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A one-carbon homologation of Knoevenagel adducts enabling the insertion of a CHAr fragment is reported. The strategy involves a sulfur ylide mediated cyclopropanation followed by the rearrangement of cyclopropanes and enables the synthesis of a series of benzhydryl derivatives. Mechanistic studies reveal that the cyclopropane rearrangement involves a Lewis acid catalyzed ring-opening followed by the 1,2-migration of an aryl group. The possibility of controlling the absolute stereochemistry of the generated stereogenic allylic carbon center using a chiral sulfonium ylide is demonstrated.

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 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.

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.