Keywords: Boc: tert-butoxycarbonyl bpy: 2, 2'-bipyridyl Bz: benzoyl Cat.: catalytic CCl 4 : carbon tetrachloride CFL: Compact Fluorescent Lamp COD: cis, cis-1, 5-cyclooctadiene dianisyl phenanthroline

Rodriguez et Frédéric Avenier pour m'avoir fait l'honneur de juger mon travail de thèse. Je les remercie également pour les discussions très intéressantes lors de la soutenance de thèse.

Je voudrais remercier tout particulièrement mon président de jury, le Professeur Bernold Hasenknopf aka « Berni », avec qui tout a commencé et tout s'est BIEN terminé ! En effet, j'ai pris contact avec toi pour la première fois le 23 Février 2009 (et oui je suis allé vérifier !!!!) pour JCEMolChem, ça en fait du temps ! Depuis j'ai travaillé avec toi pendant un moment, tu m'as donné ma chance et tu m'as beaucoup appris sur la chimie supramoléculaire.

Un grand merci pour tout !! Je remercie infiniment mes encadrants de thèse pour ces quatre ou cinq années et quelques, je ne sais plus, passées à leur coté et pour tout le savoir qu'ils m'ont apporté.

Je voudrais tout d'abord remercier JP, pour toutes ces années passées ensemble, pour nos réunions « câlins », nos longues discussions mais aussi pour toute la rigueur et tout le savoir que tu m'as inculqué, ta disponibilité etc… Mais il n'y a pas que le travail, nous avons énormément rigolé tous les deux (fait pas mal de bêtises) et nous avons aussi tissé de très fort liens à travers de soirées peu ou un petit peu arrosées, quelques parties de belotte et autour de très bons repas ! J'ai eu la chance de connaitre ta très belle famille et j'en suis très heureux ! Je n'oublie pas TOUTES les crasses que tu m'as faites j'en ai un carnet pleiiin ! Je tiens à remercier ensuite Louis, auprès de qui j'ai énormément appris depuis les cours de master (même si tu t'en souviens pas pffff) jusqu'à maintenant. Tu m'as toujours poussé à donner le meilleur de moi-même, à développer des qualités comme la rigueur, l'excellence, et je t'en remercie ! Nos réunions plus ou moins sérieuses autour de verres de rhum m'ont beaucoup apprises sur tout un tas de sujets. Nous avons également bien rigolé AIBN: 2,2'-azobis-iso-butyronitril Ar: aryl Bn: benzyl

Enfin je tiens à remercier Cyril, qui au fil de mes années de thèse est devenu plus que mon directeur de thèse mais quelqu'un de vraiment spécial pour moi ! Tu t'es tout d'abord battu pour mon financement de thèse et tu m'as permis de réaliser mes objectifs. Puis pendant ma thèse, tu m'as soutenu, supporté quand ça n'allait pas mais aussi quand tout allait bien. Tu as su me motiver et me permettre de me surpasser tout au long de ma thèse. Nous avons aussi partagé de nombreuses discussions sur un peu tout et n'importe quoi, j'ai beaucoup appris à tes côtés ! Enfin une fois sortis de la chimie, nous avons passé de bons moments et j'ai pu découvrir quelqu'un avec une personnalité et des qualités hors du commun, un danseur de folie !! Je t'ai déjà tout dis en face mais je tiens à rajouter que je suis fier d'avoir été ton étudiant.

Merci pour votre disponibilité, votre compréhension, votre patience, votre bonté et votre soutien. Vous m'avez toujours fait confiance, poussé à aller plus loin et à avoir confiance en moi. Je sors aujourd'hui grandi de cette aventure, tant sur le plan professionnel que personnel, et pour cela je vous en suis plus que reconnaissant.

Les très très trèèèès longues années que l'on passe en thèse ont été adouci par la présence des autres membres de l'équipe MACO. En effet l'équipe est composée d'une joyeuse bande de fous que je voudrais remercier.

Virginie, toujours au taquet (même le matin à 9h incroyable…), branchée sur 2000 volts, tu as ébloui mes années passées au labo par ta bonne humeur (et quelques coups de gueule), nous avons bien rigolé tous les deux ! Nous avons partagé, avec Louis, une belle passion pour le bon rhum Martiniquais et ça va me manquer ! J'ai beaucoup appris à tes côtés, toujours un bon conseil à me donner, un gros merci pour tout ! Merci aussi à Corinne, Madame la Directrice, tes expressions sorties de nulle part, ta bonne humeur, les trous espace-temps Aubert ont enchanté mes années de thèse ! Tu avais toujours LA question de la mort qui tue en séminaire de groupe, ouais ça fait mal… J'ai beaucoup appris en te côtoyant que ce soit en chimie, en recherche ou en politique etc etc ! Merci pour tout ! Ensuite un grand merci à Gilles qui est arrivé (enfin revenu) il n'y a pas longtemps, tu m'as sauvé la vie pendant ma rédaction avec ton radiateur portable, j'ai faillit pleurer. Merci pour les dvd de Robin des Bois et du Roi Lion (on lâche les dossiers), malgré la crise des radis un certain midi, nous nous sommes bien amusés et nous avons eu de belles discussions.

Un grand merci aussi à Marc, franchement nous avons pas mal déconné et rigolé au Outre le fait qu'il soit toxique, les sous-produits stanniques issus des réactions radicalaires sont extrêmement difficiles à éliminer et restent généralement présents à l'état de traces. 1 D'un point de vu général, les médiateurs radicalaires sont souvent utilisés en quantité stoechiométrique voire sur-stoechiométrique.

Avec l'avènement et la structuration de la chimie verte, dans les années 90, un effort tout particulier a été dévoué, par un nombre régulièrement croissant de groupes de recherche, au développement d'une chimie radicalaire plus verte et plus soucieuse de l'environnement.

En effet, comme l'a mentionné John Walton dans son article sur la « tyrannie de l'étain », le remplacement en synthèse de ce médiateur radicalaire toxique mais ultra-performant, a été à la base d'intenses travaux de recherche. 2 Plusieurs solutions ont déjà été proposées et divisées selon trois catégories. La première a consisté en l'utilisation de réactifs à base d'étain soit en quantités catalytiques, soit sur supports solides. La seconde a été le développement de nouveaux médiateurs comme par exemple des silanes, des dérivés du phosphore ou à base de métaux moins toxiques. Bien que certains de ces réactifs soient tout à fait intéressants, ils leur manquent le plus souvent un caractère général et souffrent parfois de coûts prohibitifs ou de difficultés d'accès. Le dernier domaine de recherche a un périmètre plus diffus et regroupe plusieurs familles de réactions. Les transferts de groupes d'atomes (sélénium, xanthates…) appartiennent à cette classe mais souffrent du fait qu'une réduction ultérieure est dans la plupart des cas nécessaires. Cependant des perspectives plus qu'intéressantes on été ouvertes avec l'utilisation des organoboranes.

Les composés à l'origine de processus mettant en jeu des transferts monoélectroniques sont de plus en plus considérés comme des médiateurs radicalaires alternatifs aux hydrures De nombreuses études ont été menées afin de rendre cette réaction beaucoup plus écocompatible. Nous pouvons noter que deux catégories se distinguent. 4,5 La première consiste au développement de versions centrées sur l'étain en rendant ce médiateur soit catalytique ou soit supporté en vue d'être recyclé plus facilement. La deuxième catégorie est, quant à elle, plus dédiée à des nouveaux médiateurs moins toxiques que les sels d'étain tels que des silanes, des dérivés du phosphore ou du bore ou d'autres métaux moins toxiques.

Néanmoins, malgré toutes ces améliorations, de nombreuses problématiques demeurent par rapport à la version originale. En effet, ces nouvelles conditions se sont avérées soit moins efficaces ou peu sélectives.

Récemment nous avons développé une nouvelle méthode de désoxygénation radicalaire basée sur la photoréduction d'espèces thiocarbamates dérivés d'alcools, comme alternative photocatalytique à la traditionnelle réaction de désoxygénation de Barton-McCombie, évitant ainsi l'utilisation de stannanes comme médiateur radicalaire. En catalyse photoredox, des colorants organiques tels que l'éosine Y, la fluorescéine ou des complexes polypyridines à base de métaux de transition tels que le ruthénium (II), l'iridium (III) ou encore le cuivre (I) sont utilisés comme photocatalyseurs capables d'absorber la lumière dans le domaine du visible. Une fois irradiés à une longueur d'onde donnée, ces catalyseurs peuvent atteindre un état excité qui possède des propriétés physico-chimiques très intéressantes et utiles pour la synthèse. 6 En fonction du photocatalyseur utilisé, ces états excités possèdent différentes durées de temps de vie qui permettent de réaliser des transferts monoélectroniques et des potentiels redox assez variés en fonction du substrat à oxyder ou à réduire.

Schéma 2. Différents photocatalyseurs organiques et non-organiques

Ce type de catalyse ne nécessite, en effet, généralement que la lumière visible comme apport énergétique, une quantité catalytique de photocatalyseur, et peu d'additifs et de solvants toxiques. Un exemple de notre d'expertise dans ce domaine est la photoréduction 6 a) S. Campagna, F. Puntoriero, F. Nastasi, G. Bergamini, V. Balzani, Top. Curr. Chem. 2007, 280, 117. b) K. Kalyanasundaram, Coord. Chem. Rev. 1982, 46, 159. c) A. Juris, V. Balzani, F. Barigelletti, S. Campagna, P. Belser, A. von Zelewsky, Coord. Chem. Rev. 1988, 84, 85. A partir de ces connaissances et de 17 Le potassium alkyl bis-catécholatosilicates ainsi formé cristallise avec une molécule de solvant ce qui réduit sa stabilité dans le temps. L'ajout de l'éther couronne [18-C-6], comme complexant du cation potassique, permet de résoudre ce problème de stabilité.

Schéma 16. Synthèse des bis-catécholatosilicates

Par la suite, un élégant procédé de génération de radicaux carbonés par oxydation

I.A. Green Radical Chemistry

I.A.1. Introduction to Radical Synthesis

In 2000, the radical chemistry community celebrated the 100th anniversary of the discovery of the first organic radical -triphenylmethyl radical -by Moses Gomberg. Despite this early discovery, the development of this field and particularly its application in synthesis has shown a slow progression. The critical milestones in its evolution include Kharasch reactions in the 30s, the discovery of EPR in the 40s, the structural and kinetic determinations that followed, also the development in polymer sciences. All set the stage for the development of versatile organic reactions. After the pioneering works of Julia and Surzur on radical cyclizations in the 60s, the main contributions of Giese, Curran, Barton, Stork and others, to improve the control of the reactivity of these species through the development of chain reactions mediated by organic or organometallic hydrides, have significantly expanded the scope of the initial processes and opened the way to total syntheses of natural products,1 for instance through the development of highly effective polycyclisations, cascade reactions 2 and in obtaining enantiopure products via highly controlled asymmetric processes. 1c

The main advantages of these radical reactions are inherent in the fact that radicals are highly reactive neutral species. Because radical reactions generally take place in salt-free conditions, the influence of aggregation states and solvatation is almost completely shut down. Furthermore, the compatibility of the radical with many functional groups as well as its ability to perform these transformations under mild conditions, have made the free radical reactions a complementary tool to ionic reactions. Finally, it should be mentioned that radical reactions are not limited only to cyclizations; intermolecular additions, substitutions and homolytic C-H functionalizations by hydrogen transfer also led to beautiful applications, especially when very reliable stereoselectivity models are available. However, radical reactions have suffered from a number of problems which have hampered their routine use.

First, the scale-up is difficult because reactions are generally run in dilute media. But the most troublesome cons remain the use of tributyltin hydride as the most effective radical mediator which is both easily available and extremely versatile. However this reagent is also extremely toxic and its byproductsas well as those of all tin hydridestend to "stick" to the products during purification and are thus generally found in traces analyses, which consequently eliminate any possibility of radical reactions being used in industry. 1

I.A.2. To a Greener Radical Synthesis

Green chemistry is a new paradigm for chemistry emerged in the 90s which provides pollution prevention related to chemical activities. This benign chemistry to the environment aims to develop products and chemical processes that reduce or eliminate the use and synthesis of hazardous substances. It applies to both the preparation of new products or processes more environmentally friendly and the search for alternative solutions or to the improvement of existing approaches. This new concept was made popular in the scientific community by the American chemists Paul Anastas , director of the Green Chemistry Institute in Washington DC, and John Warner with the publication in 1998 of the 12 principles of Green Chemistry as cited Table 1.

2

Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.

3

Wherever practicable, synthetic methodologies should be designed to use and generate substances that possess little or no toxicity to human health and the environment.

4

Chemical products should be designed to preserve efficacy of function while reducing toxicity.

5 The use of auxiliary substances (e.g. solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.

6

Energy requirements should be recognized for their environmental and economic impacts and should be minimized. Synthetic methods should be conducted at ambient temperature and pressure.

7

A raw material of feedstock should be renewable rather than depleting wherever technically and economically practicable.

8

Unnecessary derivatization (blocking group, protection/deprotection, temporary modification of physical/chemical processes) should be avoided whenever possible.

9 Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.

10

Chemical products should be designed so that at the end of their function they do not persist in the environment and break down into innocuous degradation products.

11

Analytical methodologies need to be further developed to allow for real-time, in process monitoring and control prior to the formation of hazardous substances.

12

Substances and the form of a substance used in a chemical process should be chosen so as to minimize the potential for chemical accidents, including releases, explosions, and fires.

About radical synthesis, as pointed out by J. Walton,4 it is time to escape from "the tyranny of the tin" and thus to invent new practical molecular devices to generate radicals.

Several solutions have already been proposed and divided into three directions. The first consisted in the use of tin based reagents either in catalytic amounts or on solid supports. 5 The second was the development of new mediators based for instance on silanes, phosphorus derivatives and less toxics metals. Although some of these reagents are quite interesting, they often lack generality and sometimes suffer from prohibitive costs or difficult accesses. The last avenue of research has a more diffuse perimeter and gathers several families of reactions.

Group transfers (selenium, xanthates ...) belong to this class but suffer from the fact that a further reduction is in most cases required. Interesting perspectives have been opened with the use of organoboranes. 6 Compounds responsible for processes involving one-electron transfers are increasingly regarded as alternative to tin hydrides as radical mediators, contributing de facto to the development of a more environmentally compatible chemistry. 4 However, most of these reagents, essentially metal complexes based on samarium, titanium, cerium, copper, iron, nickel… are used in substoichiometric amounts. 1,7 Furthermore, these reactions are generally specific of a function and sometimes involve a set of stringent conditions. Improved versions are therefore highly desirable. It should then develop milder catalytic versions 8 and more environmentally conscious processes, avoiding the use of toxic metal compounds, toxic solvents and energetic UV radiations, to perform radical transformations and apply them in fine chemistry.

I.B. Visible-Light Photoredox Catalysis

Millions of years of evolution have allowed nature to implement chemical and biological processes in order to preserve life by maintaining a sustainable balance. For plants, the energy required for creation of organic matter comes from a virtually inexhaustible source: the sun. The light, absorbed by chlorophyll, promotes activation of ATP production which then allows carbon sequestration provided by the CO 2 , thereby transforming solar energy into chemical energy.

Inspired by such a process the radical chemistry community participated over the last years to the use of visible light, to carry out original, selective and efficient chemical transformations involving redox processes for the generation of radical species. Visible light photoredox catalysis has recently established itself as one of the most versatile methods to conduct radical chemistry. It is also one of the most productive fields of activity in contemporary organic chemistry. As chlorophyll is fundamental in photoredox processes involved in photosynthesis, the envisaged chemical transformations require the intervention of an appropriate photocatalyst which absorbs light in the visible range. For that purpose, the photoactive complexe Ru(bpy) 3 2+ was introduced in catalytic quantity. Well known in the inorganic chemistry community as a photoredox catalyst for diverse applications such as 7 For reviews on monoelectronic transfer reactions, see: a) P. I. Dalko, Tetrahedron 1995, 51, 7579. b) Tetrahedron Symposium in Print on Electron Transfer Reagents in Organic Synthesis, Eds: D. Procter, R. Flowers, Tetrahedron 2009, 65, 10725. See also: c) U. Jahn, Top. Curr. Chem. 2012, 320, 121;191;323. 8 A. Studer, D. P. Curran, Angew. Chem. Int. Ed. 2016, 55, 58. hydrogen and oxygen production from water, methane evolution from carbon dioxide and reduction of carbon dioxide to formate, 9,10 it has witnessed only sporadic uses in organic synthesis by the groups of Kellog, 11 Pac 12 and Deronzier, 13 until recently in 2008 when David MacMillan (Princeton University) used it to merge organocatalysis with photoredox catalysis and provide an asymmetric -alkylation of aldehydes. 14

and other photocatalysts

Known for many years for its photochemical properties and its activity in photoredox catalysis, the complex Ru(bpy) 3 Cl 2 , 9 discovered by Burstall in 1936, 17 has recently shown great potential in various organic redox processes used for synthetic purposes. 18 If we consider the photochemical properties of such complex, the UV/Visible spectrum shows us three different bands of absorption which correspond to three different types of electronic transitions: one is the LC (Ligand Centered) transfer, the second MC (Metal Centered) and the most interesting is the MLCT (Metal-to-Ligand Charge-Transfer) that absorbs in the visible region. The characteristic absorption band at 452 nm, as shown in scheme 1, is responsible for the visible-light excitation of the complex of Ru(bpy) 3 Cl 2 . 9 A tuning of ligands around the ruthenium metal center, can promote a red shift of the MLCT band which induces a modification of physical properties of the complex. [Ru(bpy) 3 ] 2+* . The absorption of a photon first converts the complex in an excited singlet state 1 MLCT which undergoes a rapid intersytem crossing (ISC) to an excited triplet state 3 MLCT lower in energy with a relatively long lifetime of 890 ns in acetonitrile and 650 ns in water, enough to trigger single electron transfer reactions. 19 Thanks to this property, Ru(bpy) 3 2+ * can interact through bimolecular reactions with other solute molecules. 18 The triplet excited state can react as an electron donor (energy available = 2.12 eV) (oxidation potential: Ru(bpy) processes can also occur that cause deactivation of the complex. To control this electron transfer, a cofactor called "quencher", acting as a donor or an acceptor of electron, should be chosen carefully. Electronic transfer kinetics are important parameters to control and are brought together under the kq constant that represents the ability of a compound to allow fast electron transfer. A rapid transfer (kq > 10 9 M -1 .s -1 ) is fundamental to avoid the deactivation of the excited complex and to promote the redox process. The direct consequence is the increase of the transformation efficiency. 9

Scheme 2. Schematic energy diagram for photoexcitation of Ru(bpy) 3

2+

The photocatalyst can also consist of an organic dye such as Eosin Y, fluorescein, rose Bengal, methylene blue… or a homo-or heteroleptic transition metal complex of mainly ruthenium(II), 9 iridium(III), 20 but also copper(I), 21 gold(I) [START_REF] Luo | [END_REF] and iron(II) 23 on which the ligands (generally polypyridine ligands) influence the redox potentials.

 Reduction of onium salts

In the context of photoredox catalysis under visible light activation, Deronzier was a pioneer in the reduction of diazonium salts with transition metal-based photocatalyst like Ru(bpy) 3 Cl 2 . The arendiazonium salts to be the Q ox of the ruthenium complex excited state has been reported and applied to a photocatalytic version of Pschorr reaction (Scheme 6, eq 1). 24,[START_REF] Noble | [END_REF] More recently, König extended this process to the Merwein arylation catalyzed by photoactive transition metal complexes or organic dyes. 26,27 Arylation of unsaturated compounds has been reported with Ru(bpy) 3 Cl 2 or eosin Y. A p-Bromodiazonium salt was reduced in the presence of 5 equivalents of styrene and the ruthenium complex to afford 94% of stilbene derivative whereas a lower yield of 66% was obtained with eosin Y (Scheme 6, eq

2). After oxidative quenching of the photocatalyst excited state, the reduced diazonyl radical decomposed to liberate the corresponding aryl radical. Addition to an olefin followed by oxidation of the resulting radical allowed the formation of stilbenyl derivatives and recovery of the catalyst. The same transformation was extended to biaryl synthesis in a metal-free manner with furan, thiophene and pyrrole acceptors in good yields (Scheme 9, eq 3).

Scheme 6. Formation of aryl radical by photoreduction of diazonium salts

Our group reported the visible-light photocatalytic reduction of triarylsulfonium salts which proved to be a source of aryl radicals (Scheme 7). 28 The triarylsulfonium salts are difficult to reduce due to their high reduction potential (-1.2 V vs SCE for triphenylsulfonium). Nevertheless, they can produce aryl radical under mild conditions by using Ru(bpy) 3 Cl 2 catalyst and DIPEA as Qred. The so-generated radicals add onto olefin to afford alkylation or allylation products in good yields. 28 -alkylation of aldehydes was achieved by combining photoredox catalysis and organocatalysis. 14 The catalytic system involves the reduction of the brominated compound by the complex Ru(bpy) 3 + generating a radical species which adds to an enamine double bond. Under irradiation, the activated Ru(II)* complex formed oxidizes the radical adduct to an iminium which is subsequently hydrolyzed. Then, the regenerated Ru(bpy) photoreductive conditions. The malonyl radical undergoes a 5-exo-trig cyclization to a terminal alkene followed by a 6-endo intramolecular homolytic aromatic substitution to an indole affording a tetracyclic alkaloid compound in 79% yield as a single product.

I.C. Conclusion

The development of catalytic processes and more precisely photocatalytic redox processes using visible light appears quite appealing. For that purpose, a lot of work has relied on the use of Ru(bpy) 3 2+ complex which is introduced in catalytic amount. Several photocatalytic developments in the field of a greener chemistry have been also investigated using organic dyes as green photocatalysts. An impressive number of research groups have embarked on this topic providing new ways to conduct ancestral radical organic chemistry.

Photocatalysis can really improve reaction conditions and outcomes.

Chapter

II.A.2. Introduction

Radical chemistry has witnessed an explosive growth over the last three decades.

Owing to their mildness and high compatibility with functional groups, radical reactions have been firmly established as reliable and versatile tools for organic synthesis. 1 But the main drawback is associated with the overuse of tin mediators to propagate chain reactions. These reagents are known for being toxic and often associated to non-trivial reaction purifications.

Thus, tin residues are often detected in traces eliminating any possibility of radical reactions being used in industry. As pointed out by J. Walton, 2 it is time to escape from "the tyranny of tin" and to devise valuable alternatives for the generation of radicals. One consists in using stannane derivatives in a catalytic fashion or as supported reagents. 3 Another has dealt with the development of tin-free mediators based for instance on silanes, phosphorus derivatives and less toxics metals. 1 Interesting perspectives have been opened with the use of organoboranes 4 and compounds responsible for electron-transfer reactions have been increasingly seen as valuable alternatives to tin radical chemistry. 5 However, mild and sustainable preparative redox processes limiting the utilization of substoichiometric amounts of metal complexes are still needed. Recently, visible-light photoredox catalysis has emerged as a valuable and efficient tool for the generation of radicals by single electron transfer reactions from an appropriate photocatalyst that absorbs light in the visible region. These conditions have demonstrated their high synthetic potential in various organic redox processes for fine chemical synthesis and contributed at the same time to the development of a greener radical chemistry. 6 Among the mainstream transformations present in the synthetic toolbox of organic chemists, reduction of alcohols to alkanes has gained a place of choice. Hydroxyl functional groups can indeed participate in the construction of elaborated molecular structures and be removed in due course. However, the hydroxide anion is known as a poor leaving group, homolytic scission of non activated carbon-hydroxyl bonds is not thermodynamically feasible and direct electron transfer reduction of alcohols requires very low negative potentials. A

proposed solution was to convert the hydroxyl group to a good leaving group or to a suitable radical precursor. Yet, limitations of deoxygenation by ionic processes were encountered with sterically hindered and/or non-activated secondary and tertiary alcohols. 7 In 2015, the radical community has celebrated the 40th anniversary of the discovery of the Barton-McCombie deoxygenation reaction, unanimously considered as the most common and important process to perform such type of transformation. 8 Originally, this approach was based first on the activation of a secondary or tertiary alcohol as a thiocarbonate or thiocarbamate precursor including the well-known xanthate followed by its subsequent reduction to alkane through a nBu 3 SnH/AIBN(cat)-mediated radical chain process under thermal conditions (Scheme 1, eq. 1). Several improvements have been achieved by replacing the tin mediator with silicon hydrides, 3,9 cyclohexadienyl compounds, 10 phosphorous reagents, 11 organoboranes 4,12 or DLP/isopropanol. 13 In parallel, a great deal of effort has been devoted to the development of single electron transfer (SET) processes whose major advances will be highlighted in this brief review and will complement a former published by Hartwig in 1983. 14 Specific focus will be laid on reduction of alcohols to alkanes with emphasis on Barton-McCombie type deoxygenations of alcohol derivatives involving SET reduction of carbonyl and thiocarbonylbased functional groups. For that purpose, different methods using organic and organometallic SET reagents, electrochemical conditions and photoinduced electron transfer (PET) processes under UV light irradiation or by visible-light photoredox catalysis will be presented (Scheme 1, eq. 2). Applications to the synthesis of molecules of interest such as natural products will also be displayed.

II.A.3. Metal-Promoted Deoxygenation

Low valent metals such as alkali metals behave as good electron donors towards organic compounds. Owing to their high negative potential, these have been widely exploited in Organic Synthesis for electron transfer reduction of a range of functional groups including carbonyl moieties. The earliest observations date back to the beginning of the nineteen century with successively the so-called Bouveault-Blanc reduction of carboxylic esters to alcohols by excess of sodium in ethanol (or amyl alcohol) 15 and their bimolecular reductive coupling in refluxing aprotic solvents, better known as acyloin condensation. 16 Both involved formation of a common ketyl-like radical anion intermediate subsequent to electron transfer.

Over the years, some other unexpected reactivities have been observed. In the sixties, two different groups reported independently the uncanny ability of allylic-17 and -keto acetates 18 to be reduced to alkanes by dissolving metals (Li or Ca in liquid ammonia). Later, Stetter and

Lehmann examined the behaviour of allyl and benzyl benzoates upon reductive treatment with sodium. In this case, the transient radical anion of benzoates was supposed to undergo a -fragmentation and expel an allyl or benzyl radical which should dimerize. 19 In the same line, Boar, Barton et al. designed a selective method of deoxygenation of sterically hindered of secondary and tertiary alcohols to alkanes relying on the reduction of the corresponding acetates by alkali metals dissolved in amines. Two protocols involving either lithium in diethylamine or potassium solubilized by 18-crown-6 ether in tertbutylamine have been established and, applied for instance to the chemoselective cleavage of 6 and 12 acetates in 3,6-diacetoxy-5-cholestane and 3,12-diacetoxy-13-oleanane respectively. Conversely, less hindered acetates such as these at the 3 position are more likely to regenerate the original hydroxyl groups. It means that the degree of selectivity is strongly related to the difference of steric environments (Scheme 2, eq. 1). 20 This methodology was applied to the synthesis of various natural products such as (-)-trichodiene 21 using the Li/EtNH 2 system (Scheme 2, eq. 2), (-)-cladiella-6,11-dien-3-ol and its derivatives [START_REF] Luo | [END_REF] (Scheme 2, eq. 3) and (±)-Tormesol with K/18-C-6 in tBuNH 2 /THF 23 (Scheme 2,eq. 4). A modified protocol with lithium/t-BuOH in liquid ammonia was used by Mander et al. in the synthesis of C20 gibberellins. 24

Scheme 2. Deoxygenation of sterically hindered of secondary and tertiary alcohols by SET reduction of acetates with dissolving lithium and potassium Further optimization of the reaction conditions and mechanistic studies were undertaken by Barrett, Barton et al. [START_REF] Noble | [END_REF] They particularly showed that increasing the bulk of the acyl substituent from methyl to isopropyl, to tert-butyl and to adamantyl enhances the yield in deoxygenation products (Scheme 2, eq. 1). Running reactions in tert-butylamine or 1,2- dimethoxyethane with THF as a co-solvent is more suitable than in nucleophilic solvent such as diethylamine for impeding competitive amidolysis of acetates and regeneration of the starting alcohol. Moreover, deacylation may also be caused by the presence of "adventitious"

water and by crown ether-derived nucleophile generated by degradation along the process.

Thus, a new reduction system based on the use of the eutectic potassium/sodium alloy solubilized by the aza 18-crown- 6 1,4,7,10,13,16-hexamethyl-1,4,7,10,13,16-hexaazacyclooctadecane in tert-butylamine/THF was developed and allowed the reduction of both hindered and non-hindered esters including primary esters. As examples, reduction of 5-cholestan-3-yl and octadecyl adamantane-1-carboxylates gave the products of deoxygenation in 90% and 74% yields respectively, but in the former case a Bouveault-Blanc reduction predominates at lower temperature (Scheme 3).

Scheme 3. Reduction of both hindered and non-hindered esters with eutectic potassium/sodium alloy solubilized by the aza 18-crown-6

These experiments are fully consistent with a mechanism that involves one electron transfer from dissolving metals to carboxylic ester, followed by formation of a ketyl-radical anion intermediate which fragments spontaneously leading to an alkyl radical and a carboxylate anion, an elementary step supported by ab initio calculations. 26 Then, the expelled radical is in turn reduced to a carbanion and protonated subsequently to afford the alkane (Scheme 4). These conclusions are in accordance with previous studies reported by Pete et al. on photoreduction of acetate and benzoate esters to alkanes in hexamethylphosphoramide (HMPA) and water (vide infra).

Scheme 4. A plausible mechanism for the reduction of carboxylic esters by dissolving metals

In parallel, Barrett, Prokopiou and Barton presented an interesting extension of their previous works to the deoxygenation of non-hindered primary and secondary alcohols. They found that more stable precursors such as N,N'-dialkylthiocarbamates, and precisely N,N'diethylthiocarbamates, can be reduced to alkanes with potassium solubilized by 18-crown-6

ether in tert-butylamine/THF (Scheme 5) whereas S-methyl dithiocarbonate and Nmonoalkylthiocarbamate compounds are precluded because the transformation becomes less effective. They also observed that low temperatures (-30 °C) have a detrimental effect on deoxygenation. Finally, a similar mechanism to that of carboxylic esters was considered.27

Scheme 5. Deoxygenation of non-hindered primary and secondary alcohols by SET reduction of N,N'-diethylthiocarbamates with dissolving potassium At the same time, inspired by their successful results on photoreduction of carboxylic esters by photoactivated HMPA (vide infra), Deshayes and Pete have disclosed a more general but less selective protocol for the reduction of primary, secondary and tertiary carboxylic esters to alkanes which relies on the use of sodium in hexamethylphosphoramide (HMPA) as a reductive agent and tert-butanol as a proton source. As previously observed, the overall efficiency and selectivity of the deoxygenation process is highly dependent on the steric environment provided by the alcohol and the carboxylic acid residues. While homolytic of scission of hindered tertiary esters to alkanes is almost quantitative in 5 min at room temperature, reductive cleavage of less hindered primary and secondary esters is partly achieved and the deoxygenated products are isolated in good to moderate yields along with the starting alcohols (Scheme 6, eq. 1). 28 Of particular importance is the presence of tertbutanol that ensures an optimal conversion in alkanes. Mechanistic investigations indicates the radical anion [HMPA] • ¯ generated from HMPA and sodium and described by Normant et al., [START_REF]Si NMR spectra were recorded at 119 MHz on a Bruker AVANCE III 600 spectrometer. Chemical shifts (δ) are reported in ppm and coupling constants (J) are given in Hertz (Hz). Abbreviations used for peak multiplicity are: s (singlet); bs (broad singlet); d (doublet); t (triplet); q (quartet); quint (quintet); sept (septet); m (multiplet). Thin layer chromatographies (TLC) were performed on Merck silica gel 60 F 254 and revealed with a UV lamp (λ = 254 nm) and KMnO 4 staining. Flash Column Chromatographies were conducted on silica Geduran ® Si 60 Å (40 -63 µm)[END_REF] is capable to reduce the ester carbonyl and form a classical ketyl-like radical-anion. Its fragmentation to a carbon-centered radical and a carboxylate anion turned out to be related to its stability, the steric hindrance of both alkyl residues and the solvation of the anion moiety by tert-butanol which accelerates the homolytic scission. As confirmed by deuterium labeling experiments, the process ends up with the formation of the alkane mainly obtained by reduction of the generated radical to a carbanion and its subsequent protonation by tertbutanol, and a small amount by abstraction of a hydrogen atom to HMPA. To explain the presence of alcohol, hydrolysis, amidolysis and transesterification reactions of carboxylic esters have been suggested. 30 Finally, extensive investigations have confirmed the high potential of thiocarbamates to participate in deoxygenation processes, as already observed in reduction studies with K/18-crown-6 ether (vide supra) and in photoreduction (vide infra). [START_REF] Dagousset | [END_REF] Starting from acetates or thiocarbamates, the method found applications in the synthesis of pentalenene (Scheme 6, eq. 2) 32 and (+)-taxadiene (Scheme 6, eq. 3). . 34 Somewhat related is the reductive cleavage of acetate groups at the -position of and -lactones (Scheme 7, eq. 2), which surprisingly does not require the use of HMPA, 35 and at the anomeric position of ulosonic acid derivatives (Scheme Tetrahedron Lett. 1992, 33, 573. 7, eq. 3). [START_REF] Tasker | For reviews on nickel-catalyzed coupling reactions[END_REF] In the same vein, formation of carbon-carbon bond can be realized by homolytic scission of an activated acetate or benzoate ester followed by SET reduction of the transient radical and subsequent addition of the generated alkylsamarium to a carbonyl compound. 37 Intramolecular cyclizations have also been performed under these modified reductive conditions which proved compatible with alcohol, TBDMS ether, acetal, acetate and amide functional groups (Scheme 8). Mechanism is assumed to involve formation of a toluate radical anion by SET reduction followed by its fragmentation to a carboxylate and an alkyl radical. Then, the alkane is formed by hydrogen abstraction. The rate of decomposition is related to the stability of the intermediate which depends on the nature of the residue (allyl>tertiary>secondary>primary) and the substitution of the aromatic (toluate>benzoate).

II.A.4. Electrochemical Deoxygenation

Electrochemical processes have proven to be some of the most economical and ecofriendly methods of achieving redox synthetic transformations since the unique source of electron is the current. 39 In particular, electroreduction of organic halides and carbonyl compounds has been widely studied compared to the reductive cleavage of alcohols which required high negative potential. To realize such deoxygenation processes, alcohols have been converted into acetates, oxalates or toluates prior being electrochemically reduced.

Early research studies on this subject began in 1960 with the polarographic reduction of 2-acetoxyacetophenone to acetophenone by Henning Lund. 40 Ten years after, Utley et al.

have been interested in the reductive electrolysis of para-methoxycarbonyl benzylacetate at a lead cathode in a methanol solution of tetra-n-butylammonium acetate as the supporting electrolyte. When a potential of -1.8 V vs. SCE is applied, the corresponding methyl paratoluate was obtained in 95% yield and with a good current efficiency. It is worthy of note that under these conditions, the cathodic reduction of acetoxyacetophenone is not chemoselective and leads to a mixture of acetophenone (20%) and 1-phenylethanol (54%), which results from the cleavage of the benzylic carbon-oxygen bond and the subsequent reduction of the carbonyl group. 41 Logically, the behavior of allylic acetates was then examined. A preparative electrolysis of vitamin A acetate at a mercury pool cathode was performed in an acetonitrile solution of tetra-n-butylammonium acetate and acetic acid as a proton source at a controlled potential (-1.35V vs. Ag/AgI) and delivered axerophtene in 71% yield after the passage of 39 ). Secondary and tertiary toluate esters were efficiently reduced to the desired alkanes and addition of a protic co-solvent such as isopropanol improved the yields.

These conditions were found to be tolerant to a number of functional groups, including alkyl esters, amides, silyl ethers, ketones and free-alcohols (Scheme 9, eq. 1). 38b,47 In contrast, primary toluates gave only moderate yields but by analogy with oxalates, a co-electrolysis between primary alcohols and methyl toluate provided an effective solution to that issue (Scheme 9, eq. 2). phenyl thionocarbonate or (thiocarbonyl)imidazolide) and the functional groups present in the substrate. A SET mechanism was proposed involving electron transfer from carbon dioxide radical anion CO 2

• to the thiocarbonyl function and -scission of the tetrahedral radical anion intermediate. Deuterium labeling experiments then indicated that the expelled radical can abstract a hydrogen atom from the formate anion, the tetrabutylammonium cation and DMF to form the deoxygenated product. 50 This transformation has been applied to the synthesis of Platencin 51 and a 3-des-hydroxyl analogue of ()-clausenamide. 52 The Saito's process was then applied to various radical synthetic transformations. 67 This powerful methodology provides entries to -deoxygenation of glucono, galactono and glucorono lactones derivatives, as illustrated by de Lederkremer and Marino. Surprisingly, in this case, the photoreduction was accomplished with only 10 mol% of MCZ (Scheme 15, eq.

1)

. 68 Cyclopropylmethyl radical rearrangement for the formation of ,-unsaturated esters was achieved by Clive and Daigneault as depicted Scheme 15, eq. 2. 69 In the course of synthesis of Isocarbacyclin, Noyori et al. have demonstrated the utility of this methodology in the construction of the bicyclo [3.3.0]octane core structure obtained by generation of an silylated radical from the corresponding alcohol and its subsequent 5-exo-dig cyclization (Scheme 15, eq. 3). 70 In the same line, a radical cascade strategy implying transannular cyclizations in unsaturated macrocycles has been explored to elaborate 5-8-5 tricyclic ring

systems. An elegant approach to the tobacco diterpenoid, 7,8-epoxy-4-basmen-6-one, based on a 5-exo-trig/11-endo-trig radical cascade from an 14-membered cycloalkene-allenol was proposed by Myers and Condroski. The radical sequence was triggered by an secondary radical generated from the alcohol by using a modified Saito photochemical reduction protocol in the presence of 1,4-cyclohexadiene as a better source of hydrogen atom than the solvent (Scheme 15, eq. 4). 71 The Saito photochemical reduction was then applied to the synthesis of relevant bioactive molecules including non-natural 2'-deoxy-, 3'-deoxy-and 2',3'dideoxyribonucleosides as potent anti-cancer drugs and antiviral compounds against AIDS. 76 The strategy is based partly on the difference of reactivity between primary and secondary

II.A.6.b. Visible Light-induced Photodeoxygenation

Reactions

More appealing routes to perform photoreductive deoxygenations under milder conditions were recently reported with the rebirth of photoredox catalysis using visible light irradiation. 6 These photoinduced SET processes require the presence of photocatalysts (Pcat ) that absorbs light in the visible range, which can be polypyridine transition metal complexes.

We developed notably a photocatalytic alternative of the classical Barton preparation 82 or organic synthesis 1,83 have highlighted the strong impact of this field and demonstrated its ability to act at the interface of different scientific domains. Among the large number of known radical reactions, those dedicated to functional group transformations have been certainly the most intensively studied for methodological development and total synthesis. Notably, the Barton-McCombie deoxygenation is one of the most used radical reactions since it allows the reduction of an alcohol function to the corresponding alkane. 7,8 The reaction usually proceeds in two steps through the preliminary formation of an intermediate thiocarbonyl precursor such as xanthate, thiocarbonate, thiocarbamate (Scheme 1 and 2). As an example, the O-ergosteryl S-methyl dithiocarbonate 1 was reduced in good yield to give ergosta-5,7,22-triene 2 (Scheme 2, eq. 1). In the original version, the radical chain reaction is initiated by AIBN under thermal conditions. Then, the generated tertiary As illustrated in scheme 3, related protocols have been proposed with alternatives to the initiation process and the toxic tin hydride mediator such as silanes, 9 phosphorous derivatives (10), 11 boranes (13) 12,13 or cyclohexadienyl compounds (16). 10 The secondary alcohols previously derivatized into xanthate (9 and 12) or thiocarbonate (15) can easily undergo a reduction reaction under thermal activation. AIBN, ACN (cyclohexanylidene analog of AIBN) or peroxide species are used as radical initiator mainly in catalytic amount.

Scheme 3. Tin alternatives for deoxygenation reaction

Deoxygenation reactions have also been investigated through the reduction of benzoyl derivatives by organometallic redox processes 38,84 as well as photoinduced electron transfer sensitized by N-alkylcarbazoles under Hg-lamp irradiation (See part II.A.). 66,73 As an efficient alternative to stoechiometric redox reactions or harsh UV conditions, visible-light photoredox catalysis has re-emerged over the last decade. 85 Deronzier, Tetrahedron Lett., 1984, 25, 5517. d) H. Cano-Yelo, A. Deronzier, J. Chem. Soc. Faraday Trans. 1, 1984, 80, 3011. e) H. Cano-Yelo, A. Deronzier, J. Chem. Soc. Perkin Trans. 2, 1984, 1093. f) H. Cano-Yelo, A. Deronzier, J. Photochem., 1987, 37, 315. organic or organometallic photocatalysts and promote electron transfers and radical reactions. [START_REF] Zeitler | For reviews on visible-light photoredox catalysis[END_REF] Very few of them have been dedicated to the challenging reductive cleavage of C-O bonds because of its high bond strength.

Our group, developed an elegant photoreductive ring opening methodology of α,βepoxyketones 18 extended also to α-keto-aziridines 19 (Scheme 4). Under photoredox conditions, the carbonyl group is reduced through a single electron transfer process to provide the corresponding ketyl radical which undergo a ring opening process. The so-formed carbone-centered radical can be directly reduced by Hantzsch ester 20 to give 23 or trapped by the allylsulfone 22 to give the allylation compound 24 with a good diastereoselectivity.

High yields were obtained for both synthetic pathways. 87

Scheme 4. Photoreductive ring opening of epoxyketones and keto-aziridines

Recently, Falvey reported a photorelease of carboxylic acids based on a formal deoxygenation reaction. 88 Stephenson combined the iodination of primary and secondary alcohols with the photoreduction of the so-formed aliphatic iodide to the corresponding alkane in a one-pot two steps sequence. 89 Finally, Overman developed a photoredox-catalyzed fragmentation of tertiary alkyl N-phthalimidoyl oxalates aiming at C-C bond formation. 90 Based on all these considerations, we surmised that the development of an efficient tin-free deoxygenation reaction of secondary and tertiary alcohols to alkanes that would use visiblelight activation of a photoredox catalyst is of primary importance for the chemical community. We decided to investigate the photoreduction of thiocarbonyl compounds. We selected easy accessible thiocarbonyl derivatives and focused our attention on the imidazolyl-lthiocarbonyl substrates (Scheme 1). This functional group has been introduced by Barton and McCombie for alcohol deoxygenation and gave comparable yields than methyldithiocarbonyl, and thiobenzoyl. 8a Imidazolyl thiocarbonyl substrates have been for instance used by

II.B.3. O-Thiocarbamates as

Rasmussen for the deoxygenation of various protected carbohydrates. 91 The authors demonstrated the strong potential of this functional group toward reductive tin conditions. As an example, in scheme 5, the did not improve to the photoreduction process. It is worth noting that when the reactions were carried out with a concentration of 0.1 M, the iridium catalyst was not fully soluble in acetonitrile. At the concentration of 0.067 M, the photocatalyst was totally soluble in acetonitrile and we isolated 53% of product 31 (entry 10). So we selected acetonitrile as the best solvent for our reaction parameters.

 Selection of the light source

Fluorescent bulb lamp (14W) and blue LEDs (470 nm) gave similar results (Table 1, entries 10-11) which is consistent with a visible-light activation of the catalyst. Ir(ppy) 3 is activated at a wavelength of 375 nm, corresponding to a MLCT excitation. However blue LEDs provide a specific wavelength range without generating too much heat as the fluorescent lamps, and then limit the variation of the reaction temperature. We then selected blue LEDs as the light source for the photocatalyzed reactions.

 Selection of the reagent stoichiometry

The next step was to decrease the catalyst concentration and the stoichiometry of the DIPEA. We observed that changing the catalytic loading of Ir(ppy) 3 from 5 mol% to 1 mol% did not affect the yield of the reaction (Table 1, entries 12-14). The same observation was made for diisopropylethylamine from 10 to 5 equivalents. Thus, Ir(ppy) 3 loading was fixed to 1 mol% in the presence of 5 equivalents of Hunig's base. The reaction was conducted in acetonitrile during 24 h under blue LED irradiation and reduced product 31 was obtained in 53% isolated yield (Table 1, entry 14). These last conditions were found as the best conditions for the photoreduction of 30, and were kept as optimized conditions for the rest of the study.

We decided to set alternative conditions involving DMPU that could be a helpful solvent for the deoxygenation of very lipophilic substrates and unsoluble thiocarbamate in acetonitrile.

Higher catalyst loading (5 mol%) was necessary to keep the same efficiency of the reduction (Table 1, entry 15). This modification was set as conditions B.

 Control reactions

Control reactions have been pursued in order to secure the role of each reagents and additives. The schlenk tube was shielded with an aluminum foil during 24 hours and no reaction occurred in the dark. All the starting material was recovered (Scheme 7, equation 1).

In the absence of Ir(ppy) 3 photocatalyst, we ran the control experiment with both light sources (Scheme 7, equation 2). In the case of blue LEDs irradiation, no reaction occurred and only starting material was recovered. When we used the 14W fluorescent light bulb, the reduced product 31 was isolated in 13% yield. The small amount of 31 formed could arise from a photoinduced electron-transfer (PET) between DIPEA and the thiocarbamate due to the presence of UV bands emitted by the fluorescent bulb lamp. This result definitively encouraged us to use the blue LEDs for deoxygenation reactions.

Then, only 3% of 31 were obtained when DIPEA was omitted (Scheme 7, equation 3) but interestingly, we isolated 15% of the thiocarbamate group transfer product (compound 32).

The formation of the S-thiocarbamate 32 will be explained and detailed in the mechanistic study of the photoreductive deoxygenation.

Influence of the leaving group

We investigated the influence of the leaving group on the deoxygenation reaction.

Three different types of precursors were prepared from secondary alcohol 28 bearing a trifluoromethyl-substituted benzoate (34), an imidazolcarbamate ( 36) and a pentafluorophenyl O-thionoformate (38) group. These substrates are usually used in the conventional Barton-McCombie deoxygenation and are valuable alternatives to test in photoreductive conditions.

To be mentioned, the synthesis of product 36 was almost quantitative, but the product was not stable on chromatography column. In the same line, we increased the electrodeficiency of the heterocyclic moiety in order to favor the SET reduction. We changed the imidazolyl residue to the corresponding triazolyl.

As a donor of triazol thiocarbamoyl group, we synthesized the 1,1'-thiocarbonyldi-1,2,4triazole 41 according a previouly described method. 92 In carbon tetrachloride, a mixture of We subjected compound 42 to our photoreduction conditions. We obtained a slight improvement in the reaction efficiency since the reduction product 31 was isolated in 59% yield (Scheme 11). In order to evaluate the influence of the redox parameters, we determined the reduction potential of this O-thiocarbamate 42 and compared it with 30. We measured a potential of 1.59 V vs. SCE which is higher than the potential of the imidazolyl Othiocarbamate equivalent 30 (E red = 1.68V vs. SCE). This observation suggested that the reduction of 42 is more thermodynamically favored than the reduction of 30 in our photoreductive conditions.

We considered this slight improvement not enough significant to justify other studies with this new precursor. So, we developed our methodology with the thiocarbamate imidazole moiety as leaving group.

 Synthesis of O-thiocarbamates from primary alcohols

The commercially available free alcohols were successfully derivatized with N,N'thiocarbonyldiimidazole following the classical procedure, and thiocarbamates 43 and 44

were isolated in high yields, 90% and 88% respectively (Scheme 13).

Scheme 13. Synthesis of O-thiocarbamates from primary alcohols

 Synthesis of O-thiocarbamates from secondary alcohols

A set of thiocarbamates from secondary alcohols was designed with a large structural and functional diversity in order to investigate the functional group tolerance of our photoreduction reaction. Acyclic O-thiocarbamate 50 (83%), 51 (63%) and 52 (68%) were obtained in good yields from the corresponding alcohols. 51 and 52 would be also valuable precursors of benzylic radicals. In the cyclic series, compounds 30, 45-49 were generated from the 6-and 5-membered cyclic alcohols in high yields (66-98%). All of these substrates contain functional groups such as carbamate, sulfonamide, acetal, ester and benzoyl groups. and quantitative yields respectively.

Scheme 16. Synthesis of tertiary alcohols

With these three tertiary alcohols in hand, we tried to transform them into the corresponding tertiary O-thiocarbamates using our classical conditions. Unfortunately, no formation of thiocarbamate was observed. Heating and/or changing the amount of reagents did not furnish any products and only the starting material was recovered (Scheme 17). It is important to note that to the best of our knowledge, no O-thiocarbamates imidazolyl derivating from tertiary alcohols are reported in the literature.

Scheme 17. Synthesis of O-thiocarbamates from tertiary alcohols

In 1993, Barton and co-workers reported the unique effective way to synthesize tertiary xanthates from three different tertiary alcohols. 93 The first alcohol 64 was prepared from the commercial trans-dehydroandrosterone (DHEA) after protection of the secondary alcohol with a silyl group followed by methyl Grignard addition to the ketone group. The cedrol 66 is commercially available and the alcohol 68 was prepared by 1,2 methylation of the L-fenchone. After refluxing tertiary alcohols 64, 66 and 68 with potassium hydride, CS 2 was added at room temperature followed by addition of an excess of iodomethane to give the desired tertiary xanthates in high yields. They showed also that the use of sodium hydride or other alkyl lithium reagents was not effective for this transformation. We decided to use this methodology for the synthesis of tertiary thiocarbamates. We synthesized the same alcohols 64 and 68 in good yields. Unfortunately, treatment with potassium hydride and 1,1'-thiocarbonyldiimidazole did not allow us to isolate the thiocarbamates compounds (Scheme 19). Modifications of the conditions, such as the temperature or the reagents stoichiometry, did not give the expected products.

Scheme 19. O-thiocarbamates formation from tertiary alcohols

The group of Hirai published a study on nucleophilic reaction of alcohols or amines with in-situ-prepared thiocarbamoyl chloride precursor which allowed them to obtain the corresponding thiocarbamates or thioureas derivatives (Scheme 20, equation 1). 94 After premixing imidazole and thiophosgene in dichloromethane, a solution of tertiary alcohol is added but no reaction occurs and only the starting alcohol was isolated. The use of triethylamine instead of DMAP with a higher temperature and a longer reaction time did not give any improvement (Scheme 20, equations 2 and 3

 Photoreductive deoxygenation of primary alcohols

The O-thiocarbamates 43 and 44 were submitted to our optimized photoredox conditions. Photoreduction of 43 gave less than 7% of reduced product 78 (NMR yield). For the O-thiocarbamate 44 only 10% of product 79 were observed. In all cases, a large amount of degradation products was obtained with the presence of traces of the free alcohol. This can be explained by a slow fragmentation of the radical intermediate. Indeed, this process is not favored for a primary radical release and can explain the formation of a number of side products.

Scheme 24. Photoreduction of primary O-thiocarbamate  Photoreductive deoxygenation of secondary alcohols

The model substrate 30 was modified by changing the N-sulfonyl group to a Boc carbamate 45 that was also compatible with the reaction conditions and 80 was obtained in a comparable yield of 53% (Scheme 25). The isolation of 81 in 41% yield from 46 was a bit tedious due to its volatility but the benzylidene acetal was tolerated under such mild reduction conditions. To extend the scope, lithocholic acid derivative 47 was reduced under conditions B due to its poor solubility in acetonitrile. Indeed, DMPU was more suitable for this reaction and the corresponding deoxygenated steroid 82 was obtained in good yield of 65%.

Other very interesting chemoselectivities were highlighted in the reduction of 48 and 49.

Indeed, the diacetonide-D-glucofuranose derivative 48 was deoxygenated at the 3-position to afford the corresponding 3-deoxy compound 83 in 56% yield. Even more interestingly, the benzoyl group at the 5-position of xylofuranose derivative 49 stayed untouched and the reduction proceeded well in 70% yield (84). 38,84 The secondary aliphatic O-thiocarbamate 50

was smoothly deoxygenated giving 85 in 51% yield.

Scheme 25. Photodeoxygenated products scope

Secondary benzylic (51) and allylic (52)

II.B.4. Mechanistic Studies of the Photoredox Catalyzed

To gain insight into the mechanism of this reaction and understand the role of each constituent, we engaged O-thiocarbamate 30 without DIPEA (Scheme 28).

Scheme 28. Reaction in absence of DIPEA: O-Thiocarbamate transfer to S-thiocarbamate

In the absence of a sacrificial donor of electron (DIPEA), the deoxygenated product 31 and the S-thiocarbamate 32 were isolated in 3% and 15% yield, respectively while 65% of 30 was recovered (determined by 1 H NMR with 3-sulfolene as internal standard). The formation of 32 presumably originates from a thiocarbamate group radical transfer (scheme 29). Thus, valuable information can be deduced: without DIPEA, the carbon-centered radical is formed and the DIPEA plays an important role in the terminal hydrogen transfer to afford the resulting reduced product. 6k Indeed, in the absence of the Hunig's base, the carbon-centered radical would add on the sulfur atom of 30 to propagate the radical chain reaction. This chain reaction seems to be moderately efficient because 1 mol% of photocatalyst resulted in 15% of the group transfer compound 32 but is quite interesting in terms of mechanistic implications and perspectives.

Scheme 29 Thiocarbamate group transfer reaction

At that stage, questions arose: How 30 can be reduced by Ir(ppy) 3 ? And how does DIPEA act in the catalytic process?

We decided to answer these questions by studying the fluorescence quenching studies of Ir(ppy) 3 * (Scheme 30 and figure 1).

 Fluorescence quenching studies

Scheme 30. The fluorescence quenching test considered

Our first attempt was to determine if a reduction reaction can occur between the iridium(III) complex and particularly its excited state, and the thiocarbamate substrate 30 as described in scheme 30. Fluorescence quenching experiment are perfectly adapted for this purpose. The principle of this study is the irradiation of a molecule, such as a transition metal complex, at its maximum of absorbance, and then the emission spectrum is recorded.

Addition of a specific concentration of suspected interacting substrate should modify the emission by quenching the excited state of the molecule (such as the metal complex).

Increasing amount of potential quencher is added until no effect is observed. It is called Stern-Volmer experiment. 98 Fluorescence quenching has been done by addition of O-thiocarbamate 30 to a solution of Ir(ppy) 3 in DMF. This solvent was used because of its higher boiling point than acetonitrile that thus allowed an efficient degassing without concentration changes. The fluorescence signal of Ir(ppy) 3 was recorded under excitation at 385 nm for a maximum of fluorescence emission at 528 nm (Figure 1). 99 To a 1 mM solution of Ir(ppy) 3 maintained in the dark, 30 was added to obtain 0.6, 0.

Fluorescence  Cyclic voltammetry studies

To balance these two processes, we did cyclic voltammetry that allowed us to determine the reduction potentials of a representative set of thiocarbamates (Table 3).

 Radical trapping experiments

In order to increase the valuable impact of our photoreductive deoxygenation process, we tried to trap the secondary alkyl radical with heterocyclic compounds leading to more elaborated structures. Due to the previous mechanistic studies, we know a single electron 101 Q. Liu, H. Yi, J. Liu, Y. Yang, X. Zhang, Z. Zeng, A. Lei, Chem. Eur. J. 2013, 19, 5120. transfer process occurs between the excited iridium and the thiocarbamate 30 to afford the Ccentered radical. In absence of H-donor in the reaction medium, it could be possible to trap this radical by other acceptor and create C-C bond. The first attempt was to realize the transformation without the Hünig's base using the radical adduct as a donor of electron to regenerate the Ir(III) catalyst as shown in scheme 31. We selected furan and several heterocyclic derivatives as coupling partner for this reaction.

Scheme 31. Sequential deoxygenation/arylation in one-pot

With 1 mol% of Ir(ppy) 3 under irradiation, we tried to trap the secondary alkyl radical from the reduction of 30 with 3 equivalents of thiophene. Only starting material was observed (Table 4, entry 1). To confirm that the heterocyclic additive is not detrimental for the photoredox process, we performed the reaction in presence of DIPEA. We obtained a significant amount of reduced product 31 without formation of the arylation compound (Table 4, entries 2, 4, 6, 7, 9). With benzothiophene, methylindole, and furan, only traces of trapped adducts have been observed as well as the presence of the group transfer product, the Sthiocarbamate 32, around 20% yield. The most encouraging result was obtained when 50 equivalents of furan were engaged leading to the formation of 15% of addition product B and 23% of 32 (Table 4, entry 10). Reactions performed with electron deficient olefins such as methyl vinyl ketone or activated allyl sulfones did not give any results. Intramolecular C-C bond formation reactions, such as 5-exo-trig cyclizations, have also been done without success. The thiocarbamate transfer reaction would open new perspectives to highly versatile transformations in the fields of organic synthesis and polymer sciences. We have to investigate the radical trapping experiment under these experimental conditions. The field of carbon-heteroatom (nitrogen, sulfur…) bond-forming reaction would be also a promising research direction.

II.B.5. Miscellaneous Studies

The photocatalyzed deoxygenation of alcohols is still a challenging reaction for primary, secondary and a large variety of tertiary alcohols. We developed one of the few photocatalyzed reactions allowing the deoxygenation of the larger variety of alcohols. We tried to extend the impact of this methodology in modifying the photoredox conditions and we decided to focus on the efficiency of the reduction of secondary alcohols.

This specific reactivity of O-thiocarbamate groups forced us to consider another aspect of the photoredox reaction. We investigated other photocatalysts with a lower reductive potential at the excited state than Ir(ppy) 3 in order to target low reduction potential of thiocarbamates. As Ir(ppy) 3 is already the most reductive known metal-based photocatalyst (at the excited state), we naturally investigated organic photoredox compounds. The redox potentials at the exited state of the well-known fluorescein and eosin Y are substantially higher than for Ir(ppy) 3 * and thus explains the absence of reactivity (Scheme 32, Table 5 entries 1-4). 102 In contrast, the 10-phenylphenothiazine (Ph-PTH) excited state displays an interesting reductive potential estimated at 2.1 V.

S.M. Blue

To this end, we synthesized the 10-Ph-PTH in good yield following a reported procedure from phenothiazonine 94 and iodobenzene 95 as depicted Scheme 33. Then, we engaged the photocatalyst 93 for the reduction of 30 in various loadings (from 1 to 10 mol%) under blue LEDs irradiation (Table 5, entry 5). Unfortunately, no reaction occurred with this catalyst. (Scheme 34). In fact, this proton assistance, promoted by diphenyl phosphoric acid, could stabilize the radical-anion intermediate species leading to easier accessible radical steps.

Scheme 34. Effect of H-bonding agent

Then we decided to evaluate the possible effect of the addition of diphenyl phosphoric acid in our photocatalytic conditions (Table 6). The presence of diphenyl phosphoric acid ( 5mol%) has allowed to improve the formation of 31 in 60% yield. However, an equimolar amount or an excess of phosphoric acid had a dramatic effect on the yield (Table 6, entries 2-4). Encouraged by this result, we wanted to evaluate the effect of the solvent. When we used a protic solvent such as tert-butanol in a ratio of 95/5 or 90/10 with acetonitrile, the evolution of the yield was not enough significant. With hexafluoroisopropanol, a strong hydrogen bond donor solvent, the yield of reduced product was slightly increased to 58%. The best yield was obtained with 5% of water which allowed to isolate 31 in a very good 65% yield.

3-(Trifluoromethyl) benzoyl (1-(phenylsulfonyl)piperidin-4-yl) ester (34)

Following GP1 with 1-(phenylsulfonyl)-4-piperidinol 28 (500 mg, 2.

O-[1-(Phenylsulfonyl)piperidin-4-yl] 1H-imidazole-1-carbamate (36)

Following GP1 with 1-(phenylsulfonyl)-4-piperidinol 28 (874mg, 3.6 mmol), (20 mL), compound 36 was purified by FC (Pentane/EtOAc, 60/40) and isolated (507 mg, 42%) as a white solid.

1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.96 (s, 1H), 7.78-7.70 (m, 2H), 7.65-7.56 (m, 1H), 7.58-7.48 (m, 2H), 7.29-7.26 (m, 1H), 7.02-6.96 (m, 1H), 5.03-4.94 (m, 1H), 3.34-3.23 (m, 2H), 3.06-2.94 (m, 2H), 2.14-2.02 (m, 2H), 2.00-1.86 (m, 2H). 13 C NMR ( 101MHz, CDCl 3 ) δ (ppm) 147. 7, 136.9, 136.0, 133.1, 130.8, 129.3 (2C), 127.6 (2C), 117.0, 73.1, 43.2 (2C), 29.9 (2C).

O-[1-(Phenylsulfonyl)piperidin-4-yl] pentafluorophenyl thionoformate (38)

Following GP1 with 1-(phenylsulfonyl)-4-piperidinol 28 (700 mg, 2.9 136.7, 130.7, 117.9, 112.6, 111.8, 97.4, 84.6, 73.1, 72.6, 71.3, 60.0, 28.6, 27.3, 26.7, 18.6. IR (neat): 3127, 2990, 2932, 1466, 1384, 1326, 1285, 1189, 1125, 1082, 999, 917, 871, 835, 729. 2, 137.0, 130.9, 118.1, 110.2, 109.1, 96.4, 72.2, 71.1, 70.9, 70.5, 65.7, 26.2, 26.1, 25.1, 24.6. 110 J. Boivin, V.T. Nguyen Beilstein J. Org. Chem., 2007, 3, No. 45.

HRMS (ESI

O-[1,2-Isopropylidene-5-benzoate--D-xylofuranosyl]

O-[4-Phenylbutan-2yl] 1H-imidazole-1-carbothioate (50)

Following GP1 with the commercially available 7, 140.8, 136.8, 130.8, 128.7 (2C), 128.4 (2C), 126.4, 118.0, 81.2, 37.2, 31.8, 19.2. IR (neat): 3127, 3026, 2978, 2932, 1463, 1383, 1321, 1282, 1231, 1128, 1095, 1034, 963, 892, 831, 744, 699, 656, 642 3121, 3061, 3028, 2928, 1765, 1689, 1599, 1491, 1469, 1450, 1364, 1289, 1270, 1214, 1097, 1075, 1065, 1021, 882, 830, 747, 716, 696, 664, 642 4, 137.6, 136.0, 135.7, 134.3, 131.6, 129.1 (2C), 128.7 (2C), 128.6 (2C), 128.5, 128.3, 126.8 (2C), 125.6, 117.8, 58.2. IR (neat): 3058, 3026, 2922, 2851, 2360, 2340, 1598, 1577, 1527, 1493, 1465, 1449, 1366, 1291, 1266, 1238, 1218, 1087, 1052, 1041, 1001, 959, 825, 744, 691, 640, 609 171.4, 136.8, 131.1, 118.1, 111.3, 82.5, 76.0, 72.2, 70.8, 37.0, 36.1, 33.8, 30.1, 25.1, 24.1, 23.6. IR (neat): 3127, 2935, 2861, 1797, 1533, 1464, 1448, 1390, 1328, 1285, 1228, 1164, 1101, 1086, 1063, 1032, 1008, 984, 964, 941, 926, 890, 731, 651 ), 127.3, 72.6, 70.1, 61.9, 29.5, 26.2. IR (neat): 3361, 3063, 2937, 2860, 1453, 1361, 1229, 1156, 1093, 1059, 998, 957, 937, 734, 696. Prepared under Swern oxidation conditions with the 4-benzyloxybutane-1ol (3 g, 16.6 mmol), oxalyl chloride (2.5 g, 19.9 mmol), DMSO (4. 7 g, 59.8 mmol) and triethylamine (8.8 g, 86.6 mmol) in CH 2 Cl 2 (120 ml). 4-Benzyloxybutanal was obtained in quantitative yield as a colorless oil and was engaged in the next step without further purification.

3H). 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 211. 2, 138.5, 128.4 (2C), 127.6 (2C), 127.6, 72.8, 69.4, 38.9, 35.9, 224.0, 7.8.

A 1.0 M solution of EtMgBr in diethyl ether (808 mg, 6.1 mmol) was added to dry diethyl ether (5 mL) and cooled to 0 °C. A solution of 6benzyloxy-3-hexanone (506.8 mg, 2.5 mmol) in dry diethyl ether (5 mL) was then added dropwise and the solution was stirred at 0 °C for 10 min and then warmed to room temperature. After completion of the reaction, 10 % HCl (2 mL) were added, followed by saturated aqueous NaHCO 3 solution (15 mL). The mixture was extracted with diethyl ether (3 × 15 mL), the organic layers were combined, dried over MgSO 4 and the solvents were evaporated under reduced pressure. Column chromatography of the residue (petroleum ether/ EtOAc 70/30) gave alcohol 59 (441.2 mg, 77 %) as a colorless oil. 5, 128.5 (2C), 127.7 (2C), 127.6, 74.2, 73.0, 71.1, 35.2, 31.1, 23.9, 8.0 (2C).

8-Allyl-1,4-dioxaspiro[4.5]decan-8-ol (61)

A 1.7 M solution of allyl magnesium chloride in THF (514 mg, 5.1 mmol) was added to dry THF (25 mL) and cooled to 0 °C. A solution of 1,4-Dioxaspiro [4.5]decan-8-one (780.9 mg, 5 mmol) in dry THF (5 mL) was then added dropwise and the solution was stirred at 0 °C for 10 min and then warmed to room temperature. After completion of the reaction, 10 % HCl (2 mL) were added, followed by saturated aqueous NaHCO 3 solution (15 mL). The mixture was extracted with diethyl ether (3 × 15 mL), the organic layers were combined, dried over MgSO 4 and the solvents were evaporated under reduced pressure. Column chromatography of the residue (petroleum ether/ EtOAc 85/15) gave alcohol 62 (665 mg, 71 %) as a colorless oil.

Spectral data are in accordance with those reported in the literature.119 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 5.95-5.78 (m, 1H), 5.19-5.05 (m, 2H), 3.98-3.87 (m, 4H), 2.22 (d, J = 7.5 Hz, 2H), 1.94-1.80 (m, 3H), 1.71-1.52 (m, 6H). CAS Number: 429691-42-9.

α,α-Diethyl-4-methoxy-benzene ethanol ( 63 δ (ppm) 158. 4, 131.6, 129.6, 113.8, 74.7, 55.4, 44.0, 30.5, 8.2.

3-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-17-methyl-(3β,17β)-androst-5-en-17-ol (64)

Prepared from the commercially available androst-5-ene-17-one-3β-ol (2.00 g, 6.9 mmol), tert-butyldimethylsilyl chloride (1. 25 g, 8.3 mmol), Et 3 N (842 mg, 8.3 mmol) and DMAP (847 mg, 6.9 mmol) in CH 2 Cl 2 (30 mL) and the solution was stirred overnight at room temperature. After completion of the reaction, saturated aqueous NaHCO 3 solution (15 mL) was added, followed by saturated aqueous NH 4 Cl solution (15 mL) and then water (15 mL). The mixture was extracted with ethyl acetate (3 × 15 mL), the organic layers were combined, dried over MgSO 4 and the solvents were evaporated under reduced pressure. Column chromatography of the residue (petroleum ether/ EtOAc 80/20) gave silylated product (2.61 g, 93%) as a white solid.

Spectral data are in accordance with those reported in the literature. 120 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 5. 38-5.31 (m, 1H), 3.54-3.43 (m, 1H) A solution of methyl iodide (1.06 g, 7.5 mmol) in anhydrous ether (5 mL) was added dropwise to a stirred suspension of dry magnesium turnings (187.1 mg, 7.7 mmol) in anhydrous ether (2 mL). The resulting mixture was stirred under reflux for 1 h and a solution of silylated-DHEA (1.0 g, 2.5 mmol) in anhydrous ether (16 mL) was added dropwise. The reaction mixture was stirred under reflux for additional 4 h and then allowed to cool. A saturated aqueous solution of NH 4 CI (25 mL) was added dropwise, the resulting layers were separated, and the aqueous one was extracted with ether (3 × 50 mL). The combined extracts were washed with brine (50 mL) and dried (MgSO 4 ). Evaporation of the solvent gave alcohol 64 (600 mg, 58%), which was used without purification.

Spectral data are in accordance with those reported in the literature. 121 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 5. 38-5.27 (m, 1H), 3.53-3.42 (m, 1H), 2.33-1.89 (m, 4H), 1.89-1.39 (m, 12H), 1.36-1.23 (m, 4H), 1.21 (s, 3H), 1.02 (s, 3H), 0.88 (s, 9H), 0.86 (s, 3H), 0.06 (s, 6H).

CAS Number: 141779-17-1.

Homofenchol (68)

A solution of methyl iodide (4. 7 g, 33 mmol) in anhydrous ether (25 mL) was added dropwise to a stirred suspension of dry magnesium turnings (850 mg, 66 mmol) in anhydrous ether (5 mL). The resulting mixture was stirred under reflux for 1 h and a solution of L-fenchone (1.68 g, 11 mmol) in anhydrous ether (70 mL) was added 120 M.A. Ponce, R. Erra-Balsells, A.C. Bruttomesso, E.G. Gros Helvetica Chimica Acta, 2004Acta, , 87, 2987-3003. 121 -3003. 121 D.H.R. Barton, S.I. Parekh, C.-L. Tse Tetrahedron Lett., 1993, 34, 2733-2736. dropwise. The reaction mixture was stirred under reflux for additional 4 h and then allowed to cool. A saturated aqueous solution of NH 4 CI (25 mL) was added dropwise, the resulting layers were separated, and the aqueous one was extracted with ether (3 × 50 mL). The combined extracts were washed with brine (100 mL) and dried (MgSO 4 ). Evaporation of the solvent gave alcohol 68 (868 mg, 52%), which was used without purification.

Spectral data are in accordance with those reported in the literature.

Compound (74)

Following GP1 with commercially available Cedrol (1 g, 4.5 mmol), 9, 137.1, 130.2, 117.2, 92.0, 57.0, 56.7, 54.07, 43.5, 41.2 (2C), 36.9, 33.1, 31.3, 28.4, 27.1 25.9, 25.3, 15.5.

6-Deoxy

(V vs SCE)

-2 -1,5 -1 -0,5 0 0,5 1 1,5 2

(V vs SCE)

-2,5 -2 -1,5 -1 -0,5 0 0,5

(V vs SCE

) -1,59V -1,73 -2 -1,5 -1 -0,5 0 0,5 1 1,5 2

(V vs SCE)

-1,67 -2,00 -1,50 -1,00 -0,50 0,00 0,50 1,00 1,50 2,00

(V vs SCE)

- For this transformation, Sanford proposed a mechanism based on a dual catalysis system (Scheme 3). After irradiation of the photocatalyst by visible light, the excited ruthenium reduces the aryldiazonium salt to generate the aryl radical and concomitant the oxidation of the complex to Ru(bpy) 3 3+ . At the same time, the substrate with a directing ligand is C-H activated by the Pd II to generate the palladacycle, which reacts with the aryl radical to give the Pd III intermediate. After a single-electron transfer (SET) from the Ru(bpy) 3 3+ to the Pd III , the oxidized Pd IV undergoes a reductive elimination to give the arylated product. The Ru II and the Pd II catalysts are regenerated to afford new catalytic cycles. Few years later, Sanford took again advantages of the dual catalysis to perform a copper-catalyzed trifluoromethylation of boronic acids. 6 Usually these transformations are catalyzed by [Pd] 7,8 or [Cu] complexes and required harsh conditions (high temperature, strong acids or bases: trifluoroacetic acid or ter-BuOK for example). Moreover, the substrate scope of is limited. Through their studies on α-trifluoromethylation of aldehydes, MacMillan and co-workers, demonstrated that CF 3 I can be reduced in the presence of Ir(ppy) 2 (dtbbpy) under visible light irradiation to generate CF 3 ˙ at room temperature. 9,10 Inspired by these results, Sanford and co-workers investigated the alliance between photoreduction and copper catalysis. 6 They showed they can performed a [Cu]/[Ru] dual catalysis to obtain the trifluoromethylated aryl in moderate yield. After optimization, they achieved this transformation with various aryl-and heteroarylboronic acids with good yields (scheme 4, equation A). The substitution of the arylboronic acid by either electron-donating (ter-butyl, methoxy…) or electron-withdrawing groups (trifluoromethyl, cyano…) gave moderate to high yields of coupling products; in addition, several groups (like ketones, aldehydes, amides, esters…) are well-tolerated. Perfluoroalkylation of 4-biphenylboronic acid was also possible but the loading of copper had to be increased to give a good yield of perfluoroalkylated product (scheme 4, equation B). Once again, this study highlights the powerful advantage of dual catalysis, here involving copper-catalyzed reactions and photoredox processes, to perform challenging organic transformations under mild conditions.

Scheme 4. Cu/Ru-catalyzed trifluoromethylation and perfluoroalkylation of boronic acid

To gain the mechanistic insight (scheme 5), the Cu I complex is oxidized by the exited Ru II * in Cu II complex. Then SET reduction of CF 3 I by Ru I complex affords the radical CF 3

and regenerates the photocatalyst. The radical can then react with Cu II complex to generate a

Scheme 6. Conventional gold catalysis

In 2013, Glorius and co-workers investigated the dual gold and photoredox catalytic system to functionalize C-C multiple bonds. 13 They selected the aryldiazonium tetrafluoroborate salts as a source of aryl radical and the well known Ru(bpy) 3 (PF 6 ) 2 as photocatalyst complex. With these photoredox conditions, they used the Au I catalyst Ph 3 AuCl on 4-penten-1-ol in degassed methanol under 23W fluorescent bulb lamp irradiation which provided to the 5-exo-trig cyclization-arylation product. They next tested different gold complexes and they obtained the best yield with the cationic gold complex Ph 3 PAuNTf 2 . With the optimized conditions, the authors evaluated the scope of the process with various alkenes (Scheme 7, equation A) and aryldiazonium salts (Scheme 7, equation B). The presence of electron-withdrawing substituents and notably aryldiazoniums bearing halogen (chloro or bromo) gave better yields. The nucleophilic addition-arylation sequence worked successfully either with alcohols or tosylamides. Substitution of the alkene moiety gave good yields in 5exo cyclic arylated products. 13 B. Sahoo, M. N. Hopkinson, F. Glorius, J. Am. Chem. Soc. 2013, 135, 5505. nickel can easily replace palladium (18520 $/kg) or platinum (31210 $/kg). Recently, using the very interesting intrinsic properties of nickel, the organonickel catalysis underwent an intensive development to perform effective valuable and difficult transformations (Table 1 and scheme 11). 17 1). This property allows many transformations based on a wide range of catalytic cycles Ni 0 /Ni II but also

Ni I /Ni III , Ni II /Ni I /Ni III and Ni 0 /Ni I /Ni II /Ni II and therefore radical synthetic pathways can be envisaged. Considering all of these significant advantages, researchers developed nickelcatalyzed reactions reproducing most of the processes involving palladium catalysis and also creating new transformations.

In 2010, the group of Weix showed that cross-coupling of aryl halides with alkyl halides could be catalyzed by a Ni II complex in the presence of manganese (Scheme 12). 18 In this reaction, only 1 equivalent of each halide is necessary and they used a combination of NiI 2 complex with two ligands: 4,4'-di-tert-butyl-2,2'-bipyridine and 1,2bis(diphenylphosphino)benzene. The authors demonstrated that a wide range of functional groups on the aryl halide can be tolerated such as methyl ketone, nitrile, pinacol boronate ester and free hydroxyl group. The presence of an electron withdrawing or donating group on 18 D. A. Everson, R. Shrestha, D. J. Weix, J. Am. Chem. Soc. 2010, 132, 920. the aryl halide gave the same good yield. A variety of alkyl halide can be engaged in the coupling process with again a good functional group tolerance.

III.A.3.c. Molander's research

In 2012, Akita and co-workers reported the visible-light photocatalyzed generation of alkyl radicals from organotrifluoroborate salts in the presence of Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6

as photocatalyst under blue LEDs irradiation. 21 This effective study laid the foundations of photooxidation of organoborate salts. Inspired by these results, Molander combined this chemistry with nickel catalysis to establish a new dual catalysis method. The benzylic trifluoroborates are good sources of carbon centered radicals which can be involved in nickel catalysis. The transformation is carried out with 2 mol% of Ir III catalyst and 3 mol% of Ni 0 (Scheme 15). Under these conditions, the authors investigated the scope of the reaction with different benzyltrifluoroborate salts and bromoaryl partners. The presence of electron donating substituents on trifluoroborates provided more stabilized radicals and gave better yields in coupling products (94-97%) than trifluoroborates with electron withdrawing groups (70-75%). The reaction showed a good tolerance to a range of different functional groups on the aryl halide such as amide, phenol -NHBoc, pyrazole, etc…. A variety of heteroaryl bromides such as substituted pyridine, pyrimidine, indole, quinoline and thiophene proved to be good partner in this transformation giving moderate to good yields.

III.A.4. Conclusion

The dual catalysis and in particular the nickel/visible-light photoredox dual catalysis became during the last two years a powerful process for the formation of carbon-carbon or carbon-heteroatom bond under very mild conditions. This new kind of transformation allows access to challenging and valuable simple or more complex molecules.

III.B. Results: Alkyl Bis-Catecholato Silicates in Dual

Photoredox/Nickel Catalysis: Aryl-and Heteroaryl-Alkyl Cross Coupling Reactions

III.B.1. Objectives

Photoredox/nickel dual catalysis 32,33 has recently emerged as a novel opportunity to form C-C bonds and rapidly couple functionalized fragments for the elaboration of more complex molecules. 34 A key advantage of this strategy is to merge the mildness of visible light photoredox catalysis for the generation of hot radical entities 35 with the robustness of nickel catalyzed cross coupling reactions. [START_REF] Tasker | For reviews on nickel-catalyzed coupling reactions[END_REF] While the electrophilic partner involved in the oxidative addition to nickel has so far consisted of aryl halides and related substrates, 37 more functional variation has been brought on the radical source. To the best of our knowledge, all works have involved -amino, 30b,34,38 -O, 30b,6 -phenyl, 30b,39 -oxo, 40 and secondary 34 carboxylic acids, mixed anhydrides, 41 dimethylaniline, 30b benzyl, 30a,42 secondary 30a, 37,43 and activated (-O) primary trifluoroborates. 44 More recently, potassium and ammonium biscatecholato silicates have been reported by us as a valuable source of C-centered radicals upon visible light photooxidation using Ir[(dF(CF 3 )ppy) 2 (bpy)](PF 6 ) as catalyst. 45 The silicate substrates offer neat advantages over the related trifluoroborates in terms of solubility, of byproducts (no gas release, no fluoride, no boron) and of the scope of the possibly generated radicals (from stabilized alkyl ones to highly reactive primary ones). As a perspective, it was also found that they could be engaged in photoredox/nickel dual catalysis for C sp2 -C sp3 crosscoupling reactions, notably involving unstabilized primary radicals. 45a,46 Subsequent to the first report of these cross coupling reactions by us, 45a the group of Molander described similar transformations of related ammonium bis-catecholato secondary and primary alkyl silicates with aryl-and heteroaryl-bromides. 24,26 The limited sampling of these preliminary findings drove us to gain more insight into this transformation and define its scope by varying both partners silicates and arylbromides (Scheme 30). Herein, we focused on primary radical intermediates and bring a complementary picture to these highly powerful reactions and we decided to extend the scope of this reaction.

Scheme 30. Photoredox/nickel dual catalysis involving primary radicals from silicates

III.B.2. Synthesis of Alkyl Silicates Precursors

Bis-catecholato alkyl silicates can be easily prepared in high yield by trituration of the trialkoxysilane with 2 equivalents of catechol 1 in a mixture of potassium methoxide in methanol (Scheme 31, equation 1). The addition of crown ether allowed us to increase the stability of the silicate salt. Nevertheless, we will show later that this additive does not influence the reactivity and also is not necessary when the dual transformation is performed just after the silicate's synthesis. Another way to prepare these susbtrates consists of starting with the trichloroalkylsilane, 2 equivalents of catechol and triethylamine in THF. After this first step, a cation metathesis is carried out using tetraethyl ammonium bromide in acetonitrile (Scheme 31, equation B). The ammonium salts and the crown ether complexed potassium salts are bench stable and synthesized in high yields.

Scheme 31. Synthesis of bis-catecholato silicates

With these two procedures, we managed to synthesize a wide range of alkyl silicates such as n-hexyl 2 or 5-hexenyl 3 silicates and more activated alkyl such as benzyl 4, -amino methyl 8 and allyl 11 silicates (Scheme 32). We prepared alkyl silicates bearing a wide range of functional groups (cyano, ester, ether, epoxide, halogen) in yields between 39% and 95%.

The tert-butyl silicate 20 and the cyclopentane silicate 21 were synthesized following the procedure described in scheme 31 equation 2.

cross-coupling products were obtained (Scheme 33). We firstly tested the activated alkyl silicates and products 23-25 were obtained from benzyl, allyl and -amino silicates (4, 8 and 11) in 88%, 86% and 91% yield respectively. The less stabilized hexyl radical from silicate 2 could also be involved furnishing the corresponding coupling product 26 in high yield (85%).

With these encouraging results, we decided to extend the transformation to other silicates. We observed a very good tolerance for compounds bearing various functional groups such as an ester (31, 33), a nitrile (28, 29) an oxirane (34, 35) or halogens (30, 32).

To determine the influence of the crown ether additive, we performed the dual catalyst reaction using the potassium silicate salt 16 synthesized with no [18-C-6]. The reaction with 4-bromoacetophenone also provided a similar good yield (86%) of coupling product 31. The crown ether additive does not have any impact on the dual catalysis process.

Scheme 33. Cross coupling reactions of silicates with 4-bromoacetophenone 22

Using the same conditions, a series of arylbromides with varied substitution pattern could be used in conjunction with acetate silicate 16 (scheme 34). The reaction scope proved to be quite wide and a closer examination of these results revealed interesting features. Indeed, para-and meta-bromoacetophenone gave similar high yields (85% and 80%) of cross-coupled products 36 and 37. Reaction with arylbromides bearing electron withdrawing group such as CF 3 group (46, 47) and halogens (40-42) furnished good yields. Furthermore, the difference of reactivity between a C sp2 -Br and a C sp2 -I bond was also investigated with 1-bromo-4iodobenzene for instance. Not surprisingly, a preferred oxidative addition took place at the carbon-iodide bond47 giving a 10:1 ratio of products 42 (X = Br) and 48 (X = I).

This appeared quite opportune for electron enriched aryl substrates.

In the case of bromobenzene with an electron-donating substituent such as paraor ortho-methyl (44, 45), we observed good yields of cross-coupled products (73% and 76%). While meta-bromoanisoles could be effectively used (adducts 52 and 53), only starting material was recovered with ortho-bromoanisole and para-bromoanisole. The reluctant behavior of para-bromoanisole could be partly fixed by using the corresponding iodo derivative since cross coupling product 51 was obtained albeit in modest yield (46%). These findings contrast with Molander's report 44a in which electron rich substrates proved to be competent. Their catalytic mixture (5 mol% NiCl 2 (dme), 5 mol% dtbbpy, 2 mol% Ru(bpy) 3 (PF 6 ) 2 ) differs from ours (3 mol% Ni(COD) 2 , 3 mol% dtbbpy and 2 mol% Ir[(dF(CF 3 )ppy) 2 (bpy)](PF 6 )) implying interesting metal and ligand differences.

Remarkably, a pinacol boronate function could also be tolerated in these conditions 39 as illustrated by the formation of 48 that could be utilized for further coupling reactions. Nevertheless, direct isolation of this product after column chromatography was detrimental to the yield. Instead, when the crude reaction mixture was oxidized (NaOH, H 2 O 2 ), a higher yield (69% vs 53% for 48) of phenol product 49 was recorded. Similar protocol was applied to give phenol product 50.

Interestingly, a comparison was made with the corresponding benzyltrifluoroborate 68

precursor and showed in our conditions a more productive reaction (adduct

III.B.4. Conclusion

In conclusion of this first study, we demonstrated that bis-catecholato silicates are very reliable partners for photoredox/nickel dual catalysis. We have focused our efforts on the use of highly reactive primary radicals, which so far has remained an uncharted territory. Our generally successful results in terms of yields and structure scope, since notably heteroatomic functions and heterocyclic platforms do not appear as limiting factors in these transformations, augur well for the application of this methodology in different settings.

III.C. Results: Photooxidative Generation of Alkyl

Radicals by a Metal Free Catalytic Process:

Applications to Radical Synthesis and Dual

Catalysis

III.C.1. Introduction and objectives

The single-electron-transfer (SET) oxidation of soft carbanions is a very versatile method to access to C-centered radicals. 51 Among possible candidates, ate complexes based for instance on boron, trifluoroborates being the most popular reagents, have already shown versatile reactivities for the generation of radicals. 52 To a lesser extent, hypervalent biscatecholato silicon species have recently emerged as very promising alternatives to the boron derivatives, avoiding any release of noxious fluorinated byproducts. [START_REF] Luo | [END_REF]24 Their synthesis is known [START_REF] Cossy | Radical in Organic Synthesis[END_REF] yielding bench-stable compounds, [START_REF] Cossy | Radical in Organic Synthesis[END_REF] and their high electron density make them suitable candidates for oxidation. In this letter, we provide new elements on the SET oxidation of alkyl trifluoroborates A and silicates C, notably focusing on the use of organic oxidants (Scheme 39).

served as a preliminary probe (Scheme 43 Both substrate families showed the same trend, that is, the less stabilized is the generated radical, the lower is the yield. Thus, for trifluoroborates (Scheme 47), a gradual decrease of yield was observed from benzyl product 69 (92% of yield) to least stabilized primary radical adducts 70/71 (14% of yield). One could argue that 74, a secondary substrate, should have given a better yield. But in that case, the final radical is a tertiary one which may undergo competitive pathways and lead to only 18% of 75.

reactions that we will try to uncover. In all the successful oxidations, TEMPO would act as a sacrificial oxidant to regenerate the photocatalyst and sustain the photocatalytic cycle in agreement with the literature data. 53a, 60a

III.C.2.c. New generation of organic dyes

This study shows the unprecedented oxidation of trifluoroborates and silicates with a tritylium or an aminium salt as stoichiometric oxidant to generate C-centered radicals.

Photocatalytic oxidation could also be achieved with the Fukuzumi acridinium showing a higher reactivity of trifluoroborates than silicates in these conditions. The improvement of biscatecholato silicates photooxidation with organic dyes became our principal goal.

We decided to investigate other organic dyes taking in consideration both the redox potential and the lifetime of the excited state of irradiated dye. In 2012, Adachi and coworkers described a family of carbazoyl dicyanobenzenes, with carbazole as a donor and dicyanobenzene as an acceptor of electron, as light-harvesters for organic light-emitting diodes (Scheme 49). 63 benzyl precursor 4 (0.3 mmol), TEMPO (0.9 mmol), acting both as radical trap and presumably also as sacrificial electron acceptor, and the organic dye 86 (10 mol%). As a reminder, we reached only a moderate yield of 66% with the Fukuzumi catalyst (Table 3, entry 1). Furthermore, the catalytic loading in 4CzIPN could be diminished down to 1 mol% without any erosion of the yield (Table 3, entry 3). These preliminary results excited our interested in further uses of 4CzIPN.

III.C.4.b. General procedures

General procedure A for bis-catecholato silicate synthesis

Method A

To a stirred solution of catechol (2 eq.) in dry methanol (0.25 M) was added 18-C-6 (1 eq.). After dissolution of the crown ether, the trialkoxy organosilane (1 eq.) was added, followed by a solution of potassium methoxide in methanol (1 eq.). The reaction mixture was stirred for 3 hours and the solvent was removed under reduced pressure. The residue was dissolved in the minimum volume of acetone and diethyl ether was added until a cloudy solution was obtained (scrapping on the edge of the flask could be done to induce crystallization). The flask was placed at 20°C overnight. The crystals were collected by filtration, washed with diethyl ether and dried under vacuum to afford [18-C-6] silicate.

Method B

To a stirred solution of catechol (2 eq.) in dry THF (0.1 M) was added triethylamine (4 eq.). The reaction mixture was cooled to 0°C with an ice bath and organotrichlorosilane (1 eq.) was added dropwise. The mixture was stirred for an hour at 0°C and an additional hour at room temperature. The triethylamine hydrochloride salt was filtered off and the filtrate was evaporated under reduced pressure. The residue was taken up in acetonitrile (0.3 M) and tetraethylammonium bromide (1 eq.) was added. The mixture was stirred for an hour and the solvent was evaporated under reduced pressure. The solid was taken up in water, filtered, washed with water and dried under high vacuum to afford tetraethylammonium silicate.

To a schlenk flask was added the appropriate trifluoroborate salt or silicate salt (0.3 mmol), the oxidizing agent (0.3 mmol) and TEMPO (0.9 mmol, 141 mg). The schlenk flask was sealed with a rubber septum, and evacuated / purged with vacuum / argon three times.

Degassed DMF or diethyl ether (3 mL) was introduced followed by two freeze-pump-thaw cycles. The reaction mixture was stirred at room temperature for 24h under an argon atmosphere. The reaction mixture was diluted with diethyl ether (50 mL), washed with water (2 times), brine (2 times), dried over MgSO 4 and evaporated under reduced pressure. The reaction residue was purified by flash column chromatography on silica gel.

General procedure E for photooxidation of organo-trifluoroborate or organobis(catecholato)silicate

To a schlenk flask was added the appropriate trifluoroborate salt or silicate salt (0.3 mmol), the organophotocatalyst (0.03 mmol) and TEMPO (0.66 mmol, 103 mg). The schlenk flask was sealed with a rubber septum, and evacuated / purged with vacuum / argon three times. Degassed DMF (3 mL) was introduced followed by two freeze-pump-thaw cycles. The reaction mixture was stirred at room temperature under blue LEDs irradiation for 24h under an argon atmosphere. The reaction mixture was diluted with diethyl ether (50 mL), washed with saturated NaHCO 3 (2 times), brine (2 times), dried over MgSO 4 and evaporated under reduced pressure. The reaction residue was purified by flash column chromatography on silica gel.

General procedure F for photooxidation of bis(catecholato)silicate and addition on radical acceptors

To a schlenk flask was added potassium [18-C-6] 2952, 2870, 2236, 1702, 1599, 1484, 1353, 1245, 1227, 1098, 1011, 953, 820, 737 cm -1 . 3040, 2907, 2871, 1597, 1485, 1353, 3016, 2950, 2882, 1735, 1597, 1486, 1351, 1242, 1105, 955, 819, 749, 725

HRMS (ESI

4'-(Hexyl)acetophenone (26)

Following general procedure B with hexylsilicate 2 (0.45 mmol, 285 mg) and 4'-bromoacetophenone 22 (0.3 mmol, 60 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 99/1) to afford 26 as a colorless oil (53 mg, 85%). The spectroscopic data are in agreement with those reported in the literature. Following general procedure B with 2-cyanoethylsilicate 13 (0.45 mmol, 277 mg) and 4'-bromoacetophenone 22 (0.3 mmol, 60 mg).

The crude product was purified by flash column chromatography (pentane/diethyl ether, 1/1) to afford 29 as a colorless oil (48 mg, 85%). The spectroscopic data are in agreement with those reported in the literature. 6, 145.3, 135.6, 128.8 (2 C), 128.6 (2 C), 119.1, 34.3, 26.5, 26.5, 16.4. IR (neat): 2905, 2258, 1675, 1605, 1266 cm -1 .

4'-(3,3,3-Trifluoropropyl)acetophenone (30)

Following general procedure B with 3,3,3-trifluoropropylsilicate 14 (0.45 mmol, 290 mg) and 4'-bromoacetophenone 22 (0.3 mmol, 60 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 99/1 then 95/5) to afford 30 as a colorless oil (52 mg, 80%).

4'-(Acetoxypropyl)acetophenone (31)

Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and 4'-bromoacetophenone 22 (0.3 mmol, 60 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 99/1 then 95/5) to afford 31 as a colorless oil (56 mg, 85%). 15 6, 70.3, 50.8, 44.2, 32.3, 30.9, 26.5 1 H NMR (400 MHz, CDCl 3 ): δ 7. 88 -7.85 (m, 4H), 7.26 -7.21 (m, 4H), 3.20 -3.14 (m, 4H) 8 (197.8), 148.4 (148.3), 135.0 (135.0), 128.5 (128.5), 128.5 (128.5), 53.0 (52.5), 51.8 (51.7), 38.1 (37.8), 33.3 (33.0), 32.1 31.8), 30.6 (29.3), 27.0 (25.1), 26.5, 24.3 (23.5) 2, 171.1, 141.7, 137.3, 133.2, 128.6, 128.0, 126.3, 63.6, 32.0, 30.0, 26.6, 20.9 1, 141.8, 137.7, 133.5 (2 C), 127.9 (2 C), 63.6, 32.1, 30.0, 20.9, -1.1 (3 C) The crude product was purified by flash column chromatography (pentane/diethyl ether, 95/5) to afford 39 as CDCl 3 ): δ 171. 1, 145.3, 128.7, 128.5 (q, J = 32.3 Hz, 2 C), 125.4 (q, J = 3.9 Hz, 2 C), 124.3 (q, J = 270 Hz), 63.5, 32.1, 29.9, 21.9. 19 1 H NMR (400 MHz, CDCl 3 ):  8.15 (d, J = 5.2 Hz, 1H), 7.20 -7.16 (m, 3H), 6.94 (s, 1H), 6.78 -6.74 (m, 1H), 6.58 -6.56 (m, 2H), 4.41 (s, 2H), 4.41 (s, 1H (N-H)). 13 C NMR (100 MHz, CDCl 3 ):  164.3 (d, J = 238.8 Hz), 155.5 (d, J = 7.5 Hz), 147.7 (d, J = 15.1 Hz) 147.1, 129.34, 119.7(d, J = 3.9 Hz), 118.3, 112.8, 107.7 (d, J = 37.8 Hz) The crude product was purified by flash column chromatography (pentane/diethyl ether, 50/50) to afford 60 as a colorless oil (39 mg, 67%). 5, 147.7, 136.3, 134.4, 121.3, 63.6, 29.0, 28.5, 22.0, 20.9 0, 165.8, 153.4, 148.6, 136.8, 136.5, 125.8, 63.3, 52.4, 29.7, 29.2, 20.9

3-(Pyrimidin-5-yl)propyl acetate (63)

Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and 5-Bromopyrimidine (0.3 mmol, 48 mg). The crude product was purified by flash column chromatography 1 H NMR (400MHz, CDCl 3 ): δ 0.88 (s, 3H), 1.02 (d, J = 9.3 Hz, 1H), 1.06-1.25 (m, 18H), 1.40-1.45 (m, 6H), 1.73 (td, J = 5.9, 2.4 Hz), 1.85-1.91 (m, 1H), 2.05-2.14 (m, 1H), 2.20-2.37 (m, 3H), 4.21 (dt, J = 9.4, 4.5 Hz, 1H). 13 C NMR (100MHz, CDCl 3 ): δ 17.5, 20.5 (2 C), 22.0, 23.9, 27.6, 33.1, 34.7 (3 C), 38.5, 40.6, 40.8, 41.6, 44.5, 48.0, 59.9 (2 C), 82.4.

1-tert-Butoxy-2,2,6,6-tetramethylpiperidine (73)

Following general procedure D with potassium tert-butyltrifluoroborate 1f (0.3 mmol, 49 mg) and triphenylcarbenium tetrafluoroborate (0.3 mmol, 99 mg) in diethyl ether. The crude product was purified by flash column chromatography (pentane/diethyl ether : 99/1) to afford 73 as a colorless oil (16 mg, 25%).

The spectroscopic data are in agreement with those reported in the literature. 19 1 H NMR (400MHz, CDCl 3 ): δ 1.07 (s, 6H), 1.12 (s, 6H), 1.18 (s, 9H), 1.44-1.48 (m, 6H). Following general procedure E with potassium (1S,2R,3S,6R) -3,7,7-trimethylbicyclo[4.1.0] heptan-2-trifluoroborate (0.3 mmol, 65 mg) and 9-mesityl-10-methylacridinium perchlorate (0.03 mmol, 12.4 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether : 99/1) to afford 75 as a colorless oil (16 mg, 18%). The spectroscopic data are in agreement with those reported in the literature. However, generation of unstabilized alkyl radicals is still a challenge. Indeed methodologies have been developed to generate stabilized alkyl radicals by photooxidation of organotrifluoroborates or α-aminocarboxylates. In the second part of my Ph. D., we reported the generation of unstabilized alkyl primary radicals by photooxidation of bis(catecholato)alkylsilicates. These radicals can be trapped by radical acceptors or engaged with (hetero)aryl halides or alkenyl halides as electrophiles in dual photoredox/nickel catalysis for the formation of C(sp 3 )-C(sp 2 ) bonds. Usually, metal complexes based on ruthenium or iridium are used as photocatalysts but increasing efforts have been realized to develop processes involving organic photocatalysts. We developed an iridium-free alkyl radicals generation by photooxidation of the bis(catecholato)-alkylsilicates using the organic dye 4CzIPN.

NOUVELLES AVANCEES EN CATALYSE PHOTOREDOX : APPLICATIONS EN CHIMIE RADICALAIRE DE SYNTHESE ET EN CATALYSE DUALE

L'objectif principal des travaux de recherche décrits dans ce manuscrit de thèse, est de concevoir de nouvelles méthodes de synthèse en chimie radicalaire et organométallique, de les associer dans une catalyse duale afin qu'elles puissent être appliquées à l'élaboration de briques moléculaires élaborées.

  labo c'était génial ! Merci aussi aux permanents Etienne (et ses blagues à 2,50 F), Anne Lise, Marion et Marine pour leurs conseils et leur soutien et leur disponibilité, ainsi que leur bonne humeur. Enfin mention spéciale à ma Mumu, avec qui j'ai partagé le labo 216 pendant ma thèse. J'ai appris à te connaitre petit à petit et j'ai découvert une très belle personne ! Nous avons passé de très bons moments dans le labo avec la musique à fond, tes éclats de rire caractéristiques me vont manquer. Nous avons partagé des moments inoubliables et très forts dans mais aussi hors du labo lors de soirées bien arrosées. Tu m'as remonté le moral et soutenu quand ça n'allait pas, tu as été là pour moi et je t'en remercie ! Bonne chance pour la suite Mumu et je t'attends en Martinique !!! Je remercie aussi tous les anciens doctorants de l'équipe MACO pour tous ces bons moments passés au laboratoire notamment Alex avec qui j'ai partagé des moments inoubliables. Je remercie également les membres présents Fabrizio, Simon, Brendan, Tonio, Laura H, Thomas, sans qui ça n'aurait pas été si drôle ! Mes dernières années ont été chamboulées par l'arrivé d'un guyanais dans mon labo, alalah mon ptit Caleb, nos engueulades nos fous rires et tes hélices de bateau ont changé ma vie !! Je voudrais remercier chaleureusement ma Laura qui m'a soutenu, beaucoup engueulé (oui oui tu ne fais que ça !) et qui a toujours été la pour moi ! Bonne chance pour ta dernière année ! Un grand merci aussi à Vincent avec qui j'ai énormément appris, un vrai puits de connaissance ce mec ! Tu m'as beaucoup aidé et soutenu pendant ma rédaction merci pour tout ! Je te souhaite pleins de bonnes choses pour ton futur ! Enfin le duo de choc Djédjé et Pépito !! Alors Jérémy j'ai appris avec toi à ne pas être susceptible parce que vu le nombre de vacheries que tu débites à la minutes sur quelqu'un, il faut bien s'adapter ! Tu m'as fait beaucoup rire pendant ces 3 ans et c'était un bonheur de bosser pas très loin de ta bonne humeur ! Enfin je tiens à remercier sincèrement et chaleureusement, Christophe, mon Cricri, avec qui j'ai travaillé ! Bon tu le sais déjà je ne pouvais pas te blairer quand tu es arrivé au labo, encore un normalien imbus de luimême pfff ! Mais je me suis trompé sur toute la ligne, et quand nous avons commencé à travailler ensemble j'ai découvert quelqu'un de génial et tu es devenu un super ami ! Ton soutien, ton amitié, travailler ensemble ont été un vrai bonheur et j'ai eu beaucoup de chance ! Nous avons passé des moments formidables ! Bon courage pour ta dernière année, je serai là !!! N'oublies pas que tu m'as promis de venir en Martinique ! Un grand merci aussi à Fafoune des ROCS, qui m'a bien fait rigolé et bien soutenu !! Courage pour la suite! Je tiens aussi à remercier Mister Omar, que j'ai connu et apprécié dès son arrivé au labo ! Tu es quelqu'un de formidable, toujours disponible et tu m'as soutenu du début à la fin ! Merci pour tout Omar !!! Merci aussi à nos drôles de dames du labo Sylvie, Sylvie et Patricia ! Je remercie également Aurélie et Claire avec qui j'ai bien déliré et qui m'ont supporté pendant tout ce temps ! Un spéciale merci à Serge auprès de qui j'ai beaucoup appris toutes ces années ! Merci aussi à tous mes autres camarades et collègues, étudiants et permanents, pour cette ambiance chaleureuse (et parfois un peu bizarre quand même ...) qui règne à l'IPCM. Je tiens aussi à remercier mes amis, Didier, Manuel, Cédric, Cindy, Elodie, Corinne, Steeve x2 etc etc qui m'ont soutenu même s'ils ne comprenaient rien à ce que je faisais !!! Vous êtes ma force, merci pour tout ! Sans ma famille je ne suis pas grand-chose…. Je tiens à remercier du plus profond de mon coeur mes parents et mes soeurs, que j'aime, qui m'ont soutenu tout au long de ces trois années de thèses. Vous avez cru en moi, vous m'avez donné toute votre énergie, votre patience et votre amour pour que je puisse réussir ! Merci merci énormément pour tout ! Je tiens aussi à remercier mes grand-mères qui ont fait de moi ce que je suis et qui continuent à veiller sur moi d'où elles sont… Je vous aime ! Enfin je voudrais terminer par remercier ma femme que j'aime profondément et qui, pendant ces trois années, m'a apporté un soutien hors du commun. Ma doudou, tu m'as porté à bout de bras, tu m'as supporté et tu as toujours été présente pour moi. Merci pour tout, merci du plus profond de mon coeur !

  leurs atouts uniques, les processus mettant en jeu des espèces radicalaires se sont considérablement développés, durant ces cinquante dernières années, et font maintenant partie des outils indispensables pour la chimie de synthèse. En 2000, l'ensemble de la communauté de chimie radicalaire a célébré le 100 ème anniversaire de la découverte du premier radical organiquele radical triphénylméthylepar Moses Gomberg. Malgré cette découverte précoce, l'évolution de ce domaine et notamment son application en synthèse a fait preuve d'une progression somme toute lente. Parmi les faits marquants qui ont jalonnés son évolution, citons les réactions de Kharasch dans les années 30, la découverte de la RPE dans les années 40 et les déterminations structurales et cinétiques qui s'ensuivirent, impliquant aussi les réactions de polymérisation. Tout ceci a alors permis les premiers développements en synthèse organique. Après les travaux pionniers de Julia et de Surzur sur les cyclisations radicalaires dans les années 60, les principales contributions de Giese, Curran, Barton, Stork entre autres, pour améliorer le contrôle de la réactivité de ces espèces grâce au développement de réactions en chaînes médiées principalement par des hydrures organiques ou organométalliques, ont considérablement élargi la portée des processus initiaux, et ont notamment ouvert la voie à des applications en synthèse totale, grâce par exemple au développement de cascades polycyclisantes très efficaces, ainsi que l'obtention de produits énantiopurs via des processus asymétriques hautement contrôlés. Les principaux avantages de ces réactions radicalaires sont inhérents au fait que les radicaux sont des espèces neutres hautement réactives. Dans les conditions utilisées, généralement sans sels, on s'affranchit également des problèmes d'agrégats et de solvatation. Par ailleurs, la compatibilité des radicaux avec de nombreux groupements fonctionnels ainsi que la possibilité d'effectuer ces transformations dans des conditions douces, ont fait des réactions radicalaires un outil complémentaire aux réactions ioniques. Enfin, il convient de préciser que les réactions radicalaires ne se limitent pas aux seules cyclisations; les additions intermoléculaires, les substitutions homolytiques et les fonctionnalisations C-H par transfert d'hydrogène ont également donné naissance à de très belles applications, d'autant plus que des modèles de stéréosélectivité très fiables sont disponibles. Les réactions radicalaires permettent au chimiste d'accéder à un très large éventail de transformations, et notamment à la formation de liaisons carbone-carbone ou carbone-hétéroatome. Ces réactions sont, généralement, réalisées dans des conditions douces, ce qui permet de ne pas utiliser de groupes protecteurs lors des synthèses et donc de réduire considérablement le nombre d'étapes réactionnelles. Cependant, les réactions radicalaires souffrent d'un certain nombre de problèmes qui entravent leur utilisation systématique en synthèse et en industrie. Tout d'abord, la montée en échelle est difficile vu que les réactions sont généralement conduites en milieu dilué. Mais le problème le plus aigu demeure l'utilisation de l'hydrure de tributylétain comme médiateur radicalaire le plus performant.

  d'étain, contribuant de facto au développement d'une chimie plus écocompatible. Cependant, la plupart de ces réactifs, essentiellement des complexes métalliques à base de samarium, titane, cérium, cuivre, fer, nickel,… sont utilisés en quantités sur-stoechiométriques. D'autre part, ces réactions sont généralement spécifiques d'une fonction et impliquent parfois un ensemble de conditions rigoureuses. Des versions améliorées sont donc fortement souhaitables. Il convient alors d'en développer des versions catalytiques plus douces et plus soucieuses de l'environnement, s'affranchissant de l'utilisation de composés métalliques toxiques, de solvants toxiques et de rayonnements UV énergétiques, pour effectuer des transformations radicalaires et les appliquer en chimie fine.

Figure 1 .Schéma 1 .

 11 Figure 1. Evolution de la chimie radicalaire

Schéma 22 .Schéma 23 .

 2223 photocatalyseur 4CzIPN Dans l'optique d'améliorer la photooxydation des silicates, nous avons mis en réaction ces espèces avec l'organo-photocatalyseur. Ce dernier nous a non seulement permis de réduire la charge catalytique jusqu'à 1 mol% mais surtout, d'assurer l'oxydation de tous nos silicates synthétisés. Les radicaux ainsi générés ont été piégés lors de réactions d'allylation, d'alcynation et de vinylation ou par simple piégeage avec le TEMPO, donnant des produits variés avec de hauts rendements.

Scheme 1 .

 1 Scheme 1. Absorption spectrum of Ru(bpy) 3 Cl 2 (from ref. 9a)

  of the fortieth anniversary of the Barton-McCombie reaction, this chapter focuses on another facet of the Barton-McCombie reaction dedicated to the deoxygenation of alcohols by considering SET reduction of carboxylic ester, thiocarbonate and thiocarbamate derivatives. Various methodologies have been developed relying on the use of organic and organometallic SET reagents, electrochemical conditions, photoinduced electron transfer processes and visible-light photoredox catalysis. Applications to the synthesis of molecules of interest provide a glimpse into the scope of these different approaches.

Scheme 1 .

 1 Scheme 1. SET reduction of carbonyl and thiocarbonyl-based functional groups: Tin-free alternatives to the classical Barton-McCombie deoxygenation reaction of alcohols to alkanes

  25 a) A. G. M. Barrett, P. A. Prokopiou, D. H. R. Barton, R. B. Boar, J. F. McGhie, J. Chem. Soc., Chem. Commun. 1979, 1173; b) A. G. M. Barrett, C. R. A. Godfrey, D. M. Hollinshead, P. A. Prokopiou, D. H. R. Barton, R. B. Boar, L. Joukhadar, J. F. McGhie, S. C. Misra, J. Chem. Soc., Perkin Trans. 1 1981, 1501; c) D. H. R.Barton, W. B. Motherwell, Pure and Appl. Chem. 1981, 53, 1081.

Scheme 6 .

 6 Scheme 6. Deoxygenation of primary, secondary and tertiary alcohols by reduction of acetates and N,N'-dimethylthiocarbamates with sodium/HMPA

  34 K. Kusuda, J. Inanaga, M. Yamaguchi, Tetrahedron Lett. 1989, 30, 2945. 35 a) J. Inanaga, J. Katsuki, M. Yamaguchi, Chem. Lett. 1991, 20, 1025. b) S. Hanessian, C. Girard, J. L. Chiara,

Scheme 7 .

 7 Scheme 7. Reduction of -acetoxy esters with samarium diiodide

Scheme 10 .

 10 Scheme 10. Deoxygenation by reduction of thiocarbonyl derivatives with carbon dioxide radical anion

Scheme 20 . 1 .Scheme 1 .

 2011 Scheme 20. Visible-light photoreductive coupling of a tert-alkyl N-(acyloxy)phthalimide oxalate and methyl vinyl ketone

7 Scheme 2 .

 72 Scheme 2. Classical Barton-McCombie deoxygenation chain reaction

  photoredox catalysis has re-emerged over the last decade.85 We and others have taken an active part in the development of new catalytic processes based on visible-light to activate

  yield. b) NMR Yield. c) FBL = Fluorescent Bulb Light. d) Not Determined, only traces of 31 were observed. e) C 1 = 0.1 M, C 2 = 0.067 M Selection of the photocatalystWe investigated the ability of polypyridine ruthenium or iridium complexes to catalyze the photoreduction of 30 with Hunig's base (N,N-diisopropylethylamine = DIPEA) as sacrificial electron donor under visible light irradiation (Table1

Scheme 7 .Scheme 8 .

 78 Scheme 7. Control reactions for reduction of O-thiocarbamates

thiophosgene 39 Scheme 10 .

 3910 Scheme 10. Synthesis of triazole O-thiocarbamate

Scheme 11 .Scheme 12 .

 1112 Scheme 11. Photoreduction of triazole O-thiocarbamate

Scheme 15 .

 15 Scheme 15. Synthesis of thiocarbamate 56 from quinic acid

Scheme 18 .

 18 Scheme 18. Synthesis of tertiary xanthates

  7 and 0.99 mM as final concentrations. The corresponding fluorescence spectra showed a significant decrease of the intensity while the concentration of 30 increased. The fluorescence intensity ratio (I 0 /I c , I 0 = fluorescence intensity without quench, I c = fluorescence intensity with a quench concentration of c) at 528 nm was plotted against 30 concentration (I 0 /I c =1 + kq  [c]). A linear variation was observed and followed a Stern-Volmer law with a quenching rate constant kq = 6.5×10 5 M -1 s -1 that supports an energy transfer or an electron transfer process between the exited Ir(ppy) 3 * and thiocarbamate 30.100

Figure 1 .

 1 Figure 1. Fluorescence quenching studies of Ir(ppy) 3 * with O-thiocarbamate 30

Scheme 33 .

 33 Scheme 33. Synthesis of 10-phenylphenothiazine

) A 3 . 0 M

 30 solution of EtMgBr in diethyl ether(1.37g, 10 mmol) was added to dry diethyl ether(25 mL) and cooled to 0 °C. A solution of methyl 4-methoxyphenylacetate (901 mg, 5 mmol) in dry diethyl ether (5 mL) was then added dropwise and the solution was stirred at 0 °C for 10 min and then warmed to room temperature. After completion of the reaction, 10 % HCl (2 mL) were added, followed by saturated aqueous NaHCO 3 solution (15 mL). The mixture was extracted with diethyl ether (3 × 15 mL), the organic layers were combined, dried over MgSO 4 and the solvents were evaporated under reduced pressure. Column chromatography of the residue (petroleum ether/ EtOAc 80/20) gave alcohol 63 (989 mg, 95 %) as a colorless oil. 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.18-7.10 (m, 2H), 6.89-6.81 (m, 2H), 3.80 (s, 3H), 2.68 (s, 2H), 1.45 (q, J = 7.6 Hz, 4H), 0.92 (t, J = 7.5 Hz, 6H). 13 C NMR (101 MHz, CDCl 3 )

  carbonothioyl)oxy)-10,13-dimethylhexadecahydro-1Hcyclopenta[a]phenanthren-17-yl)pentanoate 47 (250.4 mg, 0.5 mmol), compound 82 was purified by FC (Pentane/Et 2 O, 70/30) and isolated (122.1 mg, 65%) as a white solid. Spectral data are in accordance with those reported in the literature. 125 1 di-O-isopropylidene--Dglucofuranosyl] 1H-imidazole-1-carbothioate 48 (185.2 mg, 0.5 mmol), compound 83 was purified by FC (Pentane/EtOAc, 70/30) and isolated (68 mg, 56%) as a colorless syrup.Spectral data are in accordance with those reported in the literature. 126 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 5.79 (d, J = 3.6, 1H), 4.73(t, J = 4.3 Hz, 1H), 4.16-4.05 (m, 3H), 3.83-3.78 (m, 1H), 2.16 (dd, J = 13.3, 4.0 Hz, 1H), 1.78-1.70 (m, 1H), 1.49 (s, 3H), 1.40 (s, 3H), 1.33 (s, 3H),1.30 (s, 3H). CAS Number: 4613-62-1. purified by FC (Pentane/EtOAc, 60/40) and isolated (97.6 mg, 70%) as a white solid.125 A.C. Burns, P.W. Sorensen, T.R. Hoye, Steroids 2011, 76, 291-300 126 J. D. Nguyen, E. M. D'Amato, J. M. R.Narayanam, C. R. J. Stephenson, Nat. Chem. 2012, 4, 854-859.

Scheme 1 .Scheme 2 .

 12 Scheme 1. Pd-Catalyzed C-H arylation of arylpyridine with diaryliodonium salt

Scheme 3 .

 3 Scheme 3. Proposed mechanism for the Pd/Ru-catalyzed C-H arylation

Scheme 12 .Scheme 13 .Schema 14 .Scheme 14 .

 12131414 Scheme 12. Nickel catalyzed cross-coupling of aryl halides with alkyl halides

Scheme 29 .

 29 Scheme 29. Proposed mechanism for C-S cross-coupling

12

 12

15

 15

1 H

 1 NMR (400 MHz, CDCl 3 ): δ 7.90 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 2.86 -2.82 (m, 2H), 2.58 (s, 3H), 2.33 (t, J = 7.0 Hz, 2H), 2.0 (dd, J = 7.5 Hz, 7.0 Hz, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 197.

1 H

 1 NMR (400 MHz, CDCl 3 ): δ 7.91(d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 2.95 -2.91 (m, 2H), 2.59 (s, 3H), 2.47 -2.35 (m, 2H).13 C NMR (100 MHz, CDCl 3 ): δ 197.6, 144.4, 135.8, 128.8 (2 C), 128.5 (2 C), 126.5 (q, J = 275 Hz), 35.1 (q, J = 28 Hz), 28.2 (q, J = 3 Hz), 26.5. 19 F NMR (376 MHz, CDCl 3 ): δ -66.57. IR (neat): 2871, 1677, 1607, 1266 cm -1 .

  hept-3-yl)ethylsilicate 10 (0.45 mmol, 303 mg) and 4'bromoacetophenone 22 (0.3 mmol, 60 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 80/20) to afford a 45/55 mixture of diastereoisomers of 35 as a colorless oil (48 mg, 65%).

  mg) and 4-bromo-2-fluoropyridine (0.3 mmol, 31 l). The crude product was purified by flash column chromatography (pentane/EtOAc, 80/20) to afford 55 as a colorless oil (53 mg, 86%).

1 H

 1 NMR (300 MHz, CDCl 3 ): δ 8.34 (d, J = 3.5 Hz, 1H), 7.40 (d, J = 7.5, 1H), 7.06 (dd, J = 7.6 Hz, J = 3.5 Hz, 1H), 4.10 (t, J = 6.4 Hz, 2H), 2.70 -2.65 (m, 2H), 2.53 (s, 3H), 2.05 (s, 3H) 1.96 -1.87 (m, 2H). 13 C NMR (75 MHz, CDCl 3 ): δ 171.0, 156.

  Following general procedure D with potassium (1S,2R,3S,6R)-3,7,7- trimethylbicyclo[4.1.0] heptan-2-trifluoroborate(0.3 mmol, 65 mg) and triphenylcarbenium tetrafluoroborate (0.3 mmol, 99 mg) in diethyl ether. The crude product was purified by flash column chromatography (pentane/diethyl ether : 99/1) to afford 75 as a colorless oil (48 mg, 67%).

19

 19

1 H

 1 NMR (400MHz, CDCl 3 ): δ 0.98(d, J = 7.2 Hz, 3H), 1.09(s, 3H),1.10 (s, 3H),1.12 (s, 6H),1.20 (s, 3H),1.21 (s, 3H), 1.24-1.30 (m, 2H), 1.40-1.57 (m, 6H), 1.65-1.74 (m, 2H), 2.18 The visible-light photoredox catalysis has emerged as a very powerful strategy to generate radical species replacing more and more tin-mediated or some stoichiometric redox methodologies. Many opportunities are now available to access to a large range of C-centered radicals, based either on photooxidative or reductive processes.In this Ph. D. thesis, we reported a photocatalytic alternative ofBarton-McCombie deoxygenation based on a visible-light photoreduction of O-thiocarbamates derived from secondary and tertiary alcohols. The iridium complex Ir(ppy) 3 proved to be the most efficient catalyst in the presence of Hünig's base as a sacrifial electron donor. A mechanistic determination based on fluorescence quenching and cyclic voltammetry experiments was successfully investigated to determine the photocatalytic process involved.

  Nous avons développé dans une première étude une alternative photocatalytique à la réaction de désoxygénation classique de Barton-McCombie d'alcools secondaires et tertiaires par l'hydrure de tributylétain. Celle-ci repose sur l'utilisation d'un précurseur Othiocarbamate dérivé d'alcools pouvant être réduit par catalyse photorédox. Une étude mécanistique, basée sur des expériences de fluorescence et de voltammétrie cyclique, est aussi présentée. Dans une seconde étude, une élégante méthode de génération de radicaux alkyles non stabilisés, par photooxydation de « ate-complexes » de bore ou d'espèces hypervalentes à base de silicium est présentée. Ces radicaux sont piégés en présence d'accepteurs radicalaires ou engagés dans une catalyse duale avec des complexes de Nickel. Mots clés : Catalyse photoredox, Catalyse duale, Oxydation, Réduction, Désoxygénation, Thiocarbamates, Silicates, Réactions radicalaires NEW ADVANCES IN PHOTOREDOX CATALYSIS: APPLICATIONS IN RADICAL CHEMISTRY SYNTHESIS AND DUAL CATALYSIS Visible-light photoredox catalysis has emerged as a very powerful strategy to generate radical species replacing more and more tin-mediated or stoichiometric redox methodologies. The main objective of the research described in this Ph. D. thesis is to develop new synthetic methodologies in radical and organometallic chemistry, and merge them in a dual catalysis process for the preparation of elaborated molecular building blocks. In a first study, we report a photocatalytic alternative of Barton-McCombie deoxygenation based on a visible-light photoreduction of O-thiocarbamates derived from secondary and tertiary alcohols. A mechanistic investigation is presented based on fluorescence quenching and cyclic voltammetry experiments. In a second study, a challenging method of generation of unstabilized alkyl radicals by photooxidation of borate salts or hypervalent silicon species is reported. These radicals are trapped by free radical scavengers or engaged in a photoredox/nickel dual catalysis. Key words: Photoredox catalysis, Dual catalysis, Oxidation, Reduction, Deoxygenation, Thiocarbamates, Silicates, Radical reactions

Table des matières

 des Abbreviations ........................................................................................................................................

  l'expertise acquise par notre laboratoire, nous avons commencé une étude sur la réduction de composés O-thiocarbamates par catalyse photoredox. Au début, il n'existait pas de précédents dans la littérature concernant la désoxygénation d'alcools catalysée par la lumière visible. Très rapidement, le groupe d'Overman, s'inspirant des travaux d'Okada, publia la désoxygénation d'alcools tertiaires, préalablement transformés en phthalimidoyl oxalates, par catalyse photoredox. La réduction du phtalimide, par un transfert monoélectronique, entraine une série de fragmentations radicalaires afin d'obtenir un radical tertiaire qui est en suite piégé par la méthylvinylcétone. applicable aux alcools secondaires cycliques mais aussi aux alcools acycliques nonactivés. Cette réaction de réduction tolère très bien des groupements fonctionnels tels qu'un benzoyle ou un acétal, entre autres. Oxydation de trifluoroborates avec des oxydants organiques Par la suite, nous avons montré que les trifluoroborates, dont l'inconvénient est la formation de sous-produits de fluorure de bore très polluants, pouvaient être remplacés par des espèces hypervalentes à base de silicium, lesquelles s'inscrivent plus dans le domaine d'une chimie radicalaire plus verte. Deux méthodes de synthèse ont été utilisées, la première

	Schéma 8. Réduction d'un alcool tertiaire
	Après avoir étendu ces conditions à différent types d'alcools, nous avons voulu ensuite
	connaitre l'impact que nos conditions de désoxygénation pourraient avoir en synthèse. Pour
	évaluer cela, notre méthodologie a été comparée à une réaction réalisée dans les conditions
	optimisées de Barton-McCombie. Une addition lente sur 4 heures d'une solution de Bu 3 SnH

10 Schéma 5. Désoxygénation d'alcools tertiaires par catalyse photoredox de phthalimidoyl oxalates Nous avons donc réalisé nos travaux en sélectionnant préférentiellement le groupement O-thiocarbamate (synthétisé à partir du thiocarbonyle diimidazole) par rapport aux traditionnels xanthates vu que ces derniers se sont révélés peu réactifs dans les nouvelles conditions réactionnelles. Le complexe d'iridium (III) (Ir(ppy) 3 ) a été préféré au ruthénium car son caractère plus réducteur a permis d'obtenir les meilleurs résultats. De plus, l'utilisation de ce complexe nous a permis de diminuer la quantité catalytique à 1 mol% sans affecter les rendements. Schéma 6. Photoréduction d'O-thiocarbamates Il est à noter que l'ajout d'une amine, telle que la base de Hünig (i-Pr 2 NEt), est essentiel à la continuité du cycle catalytique. Comme illustré dans le schéma 7, notre méthode 10 G. L. Lackner, K. W. Quasdorf, L. E. Overman, J. Am. Chem. Soc. 2013, 135, 15342. est Schéma 7. Réduction d'alcools secondaires cyclique et acyclique Les alcools tertiaires peuvent être aussi réduits dans ces conditions avec un bon rendement (Schéma 8). La tolérance à d'autres groupes fonctionnels de cette catalyse est une nouvelle fois mise en évidence avec la fonction lactone. L'accessibilité aux O-thiocarbamates formés à partir d'alcools tertiaires s'est révélée être un problème crucial et sera discutée dans la suite du manuscrit. et AIBN (catalytique) dans le toluène, est effectuée au pousse seringue à une solution d'Othiocarbamate portée au reflux du toluène. Après traitement et purification de la réaction, le rendement en produit réduit est inférieur à celui obtenu dans nos conditions. Notre procédé hétérocycles de types imidazoles, triazoles… a permis d'obtenir de bons rendements en produits réduits. Schéma 11. Variation du groupement O-thiocarbamate Nous avons ensuite étudié le mécanisme réactionnel impliqué dans cette transformation photocatalysée par la lumière visible. Après irradiation, le complexe d'iridium, placé dans un état excité permet la réduction du groupement O-thiocarbamate par transfert monoélectronique pour donner une espèce radical-anion. Cet intermédiaire subit des fragmentations successives qui permettent de générer un radical centré sur le carbone. La base d'Hünig (DIPEA) intervient en tant que donneur d'hydrogène pour la formation de l'alcane et donneur sacrificiel d'électron pour la régénération du photocatalyseur. Ce mécanisme a été démontré par des études de fluorescence et la comparaison des potentiels électrochimiques déterminés par voltammétrie cyclique Schéma 12. Mécanisme proposé pour la réaction de désoxygénation Ainsi, dans un contexte international compétitif, trois groupes de recherche, incluant le notre 12 , ont développé des méthodes efficaces et attractives sans étain de désoxygénation dans le domaine de la catalyse photoredox. A ce jour, nous restons le seul groupe à vraiment proposer une alternative à la désoxygénation de Barton-McCombie la plus proche et la plus générale possible. Nous avons aussi essayé de développer une réaction qui s'inscrit au plus près d'une chimie radicalaire plus verte et plus moderne. Malgré le développement d'un nombre important de précurseurs radicalaires divers et variés, 13 la nécessité d'en trouver de nouveaux est toujours aussi forte, notamment lorsqu'il s'agit d'engendrer des radicaux alkyles primaires. La génération de ces entités hautement réactives est un enjeu majeur en synthèse. Nous nous sommes donc naturellement intéressés, dans un second temps, à l'étude d'une nouvelle façon d'engendrer ces radicaux alkyles primaires par catalyse photoredox. Au cours de ces dix dernières années, des entités anioniques stables, par exemple les organoborates et plus particulièrement les alkyles trifluoroborates, se sont révélés être de bons précurseurs de radicaux alkyles. 14 En effet, ces derniers peuvent être engendrés par oxydation d'organoborates en utilisant des métaux de transition comme l'acétate de cuivre (II). Les radicaux peuvent être ensuite piégés par le TEMPO avec un très bon rendement (Schéma 13). 15 Schéma 13. Oxydation du benzyltrifluoroborate par l'acétate de cuivre (II) L'inconvénient de cette méthode est l'utilisation sur-stoechiométrique d'oxydant. Une version photocatalytique d'oxydation des sels de trifluoroborates et trialkoxyborates a été développée par Akita en utilisant 2 mol% de charge catalytique d'un complexe d'iridium comme photocatalyseur. 16 De très bons rendements en produits d'addition radicalaire ont été obtenus avec le TEMPO et l'acrylate de méthyle dans l'acétone. Schéma 14. Génération de radicaux par photooxydation des sels de trifluoroborates et trialkoxyborates En partant sur cette base, nous avons démontré que les sels potassiques de trifluoroborates pouvaient être oxydés de façon très douce en utilisant des oxydants organiques. En effet, l'utilisation d'espèces cationiques (sel de tritylium) et d'espèces radicalcation (sel d'ammoniumyle), capables d'induire un transfert électronique provoque la génération de radicaux centrés sur le carbone qui sont piégés par la suite par le TEMPO. Le développement de conditions très douces était l'un de nos principaux objectifs. Schéma 15. consiste en la réaction entre un alkyle trichlorosilane avec du catéchol en présence de triéthylamine, dans le THF, suivie d'une métathèse de cation pour obtenir l'ammonium alkyl bis-catécholatosilicates (Schéma 16, conditions A). Une deuxième méthode permet quant à elle, d'obtenir à partir d'un alkyle tri(méthoxy ou éthoxy)silane, un sel potassique du silicate en utilisant du méthanolate de potassium comme base (Schéma 16, conditions B).

  Mécanisme de photooxydation des silicates Nous avons ainsi proposé une méthode simple et facile d'accès pour engendrer des radicaux alkyles (primaires, secondaires et tertiaires) par catalyse photoredox. Ce procédé nous a permis de nous affranchir des sels d'organoborates assez polluants et de leur oxydation par des quantités stoechiométriques de métaux. Molander, 18 MacMillan et Doyle 19 ont publié simultanément, deux exemples spectaculaires de catalyse duale, photoredox / nickel, dans le but d'effectuer un couplage entre des halogénures d'aryle avec des radicaux alkyles. En combinant la génération de radicaux par catalyse Rencontre entre la catalyse au nickel et la catalyse photoredox Nous avons donc naturellement engagé les alkyles biscatécholatosilicates que nous avons développés précédemment dans cette catalyse duale. Nous avons concentré nos efforts sur la génération et la réactivité de radicaux primaires non-stabilisés très réactifs, un domaine peu exploré jusqu'à présent. Nos résultats sont généralement très bons en termes de rendements et d'étendue de la réaction, puisque les fonctions notamment hétéroatomiques et les plates-formes hétérocycliques aromatiques sont compatibles avec ces transformations.

	Depuis quelques années, une recherche intensive a été entreprise pour le
	développement de nouvelles réactions catalysées par des procédés photoredox. Grâce à celles-
	ci, il a été possible d'accomplir des transformations chimiques jusqu'alors difficiles. En 2014,
	Schéma 20. Catalyse duale photoredox/nickel avec génération de radicaux primaires à partir
	de silicates
	Toujours dans une dynamique d'amélioration de notre système catalytique, nous avons
	tenté de substituer l'utilisation de complexes d'iridium par des colorants organiques photo-
	activables. Les versions organo-photocatalysées sont généralement plus difficiles à mettre en
	oeuvre car leurs propriétés physico-chimiques (potentiels redox ou temps de vie de l'état

d'espèces hypervalentes à base de silicium en présence d'un photocatalyseur d'iridium sous irradiation par la lumière visible (LEDs bleues) a été développé. Ces alkyles silicates permettent l'accès à des radicaux alkyles stabilisés et non stabilisés. L'oxydation de ces silicates en présence d'un accepteur radicalaire tel qu'une allyle sulfone activée (Schéma 16) ou le TEMPO donne de très bon rendements de produits de piégeage. Schéma 17. Génération de radicaux par photooxydation et piégeage par allylation L'alkyle bis-catécholatosilicate est oxydé par transfert monoélectronique avec le complexe d'iridium préalablement irradié. Après dissociation, le radical engendré est piégé par allylation. Le radical tosyle libéré est ensuite réduit permettant la régénération du photocatalyseur. Schéma 18. photoredox avec un couplage au nickel, une impressionnante méthodologie a été élaborée dans des conditions extrêmement douces. En effet, cette catalyse duale ne requiert aucune activation thermique (par opposition à la catalyse au palladium par exemple), aucun additif toxique ou ligand onéreux de plus, les charges catalytiques en iridium et en nickel sont très faibles. Schéma 19. excité…) sont en général, moins favorables à celles rencontrées avec les complexes de métaux de transitions. Parmi tout le panel de photocatalyseurs organiques, nous avons essayé de trouver le plus adéquat. Nous avons finalement réalisé une étude montrant l'oxydation sans précédent des trifluoroborates et de silicates pour la génération de radicaux alkyles avec l'acridinium de Fukuzumi comme organo-photocatalyseur. Ce dernier possède en effet un exceptionnel potentiel d'oxydation à l'état excité de l'ordre de +2.06V vs. SCE. Par ailleurs, nous avons observé que la réactivité des organotrifluoroborates était supérieure à celle des biscatécholatosilicates dans ces conditions. Schéma 21. Photooxydation des benzoyles trifluoroborate et silicate par le catalyseur de Fukuzumi En 2012, le groupe d'Adachi a décrit, lors d'une étude sur le développement de diodes électroluminescentes organique (OLED, en anglais, pour Organic Light-Emitting Diode), une famille de molécules interagissant avec la lumière et ayant pour structure de base un squelette n-carbazolyl dicyanobenzene. 20 Ces molécules possèdent des propriétés photophysiques impressionnantes qui leur confèrent un intérêt synthétique. Inspirés par ces potentiels photocatalyseurs, Zhang et ses collaborateurs ont repris les travaux de Molander et de MacMillan en remplaçant le complexe d'iridium par le 1,2,3,5-tetrakis-(carbazol-yl)-4,6dicyanobenzene (4CzIPN).

21

20 H. Uoyama, K. Goushi, K. Shizu, H. Nomura, C. Adachi, Nature 2012, 492, 234. 21 J. Luo, J. Zhang, ACS Catal. 2016, 6, 873.

Table 1 .

 1 The

12 principles of green chemistry 1 It is better to prevent waste than to treat or clean up waste after it is formed.

I.B.1. Photophysical properties of Ru(bpy)3 complexes

	Since this renaissance, two other
	teams, the groups of Corey Stephenson (Boston University) and Tehshik P. Yoon (University
	of Wisconsin, Madison) have published very interesting contributions on dehalogenative
	cyclization reactions 15 and photocatalytic [2+2] cycloadditions of enones. 16

.2. Basic of photoredox catalysis

	sacrificial electron acceptor A must be introduced into the medium (reductive quenching
	cycle, Scheme 2, purple path). The alternative pathway can take place: if the complex
	transfers an electron to the substrate (or oxidative quencher (Qox)), this one is oxidized to PCat + . The reduced substrate R •-undergoes radical transformations and the presence of a sacrificial electron donor D allows the regeneration of the photocatalyst PCat (oxidative quenching cycle) (Scheme 2, blue path). Many contributions in this area have been reported I.BUpon visible light irradiation at wavelength λ max , the photocatalyst PCat reaches its exhibiting photoreduction and photooxidation of various functions and illustrated in a series
	excited state PCat*. Two scenarios can take place: of important monographs and reviews. 18
	In the first one, a sacrificial electron donor is present in the reaction medium with adequate
	reduction potential (Scheme 2, green path) which can act as a reductive quencher (Qred) of
	PCat* and generate PCat -. The reduced complex then transfers an electron to the substrate R
	which regenerates PCat in a so-called "reductive quenching cycle". The resulting radical
	anion R •-then undergoes subsequent transformations. Similarly, if the photoexcited complex
	PCat* reacts with a sacrificial electron acceptor acting, as an oxidative quencher (Qox), it
	gets oxidized to PCat + and can be reduced by a substrate R to regenerate the starting catalytic
	species (oxidative quenching cycle) and liberate the radical cation R •+ (Scheme 2, orange
	path).
	Scheme 5. Catalytic cycle when substrate and quencher are the same species
	Scheme 4. Catalytic cycle in presence of a sacrificial quench Q
	In the second scenario, the substrate R is also the quencher. If this one acts as
	20 L. Flamigni, A. Barbieri, C. Sabatini, B. Ventura, F. Barigelletti, Top. Curr. Chem. 2007, 281, 143. 21 S. Paria, O. Reiser, Chem. Cat. Chem. 2014, 6, 2477. reductive quencher (Qred), it transfers an electron to PCat* to form PCat -. The oxidized
	22 C. D. McTiernan, M. Morin, T. McCallum, J. C. Scaiano, L. Barriault, Catal. Sci. Technol. 2016, 6, 201. 23 J. Zhang, D. Campolo, F. Dumur, X. Piao, J.-P. Fouassier, D. Gigmes, J. Lalevée, J. Polym. Science, Polym. substrate R •+ will then participate in radical transformations. To regenerate the catalyst, a
	Chem. 2016, DOI: 10.1002/pola.28098

I.B.3. Photocatalytic Generation of C-Centered Radicals I.B.3.a. Formation involving photoreductive processes

  S. Donck, A. Baroudi, L. Fensterbank, J.-P. Goddard, C. Ollivier, Adv. Synth. Catal. 2013, 355, 1477.

	instance, radical-cationic MCRs have been reported by Masson for aminotrifluoromethylation
	of styrene type olefins 31 and enecarbamates 32 . In these cases, the intermediate benzylic
	carbocation, generated after radical addition of the trifluoromethyl radical to the
	olefin/oxidation, can be trapped intermolecularly by an amine or an azide.
	Scheme 7. Formation of aryl radicals by photoreduction of sulfonium salts
	It also worked with iodonium salts as source of aryl radical. This transformation gave
	the opportunity to evaluate cheaper and more sustainable alternatives to ruthenium and
	iridium catalysts. For that purpose, photoactive copper complexes appeared a valuable field of
	investigation. Copper(I)-biphenanthroline Cu(dap) 2 Scheme 9. Aminotrifluoromethylation of styrene + (dap = 2,9-bis(para-anisyl)-1,10-
	phenanthroline) and Cu(dpp) 2	+ (dpp = 2,9-diphenyl-1,10-phenanthroline) that have been
	reported by McMillin 29 raised as promising photoredox catalysts due to their excellent
	photophysical and redox properties (Scheme 8). 30 Indeed, reduction potentials of Cu(dap) 2 + *  Reduction of halides
	and Cu(dpp) 2 SCE). In 1990, Fukuzumi et al. 33 and more recently, MacMillan et al. showed that -+ * are lower than Ru(bpy) 3 2+ * (-1.43 V and -1.11 V respectively vs -0.85 V vs
	brominated carbonyl derivatives can generate carbon-centered radicals in the presence of
	catalytic amount of Ru(bpy) 3 Cl 2 during visible light irradiation. In this study, enantioselective
	Scheme 8. Reduction of iodonium salts by a photoactive copper complex
	Trifluoromethyl radical can be generated by photoreduction of Umemoto's reagent
	with photoactivated Ruthenium(II) or Iridium(III) photocatalyst and added onto alkenes. For
	29 D. R. McMillin, M. T. Buckner, B. T. Ahn, Inorg. Chem. 1977, 16, 943.
	30 N. Armaroli, G. Accorsi, F. Cardinali, A. Listorti, Top. Curr. Chem. 2007, 280, 69.

Reduction of ketoepoxides or ketoaziridines

	which triggers a 5-exo-trig/4-exo-trig cyclization sequence in a diastereoselective manner.
		Scheme 13. Intramolecular [2+2] cycloaddition of enones
	Scheme 11. Polycyclization of unsaturated bromomalonates  Epoxides and aziridines are versatile targets, but a series of works have shown that
	their photoreduction required an alpha-activation by a carbonyl group. 37 Using Hantzsch ester
	Visible light photoredox catalysis proved to be efficient for promoting radical/cationic as Qred and presumably H donor, good yields of aldol type products or beta-amino keto
	multicomponent reactions (MCR S ). Masson examined the reactivity of enecarbamates in derivatives could be obtained. Interestingly, the generated radical intermediate from keto-
	combination with diethyl-2-bromomalonate and ethanol and observed the formation of the epoxides or -aziridines can be used for further diastereoselective allylation reactions. 38
	expected -alkylated -amino ethers (Scheme 12).
		Scheme 12. Three-component radical/cationic oxyalkylation of alkenes
		 Reduction of unsaturated ketones
	Yoon's group has successfully tested this photoreductive process in intramolecular
	35 [2+2] cycloaddition of enones for the construction of bicyclic systems with cyclobutane Scheme 14. Reduction of ketoepoxides or ketoaziridines by photoreductive catalysis
	units. 16,36	Photoreduction	of	a	lithium-activated	enone	with	the
	37 E. Hasegawa, S. Takizawa, T. Seida, A. Yamaguchi, N. Yamaguchi, N. Chiba, T. Takahashi, H. Ikeda, K.
	Akiyama, Tetrahedron 2006, 62, 6581.
	35 J.W. Tucker, J.D. Nguyen, J.M.R. Narayanam, S.W. Krabbe, C.R.J. Stephenson, Chem. Commun. 2010, 46, 38 M.-H. Larraufie, R. Pellet, L. Fensterbank, J.-P. Goddard, E. Lacôte, M. Malacria, C. Ollivier, Angew. Chem.
	4985. Int. Ed. 2011, 50, 4463.

I.

B.3.b. Formation involving photooxidative processes  Oxidation of amines

	As already mentioned, tertiary amines are easily oxidized by single electron transfer
	into radical cations which can be transformed in the corresponding iminium salts by a loss of
	hydrogen atom or in the -aminoalkyl radicals by a loss of a proton (Scheme 15). Number of
	groups have investigated this dual reactivity under photoredox catalysis mediated by visible
	light. 39
	Scheme 15. Behavior of aliphatic tertiary amines under oxidative conditions
	Zheng and co-workers have shown that cyclopropylamines can participate in radical
	cascade reactions with activated olefins under photooxidative conditions. The β-carbon
	radical iminium ion, obtained by oxidation of the bicyclic cyclopropylamine with the
	photoactivated ruthenium complex and ring opening, can add to the olefin and cyclize to form
	5,5-fused bicyclic heterocycles. 40 Interestingly, the reaction was extended to alkynes, enynes
	and diynes with success. 41
	Scheme 16. Intermolecular [3+2] cycloaddition of a bicyclic cyclopropylamine with styrene
	39 J. Hu, J. Wang, T. H. Nguyen, N. Zheng, Beilst. J. Org. Chem. 2013, 9, 1977.
	40 S. Maity, M. Zhu, R. S. Shinabery, N. Zheng, Angew. Chem. Int. Ed. 2012, 51, 222.
	41 T.H. Nguyen, S.A. Morris, N. Zheng, adv. Synth. Catal. 2014, 356, 2831.



Oxidation of 1,3-dicarbonyl compounds

	Enols SET oxidation has been extensively studied for the formation of carbon-
	centered radical, which were involved in intermolecular additions or cyclizations. These
	processes were generally based on cerium (IV) or manganese (III) and used with overstoichiometric amounts of metal salts. In 2014, our lab reported versatile conditions for Scheme 18. An intramolecular radical cascade reaction
	intra or intermolecular carbon-carbon bond formations. 42 Under photoredox catalysis, 1,3-
	dicarbonyl compounds such as ethyl benzoylacetate dimerized through the formation of intermediate radical species to give 1,3-dicarbonyl dimers in excellent yields. In the presence  Oxidation of trifluoroborates
	of a radical acceptor like allylsulfone, allylated products were observed in good yields. Boron ate-complexes proved to be also precursors of alkyl radicals by SET using
	Formally resulting from a C-H activation, this transformation proceeded through the oxidation stoichiometric amount of oxidant. In 2012, Akita and Koike extend this concept to the use of
	of an enolate to the corresponding stabilized radical.
	Scheme 17. Photocatalyzed oxidation of 1,3-diketones
	We developed also an intramolecular photocatalytic oxidation process. The carbon
	centered radical generated from 1,3-dicarbonyl compound can be involved in cascade
	reactions. Upon treatment with the Ru(bpy) 3 Cl 2 /O 2 (Q ox ) oxidative system in the presence of
	two equivalents of tritylium Ph 3 CBF 4 as a sacrificial acceptor, two examples of cascade
	reactions have been realized starting from unsaturated phenyldiketones to obtain the tricyclic
	products with moderate yields. 42
	42 M. Daniel, L. Fensterbank, J.-P. Goddard, C. Ollivier, Org. Chem. Front. 2014, 1, 551.

photoredox catalytic systems (Scheme 19).

43

Organotrifluoroborates and organo(triol)borates were investigated, first in the formation of C-O bond through radical trapping experiments with TEMPO and second in C-C bond formation processes with electron-poor olefins. The latest were more effective than trifluoroborate salts for the formation of secondary and primary alkyl and aryl radical. The most efficient catalyst among a set of ruthenium and iridium complexes was [Ir(dF(CF 3 )ppy) 2 (bpy)](PF 6 ), which has the highest oxidation potential at the photoexcited state (+ 0.91 V vs Fc + /Fc). This is consistent with the fact that no additional Qox is needed for this transformation and the organoborate itself is oxidized by the [Ir(III)] excited state to generate the corresponding alkyl radical and the reduced [Ir(II)] complex.

Scheme 19. Radical formation by photooxidation of tetravalent boron compounds

43

Y. Yasu, T.

Koike, M. Akita, Adv. Synth. Catal. 2012, 354, 3414.

  33

28 H. Deshayes, J.-P.

Pete, J. Chem. Soc, Chem. Commun. 1978, 567. 29

a) H.

Normant, Bull. Soc. Chim. Soc. 1968, 791; b) H. Normant, Angew. Chem. Int. Ed. 1967, 6, 1046. 30

H. Deshayes, J.-P. Pete, Can. J. Chem. 1984, 2063. 31 a) Y. A. Dembélé, H. Deshayes, J.-P. Pete, Tetrahedron Lett. 1982, 23, 3489; b) A. Dembélé, H. Deshayes, J.-P. Pete, Bull. Soc. Chim. Fr. 1988, 671. 32 L. A. Paquette, F. Geng, Org. Lett. 2002, 4, 4547. 33 a) A. Mendoza, Y. Ishihara, P. S. Baran, Nature Chem. 2012, 4, 21; b) Y. Ishihara, A. Mendoza, P. S. Baran, Tetrahedron 2013, 69, 5685.

  38

36 S. Hanessian, C. Girard, Synlett 1994, 863. 37

a) E. J. Enholm,

S. Jiang, Tetrahedron Lett. 1992, 33, 6069; b)

E. J. Enholm, S. Jiang, K. Abboud, J. Org. Chem. 1993, 58, 4061; c) A. Malapelle, Z. Abdallah, G. Doisneau, J.-M. Beau, Angew. Chem. Int. Ed. 2006, 45, 6016. 38 a) K. Lam, I. E. Markó, Org. Lett. 2008, 10, 2773; b) K. Lam, I. E. Markó, Tetrahedron 2009, 65, 10930. Scheme 8. Reduction of toluate esters with samarium diiodide

  F/mol of current.42 Also, as shown byTsujimoto et al., electrochemical reduction of 3-(2- naphthyl)-2-butenyl acetate at a platinum cathode gave (E)-2-(2-naphthyl)-2-butene in 73% yield.43 In 2002, Frontana-Uribe et al. explored the ability of the electrogenerated tetrabutylammonium-mercury amalgam to reduce aliphatic acetates. For instance,

	current (15 mA.cm -2
	electroreduction of diosgenin acetate under a constant current (5 mA, 2.1 F/mol) gave rise to a
	ca. 1:1 ratio of alkane and alcohol, and the deoxygenated product could be isolated in 53%
	yield. These results are comparable with those obtained using alkaline metals and a similar
	mechanism involving a ketyl-like radical-anion formation and fragmentation can be proposed
	(vide supra). 44
	In that vein, oxalate esters exhibit a propensity to undergo reductive cleavage of
	valuable substrates for electrochemical deoxygenation of alcohols. A series was electrolyzed
	at 130°C in a H-type cell equipped with a carbon graphic cathode and filled with
	tetrabutylammonium tetrafluoroborate and N-methylpyrrolidone (NMP) under a constant

"Organic Electrochemistry, 4 th ed.", Eds. H. Lund, O. Hammerich, Marcel Dekker: New York, 2001.

40 H. Lund, Acta Chem. Scand. 1960, 14, 1929. 41

a) J. P. Coleman, H. G. Gilde, J. H. P.

Utley, B. C. L. Weedon, J. Chem. Soc. D 1970, 738; b)

J. P. Coleman, Naser-ud-din, H. G. Gilde, J. H. P.

Utley, B. C. L. Weedon, L. Eberson, Chem. Commun. 1973, 1903.

2 carbon-oxygen bond from alcohols at lower negative potentials (ca -1.2 vs. Ag/AgI). Electron transfer from cathode to oxalates was first highlighted by Voss with the formation of a stable semidione radical anion intermediate, evidenced by EPR experiments. This reduction turned out to be reversible for diethyl oxalate and irreversible for diallyl and dibenzyl oxalates in aprotic solution.

45

Utley et al. suggested this irreversibility comes from a rapid fragmentation of the radical anion, as already observed with acetate (vide supra), which can be accelerated in protic conditions. Studies on benzyl oxalates supported a mechanism whereby transient radical anions collapse to benzyl radicals and oxalate anions and not the reverse. However, the process was hampered by competing hydrolysis of preformed oxalates, particularly of benzylic alcohols. The solution was found by generating in situ the reactive oxalate prior to be reduced via a co-electrolysis between benzylic (or allylic) alcohols and diethyl oxalate. For instance, reduction of diphenylmethanol under these conditions (mercury cathode, DMF-Bu 4 NClO 4 , -1.6 V vs. Ag/AgI, 1 F/mol) gave diphenylmethane in 70% yield. Of interest, controlled potential electrolysis of oxalate of vicinal diols gave rise to olefinic adducts.

[START_REF]A primary carboxylic (5-phenylvaleric acid) has also been used as unstabilized radical precursor, providing the cross-coupling product but in 11% yield[END_REF]

As reported by Markó et al., aromatic esters such as toluates can also be regarded as

Electron Transfer Deoxygenation from Carbon Dioxide Radical Anion

	The chemical system (Bu 4 N) 2 S 2 O 8 /HCO 2 Na has aroused keen interest for its ability to
	generate carbon dioxide radical anion CO 2	•-by oxidation with sulfate radical anion SO 4	•-and
	then promote one-electron reductive processes. In 1991, Hu and Qing took advantage of this
	reactivity to carry out per(poly)fluoroakylation of olefins by reduction of per(poly)fluoroalkyl
	chlorides. 49 Based on this seminal work, Kim et al. developed a new method for the radical
	deoxygenation of alcohols from thiocarbonyl derivatives. Using a mixture of (Bu 4 N) 2 S 2 O 8 (3
	equiv.)/HCO 2 Na (6 equiv.)/Na 2 CO 3 (8 equiv.) in DMF at 50°C, good to excellent yields in
	alkane (up to 98%) were reached whatever the nature of the radical precursor (xanthate,

48 Scheme 9. Electrochemical reduction of toluate esters II.A.5. 47 K. Lam, I. E. Markó, Chem. Commun. 2009, 95. 48 K. Lam, I. E. Markó, Synlett 2012, 23, 1235. 49 C.-M. Hu, F.-L. Qing, J. Org. Chem. 1991, 56, 6348.

  Pioneering works on photodeoxygenation of benzoate or acetate esters in dry HMPA with a high-pressure mercury lamp were reported in the late Sixties byBeugelmans et al., who mentioned the presence of alkane side products (ca. 5% yield after 30h).[START_REF] Beugelmans | [END_REF] In 1975, Pete et al. optimized the reaction conditions by adding 5% of water to HMPA and irradiating with low-pressure mercury lamps (254 nm). Photoreduction of formate, acetate and benzoate esters gave the corresponding alkanes in moderate to good yields after 3 to 5 h of irradiation (Scheme 11, eq. 1). Primary, secondary, tertiary and neopentyl acetates could be smoothly The latter tetrahedral radical intermediate can undergo a fragmentation and release an alkyl radical which can abstract a hydrogen atom to the HMPA and furnish the deoxygenated product.[START_REF] Xie | Tritylium is known as a hydride abstractor, for a recent application[END_REF] Further investigations based on laser flash photolysis of HMPA/H 2 O solutions and quenching experiments support a mechanism involving photoinization of HMPA and reduction of carboxylic esters to transient radical anions by solvated electrons. To complete, deuterium labeling experiments with HMPA-d 18 and D 2 O reveal that hydrogen abstraction takes place preferentially at HMPA but also at the acid residue and the products. especially when other chromophores are present in the substrates. In 1986, Saito et al. found success with the development of a general procedure for deoxygenation of secondary alcohols taking advantage of this photochemical property. The transformation relies on a photoinduced electron transfer process from the excited state of 9-methylcarbazole

	II.A.6.a.	UV	Light-Induced	Photodeoxygenation
	Reactions
	(MCZ) obtained by irradiation with a 400 W high-pressure mercury lamp to a simple
	benzoate or a m-(trifluoromethyl)benzoate ester derived from the alcohol in a mixture
	THF/water or isopropyl alcohol/water (10:1) under nitrogen atmosphere at room temperature
	(Scheme 14). Of particular note, addition of magnesium perchlorate can speed up the
	photoreductive process. A similar mechanism to that obtained with HMPA was proposed.
	Reduction of the carboxylic ester by the photoactivated MCZ provides a transient radical
	The versatility of this methodology was illustrated by the synthesis of deoxysugars
	from carbohydrate 59 and amino-glucoside esters. 60 Primary, secondary and even sterically
	hindered tertiary acetates or pivalates (Scheme 13, eq. 1 and eq. 2) as well as 1,2 diacetates Scheme 13. Application to the synthesis of deoxysugars from carbohydrate and amino-

converted into alkanes in short reaction times. While these conditions are compatible with a variety of functional groups including non-activated alkene, amide, acid, alcohol, ether and acetal

(Scheme 11, eq. 2)

, limitations were encountered with activated alkenes, ketones and halides which are reduced at the same time and perfluorocarboxylic esters gave rise preferentially to -elimination of a fluorine atom.

55

The presence of other chromophores in the starting material that absorbs UV radiation may also complicate the course of the reaction.

56

A detailed mechanistic study reported by

Pete et al.

suggests that the reaction proceeds through an electron transfer process from excited HMPA to the carboxylic ester as depicted in scheme 12. Irradiation of the reaction mixture at 254 nm preferentially activates HMPA rather than esters -except with benzoates -and subsequent ester/HMPA* -or ester*/HMPAexciplex formation promotes reduction of the ester leading to a radical-ion pair. In the presence of water, the radical anion RCO 2 R' • was supposed to be trapped by protonation of the alcoholate preventing a reversal electron transfer and a regeneration of the starting materials. 58 Scheme 11. Photoinduced electron transfer reduction of steroid carboxylic esters by HMPA/H 2 O under UV irradiation Scheme 12. A plausible mechanism for the photoreduction of carboxylic Esters glucoside esters

As valuable alternatives to the use of toxic HMPA, N-methylcarbazoles proved to be quite efficient and selective electron donor photosensitizers for the photoreduction of benzoate esters, anion which undergoes subsequent protonation with water and -fragmentation. Then, Habstraction from i-PrOH by the expelled radical was confirmed by deuterium labeling experiments. In theory, MCZ should be regenerated from the radical cation (MCZ) +• by reduction with the solvent radical but in practice, at least one equivalent is required (Scheme 14). To explain, MCZ is irreversibly oxidized, as confirmed by cyclic voltammetry. 66 Scheme 14. The Saito photochemical reduction of a m-(trifluoromethyl)benzoate ester and the plausible mechanism 66 I. Saito, H. Ikehira, R. Kasatani, M. Watanabe, T. Matsuura, J. Am.

Chem. Soc. 1986, 108, 3115.

  -McCombie deoxygenation of aliphatic secondary and tertiary alcohols based on photoreduction of the corresponding imidazole O-thiocarbamates. Upon treatment with fac-Ir(ppy) 3 and DIPEA is required as both a sacrificial electron donor and a hydrogen atom donor, and water involves in the protonation of the transient radical anion RCO 2 R' •-.

	procedure under visible-light illumination. Starting from 3,5-bis(trifluoromethyl)benzoate
	esters, the reaction proceeds smoothly upon exposure to [Ir(ppy) 2 (dtb-bpy)]PF 6 catalysis in
	the presence of DIPEA and water in acetonitrile under LED lights at 40 °C. This catalytic
	system proved tolerant to a large number of functional groups. In contrast with O-

diisopropylethylamine (DIPEA, Hünig's base) in acetonitrile under LED lights at room temperature, products of reduction were obtained in good to moderate yields (Scheme 18). Excellent functional group compatibility was observed with sulfonamide and tertbutoxycarbonyl protecting groups, aromatics, alkenes, acetals, alkyl esters, lactones. By comparison, this transformation performed under standard tin hydride conditions gave the same results. However, photoreduction of the benzhydrol derivative furnished a mixture of 1,1-diphenylmethane (21%) and dimer 1,1,2,2-tetraphenylethane (37%). To gain insights into the mechanism, fluorescence quenching experiments and comparison of reduction potentials of a set of thiocarbamates (-1.11 to -1.73 V) with the Ir(IV)/Ir(III)* redox system (-1.73 V) established that photoactivated fac-Ir(ppy) 3 * reduce the O-thiocarbamates. These informations allowed to propose a reasonable mechanism where fac-Ir(ppy) 3 * can transfer an electron to the thiocarbamate moiety and the photocatalyst is regenerate in the presence of DIPEA. Then, the generated thiocarbamate radical anion fragments and affords the intermediate carboncentered radical which can abstract an hydrogen to the amine radical cation (Scheme 18). 77 Scheme 18. Photocatalytic reduction of secondary and tertiary O-thiocarbamates and the plausible mechanism In the same line, Reiser et al. have concentrated on deoxygenation of secondary benzylic, -carbonyl and -cyano alcohols. For that purpose, they revisited the Saito's thiocarbamates, no dimer was formed in photoreduction of benzhydrol derivatives (Scheme 19). As seen before, it is assumed that the iridium complex acts as a visible-light photocatalyst, 78 Scheme 19. Photocatalytic reduction of 3,5-bis(trifluoromethyl)benzoate esters In 2012, Overman et al. made use of the Okada's decarboxylation 79 to provide an efficient method for the deoxygenation of aliphatic tertiary alcohols by photoreduction of the corresponding tert-alkyl N-(acyloxy)phthalimide oxalates. The reaction relies on a combination of Ru(bpy) 3 (PF 6 ) photocatalyst (1.5 mol%) and visible-light (blue LEDs) with

Hantzsch ester and i-Pr 2 NEt.HBF 4 which presumably serves as both a reductive quencher and H-atom donor. After two successive decarboxylations, the tertiary alkyl radicals can then be trapped by electron-deficient alkenes leading to the formation of quaternary centers (Scheme 20). 80 78 D. Rackl, V. Kais, P. Kreitmeier,

O. Reiser, Beilstein J. Org. Chem. 2014, 10, 2157. 79 K. Okada, K. Okubo, N. Morita, M. Oda, Tetrahedron Lett. 1992, 33, 7377. 80

G. L. Lackner, K. W. Quasdorf, L. E. Overman, J. Am.

Chem. Soc. 2013, 135, 15342.

Table 1 .

 1 1,2,5,6-diisopropylidene-D-glucose derivate in imidazolyl thiocarbamate 25 was reduced in refluxing toluene with tri-n-butylstannane to give the deoxy product 26 in 74% yield. Under these conditions, they were able to reduce a set of thiocarbamate derivatives in high yields. Reduction of diisopropylidene protected furanose Inspired by those results, we decided to start the conditions optimization with the Othiocarbamate 30 (scheme 6). The substrate 30 was preferred to carbohydrate 25 because of the very sticky oily nature of sugars leading to a less practical handling. The synthesis of 30 starts with the nitrogen sulfonylation of 27 with benzenesulfonyl chloride to afford of the Optimization of the reaction conditions for photocatalytic reduction of O-

	Scheme 5.

alcohol 28 in 70% yield. In the dark, 28 reacted with the 1,1'-thiocarbonyldiimidazole 29 in dichloromethane in the presence of 4-(dimethylamino)pyridine (DMAP) to provide the Othiocarbamate 30 in high yield (97%). Scheme 6. Synthesis of the O-thiocarbamate substrate candidate for optimization

  ).86l We first tested the classical Ru(bpy) 3 Cl 2(5 mol%) with 10 equivalents of DIPEA in acetonitrile during 24 hours under 14W fluorescent light bulb (14W FLB) without success (Table1, entry 1). This was attributed to the low reductive potential of its exited state (E 1/2 ([Ru(bpy) 3 ] 3+ /[Ru(bpy) 3 ] 2+ *) = -0.87V (vs. SCE)). Under the same conditions, we change the catalyst to the more reductive Ir(dtbbpy)(ppy) 2 PF 6 (E 1/2 ([Ir] 2+ /[Ir] + *) = -0.96V (vs. SCE)). To our delight, the reduced compound 31 was isolated in 20%, which supported the viability of our photoreductive approach (Table1, entry 2). With the strong reductive Ir(ppy) 3 ( E 1/2 ([Ir(ppy) 3 ] + /Ir(ppy) 3 *) = -1.73 V (vs. SCE)), we improved the reduction efficiency and obtained 31 in 47 % (Table1, entry 3). We settled on this iridium catalyst for the rest of the study.

	 Selection of the solvent
	Using acetonitrile as solvent allowed us to obtain 47% of reduced product. Changing
	acetonitrile to DMPU (N,N'-dimethylpropyleneurea) gave a comparable yield (Table 1, entry
	4) but any other solvent modification (NMP, DMF, DMSO and DCM; Table 1, entries 5-9)

Table 2 .

 2 Photocatalyzed reduction of various functional groups

	Entry	Precursor	Yield of 31
	1	34	SM Only
	2	36	SM Only
	3	38	20%

Scope and limitations of the photoreductive deoxygenation of alcohols

).

94

H. Sugimoto, I. Makino, K. Hirai, J.

Org. Chem. 1988, 53, 2263

.

Scheme 20. Alternative synthesis of tertiary O-thiocarbamates

To date, tertiary O-thiocarbamates reported in the literature are limited to quinic γlactone derivatives 95 or tertiary alcohol with specific conformation.

96

Interestingly the synthesis of carbamate 74 from cedrol 66 worked smoothly in good yield (Scheme 21).

Scheme 21. Carbamate synthesis from tertiary alcohol

With this carbamate in hand, our first attempt was to transform the carbonyl into a thiocarbonyl group using the Lawesson reagent 75 in refluxing toluene. Only the product of elimination 76 was observed by 1 H NMR as major product of the reaction (Scheme 22, equation 1). We tried to reduce the carbamate 74 in cedrane 77 under our optimized photoreductive conditions. After reaction and work up, only the starting material was recovered without traces of the deoxygenated product 77 (Scheme 22, equation 2). 95 a) S. Mills, R. Desmond, R.A. Reamer, R.P. Volante, I. Shinkai, Tetrahedron Lett. 1988, 29, 281. b) Z.S. Su, L.A. Paquette, J. Org. Chem. 1995, 60, 764. c) J.D. White, J. Deerberg, S.G. Toske, T. Yakura, Tetrahedron 2009, 65, 6635. 96 a) K.C. Nicolaou, P. Maligres, T. Suzuki, S.V. Wendeborn, W.M. Dai, R.K. Chadha, J. Am. Chem. Soc. 1992, 114, 8890. b) F.A. Bermejo, A.F. Mateos, A.M. Escribano, R.M. Lago, L.M. Buron, M.R. Lopez, R.R Gonzalez, Tetrahedron 2006, 62, 8933. Scheme 22. Transformations of the carbamate 74 II.B.3.d.

Table 3 .

 3 Peaks reduction potentials of thiocarbamates a)

	The

has an influence on the potential value. With an E red

(45)

= 1.73 V vs. SCE, the potential of 45 is lower than the one of 30 (E red (30) = 1.63 V vs. SCE). For substrate 49 and the tertiary O-thiocarbamate 56, their potentials are much higher than the potential of 30. Indeed, compounds 49 and 56 were reduced at 1.67 V and 1.56 V vs. SCE respectively. The benzylic substrate 52 appeared to be more easily reduced than the others thiocabamates (1.11 V vs. SCE). These measurements support that Ir(ppy) 3 * {E 1/2 ([Ir(ppy) 3 ] + /Ir(ppy) 3 *) = 1.73 V (vs. SCE)} is able to reduce the O-thiocarbamates to the corresponding radical anions.

Substrate (Sub) 30 45 49 E red (V) b) [Sub]/[Sub] .-

  Based on all these findings, we were able to propose a mechanistic pathway for the photocatalyzed deoxygenation of imidazolyl O-thiocarbamate (Scheme 5). Under visible light activation, Ir(ppy) 3 is able to reach an excited state that could transfer one electron to the

	thiocarbamate moiety. 101 This reduction process leads to the oxidation of Ir(III) to Ir(IV)
	species that would be reduced in turn to Ir(ppy) 3 by (i-Pr) 2 NEt and starts a new catalytic
	cycle. Then, the thiocarbamate radical anion decomposes by fragmentation to afford the
	intermediate carbon-centered radical. The hydrogen transfer occurs either from the amine
	radical cation coming from the reduction of iridium catalyst or directly by (i-Pr) 2 NEt. 6k This
	mechanism is supported by the fluorescence quenching experiments and the fact that in the
	absence of "H-donor", the thiocarbamate transfer is observed.
		1.68	1.73	1.67
	Substrate (Sub)	52	56	32
	E red (V) b) [Sub]/[Sub] .-	1.11	1.56	<2

a) For cyclic voltamograms, see supporting information.

b)

The redox potentials are given in Volt versus SCE.

Moreover, no reduction wave is observed for the S-thiocarbamate 32 up to 2 V. This is consistent with the observed radical thiocarbamate group transfer (Scheme 28 and 29) when the reaction is conducted without Hünig's base and confirms that Ir(ppy) 3 * is not able to reduces S-thiocarbamates. Scheme 30. A proposed mechanism for the photoreductive deoxygenation

Table 4 .

 4 Conditions screening for C-C bond formation

	Entry	Heterocycles	DIPEA	Yield a	Observations a
	1	Thiophene	0	S.M.
	2	Thiophene	2 equiv.	54% (31)
	3	Benzothiophene	0	50% (S.M.)	Traces of B (9%) and 32 (20%)
	4	Benzothiophene	2 equiv.	50% (31)
	5	1-Methylindole	0	50% (S.M.) Traces of 31 (> 5%) and 32 (20%)
	6	1-Methylindole	2 equiv.	57% (31)
	7	Pyrrole	2 equiv.	41% (31)
	8	Furan	0	40% (S.M.)	Traces of 31 (>3%)
	9	Furan (3 to 10 equiv.) 2 equiv.	30% (31)	Traces of 32
	10	Furan (50 equiv.)	0	15% (B)	S.M. (19%); 32 (23%). Traces of 31 (>7%)

a NMR yield.

Table 5 .

 5 Screening of conditions for reduction with organic photocatalysts

	Entry	Photocatalyst	mol%	DIPEA	Yields	LEDs
	1	Fluorescein	1	5 equiv.	S.M.	Blue
	2	Fluorescein	5	--	S.M.	Blue
	3	Fluorescein	5	5 equiv.	S.M.	Blue
	4	Fluorescein	5	5 equiv.	S.M.	Green
	5	10-phenylphenothiazine	1 to 10	5 equiv.

Table 6 .

 6 H-donor phosphate or solvent assistance effects on the deoxygenation reactionTo confirm this benefit with water as an additive, we submitted the O-thiocarbamates 47 and 56 to the new conditions of photoreduction and we were glad to obtain reduced products 82 and 89 in high yields (Scheme 35). With these examples, we can thus conclude that the presence of water in the middle has a significant effect on the reaction process, which needs to be studied more deeply.We report a novel photocatalyzed deoxygenation method based on the activation of Ir(ppy) 3 by visible-light under very mild reductive conditions. This transformation allowed us to convert primary, secondary and tertiary aliphatic and benzylic alcohols to the corresponding alkanes in moderate to good yields. We also managed to improve the yield of few examples by adding 5% of water. A large range of O-thiocarbamates, from primary and secondary alcohols, needs to be tested in order to generalize these new conditions. Interesting functional group tolerances (ester, benzoyl, acetate, sulfonyl…) were observed. A preliminary mechanistic study based on fluorescence and cyclic voltammetry suggested the role of the Othiocarbamate substrates as oxidative quenches of the [Ir(ppy) Unless special mention, all reactions were carried out in oven-dried glassware and in anhydrous solvents under argon atmosphere. Photoredox reactions were run in Schlenk flask and with magnetic stirring. Solvents and liquid reagents were distilled under an argon atmosphere prior to use, particularly: Acetone, CH 3 CN, CH 2 Cl 2 , DMF, DMSO, DMPU, NMP, toluene and iPr 2 NEt from calcium hydride. Thin Layer Chromatography (TLC) was performed on Merck 60 F254 silica gel and revealed with either a ultra-violet lamp ( = 254 nm) or a specific color reagent (p-anisaldehyde, potassium permanganate). A Davisil LC 60 A silica gel (40-63 μm) was used for flash column chromatography (FC) using Still's method.

	Entry	Additive	Equivalent	Ratio (Solvent/Add)	Yield
	1	(PhO) 2 PO 2 H	5 mol%	--	60%
	2	(PhO) 2 PO 2 H	1 equiv.	--	49%
	3	(PhO) 2 PO 2 H	2 equiv.	--	S.M.
	4	(PhO) 2 PO 2 H	5 equiv.	--	S.M.
	5	t BuOH	--	95/5	54%
	6	t BuOH	--	90/10	50%

Scheme 35. Photodeoxygenation in the presence of water These conditions allowed us to increase also the yield of the photoreduction of primary Othiocarbamate 44. Indeed product 44 was reduced in an encouraging 30% yield compare to 10% with the previous experimental conditions. Scheme 36. Photoreduction of primary thiocarbamate 44 in the presence of water II.B.6. Conclusion 3 ] excited state. The unsuccessful synthesis of O-thiocarbamates from tertiary alcohols still remains the main drawback of this photoredox reaction. However, the radical trapping experiments and the thiocarbamate transfer product created a new window of possibility to realize C-C or Cheteroatom bond formation reactions. Indeed, the thiocarbamate transfer reaction would open new perspectives to highly versatile transformations in the fields of organic synthesis and polymer sciences. 105

PE refers to petroleum ether and EtOAc to ethyl acetate. The melting points reported were measured with a Bibby Stuart melting point apparatus and were uncorrected. NMR 1 H,

13

C spectra were recorded at 400, 101 and 376 MHz, respectively, using a Bruker AVANCE 400 MHz spectrometer equipped with a BBFO probe. Some NMR 1 H,

13

C were recorded at 300 and 75 MHz respectively, using a Bruker AVANCE 300 MHz spectrometer. Chemical shifts (δ) are reported in ppm, using, for 1 H and

13

C, solvent residual peak as internal standard references (CDCl 3 : δ C = 77.16 ppm; Residual CHCl 3 in CDCl 3 : δ H = 7.26 ppm). Otherwise noted, NMR spectra were recorded in CDCl 3 at 300 K. The terms m, s, d, t, q and dd represent multiplet, singlet, doublet, triplet, quadruplet, quintuplet, and doublet of doublets respectively.

Coupling constants (J) are given in Hertz

(Hz)

.IR spectra were recorded on a Bruker Tensor 27 ATR diamond PIKE spectrophotometer. Wavenumbers (ν) are given in cm -1 . High resolution mass spectrometry (HRMS) analyses were performed at the IPCM on a Bruker micrOTOF mass spectrometer (electrospray source), using Agilent ESI-L Low Concentration Tuning Mix as reference.

105 W. C.

Still, M. Khan, A. Mitra, J. Org. Chem. 1978, 43, 2923-2925.

2,3:4,6-di-O-isopropylidene-α-L-sorbofuranose) 1H-imidazole-1-carbothioate (43)

	Following	GP1	with	2,3:4,6-di-O-isopropylidene-α-L-
	sorbofuranose (1 g, 3.8 mmol), 1-1' thiocarbonyldiimidazole (820
	mg, 4.6 mmol) and DMAP (94 mg, 0.77 mmol) in CH 2 Cl 2 (20
	mL), compound 43 was purified by FC (Pentane/EtOAc, 50/50)
	and isolated (1.3 g, 90 %) as a colorless syrup.
	1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 8.23 (s, 1H), 7.55 (s, 1H), 6.90 (s, 1H), 4.90-4.70 (m,
	2H), 4.40 (s, 1H), 4.26 (d, J = 2.4 Hz, 1H), 4.07-4.02 (m, 1H), 4.01-3.86 (m, 2H), 1.40 (s,
	3H), 1.31 (s, 3H), 1.27 (s, 3H), 1.23 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 183.3,

mmol), Pentafluorophenyl chlorothionoformate (914 mg, 3.5 mmol) and DMAP (500 mg, 4.1 mmol) in CH 2 Cl 2 (20 mL), compound 38 was O-(

110 1 H NMR (400 MHz,

  ) calcd for C 16 H 22 N 2 O 6 SNa ([M+Na] + ): 393.1091; found 393.1099.

	Following GP1 with 1,2:3,4-di-O-isopropylidene-α-D-
	galactopyranose	(1.0	g,	3.8	mmol),	1-1'
	thiocarbonyldiimidazole (820 mg, 4.6 mmol) and DMAP (94
	mg, 0.77 mmol) in CH 2 Cl 2 (20 mL), compound 44 was
	purified by FC (Pentane/EtOAc, 60/40) and isolated (1.3g, 88%) as a colorless syrup.
	CDCl 3 ) δ (ppm) δ 8.39-8.32 (m, 1H), 7.65-7.61 (m, 1H), 7.07-6.99 (m, 1H), 5.55 (d, J = 5.0
	Hz, 1H), 4.85 (dd, J = 11.5, 3.9 Hz, 1H), 4.77-4.63 (m, 2H), 4.36 (dd, J = 5.0, 2.5 Hz, 1H),
	4.33-4.22 (m, 2H), 1.51 (s, 3H), 1.48 (s, 3H), 1.35 (s, 3H), 1.34 (s, 3H). 13 C NMR (101 MHz,
	CDCl 3 ) δ (ppm) 184.

6-O-(1,2:3,4-di-O-isopropylidene-α-D-galactopyranose)-1H-imidazole-1-carbothioate (44)

Spectral data are in accordance with those reported in the literature.

1H-imidazole-1-carbothioate (49)

	Following	GP1	with	O-1,2-isopropylidene-5-benzoate--D-
	xylofuranose (1.57 g, 5.33 mmol), prepared from O-1,2-
	isopropylidene--D-xylofuranose according to the literature
	procedure reported by M. Gottschaldt et al., 115 1-1'
	thiocarbonyldiimidazole (1.43 g, 8.02 mmol) and DMAP (261 mg, 2.13 mmol) in CH 2 Cl 2 (20
	mL), compound 49 was purified by FC (Pentane/EtOAc, 60/40) and isolated (1.81 g, 84%) as
	a colorless syrup.

Spectral data are in accordance with those reported in the literature. 116 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 8.33

(s, 1H), 8.00-7.97 (m, 2H), 7.57 (d, J = 1.3 Hz, 1H), 7.57-7.53 (m, 1H), 7.43-7.39 (m, 2H)

, 7.04 (dd, J = 0.7, 1.6 Hz, 1H), 6.04 (d, J = 3.8 Hz, 1H), 6.00

(d, J = 3.8 Hz, 1H), 4.79-4.76 (m, 2H), 4.60-4.58 (m, 2H)

, 1.57 (s, 3H),

1.35 (s, 3H)

. CAS Number: 160999-15-5.

O-[Diphenylmethyl] 1H-imidazole-1-carbothioate (51)

	Following GP1 with the commercially available diphenylmethanol
	(1.66 g, 9.01 mmol), 1-1' thiocarbonyldiimidazole (2.50 g, 14.03
	mmol) and DMAP (400 mg, 3.27 mmol) in CH 2 Cl 2 (50 mL),
	compound 51 was purified by FC (Pentane/EtOAc, 80/20) and isolated
	(1.67 g, 63%) as a white solid.
	Mp = 51-53 °C. 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 8.18 (s, 1H), 7.45-7.42 (m, 5H), 7.38-
	7.34 (m, 4H), 7.32-7.28 (m, 2H), 7.08 (s, 1H), 6.14 (s, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ
	(ppm) 164.9, 139.2 (2C), 135.6, 131.1, 128.9 (4C), 128.4 (4C), 128.1 (2C), 116.0, 54.2. IR
	(neat):

NMR (300 MHz, CDCl 3

	Following GP1 with the commercially available trans-1,3-
	diphenyl-2-propyn-1-ol	(2.0	g,	9.5	mmol),	1-1'
	thiocarbonyldiimidazole (2.03 g, 11.4 mmol) and DMAP (116
	mg, 1 mmol) in CH 2 Cl 2 (100 mL), compound 52 was purified by
	FC (Pentane/Et 2 O, 30/70) and isolated (2.08 g, 68%) as a yellow oil.

. HRMS (ESI) calcd for C 17 H 14 N 2 OSNa ([M+Na] + ): 317.0719; found 317.0711. (E)-O-[1,3-Diphenylallyl] 1H-imidazole-1-carbothioate (52) 1 H ) δ (ppm). 8.49 (s, 1H), 7.79 (s, 1H), 7.51-7.27 (m, 10H), 7.12 (s, 1H), 6.72 (d, J = 15.8 Hz, 1H), 6.52 (dd, J = 15.7, 7.5 Hz, 1H), 5.97 (d, J = 7.5 Hz, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ (ppm) 195.

  . HRMS (ESI) calcd for C 17 H 20 N 2 O 5 SNa ([M+Na] + ): 387.0985; found 387.0989.

	6-(Benzyloxy)hexan-3-ol (58)
	To a solution of NaH (60 % dispersion in oil, 0.98 g, 24.4 mmol) in dry
	THF (110 mL) at 0 °C was added dropwise butane-1,4-diol (2 g, 22.2
	mmol). The solution was then stirred at room temperature for 15 min and afterwards cooled to
	0 °C. Benzylbromide (2.72 mL, 22.2 mmol) was added dropwise at 0 °C and the solution was

stirred at room temperature. After 17 h, the solution was heated to reflux for 1 h. After cooling down to room temperature, water (15 mL) was added and the mixture was extracted with ethyl acetate

(3 × 20 mL)

. The organic layers were combined, dried over MgSO4 and the solvents were evaporated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/ EtOAc 70/30) to give product (3.09 g, 77 %) as a colorless oil.

The spectral data are in agreement with the data reported in the literature. 118 1 H NMR (300 MHz, CDCl 3 ) δ (ppm) 7.

44-7.20 (m, 5H), 4.53 (s, 2H)

, 3.62 (t, J = 5.9 Hz, 2H), 3.52 (t, J = 5.9 Hz, 2H), 2.73 (s, 1H), 1.80-1.58

(m, 4H)

. 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 138.

1, 128.1 (2C), 127.4 (2C

NMR (101 MHz, CDCl 3

	H NMR (400 MHz, CDCl 3 ) δ (ppm) 8.11-8.05 (m, 1H), 7.41-7.34 (m, 1H), 7.06-7.01 (m,
	1H), 2.54 (d, J = 5.2 Hz, 1H), 2.21-2.10 (m, 2H), 1.96-1.81 (m, 2H), 1.80-1.67 (m, 5H), 1.65-
	1.36 (m, 4H), 1.36-1.22 (m, 2H), 1.14 (s, 3H), 1.01 (s, 3H), 0.86 (d, J = 7.2 Hz, 3H). 13 C

1,1′-Carbonyldiimidazole (875 mg, 5.4 mmol) and DMAP (275 mg, 2.3 mmol) in CH 2 Cl 2

(20 mL)

, compound 74 was purified by FC (Pentane/EtOAc, 50/50) and isolated (484 mg, 34%) as a white solid. ) δ (ppm) 146.

Table 1 .

 1 Comparison of intrinsic properties of nickel and palladium

	Nickel	Palladium
	-1 0 +1 +2 +3 +4	0 +1 +2 +3 +4
	Smaller atomic radius	Larger atomic radius
	Less electronegative	More electronegative
	Harder	Softer
	Facile oxidative addition	Facile reductive elimination
	Facile -migratory insertion	Facile -hydride elimination
	Radical pathways more
	accessible

17

S. Z. Tasker, E. A. Standley, T. F. Jamison, Nature 2014, 509, 299.

Scheme 11. Exemple of nickel catalyzed organometallic reaction steps Nickel was isolated and classified as a chemical element in 1751 by Axel Fredrik Cronstedt. The most common oxidation state of nickel is +2, but this transition metal has also a number of other oxidation states easily accessible from 1 to +4 (Table

e. Development of the photoredox/nickel dual catalysis  Carbon-carbon bond formation

  Scheme 15. Photoredox/nickel catalyzed cross-coupling of benzylic trifluoroborates and aryl bromides For this transformation, the authors proposed the generation of a Ni II species by oxidative addition of the aryl bromide to Ni 0 catalyst (Scheme 16). After visible-light irradiation, the excited Ir III complex (E 1/2 red [Ir III */Ir II ] = +1.21V vs. SCE in CH 3 CN) oxidizes the benzyltrifluoroborate salt by a single-electron transfer yielding the reduced Ir II and a carbon centered radical. Then the activated benzylic radical undergoes an addition to the Ni II species to afford the reactive Ni III intermediate. The cross-coupling product is obtained after a reductive elimination, leading to a Ni I complex, which is reduced, into Ni 0 by the Ir II complex and consequently regenerating the catalytic system. Proposed mechanism of photoredox/nickel cross-coupling amino acid undergoes a radical decarboxylation via a photooxidation of the in-situ formed cesium carboxylate intermediate by the excited Ir III complex (E 1/2 red [Ir III */Ir II ] = +1.21V vs. SCE in CH 3 CN), to liberate the α-amino radical species and the Ir II reductant complex. This radical reacts with the aryl-nickel(II) leading to a reactive Ni III species which undergoes readily a reductive elimination to generate the desired cross-coupled product and a Ni I catalyst. The Ni 0 is regenerated by single-electron transfer from Ir II which returns to the starting photocatalyst Ir III . Recently, our group developed a groundbreaking versatile precursor of unstabilized primary alkyl radicals and its participation in dual catalytic transformations. 22a Inspired by the work of Kumada and co-workers on oxidation of organopentafluorosilicates 23 , we then considered the more soluble pentavalent bis-catecholato silicon compounds easily obtained from the corresponding organosilane and first synthesized by Frye. 22b This kind of compound can be readily oxidized by [Ir(dF(CF 3 )ppy) 2 (bpy)]PF 6 complex (E red (Ir III */Ir II ) = +1.32V vs. SCE in CH 3 CN) under blue LED irradiation. Indeed, these bench stable silicates exhibit oxidation potentials between +0.34V and +0.89V vs. SCE in DMF and suggest that these ones can be engaged in photocatalytic transformations. As a comparison the oxidation potential of MacMillan's cesium amino carboxylates are around +0.95V vs. SCE in CH 3 CN and for Molander's primary alkyltrifluoroborate salts, close to +1.50V vs. SCE. 21 As shown in scheme 19, we firstly proved by TEMPO radical trapping that silicates can generate benzylic radical easily. We next extended the scope of the reaction to the allylation of various primary silicates and intermolecular additions on various radical acceptors in moderate to high yields. Photooxidation of bis-catecholato silicate salt compounds 26 . Whatever the electronic nature of the starting alkene, corresponding coupling products with silicates were isolated in moderate to good yields (Scheme 23).

	Scheme 16. Scheme 18. Dual photoredox/nickel catalysis proposed mechanism Molander, MacMillan and Doyle developed a very powerful process leading to a challenging cross-coupling reaction between aryl halides and photo-generated alkyl radical species. All of these reactions are realized under very mild conditions, with a very low loading of catalysts. This new dual catalysis opened up the field to new and valuable transformations. In another contribution, MacMillan reported an example of photoredox/nickel dual catalysis involving an elegant CO 2 extrusion-recombination sequence of intermediate mixed anhydrides formed in situ from carboxylic acid compounds and acyl chloride partners (Scheme 24). 27 . They proposed an oxidative addition of the Ni 0 to the C-O bond of the anhydride to afford the Ni II intermediate, and then either an outer sphere oxidative decarboxylation or an inner sphere decarboxylation leading to a reactive Ni III species. A reductive elimination gave the α-amino ketone and NiI which is reduced by a SET III.A.3.Scheme 19. Scheme 23. Scope of alkenyl halides and biscatecholato silicates in dual cross-coupling regenerating the iridium and nickel catalysts.

26 N. R. Patel, C. B. Kelly, M. Jouffroy, G. A.

Molander, Org. Lett. 2016, 18, 764. 27

C. "Chip" Le, D. W. C. MacMillan, J. Am.

Chem. Soc. 2015, 137, 11938.

  23) from the silicate 16 (88% vs. 58% yield). Comparison between silicate 4 and trifluoroborate 68 The proposed catalytic cycle is outlined in Scheme 38. It is well established that excitation of photoredox catalyst Ir[(dF(CF 3 )ppy) 2 (bpy)](PF 6 ) produces a long-lived photoexcited state *Ir[(dF(CF 3 )ppy) 2 (bpy)](PF 6 ).32 The latter acts as a strong oxidant (E [*Ir III /Ir II ] = +1.32 V vs. SCE in MeCN)[START_REF] Hanss | [END_REF] and undergoes a single electron transfer (SET) with bis-catecholato silicates 2-21 (E ox between +0.34 and +0.87 V vs. SCE in DMF) 42a generating a primary alkyl radical which interacts with a Ni species. However, the mechanism of this dual catalysis is still in debate.37,49 All proposals converge toward a Ni(III) intermediateScheme 38). Some of our results in Scheme 34 with the formation of 42 and 51 highlight the importance of the oxidative addition step but do not allow to conclude at this stage. Thus, this will necessitate more investigation to clarify these points. Proposed mechanism of the photoredox/nickel dual catalysis using silicates

	Scheme 37. which upon reductive elimination delivers the cross coupling product and a Ni(I) intermediate complex, the latter being further reduced (E [Ni I /Ni 0 ] = -1.2 V vs. SCE in DMF) 50 by SET from the iridium(II) (E [Ir III /Ir II ] = -1.37 V vs. SCE in MeCN) 46 to generate a Ni(0) complex. From this zero-valent nickel entity, two possibilities have been advanced. Initial oxidative addition of the bromoaryl gives a Ni(II) species that would trap the nucleophilic radical intermediate. Alternatively, an alkyl Ni(I) species would result from the trapping of the radical intermediate by Ni(0) followed by oxidative addition of the bromoaryl to the Ni(III) intermediate (Scheme 38.

  ). It was submitted in Et 2 O and DMF to one equivalent of tritylium and aminium salt. In both solvents, tritylium gave poor yields of 69 (< 20%). However, the use of the aminium salt was more rewarding (86% of 69 in DMF, 16% in Et 2 O). In comparison, oxidation with 1 equiv. of Cu(OAc) 2 gave 45% yield of 69 and with 1 Stoichiometric oxidation of biscatecholato silicates by organic reagents by far the best one (Scheme 46). Indeed, we obtained 92% of trapped adduct 69 using 10 mol% of catalyst. Similar behavior was observed for benzylsilicate 4 product yielding to 66% of 69 adduct. Therefore we kept this catalyst for further testing.

	equiv of DMP, 26% of 69.
	Scheme 43. Stoichiometric oxidation of biscatecholato silicates by organic reagents
	This oxidant proved to be competent in DMF for secondary and primary alkyl
	substrates giving, respectively, 44% of 78 and 61% of 70/71. Tritylium can also be used as a reliable alternative oxidant for the silicates. In fact, tritylium conditions gave also moderate yield of 53% for 78. Scheme 44. Scheme 46. Photocatalytic oxidation of borates and silicates by organic dyes

Table 2 .

 2 Structures of carbazolyl dicyanobenzene organic dyesAs it showed in table 2, this organic dye shows photo-physical properties comparable even superior to polypyridine-based transition metal complexes and other organic dyes. Potentials and lifetime of excited state comparison of organic dyes with Ir complex Photoredox/nickel catalysis with organic photoredox catalyst Since our previous work on oxidation of silicate species by organic reagents, our investigations with the Fukuzumi catalyst gave only moderate yields and we were limited only to the generation of stabilized radicals such as benzyl or allyl. We decided to test the photocatalytic activity of 4CzIPN on biscatecholato silicates. Gratifyingly, a very high yield of 92% of TEMPO adduct was obtained in spin trapping experiments (Table3, entry 2). The reaction was performed in a 0.1 M DMF solution under blue LEDS irradiation (477 nm) with

				Among them, 1,2,3,5-tetrakis-(carbazol-yl)-4,6-dicyanobenzene
	(4CzIPN) displayed promising features for photoredox catalysis: a high photoluminescence
	quantum yield (94.6%), a long life-time at the excited state (5.1 µs) and a strong green-
	emission (maximum at 507 nm). Recently, Zhang and coworkers reported the redox
	properties of this photosensitizer and the given value for the oxidative potential of the
	photoexcited 4CzIPN (E 1/2	* (4CzIPN/[4CzIPN] -)=+1.35 V vs SCE) augured well for a possible
	photooxidation of alkyl bis(catecholato)silicates (E 1/2 (Ox/red)=+0.3 to +0.9 V vs SCE). 64 We
	thus decided to assess this reactivity with a series of alkylsilicates and the cheapest
	photocatalyst	4CzIPN	($0.06/mmol	for	carbazole,	$2.2/mmol	for
	tetrafluoroisophthalonitrile) 65 in both radical synthesis and dual catalysis.

63

H. Uoyama, K. Goushi, K. Shizu, H. Nomura,; C. Adachi, Nature 2012, 492, 234.

64

J. Luo, J. Zhang, ACS Catal. 2016, 6, 873.

65

In comparison: $1.3k/mmol for [Ir(dF(CF 3 )ppy) 2 (bpy)](PF 6 ), $110/mmol for Ru(bpy) 3 (PF 6 ) 2 . Prices available at http://www.Sigmaaldrich.com. Scheme 49.

Table 3 .

 3 Spin-trapping with TEMPO with benzyl silicate phenone 22 with acetoxypropylsilicate 16 in the presence of 4CzIPN (1 mol%), NiCl 2 .dme (5 mol %) and 4,4'-di-tert-butyl-LED) for 24 hours at rt. Under these conditions, an excellent 81% yield of coupling product 31 was observed. This result was extended and exploited by Christophe Lévêque in the context of his PhD research.68

	Entry	Photocatalyst	X mol%	Yield
	1	Fukuzumi	10 mol%	66%
	2	4CzIPN	10 mol%	92%
	3	4CzIPN	1 mol%	94%

68 C. Lévêque, L. Chenneberg, V. Corcé, C. Ollivier, L. Fensterbank, Chem. Commun. 2016, DOI: 10.1039/C6CC04636C.

for photooxidation of bis(catecholato)silicate and addition on radical acceptors

  bis(catecholato) silicate(1 eq., 0.3 mmol), 4CzIPN (1 mol %, 3 μmol, 2.4 mg) and the desired acceptor (4 eq., 1.2 mmol) (liquid alkenes were added with the solvent). DMF was added (3 mL). The reaction mixture was degassed by argon bubbling for 20 minutes and irradiated with blue LED (477 nm) for 24 hours. The reaction mixture was diluted with diethyl ether (50 mL), washed with saturated aqueous NaHCO 3 (2 times), brine (2 times), dried over MgSO 4 and evaporated under reduced pressure. The crude product was purified by flash column chromatography.

	General procedure G To a schlenk flask was added aryl, heteroaryl halide or alkenyl halide (1 eq., 0.3
	mmol), appropriate silicate (1.5 eq., 0.45 mmol), 4CzIPN (1 mol%, 3 µmol), and 4,4'-di-tert-
	butyl-2,2'-bipyridine (2 mol %, 6 µmol). The schlenk flask was taken into a glovebox and
	NiCl 2 .dme (2 mol %, 6 µmol) was added. The schlenk flask was sealed with a rubber septum,
	removed from the glovebox, and evacuated/purged with vacuum/argon three times. Degassed
	DMF (3 mL) was introduced (followed by the aryl or heteroaryl halide if liquid) and the
	reaction mixture was irradiated with blue LEDs (470 nm) for 24 hours. The reaction mixture
	was diluted with diethyl ether (50 mL), washed with saturated NaHCO 3 (2 times), brine (2
	times), dried over MgSO 4 and evaporated under reduced pressure. The residue was purified
	by flash column chromatography on silica gel to afford the coupling adduct.

III.C.

4.c. Compound characterizations Potassium [18-Crown-6] bis(catecholato)-hexylsilicate (2)

	NMR (100 MHz, Methanol-d 4 ): δ 150.9 (4 C), 142.8, 129.8 (2 C), 128.2 (2 C), 123.9, 119.3 1 H NMR (400 MHz, Methanol-d 4 ): δ 6.78 -6.67 (m, 4H), 6.65 -6.45 (m, 4H), 3.56 (s, 24H), 2H). 13 C NMR (100 MHz, Methanol-d4): δ 150.6 (4 C), 123.4, 119.7 (4 C), 111.7 (4 C), 71.2
	(4 C), 111.5 (4 C), 71.3 (12 C), 27.9. 29 Si NMR (119 MHz, Methanol-d 4 ): δ -80.90. 2.80 (s, 2H). 13 C NMR (100 MHz, Methanol-d 4 ): δ 150.8 (4 C), 119.6 (4 C), 111.6 (4 C), 71.3 (12 C), 14.5, 13.0. 29 Si NMR (119 MHz, Methanol-d4): δ -80.17.
	(12 C), 31.3. 29 Si NMR (119 MHz, Methanol-d 4 ): δ -85.57.
	Silicate 2 was synthesized as described following the general
	procedure A, method A. The spectroscopic data are in Potassium [18-Crown-6] bis(catecholato)-isobutylsilicate (5) Potassium [18-Crown-6] bis(catecholato)-3-cyanopropylsilicate (13)
	agreement with those reported in the literature. 22 Silicate 5 was synthesized as described following the general Potassium [18-Crown-6] bis(catecholato)-anilinomethylsilicate (8) Following the general procedure A with 3-
	1 H NMR (400 MHz, Methanol-d 4 ): δ 8.29 -8.17 (m, 4H), procedure A, method A. The spectroscopic data are in agreement Silicate 8 was synthesized as described following the general cyanopropyltriethoxysilane (5 mmol, 1.16 mL), catechol (10
	8.15 -8.04 (m, 4H), 5.09 (s, 24H), 2.91 -2.82 (m, 2H), 2.79 with those reported in the literature. 22 procedure A, method A. The spectroscopic data are in mmol, 1.10 mg), 18-Crown-6 (5 mmol, 1.32 g) and potassium
	-2.66 (m, 6H), 2.36 (t, J = 6.9 Hz, 3H), 2.27 -2.16 (m, 2H). 13 C NMR (100 MHz, Methanol-d 4 ): δ 151.1 (4 C), 119.2 (4 C), 111.4 (4 C), 71.2 (12 C), 34.2, 32.9, 25.4, 23.6, 18.5, 14.5. 29 Si NMR (119 MHz, Methanol-d 4 ): δ -75.6. agreement with those reported in the literature. 22 methoxide (5 mmol, 1.4 mL of a 3.56 M solution in methanol) 1 H NMR (400 MHz, Methanol-d 4 ): δ 6.73 -6.65 (m, 4H), 6.60 -6.52 (m, 4H), 3.57 (s, 24H), 1.80 (dp, J = 13.2, 6.6 Hz, 1H), 0.82 (d, J = 6.6 Hz, 6H), 0.67 (d, J = 6.8 Hz, 2H). 13 C NMR (100 MHz, Methanol-d 4 ): δ 151.1 (4 in 20 mL of dry methanol. The crude product was purified 1 H NMR (400 MHz, Methanol-d 4 ): δ 7.27 -6.90 (m, 2H), 6.87 -6.71 (m, 4H), 6.70 -6.54 (m, 4H), 6.55 -6.39 (m, 3H), 3.56 according the general procedure to afford 13 (2.76 g, 90%) as a white solid.
	C), 119.2 (4 C), 111.5 (4 C), 71.3 (12 C), 29.4, 26.8 (2 C), 25.7. 29 Si NMR (119 MHz, (s, 24H), 2.52 (s, 2H), NH is missing. 13 C NMR (100 MHz, Methanol-d 4 ): δ 152.2, 150.8 (4 M.p. 167.6°C. 1 H NMR (600 MHz, Methanol-d 4 ): δ 6.69 (dd, J = 5.6, 3.5 Hz, 4H), 6.57 (dd,
	Methanol-d 4 ): δ -76.14. C), 129.8 (2 C), 119.7 (4 C), 117.0, 113.4 (2 C), 111.9 (4 C), 71.3 (12 C), 34.1. 29 Si NMR J = 5.7, 3.4 Hz, 4H), 3.54 (s, 24H), 2.29 (t, J = 7.2 Hz, 2H), 1.69 -1.60 (m, 2H), 0.82 -0.75
	(119 MHz, Methanol-d 4 ): δ -50.08 and -81.36. (m, 2H).
	Silicate 3 was synthesized as described following the
	general procedure A, method A. The spectroscopic data are
	in agreement with those reported in the literature. 22 Silicate 6 was synthesized as described following the general Potassium [18-Crown-6] bis(catecholato)-(3-glycidyloxypropyl)silicate (9)
	1 H NMR (400 MHz, Methanol-d 4 ): δ 6.71 -6.62 (m, 4H), procedure A, method A. The spectroscopic data are in Silicate 9 was synthesized as described following the
	6.58 -6.52 (m, 4H), 5.69 (ddt, J = 17.0, 10.2, 6.7 Hz, 1H), agreement with those reported in the literature. 22 general procedure A, method A. The spectroscopic data
	4.89 -4.82 (m, 1H), 4.80 -4.75 (m, 1H), 3.54 (s, 24H), 1.96 -1.85 (m, 2H), 1.39 -1.20 (m, are in agreement with those reported in the literature. 22 1 H NMR (400 MHz, Methanol-d 4 ): δ 6.75 -6.68 (m, 4H), 6.62 4H), 0.71 -0.62 (m, 2H). 13 C NMR (100 MHz, Methanol-d 4 ): δ 151.1 (4 C), 140.5, 119.2 (4 -6.56 (m, 4H), 3.56 (s, 24H), 2.26 -1.90 (m, 2H), 0.90 -0.73 1 H NMR (400 MHz, Methanol-d 4 ): δ 6.74 -6.61 (m, 4H), C), 114.1, 111.4 (4 C), 71.2 (12 C), 34.8, 33.9, 25.1, 18.3. 29 Si NMR (119 MHz, Methanol-(m, 2H). 13 C NMR (100 MHz, Methanol-d 4 ): δ 150.7 (4 C), 119.6 (4 C), 111.6 (4 C), 71.3 (12 6.61 -6.49 (m, 4H), 3.57 (s, 24H), 3.53 (dd, J = 11.6, 3.1
	d 4 ): δ -75.7. C), 27.7 (t), 7.0. 19 F NMR (376 MHz, Methanol-d 4 ): δ -82.43 (tt, J = 10.3, 2.7 Hz, 3F), -Hz, 1H), 3.40 -3.32 (m, 2H), 3.20 (dd, J = 11.6, 6.0 Hz, 1H), 3.03 -2.96 (m, 1H), 2.68 (dd, J
	117.03 --117.59 (m, 2F), -122.81 --123.09 (m, 2F), -123.67 --124.06 (m, 2F), -124.32 --= 5.1, 4.2 Hz, 1H), 2.49 (dd, J = 5.1, 2.7 Hz, 1H), 1.71 -1.53 (m, 2H), 0.71 -0.60 (m, 2H).
	124.87 (m, 2F), -126.78 --127.54 (m, 2F). 29 Si NMR (119 MHz, Methanol-d 4 ): δ -78.51. 13 C NMR (100 MHz, Methanol-d 4 ): δ 151.0 (4 C), 119.3 (4 C), 111.5 (4 C), 75.6, 72.4, 71.3
	Potassium [18-Crown-6] bis(catecholato)-benzylsilicate (4) (12 C), 51.8, 44.9, 25.6, 13.9. 29 Si NMR (119 MHz, Methanol-d 4 ): δ -76.13.
	Silicate 4 was synthesized as described following the general
	procedure A, method A. The spectroscopic data are in agreement Potassium [18-Crown-6] bis(catecholato)-chloromethylsilicate (7)
	with those reported in the literature. 22 Silicate 7 was synthesized as described following the general
	1 H NMR (400 MHz, Methanol-d 4 ): δ 7.09 -6.75 (m, 5H), 6.66 -procedure A, method A. The spectroscopic data are in agreement
	6.60 (m, 4H), 6.56 -6.49 (m, 4H), 3.55 (s, 24H), 2.14 (s, 2H). 13 C with those reported in the literature. 22

Potassium [18-Crown-6] bis(catecholato)-hexenylsilicate (3) Potassium [18-Crown-6] bis(catecholato)-1H, 1H, 2H, 2H-perfluorooctylsilicate (6) 13 C NMR (151 MHz, Methanol-d 4 ): δ 150.9 (4 C), 121.6, 119.5 (4 C), 111.6 (4 C), 71.2 (12 C),

22.5, 20.2, 17.6. 29

Si NMR (119 MHz, Methanol-d 4 ): δ -77.6. IR (neat): 3039,

  -) calc. for [C 16 H 14 NO 4 Si] -312.0698; found 312.0699.

	Potassium [18-Crown-6] bis(catecholato)-3,3,3-trifluoropropylsilicate (14)
	Following	the	general	procedure	A	with	3,3,3-
	trifluoropropyltrimethoxysilane (5 mmol, 956 µL), catechol (10
	mmol, 1.10 mg), 18-Crown-6 (5 mmol, 1.32 g) and potassium
	methoxide (5 mmol, 1.4 mL of a 3.56 M solution in methanol) in
	20 mL of dry methanol. The crude product was purified
	according the general procedure to afford 14 (2.56 g, 80%) as a white solid.
	M.p. 177.7°C. 1 H NMR (600 MHz, Methanol-d 4 ): δ 6.70 (dd, J = 5.6, 3.5 Hz, 4H), 6.59 (dd,
	J = 5.7, 3.4 Hz, 4H), 3.54 (s, 24H), 2.06 -1.95 (m, 2H), 0.83 -0.76 (m, 2H). 13 C NMR (151
	MHz, Methanol-d 4 ): δ 150.8 (4 C), 130.6 (q, J = 275.6 Hz), 119.6 (4 C), 111.6 (4 C), 71.2 (12

C), 30.5 (q, J = 28.6 Hz), 9.6. 19 F NMR (376 MHz, Methanol-d 4 ): δ -70.5 (t, J = 11.1 Hz).

29 Si NMR (119 MHz, Methanol-d 4 ): δ -78.6. IR (neat):

  cm -1 . HRMS (ESI-) calc. for [C 17 H 17 O 6 Si] -345.0800; found 345.0813. HRMS calc. for [C 17 H 17 O 6 Si] -345.0800; found 345.0813.

	Potassium bis(catecholato)-acetoxypropylsilicate (16') Following the general acetoxypropyltrimethoxysilane (5 mmol, 1.05 mL), catechol (10 procedure A with mmol, 1.10 g) and potassium methoxide (5 mmol, 1.4 mL of a 3.56 M solution in methanol) in 20 mL of dry methanol. The crude product was purified according the general procedure to afford 16' (1.55 g, 62%*) as a white solid. *Silicate without [18-Crown-6] crystallizes with a molecule of acetone. Potassium [18-Crown-6] bis(catecholato)-acetoxymethylsilicate (17) Following the general procedure A with acetoxymethyltriethoxysilane (5 mmol, 1.13 mL), catechol (10 mmol, 1.10 mg), 18-Crown-6 (5 mmol, 1.32 g) and potassium methoxide (5 mmol, 1.4 mL of a 3.56 M solution in methanol) in 20 mL of dry methanol. The crude product was purified according the general procedure to afford 17 (2.92 g, 94%) as a white solid. M.p. 110°C. 1 H NMR (600 MHz, Methanol-d 4 ): δ 6.68 (dd, J = 5.6, 3.4 Hz, 4H), 6.57 (dd, J = 5.8, 3.5 Hz, 4H), 3.82 (s, 2H), 3.53 (s, 24H), 1.83 (s, 3H). 13 C NMR (151 MHz, Methanol-Following general procedure B with allylsilicate 11 (0.45 mmol, 265 mg) and 4'-bromoacetophenone 22 (0.3 mmol, 60 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 98/2) to afford 24 as a colorless oil (41 mg, 86%). The spectroscopic data are in agreement with those reported in the literature. 10 1 H NMR (400 MHz, CDCl 3 ): δ 7.90 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 5.95 (ddt, J = 17.1 Hz, 10.5 Hz, 6.7 Hz, 1H), 5.13 -5.08 (m, 2H), 3.45 (d, J = 6.7 Hz, 2H), 2.59 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 197.8, 145.8, 136.3, 135.3, 128.8 (2 C), 128.6 (2 C), 116.7, 40.1, 26.6. IR (neat): 3050, 1680, 1604, 1356, 1266 cm -1 . 4'-(Anilinomethyl)acetophenone (25) Following general procedure B with anilinomethylsilicate 8 (0.45 mmol, 294 mg) and 4'-bromoacetophenone 22 (0.3 mmol, 60 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 80/20) to afford 25 as a colorless oil (62 mg, 91%). The spectroscopic data are in agreement with those reported in the literature. 11 1 H NMR (400 MHz, CDCl 3 ): δ 7.93 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.17 -7.15 (m, 2H), 6.75 -6.71 (m, 1H), 6.66 -6.60 (m, 2H), 4.42 (s, 2H), 4.16 (s, 1H), 2.59 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 197.7, 147.7, 145.2, 136.2, 129.3 (2 C), 128.7 (2 C), 127.3 (2 C), d 4 ): δ 174.1, 150.9 (4 C), 119.5 (4 C), 111.7 (4C), 71.2 (12 C), 58.1, 20.7. 4'-(Allyl)acetophenone (24) 117.9, 112.9 (2 C), 47.9, 26.6. IR (neat): 3321, 1669, 1597, 1510 cm -1 .

M.p. 160°C. 1 H NMR

(400 MHz, Methanol-d 4

): δ

6.68 (dd, J = 5.6, 3.5 Hz, 4H), 6.56 (dd, J = 5.6, 3.5 Hz, 4H)

, 3.88 (t, J = 7.0 Hz, 2H), 1.92 (s, 3H), 1.66 -1.56 (m, 2H), 0.7 -0.65 (m, 2H). 13 C NMR (101 MHz, Methanol-d4): δ 173.3, 150.8 (4 C), 119.4 (4 C), 111.5 (4 C), 68.6,

24.9, 20.8, 13.7. IR (neat): 3016, 295024.9, 20.8, 13.7. IR (neat): 3016, , 288224.9, 20.8, 13.7. IR (neat): 3016, , 173524.9, 20.8, 13.7. IR (neat): 3016, , 159724.9, 20.8, 13.7. IR (neat): 3016, , 148624.9, 20.8, 13.7. IR (neat): 3016, , 135124.9, 20.8, 13.7. IR (neat): 3016, , 124224.9, 20.8, 13.7. IR (neat): 3016, , 1105, 955, 819, 749, 725 cm -1 . 29 , 955, 819, 749, 725 cm -1 . 29

Si NMR (119 MHz, Methanol-d 4 ): δ -85.8 (t, J = 5.

7 Hz)

. IR

(neat): 3028, 2901, 2868, 1719, 1599, 1487, 1348, 1243, 1102, 963, 830, 737 cm -1

. HRMS (ESI-) calc. for [C 15 H 13

O 6

Si] -317.0487; found 317.0495.

4'-(3-Glycidyloxypropyl)acetophenone (34)

  H NMR (400 MHz, CDCl 3 ): δ 7.88(d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 3.73 (dd, J = 11.5 Hz, 2.9 Hz, 1H), 3.57 -3.42 (m, 2H), 3.36 (dd, J = 11.5 Hz, 5.9 Hz, 1H), 3.21 -3.07 (m, 1H), 2.85 -2.64 (m, 3H), 3.60 (dd, J = 5.0 Hz, 2.7 Hz, 1H), 2.58(s, 3H), 1.92 (ddt, J = 12.7 Hz, 7.6 Hz, 6.3 Hz, 2H).13 C NMR (100 MHz, CDCl 3 ): δ 197.8, 147.7, 135.1, 128.7 (2 C), 128.5 (2 C), 71.

	Following	general	procedure	B	with	3-
	glycidyloxypropylsilicate 9 (0.45 mmol, 239 mg) and 4'-
	bromoacetophenone 22 (0.3 mmol, 60 mg). The crude product
	was	purified	by	flash	column	chromatography
	(pentane/diethyl ether, 95/5) to afford 34 as a colorless oil (29 mg, 40%).

1

  . IR (neat): 2905, 1678, 1605, 1266, 1106 cm -1 . HRMS calc for [C 14 H 18 NaO 3 ] + 257.1148; found 257.1155.

  , 2.69 -2.66 (m, 4H), 2.60 (s, 6H), 2.25 -1.99 (m, 4H), 1.89 -1.51 (m, 10H), 1.44 -1.37 (m, 2H), 1.25 -0.95 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 197.

  . IR (neat): 2935, 1671, 1604, 1568, 1298 cm -1 . HRMS calc for [C 16 H 20 NaO 2 ] + 267.1365; found 267.1135. Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and 3'-bromoacetophenone(0.3 mmol, 35 l). The crude product was purified by flash column chromatography (pentane/diethyl ether, 90/10) to afford 37 as a colorless oil(53 mg, 80%). NMR (400 MHz, CDCl 3 ): δ 7.80 -7.71(m, 2H), 7.40 -7.34 (m, 2H), 4.08 (t, J = 6.5 Hz, 2H), 2.76 -2.72 (m, 2H), 2.59 (s, 3H), 2.04 (s, 3H), 2.01 -1.94 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 198.

	3-(3-Acetylphenyl)propyl acetate (37)

1 H

  . IR (neat): 2941, 1734, 1684, 1601, 1232, 839 cm -1 . HRMS calc. for [C 13 H 16 NaO 3 ] CDCl 3 ): δ 7.46 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 4.10 (t, J = 6.6 Hz, 2H), 2.71 -2.67(m, 2H), 2.06 (s, 3H), 1.99 -1.91 (m, 2H), 0.27 (s, 9H).

+ 243.0992; found 243.0992 3-(4-(Trimethylsilyl)phenyl)propyl acetate (38) Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and (4-bromophenyl)trimethylsilane (0.3 mmol, 59 l). The crude product was purified by flash column chromatography (pentane/diethyl ether, 90/10) to afford 38 as a colorless oil (54 mg, 72%).

1 H NMR (400 MHz, 13 C NMR (100 MHz, CDCl 3 ): δ 171.

  . IR (neat): 2936, 1739, 1601, 1233 cm -1 . HRMS calc. for [C 14 H 22 NaO 2 Si] + 273.1281; found 273.1277.

	3-(4-((Trimethylsilyl)ethynyl)phenyl)propyl acetate (39)
	Following general procedure B with acetoxypropylsilicate
	16	(0.45	mmol,	292	mg)	and	((4-

bromophenyl)ethynyl)trimethylsilane

(0.3 mmol, 76 mg)

.

4-Acetoxypropylphenylboronic pinacol ester (48)

  F NMR (376 MHz, CDCl 3 ): δ -62.4. IR (neat): 2922, 1737, 1584, 1232, 845 cm -1 . HRMS calc. for [C 12 H 13 F 3 NaO 2 ] + 269.0760; found 269.0752. Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and 2-bromobenzotrifluoride(0.3 mmol, 42 l). The crude product was purified by flash column chromatography (pentane/diethyl ether, 95/5) to afford 47 as a colorless oil(51 mg, 69%). NMR (400 MHz, Chloroform-d) δ 7.62 (dd, J = 7.9, 1.3 Hz, 1H), 7.47 (td, J = 7.6, 1.3 Hz, 1H), 7.36 -7.27 (m, 2H), 4.13 (t, J = 6.4 Hz, 2H), 2.86 (ddd, J = 9.7, 6.2, 1.3 Hz, 2H), 2.06 (s, 3H), 2.01 -1.91 (m, 2H). 13 C NMR (100 MHz, CDCl 3 J = 0.8 Hz), 131.0, 128.6 (q, J = 29.8 Hz), 126.2, 126.0 (q, J = 5.8 Hz), 124.6 (q, J = 5.8 Hz), 63.8, 30.4, 29.1 (d, J = 1.7 Hz), 20.9. 19 F NMR (376 MHz, CDCl 3 ): δ -59.7. IR (neat): 2940, 1737, 1608, 1311, 1111, 1030 cm -1 . HRMS calc. for [C 12 H 13 F 3 LiO 2 ] + 253.1022; found 253.1019 Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and 4-Bromophenylboronic acid pinacol ester (0.3 mmol, 85 mg. The crude product was purified by flash column chromatography (pentane/EtOAc, 90/10) to afford 48 as a brown oil (49 mg, NMR (400 MHz, CDCl 3 ): δ 7.74 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 4.08 (t, J = 6.6 Hz, 2H), 2.72 -2.68 (m, 2H), 2.05 (s, 3H), 1.97 -1.94 (m, 2H), 1.34 (s, 12H). 13 C NMR (100 MHz, CDCl 3 ): δ 171.1, 144.6, 135.0 (2 C), 127.8 (2 C), 83.7 (2 C), 63.8, 32.4, 30.1, 24.9 (4 C), 21.0. 11 B NMR (128 MHz, CDCl 3 ): δ 30.6. IR (neat): 2960, 1737, 1611, 1357, 1235, 657 cm -1 . HRMS calc. for [C 17 H 25 BNaO 4 ] + 327.1741; found 327.1754

	3-(2-(Trifluoromethyl)phenyl)propyl acetate (47)
	53%).

1 H

1 H

3-(3,5-Dimethoxyphenyl)propyl acetate (53)

  Following general procedure B with acetoxypropylsilicate 16(0.45 mmol, 292 mg) and 1-bromo-3,5-dimethoxybenzene (0.3 mmol, 65 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 90/10) to afford 53 as a colorless oil(46 mg, 65%). H NMR (400 MHz, CDCl 3 ):  6.37 -6.29 (m, 3H), 4.09 (t, J = 6.6 Hz, 2H), 3.78 (s, 6H), 2.65 -2.61 (m, 2H), 2.06 (s, 3H),1.98 -1.91 (m, 2H).13 C NMR (100 MHz, CDCl 3 ):  171.3, 161.0, 143.7, 106.6 (2 C), 98.1 (2 C), 63.9, 55.4 (2 C), 32.6, 30.1, 21.1. IR (neat): 17343, 161.0, 143.7, 106.6 (2 C), 98.1 (2 C), 63.9, 55.4 (2 C), 32.6, 30.1, 21.1. IR (neat): , 15943, 161.0, 143.7, 106.6 (2 C), 98.1 (2 C), 63.9, 55.4 (2 C), 32.6, 30.1, 21.1. IR (neat): , 12363, 161.0, 143.7, 106.6 (2 C), 98.1 (2 C), 63.9, 55.4 (2 C), 32.6, 30.1, 21.1. IR (neat): , 12043, 161.0, 143.7, 106.6 (2 C), 98.1 (2 C), 63.9, 55.4 (2 C), 32.6, 30.1, 21.1. IR (neat): , 11473, 161.0, 143.7, 106.6 (2 C), 98.1 (2 C), 63.9, 55.4 (2 C), 32.6, 30.1, 21.1. IR (neat): , 1036 cm -1 cm -1 . HRMS calc. for [C 13 H 18 NaO 4 ] + 261.1097; found 261.1087.

1

3-(2-Methylpyridin-3-yl)propyl acetate (60)

  , 46.8 (d, J = 3.2 Hz). 19 F NMR (376 MHz, CDCl 3 ): δ -68.12. IR (neat): 3345, 3060, 1602, 1264, 732 cm -1 . HRMS calc. for [C 12 H 12 FN 2 ] + 203.0979; found 203.0977. Following general procedure B with hexylsilicate 2 (0.45 mmol, 285 mg) and 4-bromo-2-fluoropyridine (0.3 mmol, 31 µL). The crude product was purified by flash column chromatography (pentane/diethyl ether, 99/1 then 95/5) to afford 56 as a colorless oil (47 mg, 87%). NMR (376 MHz, CDCl 3 ): δ -68.84. IR (neat): 2935, 1733, 1612, 1411, 1233 cm -1 . HRMS calc. for [C 10 H 12 FLiNO 2 ] + 204.1007; found 204.1015. Following general procedure B with 3-chloropropylsilicate 15 (0.45 mmol, 281 mg) and 4-bromo-2-fluoropyridine(0.3 mmol, 31 µL). The crude product was purified by flash column chromatography (pentane/diethyl ether, 99/1 then 95/5) to afford 59 as a colorless oil (42 mg, 81%). H NMR (400 MHz, CDCl 3 ): δ 8.12 (d, J = 5.1 Hz, 1H), 7.02 (dt, J = 5.0, 1.6 Hz, 1H),6.85 - 6.68 (m, 1H), 3.53 (t, J = 6.3 Hz, 2H), 2.83 (dd, J = 8.4, 6.8 Hz, 2H), 2.19 -2.02 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 164.1(d, J = 239.5 Hz), 155.7 (d, J = 7.7 Hz), 147.6, 121.7, 109.3 (d, J = 38.0 Hz), 43.6, 32.5, 31.9 (d, J = 2.8 Hz).19 F NMR (376 MHz, CDCl 3 ): δ -68.6.IR(neat): 2926, 1613, 1558, 1411, 1275, 1148, 908, 728 cm -1 . HRMS (ESI-) calc. for [C 8 H 9 ClFNNa] + 196.0300; found 196.0306.7 Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and 3-Bromo-2-methylpyridine (0.3 mmol, 35 l).

	4-(3-Chloropropyl)-2-fluoropyridine (59)
	2-Fluoro-4-hexylpyridine (56)

1

(Trifluoromethyl)pyridin-2-yl)propyl acetate (61)

  . IR (neat): 2942, 1736, 1574, 1441, 1232, 1035, 729 cm -1 . HRMS calc. for [C 11 H 15 NNaO 2 ] + 216.0995; found 216.1003. Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and 2-Bromo-5-(trifluoromethyl)pyridine(0.3 mmol, 67 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 80/20) to afford 61 as a colorless oil (30 mg, H NMR (400 MHz, CDCl 3 ): δ 8.80 (d, J = 0.8 Hz, 1H), 7.84 (dd, J = 8.1 Hz, J = 1.9 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 4.10 (t, J = 6.4 Hz, 2H), 2.97 -2.94 (m, 2H), 2.16 -2.09 (m, 2H), 2.04 (s, 3H). 13 C NMR (75 MHz, CDCl 3 ): δ 171.1, 165.0 (d, J = 1.3 Hz), 146.3 (q, J =4.1 Hz), 133.5(q, J = 3.5 Hz), 124.4 (q, J = 30 Hz), 123.7 (q, J = 270 Hz), 122.6, 63.6, 34.6, 28.2, 20.9. 19 F NMR (376 MHz, CDCl 3 ): δ -62.3. IR (neat): 2940, 1737, 1608, 1326, 1232, 1125, 732 cm -1 . HRMS calc. for [C 11 H 12 F 3 NNaO 2 ] + 270.0712; found 270.0707. CDCl 3 ): δ 9.05(d, J = 1.7 Hz, 1H), 8.61 (d, J = 1.9, 1H), 8.12 (dd, J = 1.9 Hz, J = 1.7 Hz, 1H), 4.09 (t, J = 6.4 Hz, 2H),3.94 (s, 3H), 2.78 -2.74 (m, 2H), 2.04 (s, 3H) 2.02 -1.95 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 171.

	3-(5-40%).
	Methyl 5-(3-acetoxypropyl)nicotinate (62)
	Following general procedure B with acetoxypropylsilicate 16
	(0.45 mmol, 292 mg) and Methyl 5-bromopyridine-3-
	carboxylate (0.3 mmol, 65 mg). The crude product was
	purified by flash column chromatography (pentane/ethyl
	acetate, 60/40) to afford 62 as a colorless oil (47mg, 75%).

1 1 H NMR (400 MHz,

  . IR (neat): 2942, 1722, 1426, 1231, 1027, 765 cm -1 . HRMS calc. for [C 12 H 15 NNaO 4 ] + 260.0893; found 260.0897.

D. H. R.Barton, S. W. McCombie, J. Chem. Soc., Perkin Trans. I 1975, 1574.

a) S. W.McCombie, in "Comprehensive Organic Synthesis", Eds. B. Trost, I. Fleming, Pergamon Press, New York, 1991, Vol. 8, p. 811; b) L. Chenneberg, J.-P. Goddard, L. Fensterbank, in "Comprehensive Organic Synthesis (2nd Edition)", Eds. G.Molander, P. Knochel, Elsevier, Oxford, 2014, Vol. 8, p. 1011.

L.Chenneberg, C. Ollivier, Chimia 2016, 70,

photocatalytique s'est révélé donc être très compétitif. Nous avons par conséquent développé une méthode qui constitue un outil fondamental pour la synthèse organique. Schéma 9. Comparaison des conditions photoredox avec la classique Barton-McCombie Pour illustrer l'intérêt et la compétitivité internationale que suscite la désoxygénation, un troisième groupe de recherche, le groupe de Reiser, a publié en même temps que nous une méthode de désoxygénation photocatalysée d'alcools secondaires activés (en position benzylique ou en α d'un carbonyle) (Schéma 10). 11 Cependant, cette méthode ne permet pas la photoréduction ni d'alcools secondaires non-activés, ni d'alcools primaires. De plus, le choix du bis-trifluorométhyle benzoate impose un léger chauffage du milieu réactionnel. Schéma 10. Désoxygénation photocatalysée d'alcool benzylique Par la suite, nous avons réalisé d'autres études, afin d'améliorer notre méthodologie.En effet, nous avons effectué des variations au niveau des groupements thiocarbamates dont la réactivité a pu être évaluée en conditions photocatalytiques. Les dérivés de type benzoyle, thionoformates n'ont conduit qu'à une faible conversion en produits de désoxygénation. En revanche, la dérivatisation d'alcools en groupements O-thiocarbamates portant des 11 D. Rackl, V. Kais, P. Kreitmeier,O. Reiser, Beilstein J. Org. Chem. 2014, 10, 2157.

L. Chenneberg, A. Baralle, M. Daniel, L. Fensterbank, J.-P. Goddard, C.Ollivier, Adv. Synth. Catal. 2014, 356, 2756.

a) M. Fagnoni, D. Dondi, D. Ravello, A. Albini, Chem. Rev. 2007, 107, 2725. b) T. P. Yoon, M. A. Ischay, J. Du, Nature Chem. 2010, 2, 527. c) J. M. R. Narayanaman, C. R. J. Stephenson, Chem. Soc. Rev. 2011, 40, 102. d) J. W. Tucker, C.R. J. Stephenson, J. Org. Chem. 2012, 77, 1617. e) C. K. Prier, D. A. Rankic, D. W. C.MacMillan, Chem. Rev. 2013, 113, 5322.

C. Carzola, E. Metay, B. Andrioletti, M. Lemaire, Tetrahedron Lett. 2009, 50, 6855.

G. Sorin, R. M. Mallorquin, Y. Contie, A. Baralle, M. Malacria, J-P. Goddard, L. Fensterbank, Angew.Chem. Int. Ed. 2010, 49, 8721.

Y. Yasu, T.Koike, M. Akita, Adv. Synth. Catal. 2012, 354, 3414.

V. Corcé, L.-M. Chamoreau, E. Derat, J.-P. Goddard, C.Ollivier, L. Fensterbank, Angew. Chem. Int. Ed. 2015, 54, 11414.

J. C.Tellis, D. N. Primer, G. A. Molander, Science 2014, 345, 433.

Z. Zuo, D. T. Ahneman, L. Chu, J. A. Terrett, A. G. Doyle, D. W. C. MacMillan, Science

2014, 345, 437.

Les résultatsde Zhang, obtenus en catalyse duale photoredox/nickel avec des acides aminés ou des trifluoroborates et en présence du catalyseur 4CzIPN, combinés à nos résultats sur la photooxydation des silicates, devraient nous permettre de réaliser des réactions de couplages croisés avec les silicates. En effet, une grande variété d'alkyles biscatécholatosilicates peut être photooxydée par le 4CzIPN. D'autre part, les radicaux alkyles ainsi générés réagissent efficacement dans une catalyse au nickel avec des halogénures d'(hétéro)aryles et des halogénures d'alcènes. Ces derniers travaux, réalisés par Christophe Lévêque (en deuxième année de doctorat), montrent que la catalyse au nickel peut être combinée avec un organo photocatalyseur, utilisé avec une faible charge catalytique (de l'ordre de 1 mol%) ouvrant ainsi des perspectives très intéressantes sur le développement d'une catalyse photoredox plus verte. Schéma 24. Réaction catalyse duale avec l'organo-photocatalyseur 4CzIPN En conclusion, les projets étudiés au cours de cette thèse s'appuient sur l'utilisation et la valorisation énergétique de la lumière visible, pour réaliser des transformations chimiques originales, sélectives et efficaces faisant intervenir principalement des processus d'oxydoréduction (redox) pour la génération d'espèces radicalaires. Nous souhaitions développer une chimie radicalaire faisant intervenir des processus de transfert

For a comprehensive account on all aspects of radical chemistry in synthesis, see: a) Encyclopedia of Radicals in Chemistry,Biology and Materials, C. Chatgilialoglu, A. Studer, Eds. John Wiley & Sons Ldt, Chichester,

b) P. Renaud, M. P. Sibi in Radicals in Organic Synthesis, Vol. 1& 2, Wiley-VCH, Weinheim, 2001. c) D. P. Curran, N. A. Porter, B. Giese in Stereochemistry of Radical Reactions, VCH, Weinheim, 1996. d) C. R. J. Stephenson, A. Studer, D. P. Curran, Beilstein J. Org. Chem. 2013, 9, 2778 and references included. 2 For reviews: a) M. Albert, L. Fensterbank, E. Lacôte, M. Malacria, Top. Curr. Chem. 2006, 264, 1. b) K. C. Nicolaou, D. J. Edmonds, P. G. Bulger, Angew. Chem., Int. Ed. 2006, 118, 7134. For a book chapter, see: Radical Cascade Reactions. A. Baralle, A. Baroudi, M. Daniel, L. Fensterbank, J.-P. Goddard, E. Lacôte, M.-H. Larraufie, G. Maestri, M. Malacria, C. Ollivier, Encyclopedia of Radicals in Chemistry, Biology and Materials, C. Chatgilialoglu, A. Studer, Eds. John Wiley & Sons Ldt, Chichester, 2012, Chap 27, Vol 2, 729.

P.T. Anastas, J.C. Warner, Green chemistry: theory and practice, 1998, Oxford University Press Inc., New York.

For reviews on tin-free radical processes that respect the principles of safe, sustainable synthesis, see: a) P. A.Baguley, J. C. Walton, Angew. Chem. Int. Ed. 1998, 37, 3072. b) A. Studer, S. Amrein, Synthesis 2002, 835. c) B. C.Gilbert, A. F. Parsons, J. Chem. Soc., Perkin Trans 2 2002, 367.

A. Studer, S. Amrein, Synthesis 2002, 835.

C.Ollivier, P. Renaud, Chem. Rev. 2001, 101, 3415.

M. Montalti, A. Cedi, L. Prodi, M. T. Gandolfi, Handbook of Photochemistry 3rd edition CRC press Taylor & francis Group,

2006, 379.

Scheme 3. Examples of photocatalysts

H. Cano-Yelo, A. Deronzier, J. Chem. Soc., Perkin Trans. 2, 1984[START_REF] Palmer | -3-((1H-imidazole-1-carbonothioyl)oxy)-10,13dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate (47) Following GP1 with methyl lithocholate (2.00 g, 5.12 mmol)[END_REF]-1098.

H. Cano-Yelo, A. Deronzier, J. Photochem., 1987, 37, 315-321.

P. Schroll, D.P.Hari, B. König, ChemistryOpen, 2012, 1, 130-133.

D.P.Hari, P. Schroll, B. König, J. Am. Chem. Soc., 2012, 134, 2958-2961.

J. Du, T. P. Yoon, J. Am.Chem. Soc. 2009, 131, 14604.

P. Cremaschi, G. Morosi, M. Simonetta, Angew. Chem. Int. Ed. Engl. 1981, 20, 673

A. G. M. Barrett, P. A. Prokopiou, D. H. R.Barton, J. Chem. Soc., Chem. Commun. 1979, 1175.

L. Chenneberg, A. Baralle, M. Daniel, L. Fensterbank, J.-P. Goddard, C.Ollivier, Adv. Synth. Catal. 2014, 356, 2756.

J. W. Verhoeven, Pure Appl.Chem. 1996Chem. , 68, 2223

C. Larsen, K. Steliou, D.N. Harpp J.Org. Chem., 1978, 43, 337-339

P. Prabhakar, S. Rajaram, D.K. Reddy, V. Shekar; Y. Venkateswarlu Tetrahedron: Asymmetry, 2010,21, 216-221.

S. Vanlaer, W.M. De Borggraeve, A. Voet, C. Gielens, M. De Maeyer, F. Compernolle Eur. J. Org. Chem., 2008, 2571-2581.

D. R. Prudhomme, Z. Wang, C. J. Rizzo, J.Org. Chem. 1997, 62, 8257-8260.

D. Li, J. Ren, J.Li, Z. Wang, G. Bo, Dyes and pigments 2001, 49, 181-186

Y. Ye, M. S. Sanford, J. Am.Chem. Soc. 2012, 134, 9034.

V. V. Grushin, W. J. Marshall, J. Am.Chem. Soc. 2006, 128, 12644.

A. Zanardi, M. A. Novikov, E. Martin, J. Benet-Buchholz, V. V. Grushin, J. Am.Chem. Soc. 2011, 133, 20901.

J. C. Tellis, D. N. Primer, G. A. Molander, Science

2014, 345, 433. 20 Z. Zuo, D. T. Ahneman, L. Chu, J. A. Terrett, A. G. Doyle, D. W. C. MacMillan, Science 2014, 345, 437. 21 Y. Yasu, T. Koike,; M.Akita, Adv. Synth. Catal. 2012, 354, 3414.

J. F. Hartwig, Organotransition Metal Chemistry: From Bonding to Catalysis, University Science Books, Sausalito, 2009.

A. M. Echavarren, J. K. Stille, J. Am.Chem. Soc. 1987, 109, 5478.

G.-N. Wang, T.-H. Zhu, S.-Y. Wang, T.-Q. Wei, S.-J. Ji, Tetrahedron 2014, 70, 8079.

Remerciements

diisopropylethylamine, Hünig's base DMAP: 4-dimethylaminopyridine

Abbreviations

Chapter I

Green Radical Chemistry and Photoredox Catalysis

Scheme 15. Applications of the Saito's process to various radical synthetic transformations Inspired by the electrochemical studies of Ambrose et al. on 3-and 6-substituted 9alkylcarbazoles, 72 a catalytic version was developed by Rizzo et al., using 10-20 mol% of 3,6dimethyl-9-ethylcarbazole (DMECZ) under the same conditions. These variations significantly improved the turnover and the reactivity of the photosensitizer. In contrast to 72 a) J. F. Ambrose, R. F. Nelson, J. Electrochem. Soc. 1968, 115, 1159; b) J. F. Ambrose, L. L. Carpenter, R. F. Nelson, J. Electrochem. Soc. 1975, 122, 876. MCZ, DMECZ is reversibly oxidized during the process which ensures the regeneration of the photocatalyst. This modified protocol was tested to a series of substrates and proved to be compatible with alkene, ether, acetal, ester and lactone functions (Scheme 16, eq. 1). 73 Recently, the electron-rich 3,6-dimethoxy-9-ethylcarbazole (CAR) has emerged as a more efficient photocatalyst increasing significantly the reaction rate. 74 In addition, another study from Matsubara et al. showed that working at higher concentration (up to 0.5 M) avoids the formation of alkenes as side products. Finally, the best set of conditions relies on the use of 0.2 equiv. of CAR and 10 equiv. of 1,4-cyclohexadiene in heptane under LED (365 nm) irradiation (Scheme 16, eq. 2). 75 Scheme 16. The Saito photoreductive deoxygenation of benzoate esters under modified conditions with 3,6-disubstituted-9-ethylcarbazole as a new catalytic photosensitizer 73 D. R. Prudhomme, Z. Wang, C. J. Rizzo, J. Org. Chem. 1997, 62, 8257. 74 B. Shen, M. W. Bedore, A. Jamison, Chem. Commun. 2012, 48, 7444. 75 R. Matsubara, Y.-S. Shin, T. Shimada, M. Hayashi, Asian J. Org. Chem. 2014, 3, 1054.

Scheme 9. Synthesis of other O-functional groups

Under the optimized photoreductive conditions, 36 and 34 did not afford the reduced product 31 and only the starting material was recovered. In the same conditions, 38 yielded less than 20% of reduced product 31 (Table 2). Based on this set of substrates, we are able to highlight the influence of the sulfur atom. Indeed, 30 was smoothly reduced while 36 was inert. Concerning the aromatic moiety, it is clear that it strongly influences the reductive ability of the substrate but we do not have enough examples to rationalize this effect. Scheme 14. Synthesis of a set of O-thiocarbamates from secondary alcohols

 Synthesis of O-thiocarbamates from tertiary alcohols

The synthesis of tertiary O-thiocarbamate 56 was envisioned as followed. The protection of the D-(-)-quinic acid 53 by the cyclohexanone 54 in presence of catalytic amount of sulfuric acid allowed to isolate 55 in 30% yield. Then, 55 reacted with the 1,1'thiocarbonyldiimidazole 29 gives the desired thiocarbamate 56 in 70% yield.

Scheme 26. Benzylic radical generation and dimerization

 Photoreductive deoxygenation of tertiary alcohols

The reduction of the tertiary O-thiocarbamate 56 coming from the quinic acid allowed to isolate the corresponding product 89 in 60% yield as a single diasteroisomer. This reaction clearly showed the potentiality of the method to deoxygenate functionalized tertiary substrates in good yield.

General procedures

General Procedure 1 (GP1). O-Thiocarbamate synthesis. 106 To a solution of alcohol (10 mmol) in CH 2 Cl 2 (50 mL) was introduced 1-1' thiocarbonyldiimidazole (2.14 g, 12 mmol) and DMAP (244 mg, 2 mmol). The mixture was stirred at room temperature under argon in the dark until completion of the reaction (monitored by TLC). The mixture was concentrated under reduced pressure to give the crude thiocarbamate. The residue was purified by flash column chromatography on silica gel (Pentane/EtOAc or Et 2 O) to afford the corresponding product.

General Procedure 2, Conditions A. (GP2.A). Photoreduction of thiocarbamates. In a Schlenk tube was introduced the O-thiocarbamate (0.5 mmol), Ir(ppy) 3 (3.3 mg, 0.005 mmol), then CH 3 CN (7.5 mL) and DIPEA (435 µL, 2. 5 mmol). The mixture was degassed using the freeze-pump-thaw method (3 cycles) and irradiated by blue LEDs (470 nm) (∼ 0.5 cm away from the glassware) until completion of the reaction (monitored by TLC). The mixture was concentrated under reduced pressure and the crude was purified by flash column chromatography on silica gel (Pentane/EtOAc or Et 2 O).

General Procedure 2, Conditions B. (GP2.B). Photoreduction of thiocarbamates. In a Schlenk tube was introduced the O-thiocarbamate (0.5 mmol), Ir(ppy) 3 (16.4 mg, 0.025 mmol) then DMPU (5 mL) and DIPEA (435 µL, 2. 5 mmol). The mixture was degassed using the freeze-pump-thaw method (3 cycles) and irradiated by blue LEDs (470 nm) (∼ 0.5 cm away from the glassware) until completion of the reaction (monitored by TLC). Water was added and the mixture was extracted with Et 2 O (3 × 25 mL). The organic phases were gathered, dried over MgSO 4 , filtered and concentrated under reduced pressure. The crude was purified by flash column chromatography on silica gel (Pentane/EtOAc or Et 2 O).

General Procedure 3 (GP3). Reduction of thiocarbamates under Bu 3 SnH/AIBN conditions.

A degassed solution of Bu 3 SnH (269 µL, 1 mmol) and AIBN (8.2 mg, 0.05 mmol) in toluene (10 mL) was added over 4 h (0.25 mmol.h -1 relative to Bu 3 SnH) to a degassed solution of Othiocarbamate (0.5 mmol) in toluene (13 mL) at reflux. The resulting solution was heated at reflux for an additional hour, cooled to RT and concentrated in vacuo. The crude was purified by was purified by flash column chromatography on silica gel (Pentane/EtOAc).

106 M. Ruthkovsky, F. N. Castellano, G. J. Meyer, Inorg. Chem. 1996, 35, 6406-6412. purified by FC (Pentane/EtOAc, 60/40) and isolated (300 mg, 22%) as a white solid.

1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.83-7.72 (m, 2H), 7.68-7.48 (m, 3H), 5.33-5.19 (m, 1H), 3.31-3.07 (m, 4H), 2.22-1.98 (m, 4H). (m, 1H), 7.58-7.52 (m, 2H), 5.59-5.53 (m, 1H), 3.39-3.33 (m, 2H), 3.13-3.07 (m, 2H), 2.24-2.16 (m, 2H), 2.14-2.06 (m, 2H).

The spectral data are in agreement with the data reported in the literature. 3, 128.4, 127.7 (2C), 127.4 (2C), 73.0, 72.9, 70.6, 34.0, 30.2, 26.1, 10.0.

6-Benzyloxy-3-ethylhexan-3-ol (59)

Prepared under Swern oxidation conditions with the 6-(benzyloxy)hexan-3-ol (1.02 g, 4.9 mmol), oxalyl chloride (745.9 mg, 5.9 mmol), DMSO (1.4 g, 17.6 mmol) and triethylamine (2.6 g, 25.5 mmol) in CH 2 Cl 2 (50 ml). After completion of the reaction, the 6-benzyloxy-3-hexanone was obtained in quantitative yield as a colorless oil and was engaged in the next step without further purification. (m, 2H), 7.58-7.52 (m, 1H), 7.45-7.40 (m, 2H), 5.86 (d, J = 3.7 Hz, 1H), 4.77 (dd, J = 4.5, 4.0 Hz, 1H), 4.58 -4.50 (2H, m), 4.35 (dd, J = 11.9, 5.7 Hz, 1H), 2.17 (dd, J = 13.2, 4.3 Hz, 1H), 1.75 (ddd, J = 13.4, 10.8, 4.8 Hz, 1H),1.53 (s, 3H), 1.32 (s, 3H). 9, 141.2, 131.0, 130.7, 128.5, 127.0, 126.8, 122.6, 120.4, 116.1.

CAS

Cyclic Voltammograms

The redox potentials of O-thiocarbamates and the

III.A.2. Merging of Visible-light

Photoredox/Transition-Metal Catalysis

The recent development of this field starts with studies of Sanford and co-workers on room temperature C-H arylation of aromatics combining palladium catalyzed C-H activation and visible-light photoredox catalysis. 1 Most of C-H arylation methods require elevated temperatures. Typically, the palladium-catalyzed C-H arylation of arylpyridines with diaryliodonium salts was performed at 100 °C (Scheme 1) and the yield dropped dramatically when the reaction was done at room temperature (25 °C). 2,3 This low reactivity is attributed to the difficulty of the arylating reagent to oxidize the dimeric Pd catalyst intermediate. and the iridium photocatalyst, the reaction worked perfectly with stabilized radicals such as allyl, benzyl, -amino primary radicals as well as less stabilized radicals such as secondary and especially primary radicals which gave high yields in coupling products.

Scheme 20. Dual photoredox/nickel catalysis with bromobenzonitrile and silicate salts

Six months later, Molander published very similar results 24 showing that ammonium silicates can be readily oxidized under visible-light irradiation with a ruthenium(II) complex.

The radical was then engaged in a nickel catalysis starting a nickel(II) source allowing coupling reactions with 4-bromoanisole. Notably, unprotected amines can participate in this transformation. 24

 Carbon-heteroatom bond formation

The photoredox/nickel catalysis revealed a powerful tool to generate carbon-carbon bond formation under mild conditions. Moreover, various groups have also devoted their studies to the formation of carbon-heteroatom bonds. The group of Xiao and Lu reported the first example of carbon-heteroatom formation merging photoredox and nickel catalysis. They developed a cross-coupling method between aryl iodides and diarylphosphine oxide using a ruthenium(II) photocatalyst and a nickel(0) complex. 28 The authors suggested the generation of a P-centered radical by single-electron transfer oxidation by the exited Ru II photocatalyst.

The radical is then intercepted by the arylnickel(II) iodide. A reductive elimination provides the cross-coupled product. Either electron-donating or electron-withdrawing group on the aryl iodide are well tolerated as well as phenol, amide, amine and ether. In 2015, MacMillan and co-workers investigated the formation of carbon-oxygen bond via a dual catalysis process. [START_REF]Si NMR spectra were recorded at 119 MHz on a Bruker AVANCE III 600 spectrometer. Chemical shifts (δ) are reported in ppm and coupling constants (J) are given in Hertz (Hz). Abbreviations used for peak multiplicity are: s (singlet); bs (broad singlet); d (doublet); t (triplet); q (quartet); quint (quintet); sept (septet); m (multiplet). Thin layer chromatographies (TLC) were performed on Merck silica gel 60 F 254 and revealed with a UV lamp (λ = 254 nm) and KMnO 4 staining. Flash Column Chromatographies were conducted on silica Geduran ® Si 60 Å (40 -63 µm)[END_REF] They developed an elegant process using the photoredox catalytic cycle to modulate the oxidation states of the nickel catalyst. After an oxidative addition of the aryl bromide to Ni 0 , the substitution of bromide on the organometallic arylnickel(II) by the alcohol provides an aryl-Ni II -OR species which undergoes easily a SET by photooxidation with the ruthenium complex and then a reductive elimination to obtain the C(sp 2 )-O product. Because of the relatively inert character of Ni II to reductive elimination, the photoredox catalysis plays a significant role in the nickel catalysis.

Scheme 26. C-O Bond formation

Taking advantage of the interesting properties of nickel and the dual catalysis process, the group of Jamison simultaneously developed a synthesis of indolines from iodoacetanilides and alkenes with a challenging carbon (sp 3 )-nitrogen bond formation. 30 In nickel catalysis, βmigratory insertion is easier than β-hydride elimination. This advantageous property allowed the authors to access an organometallic nickel(II) complex which undergoes a SET event leading to the reactive Ni(III) intermediate. After the reductive elimination step, indolines were obtained in good yields with a good tolerance to a variety of functional groups on both partners.

Scheme 27. C-N bond formation

More recently, Johannes and co-workers developed a dual photoredox/nickel catalyzed cross-coupling reaction of thiols with aryl halides. [START_REF] Dagousset | [END_REF] They showed with 4-methoxy-αtoluenethiol, it is possible to generate the thiyl radical and to trap it with an olefin under visible-light photoredox conditions in good yield. Starting with this result, the authors studied the scope of this dual catalysis process and showed that alkyl thiols are as effective as thiophenol compounds.

Scheme 28. C-S bond formation

Johannes and co-workers investigated deeply the mechanism of this transformation. Following these preliminary reports, we wanted to investigate the use of nonmetallic oxidants. We initially showed that the Dess-Martin periodinane (DMP) could be efficiently used for the oxidation of trifluoroborates. 55 54.6, 54.1, 53.6, 53.4, 36.2, 33.5, 32.5, 32.5, 31.7, 31.7, 27.5, 26.4, 25.3, 24.4, 15.4, 15.1. 29 Si NMR (119 MHz, Methanol-d 4 ): δ -75.75.

Potassium [18-Crown-6] bis(catecholato)-allylsilicate (11)

Silicate 11 was synthesized as described following the general procedure A, method A. The spectroscopic data are in agreement with those reported in the literature.

Tetraethylammonium bis(catecholato)-tertbutylsilicate (20)

Silicate 20 was synthesized as described following the general procedure A, method B. The spectroscopic data are in agreement with those reported in the literature. 7, 171.0, 147.0, 135.3, 128.6 (2 C), 128.6 (2 C), 63.5, 32.2, 29.8, 26.5, 20.9 8, 146.5, 135.5, 128.8 (2 C), 128.7 (2 C), 44.1, 33.6, 32.8, 26.6. IR (neat):

2935, 1678, 1605, 1358, 1265 cm -1 .

4'-(Acetoxymethyl)acetophenone (33)

Following general procedure B with acetoxymethylsilicate 17 (0.45 mmol, 279 mg) and 4'-bromoacetophenone 22 (0.3 mmol, 60 mg).

The crude product was purified by flash column chromatography (pentane/diethyl ether, 99/1 then 95/5) to afford 33 as a colorless oil (38 mg, 66%). 141.8, 132.0 (2 C), 128.3 (2 C), 120.8, 105.1, 93.6, 63.6, 32.21, 29.9, 20.9, 0.0 (3 C) 139.4, 135.8, 130.2, 128.7, 126.1, 126.0, 64.0, 29.5, 29.0, 20.9, 19.2 The spectroscopic data are in agreement with those reported in the literature. 18 1 H NMR (400 MHz, CDCl 3 ): δ 7.12 -7.06 (m, 2H), 6.88 -6.84 (m, 1H), 6.77 -6.75 (m, 1H) 5.43 (s, 1H) 4.12 (t, J = 6.5 Hz, 2H), 2.72 -2.68 (m, 2H), 2.07 (s, 3H), 1.99 -1.94 (m, 2H), 13 C NMR (100 MHz, CDCl 3 ): δ 171. 6, 153.7, 130.3, 127.4, 127.3, 120.7, 115.4, 64.2, 28.6, 26.3, 21.0. IR (neat): 3355, 2999, 1707, 1491, 1236, 1032 cm -1 .

3-(4-Methoxyphenyl)propyl acetate (51)

Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and 4-iodoanisole (0.3 mmol, 70 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 90/10) to afford 51 as a colorless oil (29 mg, 46%).

3-(3-Methoxyphenyl)propyl acetate (52)

Following general procedure B with acetoxypropylsilicate 16 (0.45 mmol, 292 mg) and 3-bromoanisole (0.3 mmol, 38 l).

The crude product was purified by flash column chromatography (pentane/diethyl ether, 90/10) to afford 52 as a colorless oil (34mg, 54%). 1, 159.7, 142.8, 129.4, 120.8, 114.2, 111.2, 63.8, 55.1, 32.2, 30.1, 21.0. (pentane/ethyl acetate, 50/50) to afford 63 as a colorless oil (18 mg, 33%). CDCl 3 ): δ 171. 0, 151.9, 146.9, 134.2, 133.8, 129.2, 128.8, 128.0, 127.3, 126.7, 63.5, 29.8, 29.6, 20.9 2, 135.5, 132.0, 129.0, 128.7, 122.4, 120.1, 109.1, 100.5, 64.0, 32.8, 32.2, 31.0, 21.0 1, 153.6, 145.2, 135.6, 127.6, 124.8, 120.5, 111.1, 106.3, 63.8, 32.0, 30.8, 21.0 1, 143.9, 126.8, 124.5, 123.2, 63.5, 30.5, 26.3, 20.9 9, 42.1, 38.9, 38.5, 33.0, 29.9, 28.9, 24.4, 23.2, 1.6. 11

Potassium tert-butyltrifluoroborate

Following the reported procedure, the trifluoroborate salt was obtained as a white crystalline solid (2.15 g, 43%). The spectroscopic data are in agreement with those reported in the literature. Following the same procedure with potassium [18-Crown-6] The spectroscopic data are in agreement with those reported in the literature. 19 The spectroscopic data are in agreement with those reported in the literature. 5, 59.3, 40.1, 34.3, 32.6, 25.7, 24.8, 19.9, 17.1. Synth. Catal., 2012, 354, 3414-3420. purified by flash column chromatography (pentane/ethyl acetate, 95/5) to afford 91 as a colorless oil (62 mg, 93%). The spectroscopic data are in agreement with those reported in the literature. 22a

1-(Allyloxy

1 H NMR (300 MHz, CDCl 3 ):  7. 22 -7.16 (m, 2H), 7.74 -7.69 (m, 2H), 6.65 -6.62 (m, 2H), 6.27 (d, J = 1.4 Hz, 1H), 6.54 (d, J = 1.3 Hz, 1H), 4.25 (q, J = 7.1 Hz, 2H), 3.68 (bs, 1H), 3.31 (d, J = 6.8 Hz, 2H), 2.64 (td, J = 6.8, 1.1 Hz, 2H), 1.33 (t, J = 7.1 Hz, 3H). 13 C NMR (75 MHz, CDCl 3 ):  167. 1, 148.0, 138.4, 129.3 (2 C), 126.7, 117.4, 112.9 (2 C), 61.0, 43.0, 32.1, 14.3.

Ethyl 4,4-dimethyl-2-methylenepentanoate (92)

Following general procedure F with 20 (0.3 mmol, 129.5 mg) and allylsulfone 90 (4 eq., 1.2 mmol, 322 mg). The crude product was purified by flash column chromatography (pentane/ethyl acetate, 95/5) to afford 92 as a colorless oil (48 mg, 94%). The spectroscopic data are in agreement with those reported in the literature. 22a

1 H NMR (400 MHz, CDCl 3 ):  6.17 2, 139.1, 126.8, 60.6, 53.4, 44.5, 31.5, 29.2 (3 C), 14.2.

Ethyl 5-(diphenylphosphoryl)-2-methylenepentanoate (93)

Following general procedure F with 16 (0.3 mmol, 194.6 mg) and allylsulfone 90 (4 eq., 1.2 mmol, 322 mg). The crude product was purified by flash column chromatography (pentane/diethyl ether, 90/10) to afford 93 as a colorless oil (24 mg, 37%). 3, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): 29953, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): , 29493, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): , 17413, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): , 17103, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): , 16303, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): , 13683, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): , 12343, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): , 11873, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): , 11463, 167.3, 140.6, 124.8, 64.4, 60.8, 31.6, 28.3, 25.0, 21.1, 14.4. IR (neat): , 1028, 944, 813 cm -1 , 944, 813 cm -1

Dimethyl 2-cyclohexylsuccinate (102)

To a stirred schlenk flask was added potassium [18-C-6] bis(catecholato) cyclohexylsilicate 19 (1 eq., 0.3 mmol, 189.3 173.0, 51.80, 51.6, 47.1, 40.03, 33.3, 30.7, 30.2, 29.8, 26.4, 26.2.

General Conclusion

This Ph. D. thesis work led to four scientific publications, one review and one book chapter.