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.
The effect of N-substituent of α-hydroxyamides on the performance of chiral N-heterocyclic carbene-catalyzed kinetic resolution was examined. N-tert-Butyl-α-hydroxyamides provided the best performance and underwent enantioselective acylation with α-bromo aldehyde by chiral N-heterocyclic carbene/carboxylate anion co-catalysis to realize kinetic resolution in high selectivity factor up to 128.
A remote electronic effect of chiral aminoindanolderived N-heterocyclic carbene catalyst on an asymmetric benzoin reaction was investigated. The catalyst bearing remote electron-withdrawing substituents increased enantioselectivity of the reaction at the cost of the reaction rate. DFT calculations rationalized the increased enantioselectivity.
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