Victor Mamane

Paola Peluso

Emmanuel Aubert

Robin Weiss

Emmanuel Wenger

Sergio Cossu

Patrick Pale

Disubstituted Ferrocenyl Iodo-and Chalcogenoalkynes as Chiral Halogen and Chalcogen Bond Donors

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INTRODUCTION

In the last few years, halogen and chalcogen bonds (XB and ChB, respectively) have been recognized as important noncovalent interactions and rationalized through the socalled -hole which characterizes a covalently-bonded atom of Groups 13-18. 1 These atoms (-hole donors) bear a region with a positive electrostatic potential on unpopulated * orbitals allowing them to interact with a negative site (-hole acceptor: anion, lone electron pair,  electrons). Applications based on XB and ChB have rapidly grown during the last 20 years and important developments emerged in crystal engineering, in biology, in supramolecular chemistry and in catalysis. [2][START_REF] Tepper | Halogen Bonding in Solution: Anion Recognition, Templated Self-Assembly, and Organocatalysis[END_REF][4][5][START_REF] Lim | Sigma-Hole Interactions in Anion Recognition[END_REF][7][8] However, the involvement of XB and ChB in stereoselective processes remained unexplored until recently. We described XB-and ChB-driven HPLC enantioseparations of polyhalogenated 4,4'-bipyridines and related recognition mechanisms. [START_REF] Peluso | Insights into the Impact of Shape and Electronic Properties on The Enantioseparation of Polyhalogenated 4,4'-Bipyridines on Polysaccharide-Type Selectors. Evidence of Stereoselective Halogen Bonding Interactions[END_REF][START_REF] Peluso | Insights into Halogen Bond Driven Enantioseparations[END_REF][START_REF] Peluso | Polysaccharide-Based Chiral Stationary Phases as Halogen Bond Acceptors: A Novel Strategy for Detection of Stereoselective -Hole Bonds in Solution[END_REF][START_REF] Dallocchio | Halogen Bond in High-Performance Liquid Chromatography Enantioseparations: Description, Features and Modelling[END_REF][START_REF] Peluso | Enantioseparation of Fluorinated 3-Arylthio-4,4'-Bipyridines: Insights into Chalcogen and -Hole Bonds in High-Performance Liquid Chromatography[END_REF][START_REF] Peluso | Halogen Bond in Separation Science: a Critical Analysis across Experimental and Theoretical Results[END_REF] Beer's group described the enantioselective recognition of chiral anions of BINOL-based XB donors [START_REF] Lim | Enhancing the Enantioselective Recognition and Sensing of Chiral Anions by Halogen Bonding[END_REF][START_REF] Borissov | Neutral Iodotriazole Foldamers as Tetradentate Halogen Bonding Anion Receptors[END_REF][START_REF] Lim | Enantioselective Anion Recognition by Chiral Halogen-Bonding [2]Rotaxanes[END_REF][START_REF] Lim | A Chiral Halogen-Bonding [3]Rotaxane for the Recognition and Sensing of Biologically Relevant Dicarboxylate Anions[END_REF] and Kanger's group developed chiral triazole-based XB donors for the enantiodiscrimination of neutral acceptors. [START_REF] Kaasik | Synthesis and Characterisation of Chiral Triazole-Based Halogen-Bond Donors: Halogen Bonds in the Solid State and in Solution[END_REF][START_REF] Peterson | Tunable Chiral Triazole-Based Halogen Bond Donors: Assessment of Donor Strength in Solution with Nitrogen-Containing Acceptors[END_REF] In the field of catalysis, it is worth mentioning the works of Arai and co-workers who obtained good enantiomeric excesses in asymmetric Mannich reactions between malononitrile and N-Boc imines or N-Boc α-ketiminoesters using a quinidinebased chiral catalyst bearing a neutral XB donor functionality. [START_REF] Kuwano | A Chiral Organic Base Catalyst with Halogen-Bonding-Donor Functionality: Asymmetric Mannich Reactions of Malononitrile with N-Boc Aldimines and Ketimines[END_REF][START_REF] Kuwano | Catalytic Asymmetric Mannich-Type Reaction of Malononitrile with N-Boc α-Ketiminoesters Using Chiral Organic Base Catalyst with Halogen Bond Donor Functionality[END_REF] More recently, Huber and co-workers described the first example of asymmetric catalysis using a pure XB donor catalyst. [START_REF] Sutar | Bidentate Chiral Bis(imidazolium)-Based Halogen-Bond Donors: Synthesis and Applications in Enantioselective Recognition and Catalysis[END_REF] Despite these achievements, XB and ChB driven stereoselective processes and in particular asymmetric catalysis still remain huge challenges, as is the design of appropriate XB or ChB chiral donor molecules. [START_REF] Weiss | Chiral Chalcogen Bond Donors Based on the 4,4'-Bipyridine Scaffold[END_REF] In general, electron-withdrawing residues increase theholes of X and Ch atoms. In this regard, perfluorinated and cationic N-heterocyclic molecules are widely used for the synthesis of strong XB and ChB donors which found various applications to organocatalysis. 7,8 A different approach to increase -hole is to attach the halogen atom, in particular iodine, to an acetylenic unit. Indeed, in these compounds, iodine is directly attached to a Csp where contribution of the s orbital is higher compared to sp 2 and sp 3 carbons. Remarkably, iodoalkynes are good building blocks in crystal engineering [START_REF] Goroff | Designed Cocrystals Based on the Pyridine-Iodoalkyne Halogen Bond[END_REF][START_REF] Gimeno | Halogen-Bonding Complexes Based on Bis(iodoethynyl)benzene Units: A New Versatile Route to Supramolecular Materials[END_REF][START_REF] Aakero Y | Crystal Engineering with Iodoethynylnitrobenzenes: A Group of Highly Effective Halogen-Bond Donors[END_REF] but they are far less described in solution as XB donor. However, it is known for a long time that iodoalkynes can form strong XB adducts in solution with Lewis bases, such adducts being observed by UV-vis [START_REF] Laurence | 1-Iodoacetylenes. 1. Spectroscopic Evidence of Their Complexes with Lewis Bases. A Spectroscopic Scale of Soft Basicity[END_REF] and by NMR. [START_REF] Dumele | Halogen Bonding of (Iodoethynyl)benzene Derivatives in Solution[END_REF] Two recent examples highlighted the potential of these compounds in organic synthesis, the iodoalkyne behaving either as catalyst [START_REF] Matsuzawa | Iodoalkyne-Based Catalyst-Mediated Activation of Thioamides through Halogen Bonding[END_REF] or as activator. [START_REF] Perera | Organocatalysis by A Multidentate Halogen-Bond Donor: An Alternative to Hydrogen-Bond Based Catalysis[END_REF] The analogs thio-and selenoalkynes are known as stable useful synthons in organic synthesis, [START_REF] Sharma | Gold-Catalyzed Oxidation of Thioalkynes to Form Phenylthio Ketene Derivatives via a Noncarbene Route[END_REF][START_REF] Song | Rhodium(I)-Catalyzed Regioselective Azideinternal Alkynyl Trifluoromethyl Sulfide Cycloaddition and Azide-internal Thioalkyne Cycloaddition under Mild Conditions[END_REF][START_REF] Coelho | Intramolecular Hydroamination of Selenoalkynes to 2-Selenylindoles in the Absence of Catalyst[END_REF][START_REF] Baldassari | Redox-Neutral Synthesis of Selenoesters by Oxyarylation of Selenoalkynes under Mild Conditions[END_REF] but the -hole donor properties of sulfur and selenium in these derivatives have never been considered. It is thus worth exploring and possibly exploiting iodo-and more specifically thio-and selenoalkynes as XB or ChB (chiral) donors. With the aim to develop new chiral XB and ChB donor molecules, we report herein the synthesis of chiral ferrocenyl iodo-and chalcogeno-alkynes by combining the -hole donor properties of iodine, sulfur and selenium when bonded to an alkyne, and the planar chirality of ferrocene. [START_REF] Schaarschmidt | Selective Syntheses of Planar-Chiral Ferrocenes[END_REF] As the ferrocene substitution pattern might influence iodine polarizability, both 1,2-and 1,3disubstituted chiral ferrocene derivatives were considered in this work. Compared to 1,2-disubstituted ferrocenes whose applications are numerous, [START_REF] Dai | Asymmetric Catalysis with Chiral Ferrocene Ligands[END_REF][START_REF] Mamane | Metal-Catalyzed Cross-Coupling Reactions for Ferrocene Functionalization: Recent Applications in Synthesis, Material Science and Asymmetric Catalysis[END_REF] the 1,3disubstituted ferrocenes are much less described in the literature. A few derivatives have been reported with interesting activity in catalysis, [START_REF] Kuklin | Highly Active Iridium Catalysts for Alkane Dehydrogenation. Synthesis and Properties of Iridium Bis(phosphine) Pincer Complexes Based on Ferrocene and Ruthenocene[END_REF] medicinal chemistry [START_REF] Ferber | Synthesis of Optically Pure o-Formylcyclopentadienyl Metal Complexes of 17-Ethynylestradiol. Recognition of the Planar Chirality by the Estrogen Receptor[END_REF] and supramolecular chemistry, serving as hydrogen-bond [START_REF] Westwood | Binding and Electrochemical Recognition of Barbiturate and Urea Derivatives by a Regioisomeric Series of Hydrogen-Bonding Ferrocene Receptors[END_REF] or XB [START_REF] Lim | A Halogen Bonding 1,3-Disubstituted Ferrocene Receptor for Recognition and Redox Sensing of Azide[END_REF] receptors.

The -hole donor property of the selected compounds was investigated in solution by preliminary evaluation of their performance in the Ritter reaction [START_REF] Walter | Halogen-Bond-Induced Activation of a Carbon-Heteroatom Bond[END_REF] and in the benzoxazole synthesis from thioamides. [START_REF] Matsuzawa | Iodoalkyne-Based Catalyst-Mediated Activation of Thioamides through Halogen Bonding[END_REF] The potential of racemic and enantiopure ferrocenyl iodoalkynes as XB donors was also evaluated in the solid state by X-ray diffraction (XRD) analysis.

RESULTS AND DISCUSSION

Design and electrostatic potential analysis. The design of the compounds reported here was based on 1,2-or 1,3disubstituted ferrocenes, in which one of the substituents is the iodo-, thio-and selenoethynyl moiety carrying -hole and the other is an electron-withdrawing group in order to increase the adjacent-hole depth. This design was also substantiated by calculating the electrostatic potential (V) on focused regions of these molecules, so that local electron charge density, especially of -hole regions, could be anticipated. A general strategy was thus designed for the synthesis of various ferrocenyl-based iodoalkynes 9-13 and chalcogenoalkynes 16-17 starting from 1,2-or 1,3disubstituted ferrocenes 1-2 (Scheme 1). The -hole donor atom (I, S or Se) would be introduced in the late stage from silyl-protected alkynes 4-5 and 6-8 through a deprotection-functionalization sequence which can be conducted in one or two steps. Starting from bromosubstituted ferrocenyl compounds 4a and 5a (X = Br), the introduction of aryl and methyl groups would be carried out through Suzuki coupling or bromine/lithium exchange followed by electrophilic quenching. The alkyne function in derivatives 4-8 would be introduced by using a selective Sonogashira coupling with the readily available iodoferrocenyl derivatives 1-2.

In the frame of a rational design approach, the V of iodo-, thio-and selenoethynylferrocenes 9a-c, 10b, 16a, and 17a were computed on a 0.002 au molecular isosurface (VS). Scheme 1. General strategy for the synthesis of ferrocenyl-based iodoalkynes 9-13 and chalcogenoalkynes 16-17.

The VS of pentafluorobenzenes 18-20, halobenzenes 21-23 and 25-30, haloferrocenes 1b and 3a-b, as well as nonsubstituted iodoethynylbenzene 24 and iodoethynylferrocene 31 were computed as benchmarks in order to evaluate the impact of both ferrocenyl and ethynyl substructures on local electron charge density of the hole regions. For this purpose, the VS maxima (VS,max) on the -holes centred on I and Ch (S, Se) atoms were compared (Table 1) in order to explore the effect of subtle structure modifications on -hole depth. The geometry of all compounds listed in Table 1 was optimized using Density Functional Theory with B3LYP functional (completed with D3 dispersion corrections) and Def2TZVPP basis set. The local maxima of the electrostatic potential (VS,max) values were calculated on the 0.002 a.u. isodensity surface (see Supporting Information for details). As expected, these theoretical results confirmed the beneficial effect of the alkyne moiety on the iodine -hole depth (entry 4 vs 12 and 7 vs 19). The results also showed that the activation ability of the alkyne function toward iodine -hole is comparable and even slightly better than the effect of perfluorination (entry 10 vs 1). This effect can be increased by an additional electron-withdrawing halogen atom (entry 10 vs 11-13 and 16). It is worth noting that the obtained VS,max values for the series 24-27 and 30 are in good agreement with the donor/acceptor nature of substituents in other reports concerning similar iodoalkynebased structures. [START_REF] Aakero Y | Crystal Engineering with Iodoethynylnitrobenzenes: A Group of Highly Effective Halogen-Bond Donors[END_REF][START_REF] Aakeröy | Supramolecular Hierarchy among Halogen-Bond Donors[END_REF][START_REF] Torubaev | The Energy Frameworks of aufbau Synthon Modules in 4-Cyanopyridine Cocrystals[END_REF][START_REF] Torubaev | The energy frameworks of aufbau synthon modules in 4-cyanopyridine co-crystals[END_REF] Interestingly, when the chlorine was placed in 3-position, the iodine -hole increased (entry 12 vs 16). The beneficial effects on iodine -hole due to the additional halogen atom (entry 17 vs 18-20) and its position (entry 19 vs 23) are also observed in the ferrocenyl iodoalkyne series. However, lower VS,max values are always obtained for the ferrocenyl derivatives compared to the phenyl ones (entries 10-13 vs 17-20 and 16 vs 23), confirming the more electron-donating ability of ferrocene compared to phenyl. Nevertheless, the VS,max values of ferrocenyl compounds 9a-c and 10b are still comparable to the one of iodopentafluorobenzene 18 (en-try 1 vs 18-20); therefore interesting -hole based properties can be expected with these compounds. a Calculations were performed by using Gaussian09 Version D.01 program (see Supporting Information for details); b corresponds to the hole along the Cl-Ch axis; c two conformations were observed for these compounds.

Regarding the chalcogen atoms, they possess two -holes, one on the elongation of the CCF3-Ch bond and one on the elongation of the CAr/Fc-Ch or Cethynyl-Ch bond. As a matter of fact, in non-symmetrical compounds such as 22-23, 3a-b, 28-29 and 16a-17a, two conformations are observed depending on the position of the CF3 group with respect to the chlorine atom. Interestingly, in compounds 22, 23 and 3a-b (entries 5-6 and 8-9), the VS,max values along the CCF3-Ch bond for the two conformers are completely different and in three cases, the -hole of one of the two conformers cannot be observed (entries 5, 8 and 9). This effect is due to the contribution of neighboring atoms on the analyzed molecular surface. For example, in the second conformation of compound 23, the expected selenium σ-hole opposite to CF3-Se bond is directly oriented toward the negative crown of the adjacent chlorine atom, leading to a smaller VS value than in the first conformation where the same σ-hole points toward the exterior of the molecule. In the case of 3b this effect is even more pronounced since the expected σ-hole points toward an hydrogen atom of the neighboring cyclopentadienyl ring and appears buried inside the chosen molecular envelope and is thus not revealed onto this surface (see Fig. S26 in Supporting Information).

From the results, it can also be noted that the alkyne function also polarizes sulfur and selenium atoms, increasing -hole depth in both phenyl (for S: entry 5 vs 14; for Se: entry 6 vs 15) and ferrocenyl (for S: entry 8 vs 21; for Se: entry 9 vs 22) series. The calculations also confirmed the effect of shifting from sulfur to selenium in all the chalcogen series, for which the -hole depth always increases. On the basis of VS analysis, the alkyne substructure proved to be a powerful tool to polarize both iodine and chalcogens, generating -hole regions potentially able to promote the catalytic activity of ferrocenyl derivatives 9-13, 16, and 17.

Racemic synthesis.

The starting substituted iodoferrocenes 1a-d and 2a-c are described in the literature and were prepared accordingly (Scheme 2). [START_REF] Dayaker | Deprotonative Metallation of Ferrocenes using Mixed Lithium-Zinc and Lithium-Cadmium Combinations[END_REF][START_REF] Tazi | Fluoro-and Chloroferrocene: From 2-to 3-Substituted Derivatives[END_REF][START_REF] Tazi | From Ferrocene to fluorine-Containing Pentasubstituted Derivatives and all Points in-between; or, how to Increase the Available Chemical Space[END_REF] Scheme 2. Starting substituted iodoferrocenes.

The ethynyl moiety was then introduced on 1,2-and 1,3iodoferrocenes 1-2 by Sonogashira coupling with trimethylsilylacetylene. Classical conditions, based on PdCl2(PPh3)2 and CuI as catalysts and on diisopropylamine as base and solvent, [START_REF] Chinchilla | The Sonogashira Reaction: A Booming Methodology in Synthetic Organic Chemistry[END_REF] provided variable results depending on the X substituent nature. (Scheme 3, Cond. A). Optimization study performed on 1-bromo-2iodoferrocene 1a revealed that 3 equivalents of trimethylsilylacetylene were necessary to achieve complete conversion. The expected compound 4a was thus isolated with 98% yield. However, the yield dropped significantly as the electron-withdrawing ability of the atom adjacent to iodine increased and when the substituent was placed in 3-position to iodine. Along with the expected compounds 4b-c or 5a-c, a substantial amount of the deiodinated starting material was isolated. In the case of 4d, the so-formed cyanoferrocene could not be removed by chromatography (Scheme S1 in Supporting Information for more details). Scheme 3. Sonagashira coupling of iodoferrocenes 1-2.

The hydrodehalogenation reaction could be completely suppressed by using Pd(Pt-Bu3)2 previously described as a highly active catalyst in the Sonogashira reaction of 1,1'diiodoferrocene. [START_REF] Inkpen | Rapid Sonogashira Cross-Coupling of Iodoferrocenes and the Unexpected Cyclo-Oligomerization of 4-Ethynylphenylthioacetate[END_REF] Except for 4c, yields were significantly improved and compound 4d could be obtained pure after removing the unreacted starting material (Scheme 3, Cond. B). To compare with the effect of the halogeno-or cyano substituents, neutral non-electron-withdrawing groups were also introduced on the ferrocenyl unit. The simple methyl group was selected, as well as two aryl groups, phenyl and the larger 2-naphthyl (Scheme 4). The introduction of the latter was readily achieved through Suzuki reaction. Scheme 4. Arylation and methylation of bromoferrocenyl-acetylenes 4a and 5a.

Coupling phenyl-and 2-naphthyl boronic acids with bromo-substituted ferrocenylalkynes 4a and 5a were efficiently performed by using 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos) as ligand and potassium phosphate as base in toluene at 100°C. [START_REF] Wolfe | Highly Active Palladium Catalysts for Suzuki Coupling Reactions[END_REF] Indeed, good yields ranging from 80% to 98% were obtained for derivatives 6-7. The methyl group was introduced by addition of n-BuLi on compound 4a followed by quenching the lithiated ferrocenyl species. Derivative 8 was thus obtained with a good yield of 70% (Scheme 4). For the synthesis of ferrocenyl iodoalkynes 9-13, we explored the possibility to perform in one step the trimethylsilyl (TMS) group removal and the iodination of compounds 4-8. The combination of silver (I) fluoride and Niodosuccinimide (NIS) was already described for this purpose with a variety of TMS-protected alkynes. [START_REF] Nishikawa | One Pot Synthesis of Haloacetylenes from Trimethylsilylacetylenes[END_REF] Although the expected iodoalkynes were obtained in all cases, the yields were generally low to moderate (Scheme 5, a). This could be due to oxidation of the ferrocene moiety by the silver salts present in the reaction mixture. [START_REF] Carty | The Reaction of Some Ferrocenyl Ketones with Anhydrous Silver Tetrafluoroborate, a New Route to Substituted Ferricenium Salts[END_REF][START_REF] Aguado | Unexpected Formation of Ferrocene-Containing Indolizines by Tandem Cyclization-Activation Reactions Induced by Silver Salts[END_REF] Scheme 5. Preparation of ferrocenyl iodoalkynes 9-13 through deprotection-iodination of compounds 4-8.

With the aim to avoid silver salts and to increase yields, a two-step procedure was tested. TMS-alkynes 4b and 5b were first deprotected with KOH in methanol at room temperature to give alkynes 14 and 15 with good yields (Scheme 5, b). These alkynes were then treated again with KOH before addition of NIS [START_REF] Russo | Synthesis of Highly Ethynylated Mono and Dinuclear Pt(II) Tethers Bearing the 4,4'-Bis(Ethynyl)Biphenyl (debp) Unit as Central Core[END_REF] to give iodoalkynes 9b and 10b with good yields (Scheme 5, c). Since KOH is used in the two steps, a one-pot procedure was employed with 4b and 5b, furnishing directly iodoalkynes 9b and 10b with yields superior to those of the two-step procedure. This protocol was therefore applied to TMS-alkynes 4a, 4c-d and 5c, increasing greatly the yields of the corresponding iodoalkynes 9a, 9c-d, and 10c (Scheme 5, d). For the synthesis of chalcogenoalkynes 16 and 17, 2-and 3-chloroferrocenyl acetylenes 14 and 15 were functionalized through lithiation and electrophilic quenching with donors of SCF3 and SeCF3 groups. Alkyne deprotonation of 14 and 15 was performed with n-BuLi and the resulting lithioalkynes were trapped with N-methyl-N-(trifluoromethylsulfanyl)aniline [START_REF] Baert | Electrophilic Trifluoromethanesulfanylation of Organometallic Species with Trifluoromethanesulfanamides[END_REF] to give thioalkynes 16a and 16b, and with the in situ generated ClSeCF3 58 to furnish selenoalkynes 17a and 17b. Unexpectedly, 17b was obtained as an inseparable mixture with chloroalkene 18. [START_REF] Glenadel | A Metal-Free Route to Heterocyclic Trifluoromethyl-and Fluoroalkylselenolated Molecules[END_REF] Therefore, the 17b/18 mixture was treated with an excess of LiOH in DMSO [START_REF] Zhong | Preparation and Characterization of Alkenyl Aryl Tetrafluoro-l6sulfanes[END_REF] to deliver the pure compound 17b with a moderate overall yield (Scheme 6).

Scheme 6. Synthesis of ferrocenyl-based thioalkynes 16a,b and selenoalkynes 17a,b

Evaluation of ferrocenyl iodo-or chalcogeno alkynes: C-Br and thioamide activation. In order to evaluate the -hole donor properties in solution of the new ferrocenebased iodo-and chalcogeno-alkynes, we have considered two benchmark reactions: the Ritter reaction, [START_REF] Jiang | Recent Developments in Ritter Reaction[END_REF] allowing the transformation of benzhydryl bromide 32 to acetamide 33, and the synthesis of benzoxazole 36 from thioamide 34 [START_REF] Jagodzinski | Thioamides as Useful Synthons in the Synthesis of Heterocycles[END_REF] (Scheme 7). In order to study the influence of the substituent in both reactions, five compounds of the 2substituted ferrocenyl iodoalkyne family (9a-c and 11a-b) were tested. Moreover, the effects of the substituent position and the nature of the donor atom were also evaluated by using compounds 10b and 17a (Table 2). Ritter-type reactions [START_REF] Ritter | A New Reaction of Nitriles. I. Amides from Alkenes and Mononitriles[END_REF] involve the nucleophilic substitution of alcohol, sulfate or halide group by acetonitrile or related nitriles, usually used as solvent. The resulting nitrilium is then hydrolyzed to the corresponding amide by added water. Depending on the leaving group nature, electrophilic assistance could facilitate the reaction and catalysis could be established. Lewis acids could act as such and some could catalyze such reactions. [START_REF] Guérinot | Reaction: Recent Catalytic Developments[END_REF] With -hole based organocatalysts and halogenated substrates, the Ritter reaction is not catalytic due to its mechanism, close to SN1 process. In this reaction, the -hole donor interacts with the bromine of the substrate (compound 32 here; Scheme 7) up to abstract it and the nucleophilic acetonitrile solvent replaces it. Nevertheless, the Ritter reaction allows reliable evaluation of the -hole donor ability in solution. [START_REF] Perera | Organocatalysis by A Multidentate Halogen-Bond Donor: An Alternative to Hydrogen-Bond Based Catalysis[END_REF][START_REF] Walter | Halogen-Bond-Induced Activation of a Carbon-Heteroatom Bond[END_REF][START_REF] Kniep | 5-Iodo-1,2,3triazolium-Based Multidentate Halogen-Bond Donors as Activating Reagents[END_REF][START_REF] Kniep | 4,4'-Azobis(halopyridinium) Derivatives: Strong Multidentate Halogen-Bond Donors with a Redox-Active Core[END_REF] All the ferrocenyl derivatives examined were able to efficiently promote the expected transformation, except for fluoro derivatives (Table 2). In the 2-haloferrocenyl iodoalkyne series 9a-c, high conversions were obtained with the 2-bromo and 2-chloro derivatives 9a and 9b whereas a low conversion of 34% was observed with the 2-fluoro derivative 9c. This difference in reactivity was unexpected with regard to the calculated VS,max values (Table 1, entries 18-20). Comparison of the 2-and 3-chloro derivatives 9b/10b showed that the position of the halogen on the ferrocene moiety has very little impact on the reactivity, but in agreement with their slightly different VS,max values (Table 1, entry 23 vs 19). Surprisingly, the 2-aryl ferrocenyl iodoalkyne 11a-b were as effective as the 2-bromo derivative 9a, but more than the 2-chloro analog 9b, despite the stronger electronwithdrawing character of the latter.

Scheme 7. XB or ChB activation of C-Br and thioamide

These results revealed that the iodine-hole is well activated by the alkyne function and that the substituent on the ferrocene moiety only has moderate influence on reac-tivity, except for the strongly electron-withdrawing fluoride. In contrast, the nature of the -hole donor has a strong influence on the reaction efficiency. Indeed, with the seleno derivative 17a, the reaction proved to be slower giving only 35% conversion after 10h and 60% conversion after 24h. Benzoxazoles are important compounds owing to their various biological activities and their roles in fluorescent and/or electroluminescent materials. [START_REF] Gao | Recent Advances in Synthesis of Benzothiazole Compounds Related to Green Chemistry[END_REF] In 2016, Matsuzawa and coll. have shown that iodoalkynes are able to catalyze the synthesis of benzoxazole from thioamides and 2aminophenol based on iodine---sulfur interaction. [START_REF] Matsuzawa | Iodoalkyne-Based Catalyst-Mediated Activation of Thioamides through Halogen Bonding[END_REF] This reaction is thus worth for comparison (Table 2). Interestingly, all the ferrocenyl iodoalkynes were able to act as catalyst and gave the expected benzoxazole 36. High yields were obtained with the 2-chlorinated and 2-fluorinated compounds 9b and 9c whereas a lower yield was obtained with the 2-brominated analog 9a. In contrast to the Ritter results, the 3-chloro catalyst 10b proved to be less effective, as the yield significantly dropped (64 vs 86%). As for the Ritter reaction, the aryl-substituted ferrocenyl iodoalkynes 11a and 11b were very efficient, giving high to quantitative yields of benzoxazole 36. The selenium derivative 17a proved again to be less efficient than the iodinated derivatives since almost no benzoxazole was formed during the reaction. In summary, regarding the results of Table 2, the effects of nature and position of the halogen substituent on the activity of the iodoalkynes as activators or catalysts in the considered reactions are very difficult to analyze. It is however clear that the aryl-substituted compounds 11a and 11b are very active in both reactions which open the possibility to use them or other analog substituents in asymmetric catalysis. Asymmetric synthesis of ferrocenyl iodoalkynes. Considering the above results, we decided to focus only on the synthesis of enantiopure ferrocenyl iodoalkynes. As shown through the racemic synthesis, compounds 4a and 5a are key intermediates for the synthesis of ferrocenyl iodoalkynes bearing substituents of different nature. For the 1,2-disubstituted series, we considered the preparation of enantiopure (SFc)-1a as described in the literature [START_REF] Zirakzadeh | Biferrocene-Based Diphosphine Ligands: Synthesis and Application of Walphos Analogues in Asymmetric Hydrogenations[END_REF] but the yields and the enantiomeric excess we obtained were unsatisfactory. Another useful enantiopure 1,2substituted ferrocenyl synthon, the (Ss, SFc)sulfinylferrocenyl boronic acid, attracted our attention but it is suited only for the preparation of arylsubstituted ferrocenes. [START_REF] Urbano | Asymmetric Synthesis and Chiroptical Properties of Enantiopure Helical Ferrocenes[END_REF] We finally turned our attention to the Kagan's method which delivers enantiopure 2-substituted ferrocenecarboxaldehydes. [START_REF] Mamane | The Diastereoselective ortho-Lithiation of Kagan's Ferrocenyl Acetal. eneration and Reactivity of Chiral 2-Substituted Ferrocenecarboxaldehydes[END_REF] In particular, 2-bromo ferrocenecarboxaldehyde (SFc)-36 was prepared [START_REF] Riant | An Efficient Asymmetric Synthesis of 2-Substituted Ferrocenecarboxaldehydes[END_REF] and transformed to the alkyne (SFc)-37 through a Seyferth-Gilbert homologation with Ohira-Bestmann reagent 38. [START_REF] Dhameja | Reagent: A Convenient and Promising Reagent in the Chemical World[END_REF] A TMS group was then introduced on the alkyne to give the key compound (SFc)-4a. Concerning the 1,3-disubstituted series, enantiopure compound 5a was not available but the iodinated analog (SFc)-39 was described in the literature. [START_REF] Ferber | A New Efficient Route to Chiral 1,3-Disubstituted Ferrocenes: Application to the Syntheses of (Rp)-and (Sp)-17-[(3'formylferrocenyl)ethynyl]estradiol[END_REF] It was then transformed to key compound (SFc)-41 through alkyne (SFc)-40 (Scheme 8). Scheme 8. Synthesis of enantiopure key compounds (SFc)-4a and (SFc)-41.

On one hand, when applying the experimental conditions set up for the Suzuki coupling of related compounds (see Scheme 4), compounds (SFc)-4a and (SFc)-41 were very efficiently transformed to (SFc)-6a-b and (SFc)-7a-b, respectively (Scheme 9, left). On the other hand, halogenlithium exchange followed by electrophilic quenching afforded differently substituted derivatives. Starting from (SFc)-4a, quenching the lithiated species with MeI, Nfluorobenzenesulfonimide (NFSI) and p-toluenesulfonyl cyanide (TsCN) delivered compounds (RFc)-8, (SFc)-4c and (SFc)-4d, respectively. Addition of ,'-dibromoxylene to the lithiated intermediate obtained from (SFc)-41 furnished (SFc)-5a which contained small amounts of inseparable impurities (Scheme 9, right). Finally, the deprotection-iodination methods (see Scheme 5) were applied to all enantiopure/enantioenriched ferrocenyl trimethylsilylethynes. This sequence furnished diversely substituted ferrocene iodoethynes, i.e. (SFc)-9a,c,d, (SFc)-10a, (SFc)-11a,b, (SFc)-12a,b and (RFc)-13 (Scheme 10).

Scheme 9. Functionalization of (SFc)-4a and (SFc)-41

The enantiomeric purity of compounds (SFc)-9a,c,d, (SFc)-10a, (SFc)-11a,b, (SFc)-12a,b and (RFc)-13 was determined through high-performance liquid chromatography (HPLC) on polysaccharide-based chiral columns. For compound 9a,d, 10a, 11b, 12a,b and 13, the proper combination of column and mobile phase was optimized allowing for obtaining baseline enantioseparations. For compounds 9c and 11a partial separation was only achievable. For all compounds, enantiomeric excesses ≥ 92.8% were measured (Scheme 10, see Table S1 and Fig. S1-S9 in Supporting Information for details). Scheme 10. Synthesis of enantiopure ferrocenyl iodoalkynes Solid state analysis. With these racemic and chiral ferrocenyl iodoethynes in hand, their -hole donor property in the solid state was investigated by X-ray diffraction analysis (XRD) when possible. Crystal structures were determined by single crystal XRD for a selected number of compounds. Hirshfeld molecular surfaces were computed for these structures (excepted for 9c which presents a disorder linked to symmetry) and actual surface contacts were compared to equiprobable contacts in order to derive the enrichment ratios (E). [START_REF] Jelsch | The Enrichment Ratio of Atomic Contacts in Crystals, an Indicator Derived from the Hirshfeld Surface Analysis[END_REF] As seen in Table S2 (see Supporting Information), Fe atoms in these ferrocenyl compounds are almost fully buried between the cyclopentadienyl rings, offering a very small contribution to the total molecular surface; thus variations of this small surface between actual and equiprobable contacts are meaningless and not discussed. An enrichment ratio E larger (respectively smaller) than 1 means that the considered contact is enriched (respectively impoverished) in the actual crystal structure compared to the situation of equiprobable contacts. It can be noted (Tables S3-S10) that despite the richness of aromatic groups in the studied compounds, no π•••π interaction is observed, carbon In all obtained crystal structures, I•••C XBs are observed between the electropositive σ-hole of the iodine atom and electron rich π clouds (Tables S3-S10 and S11). Interestingly, the XB acceptors vary, and can be the alkyne carbon atoms [START_REF] Torubaev | Self-Assembly of Conducting Cocrystals via Iodine⋯π(Cp) Interactions[END_REF] ((SFc)-12a, (RFc)-13, (SFc)-9a), the cyclopentadienyl rings bearing the alkyne group (13, (SFc)-11a, (SFc)-11b), the unsubstituted cyclopentadienyl rings [START_REF] Baldrighi | Polymorphs and Co-Crystals of Haloprogin: An Antifungal Agent[END_REF] (9c, (SFc)-9c) or the naphthyl group (11b). The negatively charged belts usually found around polarized heavy halogen atoms (see Supporting Information) are not involved as σ-hole acceptors in these structures, thus no halogen•••halogen bonds are evidenced for these compounds. Indeed, as can be seen for example on Fig. S29 (compound 9b) the ethynyl group offers more negative VS than the bonded iodine atom itself. These halogen interactions are forming infinite corrugated molecular chains in most of the structures (9c, 11b, (RFc)-13, (SFc)-9a, (SFc)-9c, (SFc)-11a, (SFc)-11b, (SFc)-12a) (Fig. 1 and S10-S15). These chains stack to form planes which then interact through numerous H•••C contacts to form 3D structures. Further H•••F and π•••π contacts can be noticed in respectively (SFc)-9c and 9c, and in (SFc)-12a (see Supporting Information). One can distinguish two types of such planes among the structures which can be grouped in two families. In the first one the infinite chains are relatively separated ((SFc)-9a, (RFc)-13, associated with relative large in-plane area per molecule) but in the second family these chains are more intimately nested and these structures have a relative small in-plane area per molecule ((SFc)-11a, (SFc)-11b, 11b, (SFc)-12a, (SFc)-9c, 9c) (Table S11). The thickness of the planes depends on the R substituent adjacent to the iodoalkyne functionality (Fig. S16), and the thinner is obtained for the smallest R group (9c and (SFc)-9c where R = F). The thickness also depends on the molecular orientation relative to the plane, with for example (SFc)-11b and 11b where R = naphthyl exhibiting ~30% plane width difference (Table S11). The two members of the first family are isostructural ((RFc)-13 and (SFc)-9a), differing by Me/Br substitution only. In the second family, the structures offer different level of similarities. (SFc)-11a and (SFc)-11b both crystallize in P212121 space group with similar a and b unit cell parameters; these two structures are not strictly isostructural but nevertheless share common packing characteristics, both having very similar (001) molecular packing planes (Fig. S10, S11 and S17) formed by the stacking of the infinite I•••C XBs chains (Table S11). The main difference between the crystal structures of these two compounds is then the packing of their (001) planes along the [001] direction, where one of the two structures can be deduced from the other by a translation of half the b unit cell parameter. The larger difference in c unit cell parameters arises from the fact that the aromatic rings are oriented along the [001] direction (Fig. S18). (SFc)-11a and (SFc)-12a are isomers, differing by the position of the phenyl group on the substituted cyclopentadienyl ring. Although these two structures display similar in-plane area per molecule (Table S11) their molecular planes containing the I•••C motif differ by the orientations of the molecules within them (Fig. S10 andS13), and to somewhat different plane thicknesses (Table S11), making these two structures less superimposable than are (SFc)-11a and (SFc)-11b (phenyl / naphthyl substitution). (SFc)-9c and 9c crystallize in P212121 and Pnma space groups, respectively. Their crystal structures only differ by the ordering of the fluorine position in enantiopure (SFc)-9c with respect to the F/H site position disorder observed for the racemic 9c. (SFc)-11b and its racemic counterpart 11b have also similar crystal packing to some extent. Although the molecular orientations differ leading to different plane thicknesses (Table S11), the more pronounced inter-plane penetration found in (SFc)-11b leads finally to similar packing when considering the barycenter of ferrocenyl groups (Fig. S20). Beside these eight crystal structures sharing similar molecular plane packing, the methyl-substituted derivative 13 exhibits an interesting further level of sophistication in its structure. Indeed, the halogen I•••C interactions form interpenetrated helices of reversed chirality parallel to [010] direction (Fig. 2).

CONCLUSION

Two series of chiral -hole bond donors based on the ferrocenyl ethynyl scaffold were prepared and studied. In these systems, the direct attachment of the donor atoms (I, S, Se) to the alkyne function allows increasing their -hole depth. Representative compounds of each series of these new chiral -hole bond donors were used in solution for the activation of either a C-Br bond in a Ritter reaction or a thioamide for the synthesis of benzoxazole. Whereas the Se-based compound furnished low or no conversion, the ferrocenyl iodoalkyne derivatives generally showed a very good activity in both reactions. Therefore, in view of developing enantiopure XB-based organocatalysts, the asymmetric synthesis of 1,2-and 1,3-disubstituted ferrocenyl iodoalkynes was performed with functional group introduction in 2-or 3-positions of different nature. Crystal structures of some derivatives in racemic or enantiopure forms were analyzed, confirming their good -hole bond donor property also in the solid state. Indeed, several intermolecular contacts between the electropositive σ-hole of the iodine atom and electron rich π clouds were noticed, such as the C-C triple bond and the Cp ring. The search of asymmetric reactions catalyzed by appropriately decorated enantiopure ferrocenyl iodoalkynes is currently underway in our laboratory.

EXPERIMENTAL SECTION

General Information. Proton ( 1 H NMR) and carbon ( 13 C NMR) nuclear magnetic resonance spectra were recorded on the following 300, 400, or 500 MHz instruments. The chemical shifts are given in parts per million (ppm) on the delta scale. The solvent peak was used as reference values. For 1 H NMR: CDCl3 = 7.26 ppm. For 13 C NMR: CDCl3 = 77.16 ppm. Data are presented as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, m = multiplet, b = broad), integration, and coupling constants (J/Hz). High-resolution mass spectra (HRMS) data were recorded on a micrOTOF spectrometer equipped with an orthogonal electrospray interface (ESI). []D values were measured at the sodium D-line on a JASCO J-815 CD spectropolarimeter, in CHCl3 in a quartz cuvette (1 cm) at 20°C. Melting points were obtained in open capillary tubes and are uncorrected. Analytical thin layer chromatography (TLC) was carried out on silica gel 60 F254 plates with visualization by ultraviolet light. Reagents and solvents were purified using standard means. Tetrahydrofuran (THF) was distilled from sodium metal/benzophenone and used freshly. Anhydrous toluene, acetonitrile, and MeOH were obtained by passing through activated alumina under a positive pressure of argon using GlassTechnology GTS100 devices. Diisopropylamine was distilled over CaH2 and stored over KOH, under an argon atmosphere. Anhydrous reactions were carried out in flame-dried glassware and under an argon atmosphere. All other chemicals were used as received. Computational Details. The 3D structures of selected compounds (see Table 1) were optimized at the DFT level of theory using the B3LYP functional (completed with D3 dispersion corrections) and the Def2TZVPP basis set. Conformations were searched by scanning the corresponding degree of freedom and frequency calculations were performed in order to check that true energy minima were obtained. Computation of electrostatic potential mapped on 0.002 a.u. electron density isosurfaces and search for extrema VS,max were performed with AIMAll 77 and MultiWfn programs. [START_REF] Lu | A Multifunctional Wavefunction Analyzer[END_REF][START_REF] Lu | Quantitative analysis of molecular surface based on improved Marching Tetrahedra algorithm[END_REF] HPLC on chiral stationary phase. An Agilent Technologies (Waldbronn, Germany) 1100 Series HPLC system (high-pressure binary gradient system equipped with a diode-array detector operating at multiple wavelengths (220, 254, 280 nm), a programmable autosampler with a 20 L loop, and a thermostated column compartment) was employed for analytical enantioseparations. Data acquisition and analyses were carried out with Agilent Technologies ChemStation Version B.04.03 chromatographic data software. The UV absorbance is reported as milliabsorbance units (mAU). Lux Cellulose-1 (coated cellulose tris(3,5-dimethylphenylcarbamate)), i-Cellulose-5 (immobilized tris(3,5-dichlorophenylcarbamate)), and i-Amylose-3 (immobilized amylose tris(3-chloro-5-methylphenylcarbamate)) (Phenomenex Inc., Torrance, CA, USA) were used as chiral columns (250 x 4.6 mm) (5 m). i-Cellulose-5 and i-Amylose-3 were kindly provided by Prof. Bezhan Chankvetdze, University of Tbilisi (Georgia). HPLC-grade n-heptane, n-hexane, methanol and 2propanol were purchased and used as received. Analyses were performed at flow rate 0.8 mL/min and 22 °C.

General procedures for the Sonogashira reaction.

Cond. A: To the substituted iodoferrocene 1-2 (1 eq.) under argon were successively added degassed diisopropylamine (5mL/mmol), Pd(PPh3)4 (5 mol%) and CuI (10 mol%). After stirring at room temperature for 5 min, trimethylsilylacetylene (3 eq.) was added and the mixture was heated at 60°C and stirred for 15h. After cooling to room temperature, the mixture was filtered over Celite and washed with dichloromethane. The filtrate was washed with water and the organic phase was collected and dried over Na2SO4. After filtration and concentration, the crude was purified by chromatography on silica gel (pentane or pentane/Et2O 98/2) to give the expected product. Cond. B: To a flask containing iodoferrocene 1-2 (1 eq.), Pd(Pt-Bu3)2 (3 mol%) and CuI (3 mol%) were added a degassed THF/iPr2NH 3/1 mixture (1.5 mL/mmol) and finally trimethylsilylacetylene (2 eq.). After stirring at room temperature for 20h, the mixture was filtered over Celite and washed with dichloromethane. After concentration, the crude was purified by chromatography on silica gel (pentane or pentane/Et2O 98/2) to give the expected product. ((2-Bromoferrocenyl)ethynyl)trimethylsilane (4a). Cond General procedure for aldehyde homologation. Ferrocene carboxaldehyde (SFc)-36 or (SFc)-39 (1 eq.) was dissolved in THF (3 mL/mmol) and the temperature was lowered to 0°C. A solution of diazophosphonate 38 (1.2 eq) in MeOH (2.5 mL/mmol) was added followed by K2CO3 (2.2 eq.). The temperature was raised to room temperature and the mixture was stirred for 15h. After concentration, the crude was extracted with Et2O, washed with water and brine. The organic phases were collected, dried over Na2SO4 and concentrated. The crude was purified by chromatography on silica gel (pentane/Et2O 4/1) to give the expected product. (SFc)-1-Bromo-2-ethynylferrocene ((SFc)-37). Red oil (1.59 g, 89%) obtained from (SFc)-36 (6.14 mmol, 1.8 g). 1 H NMR (500 MHz, CDCl3) δ 4.50 (bs, 1H), 4.45 (bs, 1H), 4.26 (s, 5H), 4.17 (t, J = 2.5 Hz, 1H), 2.94 (s, 1H); [START_REF] Peluso | Enantioseparation of Fluorinated 3-Arylthio-4,4'-Bipyridines: Insights into Chalcogen and -Hole Bonds in High-Performance Liquid Chromatography[END_REF] General procedure for TMS protection. To a solution of ethynylferrocene (SFc)-37 or (SFc)-40 (1 eq.) at -78°C was added a freshly prepared solution of LiHMDS (1M in THF, 1.5 eq.) and the mixture was stirred for 30 min at -78°C. TMSCl (1.5 eq.) was added and stirring was continued 30 min at -78°C before raising the temperature to ambient. A saturated solution of NH4Cl was added and the mixture was extracted with Et2O and washed with water. After drying the organic phase over Na2SO4, it was filtered and concentrated. The crude was purified by chromatography on silica gel (pentane/Et2O 8/1) to give the expected product. General procedure for the Suzuki reaction. Haloferrocene 4a, 5a or (SFc)-41 (1 eq.), Pd2dba3 (2 mol%), SPhos (4 mol%), boronic acid (1.5 eq.) and crushed K3PO4 (3 eq.) were placed in a Schlenk tube under argon. Degassed toluene (3 ml/mmol) was added and the mixture was heated at 100°C and stirred for 15h. After cooling to room temperature, the mixture was filtered over Celite and washed with ethylacetate. The filtrate was concentrated and purified by chromatography on silica gel (pentane or pentane/Et2O 98/2) to give the expected product. Trimethyl((2-phenylferrocenyl)ethynyl)silane (6a). Red solid (1.05 g, 98%) obtained from 4a (3 mmol, 1.08 g). Mp: 46-48°C. 1 H NMR (500 MHz, CDCl3) δ 7.87 (d, J = 7.0 Hz, 2H), 7.35 (t, J = 7.0 Hz, 2H), 7.27 (t, J = 7.0 Hz, 1H), 4.63 (m, 1H), 4.61 (m, 1H), 4.33 (t, J = 3.0 Hz, 1H), 4.13 (s, 5H), 0.27 (s, 9H); [START_REF] Peluso | Enantioseparation of Fluorinated 3-Arylthio-4,4'-Bipyridines: Insights into Chalcogen and -Hole Bonds in High-Performance Liquid Chromatography[END_REF] C NMR (126 MHz, CDCl3) δ 138.0, 128.0, 127.9, 126.6, 104.7, 93.8, 87.9, 73.0, 71.9, 68.6, 68.5, 63.9, 0. To a solution of 4a or (SFc)-4a (1 eq.) in THF (5 mL/mmol) at -78°C was slowly added n-BuLi (1.4 M in hexanes, 1.2 eq.) and the mixture was stirred at -78°C for 1h. Electrophile (1.2 eq.) was added and stirring was continued at -78°C for 1h. The temperature was raised to 0°C before quenching with a saturated solution of NH4Cl. The mixture was extracted with ethyl acetate, washed with water and brine. After drying over Na2SO4, filtration and concentration, the crude was purified by chromatography on silica gel (pentane/Et2O 98/2) to give the expected product. Trimethyl((2-methylferrocenyl)ethynyl)silane (8). Red oil (208 mg, 70%) obtained by using 1 mmol of 4a and 1.2 mmol of MeI (neat) as the electrophile. 1 H NMR (500 MHz, CDCl3) δ 4.34 (m, 1H), 4.14 (m, 1H), 4.09 (s, 5H), 4.04 (t, J = 2.5 Hz, 1H), 2.08 (s, 3H), 0.24 (s, 9H); [START_REF] Peluso | Enantioseparation of Fluorinated 3-Arylthio-4,4'-Bipyridines: Insights into Chalcogen and -Hole Bonds in High-Performance Liquid Chromatography[END_REF] (SFc)-41 (0.452 mmol, 185 mg) was dissolved in THF (3 mL) and the solution was cooled to -78°C. t-BuLi (1.7 M in pentane, 0.95 mmol, 0.56 mL) was slowly added and the mixture was stirred at -78°C for 30min. A solution of ,'-dibromoxylene (0.54 mmol, 140 mg) in THF (2 mL) was added and stirring was continued for 30 min. The temperature was raised to ambient and water (0.5 mL) was slowly added. After filtration on Celite (Et2O), the organic phase was separated and dried over Na2SO4. After filtration and concentration, the crude was purified by chromatography on silica gel (pentane) to give a red solid (150 mg) with similar 1 H NMR spectrum than racemic 5a. However, it contained some inseparable impurities, and was used without further purification in the next step. General procedures for the deprotection-iodination. Cond. a: The ferrocenyl ethynyltrimethylsilane (1 eq.) was dissolved in acetonitrile (10 mL/mmol) and placed in the dark at room temperature. AgF (1.1 eq.) and NIS (1.1 eq.) were successively added and the mixture was stirred for 15h. After filtration General procedure for the alkyne sulfanylation. The alkyne (1 eq.) was dissolved in THF (2 mL/mmol) and the solution was cooled to -78°C. n-BuLi (1.6 M, 1 eq.) was added and stirring was continued for 1h. A solution of N-methyl-N-[(trifluoromethyl)sulfanyl]aniline (1 eq.) in THF (0.5 mL/mmol) was added ad the mixture was stirred at -78°C for 3h. HCl 6M was added and the mixture was extracted with pentane, washed with HCl 6M and water, and dried over Na2SO4. After filtration and concentration, the crude was purified by chromatography on silica gel (pentane) to give the expected product. ((2-Chloroferrocenyl)ethynyl)(trifluoromethyl)sulfane (16a). Red oil (47 mg, 68%) obtained from 14 (0.2 mmol, 49 mg). 1 H NMR (500 MHz, CDCl3) δ 4.56 (dd, J = 2.5, 1.5 Hz, 1H), 4.47 (dd, J = 2.5, 1.5 Hz, 1H), 4.29 (s, 5H), 4.20 (t, J = 2.5 Hz, 1H); [START_REF] Peluso | Enantioseparation of Fluorinated 3-Arylthio-4,4'-Bipyridines: Insights into Chalcogen and -Hole Bonds in High-Performance Liquid Chromatography[END_REF] C NMR (126 MHz, CDCl3) δ 127.8 (q, J = 313.7 Hz), 99. General procedure for the alkyne selenation. In a first flask under argon were added benzyl(trifluoromethyl)selane (1 eq.) and THF (1 mL/mmol). Sulfuryl chloride (1 eq.) was added at room temperature and the mixture was stirred for 15 min then cooled to -78°C. In a second flask, alkyne (1.5 eq.) was dissolved in THF (2 mL/mmol) and the solution was cooled to -78°C. n-BuLi (1.4 M in hexanes, 1.4 eq.) was added and the mixture was stirred for 1h. The alkynyllithium solution was cannulated to the first flask at -78°C. After stirring for 10 min, the temperature was raised to ambient. Water was added and the mixture was extracted with Et2O, and dried over Na2SO4. After filtration and concentration, the crude was purified by chromatography on silica gel (pentane) to give the expected product. ((2-Chloroferrocenyl)ethynyl)(trifluoromethyl)selane (17a). Red oil (104 mg, 71% based on benzyl(trifluoromethyl)selane) obtained from 14 (0.558 mmol, 136 mg), benzyl(trifluoromethyl)selane (0.372 mmol, 88 mg) and sulfuryl chloride (0.372 mmol, 30 L). The general procedure was performed on 15 (0.131 mmol, 32 mg), benzyl(trifluoromethyl)selane (0.087 mmol, 21 mg) and sulfuryl chloride (0.087 mmol, 5.7 L). After purification, the mixture (27 mg) was dissolved in DMSO (2 mL) and LiOH.H2O (0.66 mmol, 28 mg) was added. After stirring for 4h, the mixture was poured on ice and extracted with Et2O. After drying over Na2SO4, filtration and concentration, the crude was purified by chromatography on silica gel (pentane) to give 17b (15 mg, 44% based on benzyl(trifluoromethyl)selane) as a red solid. Mp: 36-38°C. 1 H NMR (500 MHz, CDCl3) δ 4.75 (br s, 1H), 4.51 (br s, 1H), 4.43 (br s, 1H), 4.31 (s, 5H); [START_REF] Peluso | Enantioseparation of Fluorinated 3-Arylthio-4,4'-Bipyridines: Insights into Chalcogen and -Hole Bonds in High-Performance Liquid Chromatography[END_REF] C NMR (126 MHz, CDCl3) δ 120.3 (q, J = 337.3 Hz), 106.4, 92.7, 72.5, 71.8, 70.7, 69.7, 61.5, 61.3 (d, J = 5.0 Hz). [START_REF] Kaasik | Synthesis and Characterisation of Chiral Triazole-Based Halogen-Bond Donors: Halogen Bonds in the Solid State and in Solution[END_REF] F NMR (75 MHz, CDCl3) δ -36.9. HRMS (ESI-TOF) m/z [M] + Calcd for C13H8ClF3FeSe 391.8776; Found 391.8771. General procedure for the Ritter reaction. Benzhydryl bromide 32 (0.04 mmol, 9.9 mg) was placed in a flask under argon. 2 mL of a stock solution (prepared by mixing 30 mL of CH3CN and 14.4 L of H2O) was added followed by a solution of iodoalkyne activator (0.04 mmol) in 1 mL of the same stock solution (note: iodoalkyne 11b was not soluble in CH3CN and was added as a solid). After stirring for 10h at room temperature, the mixture was filtered on Celite and evaporated. The residue was analyzed by 1 H NMR in CD3CN (see spectra in Supporting Information). General procedure for benzoxazole synthesis. Thioacetamide 34 (0.2 mmol, 15 mg), 2-aminophenol (0.4 mmol, 43.6 mg) and the catalyst (0.02 mmol) were placed in a resealable tube under argon. Degassed toluene (0.4 mL) was added and the mixture was stirred for 15h at 90°C. After cooling to room temperature, the crude was filtered on Celite, washed with diethyl ether and concentrated with a rotavapor at 20°C (the use of high vacuum must be avoided). 1 mL of a 0.2 M solution of DMF in dichloromethane was added. Dichloromethane was removed with a rotavapor at 20°C and the residue was analyzed by 1 H NMR (see spectra in Supporting Information). X-ray Structure Determination. X-ray crystallographic data were collected at low temperature on CCD or CMOS diffractometers using Mo(Kα) radiation. Crystal Data for (SFc)-9a. C12H8BrFeI. M = 414.84, monoclinic, a = 8.0567( 7

Figure 1 .

 1 Figure 1. Planes containing the stacking of chains made of I•••C halogen bonds (highlighted in cyan) in (SFc)-9a (left, (101) plane) and in (SFc)-9c (right, (010) plane).

Figure 2 .

 2 Figure 2. Views along [010] (left) and [001]* (right) of the infinite chains made of I•••C halogen bonds (shown in dashed cyan) forming interpenetrating helices (highlighted in blue and green) in 13.

  7, 63.5, 0.3. HRMS (ESI-TOF) m/z [M] + Calcd for C15H17ClFeSi 316.0132; Found 316.0140. ((3-Fluoroferrocenyl)ethynyl)trimethylsilane (5c). Cond. A: 5c (46 mg, 31%) obtained from 2c (0.5 mmol, 165 mg); Cond. B: 5c (111 mg, 74%) obtained from 2c (0.5 mmol, 165 mg). Red oil. 1 H NMR (500 MHz, CDCl3) δ 4.60 (s, 1H), 4.34 (s, 1H), 4.30 (s, 5H), 4.11 (s, 1H), 0.21 (s, 9H); 13 C NMR (126 MHz, CDCl3) δ 134.6 (d, J = 270.9 Hz), 103.2, 91.1, 71.7, 65.0, 59.6 (d, J = 15.1 Hz), 58.5 (d, J = 5.0 Hz), 57.0 (d, J = 15.1 Hz), 0.3; 19 F NMR (75 MHz, CDCl3) δ -186.1. HRMS (ESI-TOF) m/z [M] + Calcd for C15H17FFeSi 300.0427; Found 300.0435.

  C NMR (126 MHz, CDCl3) δ 80.8, 80.5, 76.8, 72.8, 70.9, 70.5, 67.4, 66.0. [α]D 20 = +21 (c = 0.7, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C12H9BrFe 287.9232; Found 287.9228. (SFc)-1-Ethynyl-3-iodoferrocene ((SFc)-40). Red oil (460 mg, 86%) obtained from (SFc)-39 (1.59 mmol, 540 mg). 1 H NMR (500 MHz, CDCl3) δ 4.72 (bs, 1H), 4.453 (s, 1H), 4.451 (s, 1H), 4.25 (s, 5H), 2.77 (s, 1H); 13 C NMR (126 MHz, CDCl3) δ 81.0, 77.8, 75.4, 75.1, 73.1, 72.6, 65.3, 38.9. [α]D 20 = +125 (c = 0.5, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C12H9FeI 335.9093; Found 335.9083.

  (SFc)-((2-Bromoferrocenyl)ethynyl)trimethylsilane ((SFc)-4a). Red oil (1.75 g, 99%) obtained from (SFc)-37 (4.84 mmol, 1.4 g). [α]D 20 = -16 (c = 0.7, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C15H17BrFeSi 359.9627; Found 359.9637. ((SFc)-((3-Iodoferrocenyl)ethynyl)trimethylsilane ((SFc)-41).Red solid (540 mg, 99%) obtained from (SFc)-40 (1.335 mmol, 450 mg). Mp: 50-52°C.1 H NMR (500 MHz, CDCl3) δ 4.69 (s, 1H), 4.43 (s, 1H), 4.41 (s, 1H), 4.22 (s, 5H), 0.22 (s, 9H); 13 C NMR (126 MHz, CDCl3) δ 102.4, 92.3, 77.8, 75.3, 73.2, 72.5, 66.3, 39.1, 0.3. [α]D 20 = +126 (c = 0.6, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C15H17FeISi 407.9488; Found 407.9486.

  2. HRMS (ESI-TOF) m/z [M] + Calcd for C21H22FeSi 358.0835; Found 358.0823. (SFc)-Trimethyl((2-phenylferrocenyl)ethynyl)silane ((SFc)-6a). Red oil (160 mg, 89%) obtained from (SFc)-4a (0.5 mmol, 180 mg). [α]D 20 = -16 (c = 0.5, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C21H22FeSi 358.0835; Found 358.0829. Trimethyl((2-(naphthalen-2-yl)ferrocenyl)ethynyl)silane (6b). Red oil (572 mg, 93%) obtained from 4a (1.5 mmol, 542 mg). 1 H NMR (500 MHz, CDCl3) δ 8.33 (s, 1H), 8.00 (dd, J = 8.5, 1.5 Hz, 1H), 7.83 (m, 3H), 7.47 (m, 2H), 4.74 (m, 1H), 4.65 (m, 1H), 4.38 (t, J = 3.0 Hz, 1H), 4.13 (s, 5H), 0.29 (s, 9H); 13 C NMR (126 MHz, CDCl3) δ 135.6, 133.5, 132.4, 127.85, 127.8, 127.4, 126.7, 126.3, 125.8, 125.6, 104.7, 93.9, 87.5, 73.4, 71.9, 68.85, 68.8, 63.9, 0.3. HRMS (ESI-TOF) m/z [M] + Calcd for C25H24FeSi 408.0991; Found 408.0997. (SFc)-Trimethyl((2-(naphthalen-2yl)ferrocenyl)ethynyl)silane ((SFc)-6b). Red oil (200 mg, 98%) obtained from (SFc)-4a (0.5 mmol, 180 mg). [α]D 20 = +107 (c = 0.5, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C25H24FeSi 408.0991; Found 408.0971. Trimethyl((3-phenylferrocenyl)ethynyl)silane (7a). Red solid (60 mg, 82%) obtained from 5a (0.208 mmol, 75 mg). Mp: 120-122°C. 1 H NMR (500 MHz, CDCl3) δ 7.45 (d, J = 7.0 Hz, 2H), 7.30 (t, J = 7.0 Hz, 2H), 7.21 (t, J = 7.0 Hz, 1H), 4.93 (m, 1H), 4.66 (m, 1H), 4.58 (m, 1H), 4.09 (s, 5H), 0.25 (s, 9H); 13 C NMR (126 MHz, CDCl3) δ 138.3, 128.6, 126.5, 126.3, 104.0, 91.2, 86.3, 72.6, 71.8, 70.1, 67.3, 65.8, 0.4. HRMS (ESI-TOF) m/z [M] + Calcd for Calcd for C21H22FeSi 358.0835; Found 358.0843. Red solid (130 mg, 84%) obtained from (SFc)-41 (0.43 mmol, 175 mg). Mp: 142-144°C. [α]D 20 = +65 (c = 0.5, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C21H22FeSi 358.0835; Found 358.0837. Trimethyl((3-(naphthalen-2-yl)ferrocenyl)ethynyl)silane (7b). Red solid (46 mg, 80%) obtained from 5a (0.141 mmol, 51 mg). Mp: 85-87°C. 1 H NMR (500 MHz, CDCl3) δ 7.86 (s, 1H), 7.79 (m, 3H), 7.61 (dd, J = 8.5, 1.5 Hz, 1H), 7.46 (m, 2H), 5.07 (m, 1H), 4.79 (m, 1H), 4.65 (t, J = 3.0 Hz, 1H), 4.10 (s, 5H), 0.26 (s, 9H); 13 C NMR (126 MHz, CDCl3) δ 135.8, 133.7, 132.4, 128.1, 127.9, 127.7, 126.5, 125.6, 125.2, 124.0, 103.9, 91.3, 86.1, 72.8, 71.9, 70.3, 67.4, 66.1, 0.4. HRMS (ESI-TOF) m/z [M] + Calcd for C25H24FeSi 408.0991; Found 408.0994. (SFc)-Trimethyl((3-(naphthalen-2yl)ferrocenyl)ethynyl)silane ((SFc)-7b). Red solid (150 mg, 85%) obtained from (SFc)-41 (0.43 mmol, 175 mg). Mp: 95-97°C. [α]D 20 = +131 (c = 0.7, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C25H24FeSi 408.0991; Found 408.0991. General procedure for the lithiation/electrophilic trapping.

  C NMR (126 MHz, CDCl3) δ 104.0, 92.5, 87.0, 70.9, 70.6, 69.7, 67.1, 65.8, 13.7, 0.5. HRMS (ESI-TOF) m/z [M] + Calcd for C16H20FeSi 296.0678; Found 296.0671. (RFc)-Trimethyl((2-methylferrocenyl)ethynyl)silane ((RFc)-8). Red solid (120 mg, 73%) obtained by using by using 0.55 mmol of 4a and 0.66 mmol of MeI (neat) as the electrophile. Mp: 33-35°C. [α]D 20 = -49 (c = 0.3, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C16H20FeSi 296.0678; Found 296.0662. (SFc)-((2-Fluoroferrocenyl)ethynyl)trimethylsilane ((SFc)-4c). Red oil (118 mg, 71%) obtained by using 0.55 mmol of 4a and 0.66 mmol of NFSI (solid) as the electrophile. [α]D 20 = -4 (c = 1.4, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C15H17FFeSi 300.0427; Found 300.0431. (SFc)-2-((Trimethylsilyl)ethynyl)cyanoferrocene ((SFc)-4d). Red oil (70 mg, 41%) obtained by using 0.55 mmol of 4a and 0.66 mmol of TsCN (in THF) as the electrophile. [α]D 20 = -37 (c = 0.2, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C16H17FeNSi 307.0474; Found 307.0465. (SFc)-((3-Bromoferrocenyl)ethynyl)trimethylsilane ((SFc)-5a).

(

  SFc)-1-(Iodoethynyl)-2-(naphthalene-2-yl)ferrocene ((SFc)-11b). Cond. a: (SFc)-11b (137 mg, 67%) obtained from (SFc)-6b (0.44 mmol, 180 mg). Red solid. Mp: 127-129°C. [α]D 20 = +90 (c = 0.4, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C22H15FeI 461.9562; Found 461.9541.1-(Iodoethynyl)-3-phenylferrocene (12a).Cond. a: 12a (10 mg, 45%) obtained from 7a (0.053 mmol, 19 mg). Red solid. Mp: 120-122°C.1 H NMR (500 MHz, CDCl3) δ 7.42 (dd, J = 8.0, 1.5 Hz, 2H), 7.27 (t, J = 8.0 Hz, 2H), 7.19 (dt, J = 7.5, 1.5 Hz, 1H), 4.90 (t, J = 1.5 Hz, 1H), 4.64 (dd, J = 2.5, 1.5 Hz, 1H), 4.57 (dd, J = 2.5, 1.5 Hz, 1H), 4.09 (s, 5H);[START_REF] Peluso | Enantioseparation of Fluorinated 3-Arylthio-4,4'-Bipyridines: Insights into Chalcogen and -Hole Bonds in High-Performance Liquid Chromatography[END_REF] C NMR (126 MHz, CDCl3) δ 138.0, 128.6, 126.6, 126.3, 91.9, 86.3, 72.6, 71.7, 70.1, 67.2, 66.5, 0.0. HRMS (ESI-TOF) m/z [M] + Calcd for C18H13FeI 411.9406; Found 411.9391. (SFc)-1-(Iodoethynyl)-3-phenylferrocene ((SFc)-12a). Cond. a: (SFc)-12a (65 mg, 56%) obtained from (SFc)-7a (0.28 mmol, 100 mg). Red solid. Mp: 132-134°C. [α]D 20 = +33 (c = 0.5, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C18H13FeI 411.9406; Found 411.9400. 1-(Iodoethynyl)-3-(naphthalene-2-yl)ferrocene (12b). Cond. a: 12b (8 mg, 44%) obtained from 7b (0.039 mmol, 16 mg). Red solid. Mp: 66-68°C. 1 H NMR (500 MHz, CDCl3) δ 7.84 (s, 1H), 7.79 (t, J = 8.0 Hz, 3H), 7.60 (dd, J = 8.5, 1.5 Hz, 1H), 7.46 (m, 2H), 5.05 (br s, 1H), 4.79 (m, 1H), 4.65 (m, 1H), 4.13 (s, 5H); 13 C NMR (126 MHz, CDCl3) δ 135.6, 133.7, 132.4, 128.1, 127.9, 127.7, 126.5, 125.7, 125.1, 124.6, 91.9, 86.1, 72.9, 71.7, 70.2, 67.2, 66.8, 0.2. HRMS (ESI-TOF) m/z [M] + Calcd for C22H15FeI 461.9562; Found 461.9554. (SFc)-1-(Iodoethynyl)-3-(naphthalene-2-yl)ferrocene ((SFc)-12b). Cond. a: (SFc)-12b (55 mg, 49%) obtained from (SFc)-7b (0.28 mmol, 100 mg); Cond. d: (SFc)-12b (14 mg, 62%) obtained from (SFc)-7b (0.049 mmol, 20 mg). Red solid. Mp: 68-70°C. [α]D 20 = +60 (c = 0.3, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C22H15FeI 461.9562; Found 461.9559. 1-(Iodoethynyl)-2-methylferrocene (13). Cond. a: 13 (47 mg, 50%) obtained from 8 (0.27 mmol, 80 mg). Red solid. Mp: 93-95°C. 1 H NMR (500 MHz, CDCl3) δ 4.35 (dd, J = 2.5, 1.5 Hz, 1H), 4.14 (m, 1H), 4.13 (s, 5H), 4.04 (t, J = 2.5 Hz, 1H), 2.09 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 91.8, 87.2, 70.8, 70.7, 69.6, 67.0, 66.5, 13.8, 0.3. HRMS (ESI-TOF) m/z [M] + Calcd for C13H11FeI 349.9249; Found 349.9236. (RFc)-1-(Iodoethynyl)-2-methylferrocene ((RFc)-13). Cond. a: (RFc)-13 (46 mg, 39%) obtained from (RFc)-8 (0.338 mmol, 100 mg); Cond. d: (RFc)-13 (12 mg, 73%) obtained from (RFc)-8 (0.047 mmol, 14 mg). Red solid. Mp: 153-155°C. [α]D 20 = -9 (c = 0.47, CHCl3). HRMS (ESI-TOF) m/z [M] + Calcd for C13H11FeI 349.9249; Found 349.9233.

  ) Å , b = 9.2384(8) Å , c = 8.9782(7) Å , β = 115.956(3) °, V = 600.85(9) Å 3 , T = 100(2) K, space group P21, Z = 2, μ(Mo Kα) = 7.111 mm -1 , 30382 reflections measured, 5746 independent reflections (Rint = 0.0394). Flack parameter = 0.007(9). The final R1 values were 0.0224 (I > 2σ(I)) and 0.0241 (all data). The final wR(F 2 ) values were 0.0533 (I > 2σ(I)) and 0.0540 (all data). The goodness of fit on F 2 was 1.041. CCDC no. 1995956. Crystal Data for (SFc)-9c. C12H8FFeI. M = 353.93, orthorhombic, a = 16.4655(16) Å , b = 8.9985(8) Å , c = 7.3936(7) Å , V = 1095.47(18) Å 3 , T = 100(2) K, space group P212121, Z = 4, μ(Mo Kα) = 4.168 mm -1 , 32379 reflections measured, 5244 independent reflections (Rint = 0.0331). Flack parameter = 0.00(2). The final R1 values were 0.0176 (I > 2σ(I)) and 0.0184 (all data). The final wR(F 2 ) values were 0.0441 (I > 2σ(I)) and 0.0444 (all data). The goodness of fit on F 2 was 1.090. CCDC no. 1995957. Crystal Data for 9c. C12H8FFeI. M = 353.93, orthorhombic, a = 16.43910(10) Å , b = 8.99930(10) Å , c = 7.41700(10) Å , V = 1097.27(2) Å 3 , T = 100(2) K, space group Pnma, Z = 4, μ(Mo Kα) = 4.161 mm -1 , 79465 reflections measured, 2761 independent reflections (Rint = 0.0482). The final R1 values were 0.0183 (I > 2σ(I)) and 0.0198 (all data). The final wR(F 2 ) values were 0.0483 (I > 2σ(I)) and 0.0490 (all data). The goodness of fit on F 2 was 1.090. CCDC no. 1995952. Crystal Data for (SFc)-11a. C18H13FeI. M = 412.03, orthorhombic, a = 8.8955(9) Å , b = 10.9653(11) Å , c = 15.3106(17) Å , V = 1493.4(3) Å 3 , T = 100(2) K, space group P212121, Z = 4, μ(Mo Kα) = 3.063 mm -1 , 190633 reflections measured, 8528 independent reflections (Rint = 0.0328). Flack parameter = -0.017(14). The final R1 values were 0.0208 (I > 2σ(I)) and 0.0245 (all data). The final wR(F 2 ) values were 0.0462 (I > 2σ(I)) and 0.0473 (all data). The goodness of fit on F 2 was 1.072. CCDC no. 1995958. Crystal Data for (SFc)-11b. C22H15FeI. M = 462.09, orthorhombic, a = 8.4360(6) Å , b = 10.9150(7) Å , c = 19.1274(13) Å , V = 1761.2(2) Å 3 , T = 100(2) K, space group P212121, Z = 4, μ(Mo Kα) = 2.608 mm -1 , 28923 reflections measured, 8376 independent reflections (Rint = 0.0342). Flack parameter = -0.01(2). The final R1 values were 0.0381 (I > 2σ(I)) and 0.0609 (all data). The final wR(F 2 ) values were 0.0730 (I > 2σ(I)) and 0.0802 (all data). The goodness of fit on F 2 was 1.033. CCDC no. 1995959. Crystal Data for 11b. C22H15FeI. M = 462.09, monoclinic, a = 8.1177(2) Å , b = 11.1905(2) Å , c = 18.9284(5) Å , β = 90.164(2) °, V = 1719.47(7) Å 3 , T = 100(2) K, space group P21/n, Z = 4, μ(Mo Kα) = 2.671 mm -1 , 31600 reflections measured, 5160 independent reflections (Rint = 0.0445). The final R1 values were 0.0412 (I > 2σ(I)) and 0.0505 (all data). The final wR(F 2 ) values were 0.0887 (I > 2σ(I)) and 0.0925 (all data). The goodness of fit on F 2 was 1.064. CCDC no. 1995954. Crystal Data for (SFc)-12a. C18H13FeI. M = 412.03, monoclinic, a = 9.7598(10) Å , b = 7.8063(8) Å , c = 10.0468(11) Å , β = 105.676(4) °, V = 736.97(13) Å 3 , T = 100(2) K, space group P21, Z = 2, μ(Mo Kα) = 3.103 mm -1 , 43287 reflections measured, 7044 independent reflections (Rint = 0.0478). Flack parameter = -0.01(2). The final R1 values were 0.0330 (I > 2σ(I)) and 0.0461 (all data). The final wR(F 2 ) values were 0.0588 (I > 2σ(I)) and 0.0620 (all data). The goodness of fit on F 2 was 1.067. CCDC no. 1995960. Crystal Data for (RFc)-13. C13H11FeI. M = 349.97, monoclinic, a = 8.1541(11) Å , b = 8.9666(12) Å , c = 9.0907(12) Å , β = 116.395(4) °, V = 595.37(14) Å 3 , T = 100(2) K, space group P21, Z = 2, μ(Mo Kα) = 3.822 mm -1 , 61869 reflections measured, 5702 independent reflections (Rint = 0.0333). Flack parameter = 0.007(12). The final R1 values were 0.0118 (I > 2σ(I)) and 0.0121 (all data). The final wR(F 2 ) values were 0.0318 (I > 2σ(I)) and 0.0319 (all data). The goodness of fit on F 2 was 1.043. CCDC no. 1995953. Crystal Data for 13. C13H11FeI. M = 349.97, monoclinic, a = 13.14030(10) Å , b = 12.99390(10) Å , c = 14.08200(10) Å , β = 103.6150(10) °, V = 2336.85(3) Å 3 , T = 100(2) K, space group P21/c, Z = 8, μ(Mo Kα) = 3.895 mm -1 , 87060 reflections measured, 11589 independent reflections (Rint = 0.0341). The final R1 values were 0.0209 (I > 2σ(I)) and 0.0285 (all data). The final wR(F 2 ) values were 0.0471 (I > 2σ(I)) and 0.0493 (all data). The goodness of fit on F 2 was 1.046. CCDC no. 1995955.

Table 1 . VS,max [kJ/mol] values calculated on I and Ch - holes (B3LYP-D3/Def2TZVPP) a VS,max [kJ/mol] a

 1

	Entry Compound	I	Ch (CAr/Fc-Ch) b	Ch (Cethynyl-Ch) b	Ch (CCF3-Ch) b
	1	18	181	--	--	--
	2	19	--	100	--	140
	3	20	--	136	--	158
	4	21	122	--	--	--
	5 c	22	--	54/56	--	94/-
	6 c	23	--	87/87	--	113/33
	7	1b	119	--	--	--
	8 c	3a	--	47/51	--	-/81
	9 c	3b	--	81/86	--	-/101
	10	24	183	--	--	--
	11	25	187	--	--	--
	12	26	188	--	--	--
	13	27	189	--
	14 c	28	--	--	95/95	97/106
	15 c	29	--	--	138/135	124/131
	16	30	194	--	--	--
	17	31	176	--	--	--
	18	9c	182	--	--	--
	19	9b	182	--	--	--
	20	9a	182	--
	21 c	16a	--	--	78/83	91/84
	22 c	17a	--	--	119/124	115/110
	23	10b	185	--	--	--

Table 2 . Results of Ritter reaction and benzoxazole synthesis

 2

	XB/ChB donor X/Ch	R	33 (%) a	36 (%) c
	9a	I	2-Br	100	72
	9b	I	2-Cl	91	86
	10b	I	3-Cl	94	64
	9c	I	2-F	35	86
	11a	I	2-Ph	100	97
	11b	I	2-Naph	100	83
	17a	Se	2-Cl	35 b	<5%

a 1 H NMR conversions obtained by integration of peaks at 6.44 ppm (starting material) and at 5.77 ppm (product) in CD3CN (ref. 31); b 60% conversion after 24h; c 1 H NMR yields by using DMF as an internal standard (ref.

30)

.

  •••carbon contacts being clearly under-represented (E(C••C)=0.7-0.8), excepted for (SFc)-12a in which the phenyl groups stacks in somewhat long π••• π contact (E(C,C)=1.06; intercentroid distance of 4.187Å; tilt angle of 23.96°). Whereas H•••H contacts are as well under-represented, contacts of hydrogen atoms with carbon and iodine atoms are overrepresented (excepted in 13 with E(H,I)=0.97).

  : 4b (82 mg, 94%) obtained from 1b (0.277 mmol, 96 mg). Red solid. Mp: 45-47 °C. 1 H NMR (500 MHz, CDCl3) δ 4.45 (m, 1H), 4.37 (m, 1H), 4.24 (s, 5H), 4.08 (m, 1H), 0.27 (s, 9H); 13 C NMR (126 MHz, CDCl3) δ 100.9, 94.7, 94.5, 72.5, 69.5, 68.4, 66.0, 65.1, 0.3. HRMS (ESI-TOF) m/z [M] + Calcd for C15H17ClFeSi 316.0132;

	Found 316.0143.
	((2-Fluoroferrocenyl)ethynyl)trimethylsilane (4c). Cond. A: 4c
	(127 mg, 42%) obtained from 1c (1 mmol, 330 mg); Cond. B: 4c
	(49 mg, 46%) obtained from 1c (0.352 mmol, 116 mg) (50 mg of
	starting material was recovered). Red oil. 1 H NMR (500 MHz,
	CDCl3) δ 4.35 (s, 1H), 4.28 (s, 5H), 4.11 (s, 1H), 3.82 (s, 1H), 0.25
	(s, 9H); 13 C NMR (126 MHz, CDCl3) δ 135.4 (d, J = 274.9 Hz), 99.5
	(d, J = 3.8 Hz), 94.4, 71.6, 65.3 (d, J = 2.5 Hz), 60.9 (d, J = 3.8 Hz),
	56.5 (d, J = 13.9 Hz), 54.6 (d, J = 12.6 Hz), 0.3; 19 F NMR (75 MHz,
	CDCl3) δ -186.7. HRMS (ESI-TOF) m/z [M] + Calcd for C15H17FFeSi
	300.0427; Found 300.0424.
	2-((Trimethylsilyl)ethynyl)cyanoferrocene (4d). Cond. A: 4d
	was obtained from 1d (0.816 mmol, 275 mg) as a 3:2 mixture
	with cyanoferrocene (180 mg); Cond. B: 4d (20 mg, 55%) ob-
	tained from 1d (0.118 mmol, 39.6 mg). Red oil. 1 H NMR (500 MHz,
	CDCl3) δ 4.66 (bs, 1H), 4.63 (bs, 1H), 4.39 (t, J = 2.5 Hz, 1H), 4.36
	(s, 5H), 0.25 (s, 9H); 13 C NMR (126 MHz, CDCl3) δ 118.8, 99.3, 96.2,
	73.8, 72.9, 72.1, 70.8, 69.4, 55.8, 0.2. HRMS (ESI-TOF) m/z [M] +
	Calcd for C16H17FeNSi 307.0474; Found 307.0455.
	((3-Bromoferrocenyl)ethynyl)trimethylsilane (5a). Cond. A:
	5a (176 mg, 48%) obtained from 2a (1.023 mmol, 400 mg); Cond.
	B: 5a (118 mg, 91%) obtained from 2a (0.358 mmol, 140 mg).
	Red solid. Mp: 58-60 °C. 1 H NMR (500 MHz, CDCl3) δ 4.69 (m, 1H),
	4.43 (m, 1H), 4.37 (m, 1H), 4.26 (s, 5H), 0.21 (s, 9H); 13 C NMR
	(126 MHz, CDCl3) δ 102.5, 92.1, 77.2, 73.5, 72.8, 71.0, 70.8, 64.6,
	0.3. HRMS (ESI-TOF) m/z [M] + Calcd for C15H17BrFeSi 359.9627;
	Found 359.9619.
	((3-Chloroferrocenyl)ethynyl)trimethylsilane (5b). Cond. A:
	5b (55 mg, 38%) obtained from 2b (0.462 mmol, 160 mg); Cond.
	B: 5b (134 mg, 92%) obtained from 2b (0.462 mmol, 160 mg).
	Red oil. 1 H NMR (500 MHz, CDCl3) δ 4.67 (s, 1H), 4.40 (m, 1H),
	4.33 (s, 1H), 4.27 (s, 5H), 0.21 (s, 9H); 13 C NMR (126 MHz, CDCl3) δ
	102.6, 92.2, 91.8, 72.5, 71.3, 69.8, 68.
	. A:
	4a (3.04 g, 98%) obtained from 1a (8.57 mmol, 3.35 g); Cond. B:
	4a (115 mg, 89%) obtained from 1a (0.358 mmol, 140 mg). Red
	solid. Mp: 38-40 °C. 1 H NMR (500 MHz, CDCl3) δ 4.47 (s, 1H), 4.41
	(s, 1H), 4.23 (s, 5H), 4.14 (s, 1H), 0.26 (s, 9H); 13 C NMR (126 MHz,
	CDCl3) δ 101.7, 94.5, 81.0, 72.9, 70.8, 70.2, 67.3, 67.0, 0.3. HRMS
	(ESI-TOF) m/z [M] + Calcd for C15H17BrFeSi 359.9627; Found
	359.9613.
	((2-Chloroferrocenyl)ethynyl)trimethylsilane (4b). Cond. A:
	4b (540 mg, 62%) obtained from 1b (2.77 mmol, 960 mg); Cond.

B

  Hz), 101.0, 92.8, 72.5, 72.0, 71.0, 69.9, 63.6 (d, J = 4.3 Hz), 60.8. 19 F NMR (75 MHz, CDCl3) δ -44.4. HRMS (ESI-TOF) m/z [M] + Calcd for C13H8ClF3FeS 343.9331; Found 343.9332.

	4, 95.5, 72.6, 70.6,
	69.6, 67.2, 66.2 (d, J = 4.2 Hz), 62.6. 19 F NMR (75 MHz, CDCl3) δ -
	44.4. HRMS (ESI-TOF) m/z [M] + Calcd for C13H8ClF3FeS 343.9331;
	Found 343.9352.
	((3-Chloroferrocenyl)ethynyl)(trifluoromethyl)sulfane
	(16b). Red oil (22 mg, 52%) obtained from 15 (0.123 mmol, 30
	mg). 1 H NMR (500 MHz, CDCl3) δ 4.76 (br s, 1H), 4.52 (br s, 1H),
	4.44 (br s, 1H), 4.31 (s, 5H); 13 C NMR (126 MHz, CDCl3) δ 127.8 (q,
	J = 313.4

-Chloroferrocenyl)ethynyl)(trifluoromethyl)selane (17b).

	1 H NMR (500 MHz, CDCl3) δ 4.55
	(br s, 1H), 4.46 (br s, 1H), 4.29 (s, 5H), 4.19 (t, J = 2.5 Hz, 1H); 13 C
	NMR (126 MHz, CDCl3) δ 120.3 (q, J = 337.4 Hz), 104.7, 95.3, 72.5,
	70.3, 69.3, 67.0, 63.3, 61.3 (d, J = 3.2 Hz). 19 F NMR (75 MHz, CDCl3)
	δ -36.9. HRMS (ESI-TOF) m/z [M] + Calcd for C13H8ClF3FeSe
	391.8776; Found 391.8793.
	((3

H and[START_REF] Peluso | Enantioseparation of Fluorinated 3-Arylthio-4,4'-Bipyridines: Insights into Chalcogen and -Hole Bonds in High-Performance Liquid Chromatography[END_REF] C NMR spectra of all new compounds; HPLC and computational details; XRD details for structures of SFc-9a, SFc-9c, 9c, SFc-11a, SFc-11b, 11b, SFc-12a, RFc-13, 13 (PDF) and the corresponding cif files.

ACKNOWLEDGMENT

This work was supported by the CNRS and University of Strasbourg. P. Peluso and S.C. are grateful to Università Ca' Foscari Venezia, Italy (Dipartimento di Scienze Molecolari e Nanosistemi, DSMN ADIR funds). We thank the PMD²X X-ray diffraction facility of the Institut Jean Barriol, Université de Lorraine, for X-ray diffraction measurements, data processing and analysis, and providing of reports for publication: http://crm2.univ-lorraine.fr/lab/fr/services/pmd2x). The EXPLOR mesocentre is thanked for providing access to computing facility (project 2019CPMXX0984/wbg13). We thank J. N. Abergel for his help in the preparation of starting dihaloferrocenes.

ASSOCIATED CONTENT Supporting Information

The Supporting Information is available free of charge on the ACS Publications website.

Accession Codes

CCDC 1995952-1995960 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif,orbyemailingdata_requ est@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

AUTHOR INFORMATION Corresponding Authors

* E-mail for V.M.: vmamane@unistra.fr; e-mail for P.P.: paola.peluso@cnr.it

Notes

The authors declare no competing financial interest.


Kenshi Harada

Thi Kim

Ngan Nguyen

Yoshio Matsui

Kazuko Fujii

Fabien Grasset

Naoki Ohashi

Motohide Matsuda

Tetsuo Uchikoshi
email: uchikoshi.tetsuo@nims.go.jp

Observation of stacking faults and photoluminescence of laurate ion intercalated Zn/Al layered double hydroxide

Keywords: Ceramics, LDH, Defects, Microstructure, Intercalation, Photoluminescence

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Layered double hydroxides (LDHs), which consist of two-dimensional (2D) stacking structures, are so-called clay minerals having anion exchange properties, and widely known as host materials in composite materials [1,2]. Because of their advantages, such as being easy to prepare, high stability in air, significant anion-exchange property, and diversity of constituent elements, LDHs have been used for technological applications in variety of fields including catalyst, medicine, gas sorption, and fire retardants [3][4][5][6]. In general, LDHs are represented by the general formula

[M 2+ (1-x) M 3+ x (OH) 2 ] x+ [A n- x/n ・mH 2 O],
where M 2+ = Mg, Zn, Ca, Co, Fe, Ni, Cu, Li,,etc., M 3+ = Al, Fe, Cr, Ga, etc., x is the charge density value of the hydroxide layer, A n-= Cl -, CO 3 2-, NO 3 -, etc. [3][4]21], n is the formal charge of anion, and m is an amount of water molecules [22]. LDHs have positively-charged metal hydroxide layers, in which the anions are stabilized in order to compensate the positive layer charges. Actual LDHs, however, would not be ideally-structured but could partly contain many defects. Recently, it has been pointed out that the defects in the layer structure of layered zinc hydroxide lead to photoluminescence (PL) [7]. Zhang et al. and Xu et al. have observed the PL of exfoliated Zn/Al LDH and Mg/Al LDH in a formamide solvent, and concluded that numerous surface defect sites may be responsible for the PL observed [8,9]. However, no supporting results have been shown for the existence of defects in the previous reports.

. have reported the existence of stacking faults in the LDHs composed of Ni 0.67 Cr 0.33 (OH) 2 (CO 3 ) 0.16 •mH 2 O (3D structure) and Mg 0.67 Al 0.33 (OH) 2 (NO 3 ) 0.33 (2D layered structure) by powder XRD analysis [10].

Although being an effective method to study microstructures including defects, high-resolution transmission electron microscopy (HRTEM) has been limited in the use to confirm their plate-like shapes and survey the interlayer spacing for LDH [11][12][13][14][15]; there seems to be no report showing actually the existence of stacking faults by observation. In considering the previous reports, it must be significant to make a direct observation of stacking faults for further study. The authors have synthesized NO 3 type Zn/Al LDH by co-precipitation method; the interlayers of the LDH synthesized can be expanded by intercalating long chain organic anions between the metal hydroxide layers by ion exchange method. The purpose of the expansion is to get it easier to distinguish single layer of the LDH by HRTEM observation. In this report, structural defects of the LDH expanded by laurate ion whose chain size is about 1.7 nm were characterized by HRTEM observation. In addition, PL measurements were made for the laurate ion-intercalated LDH for further characterization of the defects.

Experimental

Regent grade Zn(NO 3 ) 2 ・6H The interlayer NO 3 -ions give a strong absorption band at 1385 cm -1 [2,16]. The FT-IR spectrum of the expanded-LDH shows absorption peaks at 2800-3000 cm -1 assigned to the asymmetric and symmetric stretching vibrations of methyl and methylene groups, respectively. In addition, two other peaks at 1540 and 1410 cm -1 are associated to the asymmetric and symmetric carboxylate stretching vibrations [17,23]. The absorption around 800 cm -1 is due to metal-oxygen vibrations [16,20].

Those characteristic absorption peaks observed for the expanded LDH clearly indicate the presence of laurate ions in the samples measured, proving that the interlayers of LDH were expanded with the intercalation of laurate anions. Moreover, from the value of the basal spacing determined as 3.87 nm by XRD measurement, it is considered that two molecules of laurate ions with 1.7 nm in a longitudinal size [18] are upright present between the hydroxide layers of which the thickness was 0.48 nm [19]. In Fig. 1, a schematic is shown for double layers consisting of intercalated laurate ions between the hydroxide layers.

Figure 3 shows an HRTEM image of the expanded-LDH with the intercalation of laurate ions.

The dark and bright stripes represent hydroxide layers and laurate ion layers, respectively. The TEM Fig. 1 Fig. 2 Fig. 3 observation provides direct evidence of the formation of layered structures and a defective part: Not only ideal layered structures but also the existence of a stacking defect are obviously confirmed inside the LDH. Our result would be the first case that a stacking defect in an LDH was directly observed by HRTEM.

Photoluminescence spectra of the expanded-LDH measured at the n-times, NO 3 -type LDH, and sodium laurate molecules are shown in Fig. 4. Emission peaks at approximately 400 nm and 440 nm were confirmed with all the expanded-LDH samples by the irradiation of the 325 nm He-Cd laser light. In addition, the photoluminescent intensity of the expanded-LDH was obviously stronger than that of the NO 3 -type LDH and the sodium laurate molecules. According to the previous reports [7][8][9], the reason was probably due to the presence of a lot of defects in the expanded LDH which would be induced by the interaction between the heterogeneous substances (LDH and laurate ion).

As mentioned in the introduction, Zhang et al. and Xu et al. have reported the phenomenon that both the Zn/Al LDH (Zn/Al = 4) and Mg/Al LDH colloids containing their exfoliated nanoparticles exhibited photoluminescent emission spectra at 417 and 441 nm, respectively, under the irradiation of 378 nm UV light due to the increased surface defects resulting from the significant exfoliation [8,9]. Our results give out that similar photoluminescent phenomenon is obviously detected by expanding the interlayer of the LDH even without exfoliation. Interestingly, the PL intensity decreased when the photoluminescence measurements of the same sample were repeated; the energy of excitation laser might influence on the LDH and/or the intercalated laurate ions.

Conclusions

Defects in Zn/Al LDH were investigated by HRTEM observation. HRTEM observation of the expanded-LDH showed multilayer structure. In addition, defects with disordered stacking could be observed. PL measurement of the expanded-LDH showed very strong emission than those of the sodium laurate and nitrate LDHs. It was probable that the PL was observed due to the introduction of the defects in the LDH structure. However, the PL was weakened by repeating the measurements.

Acknowledgment

This study was carried out as part of the France-Japan international collaboration framework through the Laboratory for Innovative Key Materials and Structures (UMI 3629-LINK Center). The study was financially supported by the National Institute for Materials Science (NIMS), Kumamoto Univ., Saint-Gobain (France) and CNRS. The authors wish to thank David Lechevalier of Saint-Gobain KK (Tokyo, Japan) involved in LINK and related activities.  LDH with intercalation of laurate ions exhibited photoluminescence.

 Interlayer of LDH was expanded by intercalating laurate ions.

3 .

 3 2 O, Al(NO 3 ) 3 ・9H 2 O, sodium nitrate (KISHIDA CHEMICAL Co., Ltd.) and sodium laurate (Nacalai Tesque Inc.) were used as raw materials without further purification. The Zn/Al LDH was prepared by co-precipitation method under nitrogen atmosphere to avoid the contamination of carbonates between the LDH layers. An aqueous mixed solution (42 mL) containing Zn(NO 3 ) 2 6H 2 O (0.028 mol) and Al(NO 3 ) 3 9H 2 O (0.014 mol) was continuously added dropwise to 1M NaNO 3 aqueous solution (140 mL) with stirring at room temperature. The pH value of the mixed solution was adjusted at pH=10 throughout the precipitation by adding 1 M NaOH aqueous solution. The precipitate was centrifuged at 15000 rpm for 10 min to remove the supernatant liquid and then washed with distillated water several times. The resulting white slurry was dried at 50C. The prepared NO 3 -type Zn/Al LDH powder (0.1 g) was dispersed in distilled water (10 mL), and then a few drops of 1 M NaOH aqueous solution were added to adjust the pH of the slurry at about 10. After that, 0.1 M sodium laurate solution (10 mL) was added and the mixture was stirred for about 15 hours. X-ray powder diffraction (XRD) analyses were carried out on a Rigaku MiniFlex600 diffractometer with CuK r d on (λ=1.5418 Å), using the operation voltage and current of 40 kV and 15 mA, respectively. Fourier transform infrared (FT-IR) spectra were measured on an ATR PRO 450-S spectrometer in the range of 800-4000 cm -1 using the KBr pellet technique. HRTEM analysis was carried out on a JEOL JEM-2100F at 200 kV in bright field imaging. A micro PL system (Horiba, LabRAM HR) with a 325 nm He-Cd laser system was used to record the photoemission peaks in the wavelength range 350 nm and 1000 nm. The PL measurement was conducted several times on the same sample. Results and discussion XRD patterns of the synthesized NO 3 -type Zn/Al LDH before and after the reaction with sodium laurate solution are shown in Fig. 1. The XRD pattern of the NO 3 -type Zn/Al LDH displays typical diffraction peaks based on a nitrate form of the LDH indexed with rhombohedral symmetry (d 003 =0.89 nm) [2, 16]. A pronounced change was observed in the XRD pattern after the reaction: the XRD peaks shifted to o r 2θ ng compared with the NO 3 -type Zn/Al LDH. The low angle pattern is shown in Fig. 1 (b). These peaks are indexed as (00l) diffractions; therefore, it was identified as expanded-LDH intercalated by laurate ions (d 003 =3.87 nm). It was concluded that the use of the laurate ions attain high effectiveness in expanding the distance of LDH. FT-IR spectra of the NO 3 -type Zn/Al LDH and the expanded-LDH are shown in Fig. 2. The FT-IR spectrum of the NO 3 -type Zn/Al LDH presents broad absorption peaks in the wavelength range of 3200-3600 cm -1 and at 1620 cm -1 , which are assigned to the O-H stretching absorption of the hydroxide layers and the deformation vibration of the interlayer water molecules, respectively.

Fig. 4

 4 Fig. 4

Figure Captions:Fig. 1 XRD

 1 Figure Captions:

Fig. 2 FT

 2 Fig. 2 FT-IR spectra of (a) NO 3 -type Zn/Al LDH and (b) LDH expanded by reaction with sodium laurate

Fig. 4

 4 Fig. 4 PL spectra of (a) expanded-LDH measured at the n-times, (b) sodium laurate, and (c) NO 3 -type LDH, respectively.

Fig. 1 Fig. 3

 13 Fig.1

Fig. 2 Fig. 4 Highlights

 24 Fig. 2