalisé des nanoparticules magnétiques avec plusieurs ligands présentant des ancrages de type phosphoniques ou catéchol et également differentes fonctions chélatantes comme les carboxylates ou les amines (tableau C).

Figure E .

 E Figure E. NCM à base de sucre

3

 3

Scheme 1 .

 1 Scheme 1. First classic aziridination reaction.

4

 4

Figure 6 .

 6 Figure 6. Hybridization in aziridine.

Scheme 2 .

 2 Scheme 2. (a) Activated and (b) Non-activated aziridine.

Figure 9 .

 9 Figure 9. The sulfonamide groups.

Scheme 3 .

 3 Scheme 3. N-sulfonyl aziridine ring opening.

Figure 10 .

 10 Figure 10. The phosphoryl groups.

Scheme 4 .

 4 Scheme 4. N-phosphoryl aziridine ring opening.

21

 21

Figure 12 .

 12 Figure 12. Miraziridine.

Figure 13 .

 13 Figure 13. Azinomycin.

23

 23

Figure 14 .

 14 Figure 14. Maduropeptin chromophore.

25

 25

Figure 15 .

 15 Figure 15. Five members of mitosane family.

25

 25

27

 27

Scheme 9 .

 9 Scheme 9. Hypothetical biosynthesis of the azicemicin.27

2 Scheme 13 .

 213 Scheme 13. Staudinger aziridination reaction

Scheme 17 .

 17 Scheme 17. Carbene insertion to imine.

Scheme 18 .

 18 Scheme 18. Addition of metal-nitrenes to olefins.

Scheme 19 .

 19 Scheme 19.Copper catalyzed aziridination reaction.

Figure 16 .

 16 Figure 16. Halfen catalytic system for olefin aziridination.

Scheme 21 .

 21 Scheme 21. Rh-catalyzed aziridination reaction.

Scheme 22 .

 22 Scheme 22. Rh-catalyzed aziridination of styrene with chiral bidentate chiral ligand.

Figure 18 .

 18 Figure 18. Cycle for the Cu-catalyzed aziridination of alkenes with PhI=NR. 48

49

 49

Figure 19 .

 19 Figure19. Potential free energy surface of Norrby's system.49

  Functional group: N 3 , SH, OH, NR 2 , ... Alkyl, aryl organosilicasmesoporous ML n = metal-ligand complex

Figure 20 .

 20 Figure 20. Templated formation of mesoporous organosilicas and idealized regular distribution of organic moieties at the silica surface. 59

69

 69

Figure 21 .

 21 Figure 21. Effect of an external magnetic field on MNPs used as catalysts for the reaction between A and B.

FeSO 4 . 4 FeScheme 24 .

 4424 Scheme 24. Synthesis of Fe 3 O 4 MNPs using precipitation method.77

Figure 22 .

 22 Figure 22. Morphology control with thermal decomposition method (a) spherical and (b) cubic γ-Fe 2 O 3nanoparticles.81

Figure 23 .

 23 Figure 23. The liquid-solid-solution (LSS) phase transfer synthetic strategy.

Scheme 25 .

 25 Scheme 25. Synthesis procedure of Fe 3 O 4 @C core-shell NPs.

Figure 24 .

 24 Figure24. Surface modification of Fe 3 O 4 @SiO 2 nanoparticles with Azo-polymer and drug release after magnetic heating.97 In other example, Buzoglu et al. modified Fe 3 O 4 with (3-Aminopropyl) tri-ethoxysilane (APTES) and investigated the interaction between the drug donepezil® and human serum albumin (HSA) on the surface of this amino modified Fe 3 O 4 (Scheme 27).98 In this research, Fe 3 O 4 was obtained from precipitation of FeCl 3 •6H 2 O and FeCl 2 •4H 2 O salts with NH 4 OH and then modified with (3-aminopropyl)triethoxysilane (APTES) to obtain functional amine groups on the nanoparticles' surface. After, HSA was bonded to the APTES-modified SPIO. Finally, donepezil® was grafted on modified MNPs with HAS-SPIO.

Feprecipitation 28 .

 28 Scheme 28. Systematic procedure for the immobilization of urease on the functionalized Fe 3 O 4 MNPs.

Figure 26 .

 26 Figure 26. Structure of Fe 2 O 3 before and after surface modification with dopamine (Red =O, Gray = Fe, Blue=C, dark blue=N). 106

107

 107

Figure 27 .

 27 Figure 27.Chemical structures of catechol stabilizer with PEG.107

Figure 28 . 108 2. 6 .

 281086 Figure 28. Legionella pneumophila determination based on a disposable core-shell Fe 3 O 4 @poly(dopamine) magnetic nanoparticles immunoplatform. 1082.6. Chelating metal on surface of modified MNPs, synthesis of MNCs and applications in organic chemistry.As mentioned before, MNPs and MNCs take place in different field of research. Also, the use of magnetic nanoparticles as efficient supports for catalysts has become a subject of organic chemistry. This is because MNPs can be well dispersed in reaction mixtures without a magnetic field, providing a large surface area that is readily accessible to substrate molecules. In this way, chelating metal catalysts such as Cobalt, nickel, copper, palladium, ferrites, as well as gold, silver, rhodium on the surface of MNPs become an interesting subject in organic chemistry. This section deals with immobilization of metal catalyst on MNPs and its application in different organic reactions.

Scheme 29 .

 29 Scheme 29. Synthesis of palladium-MNCs.77

Figure 29 .

 29 Figure 29. XRD pattern of Fe 3 O 4 and Fe 3 O 4 @Cu.

Figure 30 .

 30 Figure 30. SEM images of iron oxides with six different shapes (a) nanorod, (b) nanohusk, (c) distorted cubes, (d) nanocubes, (e) porous spheres and (f) self-oriented flowers.

117

 117

Figure 31 .

 31 Figure 31. (A) The effect of carboxylate layer and phosphonate layer in the presence of an applied magnetic field (arrows depict the resultant ferrimagnetic moment). (B) Magnetization curves from SQUID at 300 K.

Figure 32 .

 32 Figure 32. FT-IR spectra of (a) Fe 3 O 4 (b) Fe 3 O 4 @AEPH 2

Scheme 33 .

 33 Scheme 33. Formation of PhI=NTs from BAIB and H 2 NTs.

Scheme 34 .

 34 Scheme 34. Synthesis of Fe 3 O 4 from Fe(II) and Fe(III) precursor.

Figure 33 .

 33 Figure 33. XRD patterns of iron oxide nanoparticles. The relative intensities of the diffraction peaks matched well with the standard XRD data of the Joint Committee on Powder Diffraction Standards (JCPDS) card number (19-0629) for Fe 3 O 4 crystal.77

Figure 34 .

 34 Figure 34. TEM images of Fe 3 O 4 .

Figure 35 .

 35 Figure 35. FT-IR spectra of modified Fe 3 O 4 .

Figure 36 .

 36 Figure 36. FT-IR of modified Fe 3 O 4 before and after adding copper.

Figure 37 .

 37 Figure 37. TEM of Fe 3 O 4 -Dop-Cu.

Figure 38 .

 38 Figure 38. Capturing of Fe 3 O 4 nanoparticles with molecular sieve (hexagon= MS).

Scheme 37 .

 37 Scheme 37. Postulated mechanism of aziridination with MNC.

Temp

  Styrene (1eq.), PhI=NTs (1.4 eq.), MNC (0.1 eq.)

Figure 39 .

 39 Figure 39. Catalyst recovering with external magnet.

Figure 40 .

 40 Figure 40. First turnover experiments with MNC.

Figure 41 .

 41 Figure 41. XRD pattern of MNC before and after reaction.

Figure 42 .

 42 Figure 42. FT-IR of MNC before and after reaction.

138

 138

Figure 43 .

 43 Figure 43. Turnover experiment with (a) Fe 3 O 4 -Dopa-Cu(II) and (b) Fe 3 O 4 -Dopa-Cu(I).

Figure 44 .

 44 Figure 44. Comparing styrene aziridination with activated and deactivated catalyst.

Figure 45 .

 45 Figure 45. Turnover experiments with extra care of catalyst under argon atmosphere.

Scheme 40 .

 40 Scheme 40. Effect of homogeneous copper in reaction.

Figure 46 .

 46 Figure 46. Turnover reactions with microwave assistance.

7 Scheme 42 .

 742 Scheme 42. Amine protection with acetyl group.

Scheme 43 .

 43 Scheme 43. Azirination with protected amine functional group.

4 Scheme 44 .

 444 Scheme 44. Azirination with 4-methoxyaziridine.

Scheme 45 .

 45 Scheme 45. Oxidation reaction of amino-alcohol by-product.

Figure 47 .

 47 Figure 47. (A') DEPT NMR before and after oxidation; (A) DEPT NMR of the starting material

Scheme 46 .

 46 Scheme 46. Aziridination with cinnamic derivatives.

Figure 48 .

 48 Figure 48. Surface modified MNP as magnetic catalysts for aziridination reaction.

FeFigure 49 .

 49 Figure 49. Surface modification of MNP with catechol anchoring and different chelating groups.

FeFigure 50 .

 50 Figure 50. Surface modification of MNP with phosphonic anchoring and different chelating groups.

Figure 51 .

 51 Figure 51. FTIR of Fe 3 O 4 -APPA-Cu before and after reaction.

Conditions:Table 25 .

 25 Styrene (1 eq.), PhI=NTs (1.2 eq.), MNC=Fe 3 O 4 -CPPA-Cu Aziridination reaction with Fe 3 O 4 -CPPA-Cu in MW versus CHM.

Figure 52 .

 52 Figure 52. Turn over reaction with Fe 3 O 4 -CPPA-Cu.

Figure 53 .

 53 Figure 53. Copper leaching behavior after 5 runs with Fe 3 O 4 -Dopa-Cu and Fe 3 O 4 -CPPA-Cu in aziridination reaction.

Figure 54 .

 54 Figure 54. Sugar based linker

Scheme 50 .

 50 Scheme 50. Formation of the carboxylic acid.

Figure 55 .

 55 Figure 55. Silyl group deprotection of 19.

Figure 56 .

 56 Figure 56. Comparing chemical shift of anomeric proton of compounds 18, 22ˈ, and 23.

Scheme 51 .

 51 Scheme 51.Treating the compound with bulkier protecting group.

157

 157

Scheme 52 .

 52 Scheme 52. The product after deprotection reaction.

Scheme 53 .

 53 Scheme 53. One pot desilylation-oxidation reaction.

Scheme 54 .

 54 Scheme 54. Aziridination reaction with MNC

Figure 57 .

 57 Figure 57. aziridination and catalyst recovering with external magnet

13 C

 13 NMR (101 MHz, CDCl 3 ) δ 144.72(C Ar ), 138.29(C Ar ), 135.11(C Ar ), 132.09(C Ar ), 129.87(C Ar ), 129.36(C Ar ), 128.04(C Ar ), 126.58(C Ar ), 41.20 (C B ), 35.96 (C A ), 21.80 (R), 21.30(CH 3 ). TLC: R f = 0.46 (cyclohexane/EtOAc 2:8) MS:[M+H] + = 288.0980 HRMS: 288.1052 Yield: 70 % Conversion: 95 % IR (cm -1 ): 1159 (SO 2 ), 1317 (NO 2 ), 1510 and 1589 (C=C), 2841 (sp 3 CH), 2904 (ArH) (400 MHz, Chloroform-d) δ 8.13 (d, J = 8.7 Hz, 2H), 7.86 (d, J = 8.3 Hz, 2H), 7.37 (dd, J = 21.0, 8.4 Hz, 4H), 3.83 (dd, J = 7.2, 4.2 Hz, 1H, H B ), 3.04 (d, J = 7.1 Hz, 1H, H A ), 2.43 (s, 3H), 2.37 (d, J = 4.2 Hz, 1H, H A ).

13 C

 13 NMR (101 MHz, CDCl 3 ) δ 147.92(C Ar ), 145.24(C Ar ), 142.61(C Ar ), 134.54(C Ar ), 130.00(C Ar ), 128.08(C Ar ), 127.56(C Ar ), 123.91(C Ar ), 39.80 (C B ), 36.62 (C A ), 21.76(CH 3 ). TLC: R f = 0.28 (cyclohexane/EtOAc 8:2) MS:[M+H] + = 319.0753 HRMS: 319.0741 Yield: 91 % Conversion: 95 % IR (cm -1 ): 1319 (SO 2 ), 1344 (NO 2 ), 1510 and 1598 (C=C), 2835 (sp 3 CH), 2904 (ArH)

142

 142

  19 NO 4 S MW: 321 g.mol -1 1 H NMR (400 MHz, Chloroform-d) δ 7.71 (d, J = 8.3 Hz, 1H), 7.63 (d, J = 8.3 Hz, 2H), 7.26 -7.16 (m, 2H), 7.09 (d, J = 8.5 Hz, 1H), 6.74 (d, J = 8.7 Hz, 2H), 4.63 (dd, J = 8.8, 3.6 Hz, 1H), 3.69 (s, 3H), 3.15 -3.01 (m, 1H), 2.91 (dd, J = 13.1, 8.8 Hz, 1H), 2.32 (s, 3H).

13 C

 13 NMR (101 MHz, Chloroform-d) δ 159.47 (C Ar ) , 143.55(C Ar ) , 136.82(C Ar ) , 133.16(C Ar ) , 127.46 -125.28 (m, C Ar ), 114.02(C Ar ) , 72.34 , 55.36 , 50.39 , 21.60 . TLC: R f = 0.4 (cyclohexane/EtOAc 5:5) MS:[M+Na] + = 344.0932 HRMS: 344.0924 Yield: 58 % Conversion: 99 % IR (cm -1 ): 1089-1157 (C-O), 1246-1323 (CH 3 ), 1438-1598 (C=C), 2821-2968 (Sp 3 CH 3 ), 3128-3352 (OH and N-H stretch) g.mol -1 1 H NMR (400 MHz, Chloroform-d) δ 7.

  TLC: R f = 0.66 (cyclohexane/EtOAc 1:9) MS:[M+Na] + = 213.0891 Yield: 78 % Conversion: 80 % IR (cm -1 ): 2972( C-H aromatic), 1707 (C=O), 1249 (C=C), 1110(C-O-C).

1 H

 1 NMR (400 MHz, CDCl 3 ) δ 5.69 (d, J = 6.4 Hz, 1H), 5.38 -5.21 (m, 2H), 4.76 -4.15 (m, 6H), 4.06 -3.94 (m, 1H), 3.58 (d, J = 4.9 Hz, 2H), 2.12 -1.63 (m, 1H), 1.29 (ddd, J = 63.4, 14.0, 6.7 Hz, 12H).

13 C

 13 NMR (101 MHz, CDCl 3 ) δ 112.22(C q ), 102.81(C-1), 87.73(C-4), 86.79(C-3), 81.71(C-2), 63.57(C-5), 26.41(CH 3 ), 24.72(CH 3 ). TLC: R f = 0.07 (cyclohexane/EtOAc 2:8) MS:[M+Na] + = 213.0739 HRMS: 213.0732 Yield: 23 % Conversion: 99 % IR (cm -1 ): 1064-1157 (C-O), 1375 (CH 3 ), 2935-2939 (C-H), 3030-3554 (OH)

1 H

 1 NMR (400 MHz, Chloroform-d) δ 7.61 -7.54 (m, 7H), 7.43 -7.23 (m, 10H), 5.26 (s, 1H), 4.69 (dd, J = 6.2, 1.0 Hz, 1H), 4.63 (dd, J = 5.9, 1.0 Hz, 1H), 4.57 (dd, J = 6.2, 4.0 Hz, 1H), 4.51 (d, J = 5.9 Hz, 1H), 4.19 (td, J = 3.2, 0.9 Hz, 1H), 4.06 (dt, J = 2.5, 1.4 Hz, 1H), 3.72 (ddd, J = 11.1, 4.9, 3.1 Hz, 2H), 3.56 (ddd, J = 13.5, 11.2, 2.6 Hz, 2H), 1.46 (s, 1H), 1.38 (s, 3H), 1.30 (s, 1H), 1.22 (s, 3H), 1.00 (s, 9H), 0.97 (s, 4H).

13 C

 13 NMR (101 MHz, CDCl 3 ) δ 135.75(C Ar ), 135.60(C Ar ), 135.59(C Ar ), 135.57(C Ar ), 131.82(C Ar ), 131.75(C Ar ), 130.41(C Ar ), 130.24(C Ar ), 130.07(C Ar ), 129.99(C Ar ), 128.13(C Ar ), 128.07(C Ar ), 127.95(C Ar ), 112.14 (C q ), 103.38(C-1), 87.06(C-4), 81.29(C-3), 79.56(C-2), 65.52(C-5), 26.96, 26.92, 26.53, 26.20, 25.03, 24.74, 19.19, 19.10. TLC: R f = 0.44 (cyclohexane/EtOAc 2(cm -1 ): 856-997(C Ar ), 1068-1082 (C-O), 1262-1373 (CH 3 ), 1421(C=C), 2935-2939 (C-H), 3043(OH)

13 C 1 To 19 ( 13 C

 1311913 NMR (101 MHz, CDCl 3 ) δ 171.41(C=O), 136.03(C Ar ), 135.98(C Ar ), 135.40(C Ar ), 135.34(C Ar ), 128.36(C Ar ), 127.70(C Ar ), 67.07, 67.01, 60.57, 27.19, 27.15, 21.85, 13.90. TLC: R f = 0.53 (cyclohexane/EtOAc 5:5) MS:[M+H] + =363.1361 HRMS: 363.1361 Yield: 61 % Conversion: 99 % IR (cm -1 ): 993(P-O), 1236(C-O), 1371-1465(CH 3 ), 1728(C=O), 2736-3097(C-H) 70 mg, 0.19 mmol) in THF was added LiOH (20 mg, 0.475 mmol) which was dissolved in a minimum amount of water. The mixture was stirred overnight at room temperature, and water (3 mL) added. Extraction with EtOAc (1 × 10 ml) and the aqueous layer acidified (pH = 2) with an aqueous 4 M HCl solution and extracted with EtOAc (3 x 10 ml). The combined organic layers be dried, filtered and evaporated to dryness yielding as colorless oil, Rf = 0.03 (EtOAc) 1 H NMR (400 MHz, Chloroform-d) δ 7.35 (s, 10H), 5.12 -4.90 (m, 4H), 2.60 (ddd, J = 13.3, 8.9, 7.0 Hz, 2H), 2.22 -2.01 (m, 2H). NMR (101 MHz, Chloroform-d) δ 175.59 (d, J = 17.9 Hz), 136.09 (d, J = 6.1 Hz), 128.45 (d, J = 64.7 Hz), 67.80 (d, J = 6.5 Hz), 29.84 , 27.26 (d, J = 3.8 Hz). TLC: R f = 0.03 (cyclohexane/EtOAc 5:5) MS:[M+Na] + =357.0868 HRMS: 357.0861 Yield: 80 % Conversion: 99 % IR (cm -1 ): 995(P-O), 1132-1274(C-O), 1394-1446(O-H), 1722(C=O), 2846-2941(C-H and O-H stretch)

1 H 13 C

 113 NMR (400 MHz, Chloroform-d) δ 7.73 -7.52 (m, 4H), 7.52 -7.23 (m, 16H), 6.11 (s, 1H,C-1), 5.06 -4.83 (m, 4H), 4.77 (d, J = 1.0 Hz, 1H, C-3), 4.56 (d, J = 5.9 Hz, 1H, C-2), 3.65 (dd, J = 10.7, 5.1 Hz, 1H, C-4), 3.53 (dd, J = 10.7, 7.9 Hz, 2H), 2.33 (dddd, J = 18.0, 12.0, 9.7, 6.2 Hz, 2H), 1.96 (dtd, J = 18.5, 9.2, 6.2 Hz, 2H), 1.49 (s, 3H), 1.32 (s, 3H), 1.05 (s, 9H). NMR (101 MHz, Chloroform-d) δ 170.63 (d, J = 19.5 Hz), 135.65 (d, J = 4.1 Hz, C Ar ), 133.11 (d, J = 18.0 Hz, C Ar ), 130.06 (d, J = 2.8 Hz, C Ar ), 129.80 -126.32 (m, C Ar ), 113.01(C q ) , 103.20(C-1) , 88.17(C-3) , 85.23(C-2) , 81.66 (C-4) , 67.48 (dd, J = 6.4, 3.7 Hz), 64.26(C-5) , 27.57 (d, J = 3.6 Hz), 26.96 , 26.67 , 25.26 , 21.80 , 20.37 . TLC: R f = 0.17 (cyclohexane/EtOAc 2:8) MS:[M+Na] + =767.2781 HRMS:767.2767 Yield: 80 % Conversion: 99 % IR (cm -1 ): 995(P-O), 1107(C-O), 1234-1381(CH 3 ), 1421-1477(C=C), 1743(C=O), 2850-3003(C-H) g.mol -1

1 H

 1 NMR (400 MHz, Chloroform-d) δ 7.33 (dq, J = 3.9, 2.0 Hz, 10H), 5.44 (s, 1H), 5.07 -4.87 (m, 4H), 4.67 -4.57 (m, 2H), 4.38 -4.18 (m, 2H), 4.16 -4.03 (m, 2H), 2.63 -2.47 (m, 2H), 2.16 -2.02 (m, 2H), 1.46 (d, J = 2.1 Hz, 3H), 1.30 (d, J = 2.1 Hz, 3H).

13 C

 13 NMR (101 MHz, Chloroform-d) δ 173.42 -169.32 (m), 136.08 (dd, J = 6.0, 2.1 Hz), 128.35 (d, J = 61.9 Hz,C Ar ), 112.51 (d, J = 2.0 Hz, C q ), 102.96 (C-1), 85.99(C-3) , 81.92(C-4) , 67.57(C-2) , 67.54 , 67.51 , 65.73(C-5) , 27.37 , 26.51 , 25.01 , 22.05 . TLC: R f = 0.32 (cyclohexane/EtOAc 5(cm -1 ): 993(P-O), 1159-1209(C-O), 1371 (C=C), 1737(C=O), 3082-3549(OH).

1 H 13 C

 113 NMR (400 MHz, Chloroform-d) δ 7.41 -7.29 (m, 10H), 5.00 (dddd, J = 38.3, 11.7, 8.8, 2.2 Hz, 4H), 4.70 (dd, J = 5.8, 3.6 Hz, 2H, C 2 and C 3 ), 4.60 (d, J = 5.7 Hz, 1H, C 1 ), 4.26 (dd, J = 12.3, 2.9 Hz, 1H,C 4 ), 4.15 (dd, J = 12.3, 2.5 Hz, 1H,C 4 ), 2.49 (dt, J = 13.8, 7.8 Hz, 2H), 2.04 (ddt, J = 18.4, 10.7, 7.7 Hz, 2H), 1.48 (s, 3H), 1.39 (s, 3H). NMR (101 MHz, Chloroform-d) δ 173.47 , 171.03 (d, J = 17.2 Hz), 136.13 (d, J = 5.8 Hz), 113.95(Cq) , 79.51(C-3) , 77.73(C-1) , 75.23(C-2) , 69.65 -66.89 (m), 64.01(C-4) , 27.29 (d, J = 3.8 Hz), 26.84 , 25.71 , 22.07 , 20.63 . TLC: R f = 0.01 (cyclohexane/EtOAc 4-1 ): 993(P-O), 1053(C-O), 1172-1232(CH 3 ), 1377-1452-1465(C=C), 1743-1745(C=O), 2748-3153(C-H and O-H)

1 H 13 CHRMS

 113 NMR (400 MHz, Chloroform-d) δ 5.33 -5.22 (m, 1H, C-1), 4.78 -4.66 (m, 1H, C-2), 4.49 (d, J = 5.9 Hz, 1H, C-3), 4.34 (s, 1H, C-4), 3.75 (dd, J = 4.5, 2.2 Hz, 2H), 1.48 (s, 3H), 1.33 -1.29 (m, 3H), 0.92 (s, 9H), 0.13 (d, J = 2.7 Hz, 6H). NMR (101 MHz, Chloroform-d) δ 112.17(C q ) , 103.61(C-1) , 87.77(C-3) , 87.12 (C-4) , 81.89 (C-2) , 64.95(C-5) , 26.61 , 25.90 , 25.07 , 18.39 . TLC: R f = 0.28 (cyclohexane/EtOAc 1:9) MS:[M+H] + =327.1604 -1 ): 831-985(Si-H deformation), 1157-1064(Si-O), 1255(Si-C), 2723-33005(C-H), 3100-3379(O-H).

1 H 13 C

 113 NMR (400 MHz, Chloroform-d) δ 7.42 -7.30 (m, 10H), 6.14 (s, 1H, H-1), 5.08 -4.83 (m, 5H), 4.74 (dd, J = 6.0, 1.0 Hz, 1H, H-2), 4.62 (d, J = 5.9 Hz, 1H, H-3), 4.28 (ddd, J = 8.3, 5.0, 1.0 Hz, 1H, H-4), 3.63 (dd, J = 10.5, 5.0 Hz, 1H, H-5), 3.47 (dd, J = 10.6, 8.3 Hz, 1H, H-5), 2.61 -2.41 (m, 2H), 2.13 -1.99 (m, 2H), 1.49 (s, 3H), 1.33 (s, 3H), 0.88 (s, 9H). NMR (101 MHz, Chloroform-d) δ 170.68 (d, J = 19.9 Hz, P), 136.24 (d, J = 6.1 Hz, C Ar ), 130.36 -125.00 (m, C Ar ), 112.97(C q ) , 103.26 (C-1) , 88.31(C-4) , 85.23(C-3) , 81.77(C-2) , 67.53 (dd, J = 6.3, 2.5 Hz), 63.54 (C-5) , 30.00 -24.30 (m), 21.94 , 20.50 , 18.38 . TLC: R f = 0.6 (cyclohexane/EtOAc 5(cm -1 ): 837 (Si-H deformation) 993(P-O), 1103(Si-O), 246(C-O), 1371(C=C), 1745(C=O), 2742-3005(C-H)

13 CHRMS

 13 NMR (101 MHz, Chloroform-d) δ 172.42-169.49 (m, C Ar ), 138.39 -134.84 (m, C Ar ), 130.00 -126.84 (m, C Ar ), 112.58 (C q ) , 103.02(C-1) , 84.24(C-4) , 81.91(C-2) , 79.30(C-3) , 67.55 , 65.76 (C-5), 60.46(C-5) , 27.42 , 26.55 , 25.04 , 21.10 . TLC: R f = 0.18 (cyclohexane/EtOAc 5:5) MS:[M+H] + =507.1784 -1 ): 993(P-O), 1159-1209(C-O), 1371 (C=C), 1737(C=O), 3082-3549(OH).

27. 3 -

 3 [bis(phenylmethoxy)phosphinyl]-propanoate de l'acide 2

1 H

 1 NMR (400 MHz, Chloroform-d) δ 7.32 (qd, J = 5.3, 3.2 Hz, 10H), 6.22 (s, 1H), 5.27 (d, J = 5.8 Hz, 1H), 5.11 -4.82 (m, 4H), 4.71 (s, 1H), 4.64 (d, J = 5.8 Hz, 1H), 2.69 -2.40 (m, 2H), 2.18 -2.06 (m, 2H), 1.49 (s, 3H), 1.34 (s, 3H).

13 C 5 . 3 .Synthesis of the catalysts 5 . 3 . 1 . 4 ) 5 . 3 . 2 .( 3 .

 135353145323 NMR (101 MHz, Chloroform-d) δ 174.90 , 171.42 , 170.28 (d, J = 18.6 Hz), 136.66 -133.57 (m, C Ar ), 130.43 -126.35 (m, C Ar ), 113.46(C q ) , 101.80 (C-1) , 84.79(C-2) , 83.97(C-3) , 82.32(C-4) , 68.15 (dd, J = 25.6, 6.6 Hz), 26.43 , 25.17 , 19.94 . TLC: R f = 0.03 (cyclohexane/EtOAc 5:5) MS:[M] -=519.1426 Yield: 70 % Conversion: 99 % IR (cm -1 ): 993(P-O), 1053(C-O), 1172-1232(CH 3 ), 1377-1452-1465(C=C), 1743-1745(C=O), 2748-3153(C-H and O-H) Synthesis of magnetic nano-ferrites (Fe 3 O FeSO 4 •7H 2 O (10 g) and Fe 2 (SO 4 ) 3 (7 g) were dissolved in 200 ml water in a 500 ml beaker. Ammonium hydroxide (25 %) was added slowly to adjust the pH of the solution to 10. The reaction mixture was then countinously stirred for 1 h at 60 • C. The precipitated nanoparticles were separated magnetically, washed with water until the pH reached 7, and then dried under vacuum at 60 • C for one night. Ferrite was characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). This magnetic nano-ferrite (Fe 3 O 4 ) was then used for further chemical modification. XRD: (JCPDS file, NO. 00.19-0629) 2θ (Deg): 30.1 ○ , 35.4 ○ , 43.1 ○ , 53.5 ○ , 57.02 ○ , 62.6 ○ TEM: 11 (nm) Yield: 80 % Synthesis of Fe 3 O 4 -Dopamine Fe 3 O 4 (1000 mg) was dispersed in 15 ml water by sonication for 30 min. Dopamine hydrochloride (330 mg) dissolved in 5 ml of water was added to this solution and again sonicated for 2h. The amine-functionalized nanomaterial was then precipitated using 45 ml acetone, isolated by centrifugation, and dried under vacuum at 60 • C for 2h. XRD: (JCPDS file, NO. 00.19-0629) 2θ (Deg): 30.1 ○ , 35.4 ○ , 43.1 ○ , 53.5 ○ , 57.02 ○ , 62.6 ○ IR (cm -1 ): 788-885 (Dopamine identification peaks), 1012-1078 (F-O), 1263 (C-N), 1400-1680 Synthesis of Fe 3 O 4 -Dopa-Cu (5 wt %)

5 Yield: 87 % 5 . 3 . 4 . 5 . 5 Yield: 80 % 5 . 3 . 6 . 9 .

 58753455805369 XRD: (JCPDS file, NO. 00.19-0629) 2θ (Deg): 30.1 ○ , 35.4 ○ , 43.1 ○ , 53.5 ○ , 57.02 ○ , 62.6 ○ IR (cm -1 ): 788-885 (Dopamine identification peaks), 1253 (C-N), 1400-1680 (C=C).AAS (Cu wt %): Synthesis of Fe 3 O 4 -hydrocaffeic acidFe 3 O 4 (1000 mg) was dispersed in 15 ml water by sonication for 30 min. Hydrocaffeic acid (400 mg) dissolved in 5 ml of water was added to this solution and again sonicated for 2h. The Carboxylic acid-functionalized nanomaterial was then separated magnetically and washed four times with water followed by ethanol, and dried under vacuum at 60 • C for 2h. XRD: (JCPDS file, NO. 00.19-0629) 2θ (Deg): 30.1 ○ , 35.4 ○ , 43.1 ○ , 53.5 ○ , 57.02 ○ , 62.6 ○ IR (cm -1 ): 771 (ring torsion), 1251( C-O), 1390 (hydrocaffeic acid identification peaks), 1462(C-O-H), 1720 (C=O). Synthesis of Fe 3 O 4 -hydrocaffeic acid-Cu (5 wt %) Fe 3 O 4 -Fe 3 O 4 -hydrocaffeic acid (400 mg) was dispersed in water-Ethanol mixture (1:1). CuCl 2(54 mg) solution in water was added to the reaction mixture. Triethylamine (TEA) solution in water was added drop wise to bring the pH of this mixture to 6. The reaction mixture was then stirred for 24 h at room temperature. The product was allowed to settle, washed several times with acetone, and dried under vacuum at 60 • C for 2h. XRD: (JCPDS file, NO. 00.19-0629) 2θ (Deg): 30.1 ○ , 35.4 ○ , 43.1 ○ , 53.5 ○ , 57.02 ○ , 62.6 ○ IR (cm -1 ): 771 (ring torsion), 1200 (hydrocaffeic acid identification peaks), 1361( C-O), 1539(C-O-H), 1720 (C=O). AAS (Cu wt %): Synthesis of Fe 3 O 4 -L-Dopa Fe 3 O 4 (1000 mg) was dispersed in 15 ml water by sonication for 30 min. L-Dopa (1000 mg) dissolved in 5 ml of water was added to this solution and again sonicated for 2 h. The amino acid-functionalized nanomaterial was then separated magnetically and washed four times with water followed by ethanol, and dried under vacuum at 60 • C for 2h. XRD: (JCPDS file, NO. 00.19-0629) 2θ (Deg): 30.1 ○ , 35.4 ○ , 43.1 ○ , 53.5 ○ , 57.02 ○ , 62.6 ○ IR (cm -1 ): 815 (ring torsion), 921, 1002, 1101 (L-Dopa identification peaks), 1226( C-O), 1519(C-O-H), 1722 (C=O), 2858-3100-(O-H), 3100-3200 (N-H). Synthesis of Fe 3 O 4 -APPA-Cu (5 wt %) Fe 3 O 4 -APPA (400 mg) was dispersed in water-Ethanol mixture (1:1). CuCl 2 (54 mg) solution in water was added to the reaction mixture. Hydrazine monohydrate solution in water was added drop wise to bring the pH of this mixture to 9, followed by the addition of 13 mg of NaBH 4 . The reaction mixture was then stirred for 24h at room temperature. The product was allowed to settle, washed several times with acetone, and dried under vacuum at 60 • C for 2 h. XRD: (JCPDS file, NO. 00.19-0629) 2θ (Deg): 30.1 ○ , 35.4 ○ , 43.1 ○ , 53.5 ○ , 57.02 ○ , 62.6 ○ IR (cm -1 ): 736,792 (ring torsion), 966 (P-O), 1147, 1195 (C-N), 1338 (P=O), 1506,1681 (APPA identification peaks) AAS (Cu w %): 5 Yield: 85 % 5.3.10. Synthesis of Fe 3 O 4 -CPPA Fe 3 O 4 (1000 mg) was dispersed in 15 ml water by sonication for 30 min. 3-phosphonopropionic acid (332 mg) dissolved in 5 ml of water was added to this solution and again sonicated for 2h. The Carboxylic acid-functionalized nanomaterial was then separated magnetically and washed four times with water followed by ethanol, and dried under vacuum at 60 • C for 2h. XRD: (JCPDS file, NO. 00.19-0629) 2θ (Deg): 30.1 ○ , 35.4 ○ , 43.1 ○ , 53.5 ○ , 57.02 ○ , 62.6 ○ IR (cm -1 ): 746,794 (ring torsion), 937, 1008 (P-O), 1184, 1205 (P=O), 1409 (C-O-H)

Table 1 .

 1 Copper catalyzed aziridination of representative olfeins. ..............................................

Table 2 .

 2 Intramolecular copper-catalyzed reaction. 45 .................................................................

Table 3 .

 3 Stereoselective aziridination of sulfamate glycal. 46 .....................................................

Table 4 .

 4 Summary comparison of the different synthetic methods to obtain MNPs. ..................

Table 5 .

 5 Alcohols oxidation with RuHAP-γ-Fe 2 O 3 . ...................................................................

Table 6 .

 6 Suzuki coupling reactions of aryl halides using Fe 3 O 4 @ SiO 2 -Pd catalyst. .................

Table 7 .

 7 Effect of different parameters in aziridination of styrene. .............................................

Table 8 .

 8 Aziridination reaction of styrene with PhI=O and H 2 NTs. ............................................

Table 9 .

 9 Primary catalytic test with MNC and PhI=O. ................................................................

Table 10 .

 10 Temperature and time effects on aziridination with PhI=NTs. ....................................

Table 11 .

 11 Secondary catalytic test with MNC and PhI=NTs .......................................................

Table 12 .

 12 Effect of temperature and time on conversion and yield with MNC. ..........................

Table 13 .

 13 Effect of PhI=NTs equivalent on conversion and yield with MNC. ..........................

Table 14 .

 14 Effect of copper loading and amount of MNC on conversion and yield. ..................

Table 15 .

 15 Effect of temperature and time on microwave-assisted aziridination with MNC. .....

Table 16 .

 16 Effect of solvent on yield of aziridine and on leaching of copper. ............................

Table 17 .

 17 Effect of catalyst amount on yield of product and on leaching of copper. ................

Table 18 .

 18 Aziridination of vinyl toluene derivatives.

  Calculated N-inversion energies of substituted aziridines.

		H	Me	SO 2 Ph	Ph	CO 2 Me
		N	N	N	N	N
	E inv ( kcal/mol)	16.947	16.976	12.189	8,915	5.483
	T ( o C) =25 o	C
	Figure 8.

  14

	N H		NH 2		O
		NaN 3 , NH 4 Cl	Ph		H 2 , Pd/C
						NH
	Ph	MeOH, H 2 O	N 3	CO 2 Me	MeOH
	CO 2 Me				H 2 N	Ph
	Figure 11. Aminolactam synthesis from non-activated aziridine.

  37

Table 1 .

 1 Copper catalyzed aziridination of representative olfeins.

	Entry	Olefin	Catalyst	Yield
				(%)
	1	Ph	Cu(MeCN) 4 ClO 4
			Cu(acac) 2
			Mn(TPP)Cl
	2	Ph	Cu(MeCN) 4 ClO 4
	Ph
			Cu(acac) 2
			Fe(TDCPP)ClO 4
	3	CO 2 Et	Cu(MeCN) 4 ClO 4
	Ph
			Cu(acac) 2
	4		Cu(MeCN) 4 ClO 4
			Cu(acac) 2
	5		Cu(MeCN) 4 ClO 4
			Cu(acac) 2
			Mn(TDTPP)ClO 4	0
	6		Cu(MeCN) 4 ClO 4
			Cu(acac) 2

  44

			Cl
		Cl
			Cl
			Cl
		O
			N
		t-Bu
			O
		H
							O	O
							PH
				O	O
							O	O
		O	O
				Rh	Rh
							Rh	Rh
		Rh	Rh
	Rh	2 (S-TCPTTL) 4	Rh 2 (R-ODACA)	4	Rh 2 (R-BNP)	4
					Bn
							O
			O	CO 2 Me		N
			N
							CO 2 Me
						O	N
			O
			Rh Rh
						Rh	Rh
			Rh 2 (4S-MEOX)	4	Rh 2 (4S-MPPIM)

4 Figure 17. Chiral dirhodium(II,II) catalysts used by Che.

Table 4 .

 4 Summary comparison of the different synthetic methods to obtain MNPs.

				Time Solvent Surface	Size	Shape	Yield
						-agents capping	(nm) Size range distribution	control
	precipitation	Simple,	20-90	min	Water	Needed,	Relatively	Not	High/sc
		ambient				added	narrow	good	alable
		conditions				during or after	(20-50)
						reaction
	Thermal	Complicate,	100-320 hours-	Organic Needed,	Very narrow	Very	High/
	decomposition	inert atmosphere		days		added during	(10-20)	good	scalable
						reaction
	Microemulsion Complicate,	20-50	hours Organic Needed,	Relatively	Good	low
		ambient				added	narrow
		conditions				during reaction	(1-50)
	Hydrothermal	High	220	hours	Water-	Needed,	Very narrow	Very	medium
	synthesis	pressure			ethanol	added during	(5-20)	good
						reaction

  102 Figure 25. Mono-, bi-, or tridentate anchorage of a phosphonate linker.

	HO	P	O	P	O	PH
		O	O	O	O	O O
		Fe 3 O 4	Fe 3 O 4	Fe 3 O 4

  110

				H 2
		NO 2				NH 2
			Pd/SiO 2 /Fe 2 O 3
				SH
			HS		SH
			HS			SH
	SiO 2 /Fe 2 O 3	H s (C H 2 )S i( O M e ) 3	SH HS-SiO 2 /Fe 2 O 3 HS	SH
						pd
						Pd(OAc) 2
						pd	pd
	H 2 N ( C H 2 ) N H ( C H 2 ) 3 S i( O M e ) 3	H 2 N	NH 2	MW. Toluene NH 2	pd
			H 2 N			NH 2
			H 2 N		NH 2
				NH 2
				H 2 N-SiO 2 /Fe 2 O 3
	Scheme 30. Hydrogenation reaction with magnetic nanocatalyst. 110

Table 5

 5 ).

	Substrate	Conv (%)	Yield (%)
	OH	>99	>98
	O	>99	>99
	OH
	O
	OH	95	91
	OH	>99	98
	OH	91	86
	S	>99	96
	OH
	OH	>99	>99
	7	87	83
	OH

Table 5 .

 5 Alcohols oxidation with RuHAP-γ-Fe 2 O 3 .

Table 6 .

 6 Suzuki coupling reactions of aryl halides using Fe 3 O 4 @ SiO 2 -Pd catalyst.

Table 7 .

 7 Effect of different parameters in aziridination of styrene.

		Time	Temp. (°C)	Copper source Yield (%)	Conversion (%)
		(h)
	1	6	0	Cu(OTf) 2	12	~30
	2	9	0	Cu(OTf) 2	15	~30
	3	18	0	Cu(OTf) 2	21	~30
	4	18	25	Cu(OTf) 2	11	~20
	5	18	40	Cu(OTf) 2	0	0
	6	18	0	CuPF 6	16	~20
	7	24	0	Cu(OTf) 2	18	~30

Conditions: Styrene (1eq.), BAIB (1.4 eq.), H 2 NTs (1.4 eq.), Cu complex (0.1eq.), and MgO (2.8 eq.)

Table 8 .

 8 Aziridination reaction of styrene with PhI=O and H 2 NTs.

		Time (h) Temp. (°C) Copper source Yield (%) Conversion (%)
	1	18	0	Cu(OTf) 2	92	<95
	2	18	0	CuPF 6	78	<80
	3	18	25	Cu(OTf) 2	88	<90
	4	18	40	Cu(OTf) 2	0	0
	5	12	0	Cu(OTf) 2	93	<95
	6	6	0	Cu(OTf) 2	93	<95
		Conditions: Styrene (1eq.), PhI=O (1.4 eq.), H 2 NTs (1.4 eq.), Cu complex (0.1eq.)

Table 9 .

 9 Primary catalytic test with MNC and PhI=O.

	NTs
	MNC, H 2 NTs, PhI=O
	MeCN, Ar, 0 °C, 6 h
	MS(4Å)

Table 11 .

 11 Secondary catalytic test with MNC and PhI=NTs

  It was shown that the catalyst support can affect the metal catalyst performance. As an example, Woo et. al. observed that the reaction temperature was the most important parameter in the reduction of nitriles to amines with recyclable Fe 3 O 4 supported Ag.

	reaction temperature and
	Catalyst	Catalyst	Cu	Yield (%)	AAS	AAS
	(mmol %)	in catalyst		Before	After
			(wt %)		reaction	reaction
					Cu (wt %)	Cu (wt %)
	Fe 3 O 4 -Dopa-Cu	0.04	10.0	18	10.0	7.8

Table 12 .

 12 Effect of temperature and time on conversion and yield with MNC.

  40

	Entry Cu loaded in	Amount	Yield	Conversion	AAS before	AAS after
		MNC (wt %)	of MNC	(%)	(%)	reaction	reaction
			(mmol %)			Cu (wt %)	Cu (wt %)
	1	10	0.04	90	>90	9.9	7.5
	2	5	0.04	76	>80	5.0	4.2
	3	1	0.04	79	>80	1.0	0.7
	4	10	0.02	55	>60	10.0	5.4

Table 15 .

 15 Effect of temperature and time on microwave-assisted aziridination with MNC.

Table 16 .

 16 Effect of solvent on yield of aziridine and on leaching of copper.

		Solvent	Relative	Yield (%)	AAS before	AAS after
			Polarity		reaction	reaction
					Cu (wt %)	Cu (wt %)
	1	MeCN	0.460	87	10.0	8.0
	2	Water	1	0	10.0	10.0
	3	Acetone	0.355	45	10.0	8.0
	4	methylene	0.309	64	10.0	9.0
		chloride
	5	THF	0.207	0	10.0	10.0
	6	MeOH	0.762	0	10.0	9.0

Table 17 .

 17 revealed about 20 % of copper migrate from magnetic nanocatalyst into the solution after each reaction. Effect of catalyst amount on yield of product and on leaching of copper.

			Catalyst	Copper in	Yield	AAS	AAS after
	Entry	Catalyst	(mmol %)	catalyst	(%)	before	reaction
				(wt %)		reaction	Cu (wt %)
						Cu (wt %)
	1	Fe 3 O 4 -Dop-Cu	0.04	10	91	10.0	8.0
	2	Fe 3 O 4 -Dop-Cu	0.02	10	60	10.0	8.0
	3	Fe 3 O 4 -Dop-Cu	0.04	5	86	5.0	3.4
	4	Fe 3 O 4 -Dop-Cu	0.02	5	86	5.0	3.2
	5	Fe 3 O 4 -Dop-Cu	0.04	1	86	1.0	0.7
	6	Fe 3 O 4 -Dop-Cu	0.02	1	97	1.0	0.8
	7	Fe 3 O 4 -Dop-Cu	0.004	1	80	1.0	0.7

Table 20 .

 20 Aziridination of chalcone and stilbene.

Table 21 .

 21 Aziridination of unactivated olefin.

Table 22 .

 22 Aziridination of the sugar derivatives.

Table 23 .

 23 Aziridination with catechol anchor and different chelating groups

	Catalyst	Linker	Yield (%)	AAS Before reaction Cu (wt %)	AAs After reaction Cu (wt %)	Cu leaching (%)
	1
	Fe 3 O 4 -Dopa-
	Cu		86	5.0	3.4	32
	2
	Fe 3 O 4 -
	Hydrocaffeic		93	5.0	3.8	24
	acid-Cu
	3
	Fe 3 O 4 -L-
	Dopa-Cu		95	1.3	0.8	41

Table 24 .

 24 Aziridination with phosphonic anchor and different chelating group.

		Catalyst	Linker	Yield (%)	AAS Before reaction Cu (wt %)	AAs After reaction Cu (wt %)	Cu leaching (%)
	1	Fe 3 O 4 -					57
		APPA -Cu		32	5	2.1
	2	Fe 3 O 4 -CPPA
		-Cu		85	5	4.1	18
	3	Fe 3 O 4 -PMIDDA -Cu		18	2.62	2.0	22

Table 26 .

 26 Aziridination reaction with different loading and amounts of copper in Fe 3 O 4 -CPPA-Cu.

			Copper
		Heating method	amount in reaction (mmol)	Copper loaded in catalyst (wt %)	Yield (%)	AAS Before reaction Cu (wt %)	AAs After reaction Cu (wt %)	Cu leaching (%)
			%
	1	CH	0.04	5%	65	5.0	3.8	23
	2	MW	0.04	5%	85	5.0	4.1	18

  Scheme 47.Synthesis of D-ribose part of linker.The synthesis of the phosphonate linker is shown in Scheme 48. Treatment of the commercially available ethyl-3-bromopropionate with dibenzyl phosphite in the presence of NaH in THF gave the compound 19 in 61 % yields (Scheme 48, 19).149 Then hydrolysis of the ethyl ester was performed in THF with lithium hydroxide in a minimum amount of water to obtain 20 in 80 % yield.

	HO	O	OH	I 2	HO	O	OH	t-BuPh 2 SiCl	t-BuPh 2 SiO	O	OH
				Acetone				DMF, 0 °C, 1 h
	HO	OH	18 h, 25	°C	O	O		O	O
	D-ribose				yield: 30%		Yield: 80%
						: 25/75		: 20/80
						17				18
				BnO
											O
				PH			O
	O		BnO
					NaH
									BnO
						BnO		LiOH, H 2 O
				O
										P	OH
							P	O
	Br	O				BnO			BnO
								THF, 18 h, R.T.
				THF, 48 h, 0 °C		O			O
						Yield: 61%		Yield: 80%
							19
											20
					Scheme 48. Synthesis of linker phosphonate
	The next step was to the coupling of the D-ribose with the phosphonate linker (Scheme
	49).
							O
					BnO
											O
						P		OH
				O	BnO
					OH				O
									O		P
	t-BuPh 2 SiO			O		t-BuPh 2 SiO		OBn
						DCC				OBn
									O
				O	DCM, 0°C, 16 h
				O					O
									O
									Yield: 80%
				18					21
					Scheme 49. Linking D-ribose part to phosphonate part.

Table 28 .

 28 Esterification of D-ribose derivative(16) with phosphonate derivative(18)

		Reagent	Phosphonate	Reagent	Temp. ( o C)	Time	Conversion	Yield
			(mmol)	equivalent		(h)	(%)	(%)
	1	SOCl 2	0.3	1.2	60	48	0	0
	2	DMAP/TEA	0.3	0.15/0.6	r.t.	48	0	0
	3	DCC	0.08	0.12	0	16	90	80

(4-methylphenyl)-1-[(4-methylphenyl)sulfonyl]-aziridine

  Hz, 2H), 3.69 (dd, J = 7.2, 4.5 Hz, 1H, H B ), 2.90 (d, J = 7.2 Hz, 1H, H A ), 2.34 (s, 3H), 2.30 (d, J = 4.5 Hz, 1H, H A ). NMR (101 MHz, Chloroform-d) δ 144.75(C Ar ) , 130.69 -126.02 (m, (C Ar )), 41.16(C B ) , 36.03(C A ) , 21.75(CH 3 ). NMR (600 MHz, Chloroform-d) δ 7.86 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.10 (s, 4H), 3.74 (dd, J = 7.2, 4.5 Hz, 1H, H B ), 2.97 (d, J = 7.2 Hz, 1H, H A ), 2.43 (s, 3H), 2.38 (d, J = 4.5 Hz, 1H, H A ), 2.31 (s, 3H).

	N 4. 2-N S O O	S	O	O
	C 15 H 15 NO 2 S
	MW: 273g.mol -1 C 16 H 17 NO 2 S
	MW: 287 g.mol -1
	1 H NMR (400 MHz, Chloroform-d) δ 7.78 (s, 1H), 7.26 -7.18 (m, 4H), 7.13 (dd, J = 7.4 Hz, 2.2 1 H
	TLC: R f = 0.42 (cyclohexane/EtOAc 8:2)
	MS:[M+H] + = 274.0823
	HRMS: 274.0897
	Yield: 91 %
	Conversion: 95 %
	IR (cm -1 ): 1321 (SO 2 ), 1456 and 1593 (C=C), 2831 (sp 3 CH), 2908 (ArH)

13 C

-methyl-3-phenylprop-2-enoate d'éthyle

  80 (dd, J = 19.8, 8.6 Hz, 4H), 7.38 -7.16 (m, 2H), 6.92 (d, J = 8.9 Hz, 2H), 4.39 (d, J = 4.5 Hz, 2H), 3.86 (s, 3H), 2.39 (s, 3H). NMR (101 MHz, Chloroform-d) δ 190.91, 164.62, 143.83, 136.26, 131.63 -124.75 (m), 114.30 , 55.74 , 48.34 , 21.66 . NMR (101 MHz, CDCl 3 ) δ 144.09(C Ar ), 136.00(C Ar ), 129.66(C Ar ), 127.68(C Ar ), 39.90, 22.89, 21.69, 19.52(CH 3 ).

	12. 2O O
	C 12 H 14 O 2
	MW: 190 g.mol -1
	1 H NMR (400 MHz, Chloroform-d) δ 7.67 (s, 1H), 7.34 (d, J = 3.1 Hz, 2H), 4.23 (dd, J = 7.2,
	3.3 Hz, 2H), 1.31 (s, 1H).
	TLC: R f = 0.4 (cyclohexane/EtOAc 4:6)
	MS:[M+Na] + = 342.0776
	HRMS: 342.0777
	Yield: 93 %
	Conversion: 99%

13 C 13 C

,10-(N-tosylaziridinyl)-octadecanoate de méthyle

  NMR (101 MHz, CDCl 3 ) δ 174.43(CO), 144.38(C Ar ), 135.66(C Ar ), 129.67(C Ar ), 128.29(C Ar ), 51.67(C A ), 45.54-45.38(C B ),, 34.24, 32.05, 29.59, 29.40, 29.32, 29.24, 29.18, 29.14, 27.48, 27.44, 26.94, 26.90, 25.08, 22.86, 21.80, 14.32(CH 3 ).

	tosylaziridin-2-yl)methanone 15. 9CB 16. 7-	N	CA	O	O	1-
		O	S	O
		S C 26 H 43 NO 4 S O O
				N
	MW: 465 g.mol -1
	O 1 H NMR (400 MHz, Chloroform-d) δ 7.71 (d, J = 8.3 Hz, 2H), 7.23 -7.19 (m, 2H), 3.55 (s,
	3H), 2.70 -2.57 (m, 2H), 2.32 (s, 3H), 1.48 (p, J = 7.5 Hz, 2H), 1.38 -0.99 (m, 26H), 0.77 (t, J
	= 7.0 Hz, 3H).	C 22 H 19 NO 3 S
	MW: 377 g.mol -1
	TLC: R f = 0.53 (cyclohexane/EtOAc 2:8)
	13 C NMR (101 MHz, CDCl 3 ) δ 190.44(CO), 144.48(C Ar ), 136.75(C Ar ), 136.10(C Ar ), 134.18(C Ar ), MS:[M+Na] + = 488.2810
	133.04(C Ar ), 129.62(C Ar ), 129.05(C Ar ), 128.99(C Ar ), 128.90(C Ar ), 128.75(C Ar ), 127.83(C Ar ), HRMS: 488.2800
	127.64(C Ar ), 50.30(C B ), 47.61(C A ), 21.72(CH 3 ). Yield: 32 %
	TLC: R f = 0.4 (cyclohexane/EtOAc 2:8) Conversion: 40 %
	MS:[M+Na] + = 400.4459 IR (cm -1 ): 1265 (SO 2 ), 1352 -1469(CH 3 ),1722 (C=C), 2833 (sp 3 CH), 2914 (ArH)
	HRMS: 400.0973
	Yield: 40 %
	Conversion: 80 %
	IR (cm -1 ): 1157 (SO 2 ), 1386(CH 3 ),1560 (C=C), 1678(C=O), 2947 (sp 3 CH), 3022 (ArH)

1 H NMR (400 MHz, Chloroform-d) δ 8.00 -7.93 (m, 2H), 7.67 -7.60 (m, 2H), 7.57 -7.49 (m, 1H), 7.40 (t, J = 7.8 Hz, 2H), 7.26 (s, 5H), 7.14 (d, J = 8.0 Hz, 2H), 4.44 (d, J = 4.2 Hz, 1H), 4.20 (d, J = 4.2 Hz, 1H), 2.31 (s, 3H).

13 C

[( p-Toluenesulfonyl]-7-azabicyclo[4.1.0]heptane

  NMR (101 MHz, CDCl 3 ) δ 144.09(C Ar ), 136.00(C Ar ), 129.66(C Ar ), 127.68(C Ar ), 39.90, 22.89, 21.69, 19.52(CH 3 ).

		O
	N	S
		O
	C 13 H 17 NO 2 S
	MW: 251 g.mol -1
	1 H NMR (400 MHz, Chloroform-d) δ 7.84 -7.77 (m, 2H), 7.35 -7.27 (m, 2H), 3.00 -2.90 (m,
	2H), 2.42 (s, 3H), 1.82 -1.72 (m, 4H), 1.47 -1.32 (m, 2H), 1.28 -1.12 (m, 2H).
	TLC: R f = 0.2 (cyclohexane/EtOAc 9:1)
	MS:[M+H] + =252.1058
	Yield: 40 %
	Conversion: 95 %
	IR (cm -1 ): 962 (C-N), 1157 (SO 2 ), 1317 (CH 2 ), 2846 (sp 3 CH), 2929 (ArH).

13

C

19. 3-[bis(phenylmethoxy)phosphinyl]-propanoate d'éthyle

  Dibenzyl phosphite(178 mg, 0.45 mmol) and THF at 0°C added NaH( 16 mg, 0.68 mmol) After 15 min Ethyl 3-bromopropionate (82 mg, 0.45 mmol) was added at 25°C, mixture stirred for 48 h. At the end, reaction quenched with a saturated aqueous NH 4 Cl solution and was extracted with Et 2 O (3 x 30 ml). Organic layers was dried, filtered and evaporated to dryness. Flash chromatography (EtOAc/cyclohexane, 5:5). RF = 0.62 yellowish oil. 1 H NMR (400 MHz, CDCl 3 ) δ 7.30 (dd, J = 7.1, 4.4 Hz, 10H), 5.27 -4.64 (m, 4H), 4.25 -3.81 (m, 2H), 2.52 (dtt, J = 12.3, 8.6, 4.0 Hz, 2H), 2.26 -1.93 (m, 2H), 1.29 -0.98 (m, 3H).

		O
	O
	O	P	O
		O
	C 19 H 23 O 5 P
	MW: 362 g.mol -1

X 1 X 2 X 3 X 1 X 2

Scheme 35. Surface modification of Fe 3 O 4 with Dopamine.

We began the optimization of the aziridination reaction by replacing PhI=O with a stoichiometric amount of PhI=NTs as the nitrene source, 1 equivalent of styrene and 10 wt % of Cu(OTf) 2 as the catalyst (Table 10).

Conditions: Styrene (1eq.), PhI=NTs (portionwise addition, 1.4 eq.), Cu(OTf) 2 (0.1eq.) According to this Table, for 15 and 30 minutes of reaction, a moderate to good yields of the product can be observed (entry 1, 2). After 1 h reaction (entry 3) was an optimum time of reaction with 85 % yield. Also, it is obvious that the leaching of copper is not time dependent because it was in the same order in each experiment.

In continues, catalyst reusability was evaluated in turnover reactions. The reaction was stopped after 1 h (i.e. at the optimum time of reaction) and the catalyst was removed from the reaction mixture using an external magnet. Figure 52 shows the results obtained after five reuse cycles.

#

C. FT-IR Spectroscopy

All the synthesized compounds were characterized by Fourier transform infrared (FTIR) spectroscopy using a Shimadzu ATR spectrometer.

D. Column chromatography

All the products were purified with flash chromatography using a Reveleris™ Flash System contains UV-Vis light and Reveleris™ Silica Flash Cartridge.

E. Microwave

All reactions were done in CEM Discover Automated Microwave.

F. Transmission Electron Microscopy (TEM)

The size of Magnetic Nano Particle analyzed with FEI Transmission Electron Microscopy: model Tecnai F20 S-TWIN

G. Atomic Absorption Spectroscopy (AAS)

Copper content on the surface of Magnetic Nano particle was detected with Perkin Elmer AAS: model Aanalyst 300

H. X-ray diffraction (XRD) pattern

X-ray Diffraction analysis of Magnetic Nano particles were done with Diffractometer Bruker D8.

I. Thermo Gravimetric Analysis (TGA)

NetzschA TG-DSC coupled Mass Spectrometer: model STA449C Jupiter; QMS Aëolos 32 used for thermo gravity analysis of catalysts. phosphonic acid (300 mg) dissolved in 5 ml of water was added to this solution and again sonicated for 2h. The amine-functionalized nanomaterial was then precipitated using 45 ml acetone, isolated by centrifugation, and dried under vacuum at 60

2-(2-methylphenyl)-1-[(4-methylphenyl)sulfonyl]-aziridine

2-(4-acetamidophenyl)-1-[(4-methylphenyl)sulfonyl]-aziridine