Search

We present a thought-provoking development in chiral resolution. Using a resolving agent of a given handedness, L-proline, we show that both R- and S-enantiomers of mandelic acid can be resolved from a racemic mixture simply by varying the stoichiometry. We are the first to report this specific feature, achieved by the existence of stoichiometrically diverse cocrystal systems between R- and S-mandelic acid and L-proline.

We tap into an unexplored area of preferential crystallization, being the first to develop simultaneous chiral resolution of two racemic compounds by preferential cocrystallization. We highlight how the two racemic compounds RS-mandelic acid (MAN) and RS-etiracetam (ETI) can be combined together as enantiospecific R-MAN:R-ETI and S-Man:S-ETI cocrystals forming a stable conglomerate system and subsequently develop a cyclic preferential crystallization allowing to simultaneous resolve both compounds. The developed process leads to excellent enantiopurity both for etiracetam (ee>98%) and mandelic acid (ee~95%) enantiomers.

ortho-Substituted and unsymmetrical 9-phospha-triptycenes were synthesized via two synthetic approaches involving densely functionalized ortho-halogenated triarylmethane or phosphine precursors. ortho-Substituents imposed a considerable steric shielding due to the tricyclic cage-shaped structure with the aryl rings p-systems orthogonal to the phosphorus electron pair. A series of Au(I) and Rh(I) complexes were analysed in the solid state to determine Tolman electronic parameters, cone angles and buried volumes of these unprecedented functionalized phosphines. Quantum chemical calculations of electronic and steric descriptors revealed that these cage-shaped phosphines are electron-poor and that single methyl substituent is enough to provide the largest effect on steric shielding reported so far in triarylphosphines. An unsymmetrically substituted 9-phosphatriptycene was resolved by chiral HPLC, opening the avenue towards stable P-chirogenic triarylphosphines with unlimited configurational stability for new catalyst development in asymmetric transition-metal catalysis.

We recently introduced a thermodynamically based deracemization process, co-crystallization-induced spontaneous deracemization (CoISD). Following the successful development of the CoISD process, we aimed at improving both yield and deracemization and, consequently, the productivity of the process. As the process is based on co-crystallization of the target enantiomer combined with a racemization reaction of the undesired enantiomer, both reaction and crystallization kinetics and thermodynamics need to be considered for optimization. Taking previously published kinetic parameters into account, here we investigate the nature of the solvent, concentration of the racemizing agent, equivalent of the acid co-former, and temperature of the crystallization cell. The evaluation of each parameter allowed for improvement of the yield and/or deracemization, ultimately providing an optimized process with a yield of 73% of pure co-crystals for an overall deracemization of 80%, in parallel, highlighting the viability of recycling the remaining mother liquors.

In this paper, we identified a cocrystal conglomerate of mandelic acid using a drug compound as a coformer. We then developed a chiral resolution process based on preferential cocrystallization. Several versions of such a process were explored and optimized, leading to a successful resolution of mandelic acid, evidencing the efficiency of our system. Excellent enantiopurity (98–99%) was obtained with a process that can run for multiple cycles.

The enantioselective synthesis of synthetically significant (  -hydroxyallyl)silanes, (  -hydroxyaryl)silanes and (  hydroxyalkyl)silanes is reported. The present copper-catalysed 1,2hydroborylation of acylsilanes affords the aforementioned products in high yields and high enantiomeric excesses. This robust and scalable additive-free catalytic system relies on the use of low copper(II) acetate and diphosphine ligand loadings at room temperature in the presence of a commercially available and bench stable hydride source.

The total oil production capacity of isano oil is estimated at about 10,000 tons annually. Previous studies of this oil revealed that it is rich in fatty acids including a conjugated diyne moiety. This makes isano oil an excellent candidate for sustainable applications development. However, only a few of its fatty acids have been isolated and identified so far. In this study, we have reinvestigated this oil by characterizing its physicochemical properties and isolating several of its fatty acids as ethyl esters for their detailed structural analysis and identification. Six ethyl esters of fatty acids constituting isanic oil were isolated by flash column chromatography and semi-preparative HPLC. The detailed structural analysis of these fatty acid esters by IR, (HR)MS, and NMR (1D and 2D) allowed determining unequivocally their chemical structure. The main fatty acid component of the oil (35.7 %) was identified as isanic acid. Four minor acids were found to possess also two conjugated triple bonds while the sixth fatty acid does not contain carbon-carbon triple bonds nor double bonds but possess a cis epoxide function. Results obtained in this study are currently being used to explore potential applications of isano oil.

We report herein the application of polymer brushes for the immobilization of tris[(1,2,3-triazolyl)methyl]amine CuCl catalysts. Well-defined catalytic brushes were prepared through grafting-from and postpolymerization modification approaches on Si surfaces and characterized by X-ray reflectivity, X-ray photoelectron spectroscopy, and inductively coupled plasma mass spectrometry. Hairy catalysts of varying thickness and grafting density were investigated in a model CuI-catalyzed azide-alkyne cycloaddition reaction and showed remarkable activity at loadings as low as 0.02 mol-% as a result of the unique catalytic site density and nuclearity found in the brush. We demonstrate that thickness and grafting density parameters can be adjusted to maximize catalytic activity along the brush thickness. Take the dense floor: Polymer brushes of varying thickness and grafting density are used for the immobilization of tris[(1,2,3-triazolyl)methyl]amine CuCl catalysts and evaluated in a model CuI-catalyzed azide-alkyne cycloaddition reaction. Kinetic studies reveal that effective turnovers can be achieved throughout the volume of the brush by tuning thickness and density parameters to enable accessibility to the lower layers of the catalytic brush

This paper describes a tunable and stereoselective dual catalytic system that uses copper and palladium reagents. This cooperative silylcupration and palladium-catalyzed allylation readily affords trisubstituted alkenylsilanes. Fine-tuning the reaction conditions allows selective access to one stereoisomer over the other. This new methodology tolerates different substituents on both coupling partners with high levels of stereoselectivity. The one-pot reaction involving a CuI/Pd0 cooperative dual catalyst directly addresses the need to develop more time-efficient and less-wasteful synthetic pathways. © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The goal of this contribution is to guide the reader through the construction and the understanding of quaternary phase diagrams in the pursuit of optimal conditions for a chiral resolution through cocrystallization in solution. The overall description will be illustrated by experimental results on a system involving RS-2-(2-oxopyrrolidin-1-yl) butanamide as chiral API to be separated, and S-mandelic acid as chiral coformer. © 2013 The Royal Society of Chemistry.

Tris(tetrathioaryl)methanols and tris(tetrathioaryl)methanes are direct precursors and metabolites, respectively, of tris(tetrathioaryl)methyl radicals, which are very attractive paramagnetic spin probes for many magnetic resonance applications. Due to steric hindrance, these propeller-shaped molecules display slow interconversion between their two enantiomeric conformations (right-handed and left-handed propeller conformations). Syntheses and HPLC resolutions carried out on a chiral stationary phase have been achieved. The influence of the hybridization of the central carbon atom as well as the para substitutient on the conformational stability were experimentally and theoretically studied. Depending on their particular structure, the free activation energy for the isomerization process determined by kinetics of racemization varies from 24.4 to 26.4 kcal mol -1 and corresponds to racemization half-lives of 12 and 343 h, respectively. Computational and NOESY/exchange spectroscopy (EXSY) studies are consistent with a two-ring flip mechanism for the isomerization process of tris(tetrathioaryl)methanols, radicals and tris(tetrathioaryl) methanes. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The synthesis and characterization of imidazole-containing macrocycles displaying planar chirality has been achieved. HLPC and NMR studies revealed the crucial role of the alicyclic chain length in determining the rate of stereoisomerisation: 15- and 16-membered cyclic compounds are chiral whereas their larger-ringed analogues equilibrate rapidly at room temperature. Computational calculations are in good agreement with experimental observations and allow us to understand the mechanism and the interactions involved in the conformational equilibrium between the two atropisomers. Separation of the two enantiomers of the 15-membered macrocycle by semipreparative chiral HPLC allowed us to investigate the influence of chirality on its biological activity.