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

Abstract

We describe a new way of understanding enhanced molecular recognition through substrate–additive complex formation and the development of the first catalytic kinetic resolution of α-hydroxythioamides, which are versatile synthetic building blocks, using chiral N-heterocyclic carbene-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.