Enhanced Molecular Recognition through Substrate–Additive Complex Formation in N-Heterocyclic-Carbene-Catalyzed Kinetic Resolution of α-Hydroxythioamides

We describe a way of understanding enhanced molecular recognition through substrate–additive complex formation, and the development of the catalytic kinetic resolution of α-hydroxythioamides, which are versatile synthetic building blocks, using chiral N-heterocyclic carbine-catalyzed enantioselective acylation assisted by a carboxylate additive. Mass spectrometry provided evidence for the role of the additive, which forms a hydrogen-bonded complex with α-hydroxythioamide, resulting in both rate and selectivity enhancements. The synthetic applications of the resolved α-hydroxythioamides highlight the usefulness of the developed method.

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Catalysis, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acscatal.2c01579.