Search

International audience; Crystal engineering based on σ -hole interactions is an emerging approach for realization of new materials with higher complexity. Neutral inorganic clusters derived from 1,2-dicarba- closo -dodecaborane, substituted with -SeMe, -TeMe, and -I moieties on both skeletal carbon vertices are experimentally demonstrated here as outstanding chalcogen- and halogen-bond donors. In particular, these new molecules strongly interact with halide anions in the solid-state. The halide ions are coordinated by one or two donor groups ( μ 1 - and μ 2 -coordinations), to stabilize a discrete monomer or dimer motifs to 1D supramolecular zig-zag chains. Crucially, the observed chalcogen bond and halogen bond interactions feature remarkably short distances and strong directionality. Electrostatic potential calculations further demonstrate the efficiency of the carborane derivatives, with V s,max being similar or even superior to that of reference organic halogen bond donors such as iodopentafluorobenzene.

International audience; The successful topochemical polymerization of bis(selenocyanatomethyl)butadyine 1 is achieved upon association in a 1 : 1 co-crystal with 1,2-bis(2-pyridyl)ethylene (2-bpen) through strong and linear (NC)-Se⋅⋅⋅N(Py) chalcogen bonding (ChB) interactions, allowing for an appropriate parallel alignment of the diacetylene moieties toward the solid-state reaction. Co-crystal 1⋅(2-bpen) undergoes polymerization upon heating at 100 °C. The reaction progress was monitored by IR, DSC and PXRD. An enhancement of the polymer conductivity by 8 orders of magnitude is observed upon iodine doping. Strikingly, the course of polymerization is accompanied with sublimation of the ChB acceptor molecules 2-bpen, providing the polymer in a pure form with full recovery of the co-former, at variance with the usual hydrogen-bonded co-crystal strategies toward polydiacetylenes.

New chiral tetra- and bidentate ligands derived from the (R)-1,2-diaminobicyclo[2.2.2]octane scaffold have been synthesized and the influence of ligand N,N'-substituents on the catalytic activity of their corresponding copper(II) complexes toward nitroaldol reaction have been investigated. Among them, the complex generated in situ by the interaction of the (R)-N,N'-Bis(1-naphthylmethyl)-1,2-diaminobicyclo[2.2.2]octane ligand L10 with Cu(OAc)2 proved to be the most effective for the asymmetric Henry reaction of nitromethane with various aldehydes, providing b-nitroalcohols in moderate to good yields, and enantioselectivity (up to 86%). In an attempt to rationalize the factors that control enantiodifferentiation, the most stable geometries of this C1-symmetric bicyclic copper ligand complex, as well as plausible transition structures of the nitroaldol reaction, were investigated by DFT calculations.

Cryptophanes are receptors consisting of two bridging concave cyclotribenzylene (CTB) subunits. The formation of cryptophanes in basic aqueous solutions (0.1 m MOD; M = Li, Na, K, and Cs) by disulfide bridge formation has been investigated. Two original CTBs, 1H6 and 2H6, derived from cyclotriphenolene through the introduction of mercaptomethyl and mercapto substituents, respectively, were synthesized. Cryptophane formation by slow oxygenation of 16– was observed only in the presence of Me4N+ as template, which yielded the diastereomeric forms in a ratio of around 82:18. By contrast, the rigid CTB 2H6 yielded a cryptophane stereoselectively without a template. Interestingly, air oxidation of a 1:1 mixture of 16– and 26– in the presence of Me4N+ (0.5–1 equiv./16–) in 0.1 m LiOD led to the exclusive formation of the cryptophane complex [(1·1)6–⊃+NMe4], (2·2)6– being formed only in very minor amounts. No mixed species were detected in the reaction mixtures. The stabilities of the diastereomers of the protonated cryptophanes were calculated in the gas phase by DFT at the ωB97XD 6-311G(d,p) level of theory.

The term Atropisomerism defines a type of enantiomerism that arises from hindered rotation around an axis that makes two rotational isomers enantiomers. Atropisomeric compounds are present in nature, being important building blocks of many biologically active compounds. Atropisomers have been extensively studied in environmental and toxicological chemistry and, in particular, separating them has become a need in specific fields as organic synthesis and pharmaceutical research. High-performance LC has been fruitfully applied in this context, and despite HPLC separation on chiral stationary phase is considered as mature technology nowadays, in the last years several advancements and applications contributed to study compounds where axial chirality is of utmost importance. Moreover, dynamic chromatography has been exploited as a versatile tool for kinetic studies of systems with slow internal motion gaining essential information on their stereodynamic behavior. On this basis, current topics and trends in liquid-phase chromatography enantioseparation of atropisomers are presented herein with specific focus on new representative applications with HPLC, covering years 2010-2016. Some examples concerning supercritical fluid chromatography applications are also reported. This review aims to provide the reader with a modern overview of the field to highlight the renewed interest toward the chemistry of molecules with atropisomeric properties. A systematic compilation of all published literature has not been attempted.

An investigation on the high-performance liquid chromatography enantioseparation of 12 polyhalogenated 4,4'-bipyridines on polysaccharide-based chiral stationary phases is described. The overall study was directed toward the generation of efficient separations in order to obtain pure atropisomers that will serve as ligands for building homochiral metal organic frameworks. Four coated columns--namely, Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-4, and Lux Amylose-2--and two immobilized columns--namely, Chiralpak IC and IA--were used under normal, polar organic, and reversed-phase elution modes. Moreover, Chiralcel OJ was considered under normal-phase and polar organic conditions. The effect of the chiral selector and mobile phase composition on the enantioseparation, the enantiomer elution order and the beneficial effect of nonstandard solvents were studied. The effect of water in the mobile phase on the enantioselectivity and retention was investigated and retention profiles typical of hydrophilic interaction liquid chromatography were observed. Interesting phenomena of solvent-induced enantiomer elution order reversal occurred under normal-phase mode. All the considered 4,4'-bipyridines were enantioseparated at the multimilligram level.

The HPLC enantioseparation of nine atropisomeric 3,3',5,5'-tetrasubstituted-4,4'-bipyridines was performed in normal and polar organic (PO) phase modes using two immobilized polysaccharide-based chiral columns, namely, Chiralpak IA and Chiralpak IC. The separation of all racemic analytes, the effect of the chiral selector, and mobile phase (MP) composition on enantioseparation and the enantiomer elution order (EEO) were studied. The beneficial effect of nonstandard solvents, such as tetrahydrofuran (THF), dichloromethane (DCM), and methyl t-butyl ether on enantioseparation was investigated. All selected 4,4'-bipyridines were successfully enantioseparated on Chiralpak IA under normal or PO MPs with separation factors from 1.14 to 1.70 and resolutions from 1.3 to 6.5. Two bipyridines were enantioseparated at the multimilligram level on Chiralpak IA. Differently, Chiralpak IC was less versatile toward the considered class of compounds and only five bipyridines out of nine could be efficiently separated. In particular, on these columns, the ternary mixture n-heptane/THF/DCM (90: 5: 5) as MP had a positive effect on enantioseparation. An interesting phenomenon of reversal of the EEO depending on the composition of the MP for the 3,3'-dibromo-5,5'-bis-(E)-phenylethenyl-4,4'-bipyridine along with an exceptional enantioseparation for the 3,3'-dibromo-5,5'-bis-ferrocenylethynyl-4,4'-bipyridine (alpha = 8.33, R-s = 30.6) were observed on Chiralpak IC.

The preparation of 27 isomers of chiral hexahalogeno-4,4′-bipyridines by means of two complementary methods is described. The first one is convergent and based on the LDA-induced 4,4′-dimerization of trihalopyridines, whereas the second method is divergent and achieved through regioselective halogenation reactions of 4,4′-bipyridine-2,2′-diones. Iodine in 2,2′-positions of the 4,4′-bipyridines was introduced by a copper-catalyzed Finkelstein reaction (Buchwald procedure) performed on 2,2′-dibromo derivatives. Selected compounds of this new family of atropisomeric 4,4′-bipyridines were enantioseparated by high performance liquid chromatography on chiral stationary phases, and the absolute configurations of the separated enantiomers were assigned by using X-ray diffraction analysis. The latter revealed that various halogen bond types are responsible for crystal cohesion.

Catalytic properties of 15 N-pyrrolidine-based α,β-peptides incorporating a constrained 2-aminobicyclo[2.2.2]octane carboxylic acid (ABOC) are evaluated in the asymmetric aldol reaction from acetone and some p-substituted benzaldehydes.

The oxidation of racemic methylthio-substituted C3-symmetric cyclotriveratrylene (CTV) 2 produces the corresponding trisulfoxides 3 as follows. Oxidation with m-chloroperoxybenzoic acid (m-CPBA) in dichloromethane leads to the formation of a distribution of the four possible diastereomers that is relatively close to the statistical outcome, in which the C3-symmetric stereoisomers are the minor species. In contrast, the optically active Davis reagent [oxaziridine (+)-4] in carbon tetrachloride at room temperature leads to a biased (73 %) distribution in favor of the C3-symmetric MRRR/PSSS diastereomer of 3 with 56 % ee (PSSS enantiomer according to the model of Davis). Interestingly, when the oxidation is carried out in toluene at reflux, the distribution is switched to approximately equal amounts of the C3-symmetric MSSS/PRRR and asymmetric MRSS/PSRR diastereomers of 3. Overall, however, these results point to the negligible role played by the chirality of the CTV platform on the induction of chirality at the sulfur prochiral centers.

Molecular recognition between receptor and substrate is optimized when these compounds show complementary shapes, sizes, and interacting moieties. A family of C3v-symmetric macrotricycles 1–4 is presented that incorporate resorcinol- and mesitylene-derived “walls” and “cap”, respectively. These compounds feature, in principle, a tetrahedral π-basic cavity. This paper reports the effect of substituents in the “walls” and the “cap” on the shapes of the macrotricycles in solution (1H NMR), the solid state (X-ray diffraction), and gas phase (calculations). Substitution of the lower position of the “walls” by Br (in 3) or MeS (in 4) has the same effect as ethyl substitution of the “cap” (in 2), that is, imparting high rigidity to the molecules and deforming their expected spherical shape to a cylindrical one.

Lithiation of the achiral tetrahalogenated 4,4′-bipyridine 1 with alkyllithiums was investigated. n-BuLi was found to induce either the chlorine-directed deprotolithiation reaction alone or with a concomitant halogen–lithium exchange furnishing after iodine trapping chiral 4,4′-bipyridines 2 and 6, respectively. The role of n-BuLi in the deprotolithiation process of 1 was elucidated on the basis of isolated secondary derivatives. After deprotolithiation, the lithiated species could be trapped by different electrophiles such as MeI, TMSCl, MeSSMe, R3SnCl (R = Me or n-Bu), and PPh2Cl. Moreover, 4,4′-bipyridine 2 was submitted to cross-coupling reactions (Suzuki and Sonogashira) which occurred selectively at the carbon–iodine bond. All compounds of this new family of atropisomeric 4,4′-bipyridines were separated by chiral HPLC (high-performance liquid chromatography), and the absolute configurations of obtained enantiomers were mainly assigned by XRD (X-ray diffraction) using anomalous dispersion.

International audience; Cryptophanes are macropolycyclic cyclophanes constructed from two triply bridged concave cyclotriveratrylene analogues that encapsulate a large range of molecular and monoatomic substrates. Self-assembled metallo-organic cryptophanes based on M2+–carbonitrile (M = Pd or Pt) interactions have been obtained through the reactions of chiral nitrile-substituted cyclotribenzylenes (CTBs) 1 and 2 with [M(dppp)][OTf]2 (dppp = 1,3-bisdiphenylphosphinopropane, OTf = triflate) in 2:3 ratios in chlorinated solvents. The cryptophanes [Pd3(dppp)3(1)2]6+ and [Pd3(dppp)3(2)2]6+ were obtained exclusively in the chiral anti form in solution at room temperature whatever solvent was used; however the meso,syn form was identified as the major isomer of [Pd3(dppp)3(1)2]6+ at low temperature in CD2Cl2, and – in the case of [Pt3(dppp)3(1)2]6+ – it formed in a minor amount at room temperature. [Pd3(dppp)3(1)2][OTf]6 and [Pt3(dppp)3(1)2][OTf]6 crystallized in the anti forms with an encapsulated chloroform molecule, and gas-phase DFT calculations with the dispersion-corrected B97-D3 functional show that it is stabilized by 34.6 kJ mol–1. Interestingly, the heteroleptic cryptophane [Pd3(dppp)3(1)(2)]6+ was not detected in mixtures of [Pd(dppp)]2+ and CTBs 1 and 2 in a 3:1:1 ratio or through the equilibration of a 1:1 mixture of the preformed homoleptic cryptophanes; this points to favored self-sorting processes.

A new family of pentacyclic compounds incorporating a central 1,2-dihydropyridine core is obtained through a pseudo three-component reaction. Four new bonds and two stereocenters with trans relationship are produced during the cascade process under palladium catalysis.

Treatment of halogenated pyridines with LDA results in convenient formation of 4,4′-bipyridines.

The reaction of 2-picoline at the methyl group with NDA and KDA followed by dimethyldisulfide trapping furnished, respectively, dithioacetals and trithioortho esters with high selectivity. The method was successfully applied to other methyl-substituted pyridines, quinolines, and pyrazines. Dithioketals were prepared by a one-pot procedure involving the reaction of metalated 2-picoline with 2 equiv of dimethyldisulfide followed by in situ trapping with a second electrophile. All of the generated thio-substituted compounds were efficiently transformed in presence of mercury salts or under oxidizing conditions to other functional groups comprising aldehydes, ketones, ketals, thiol esters, orthoesters, and esters.