Asymmetric synthesis of trisubstituted tetrahydrothiophenes bearing a quaternary stereocenter via double Michael reaction involving dynamic kinetic resolution

Abstract

The stereoselective synthesis of highly functionalized tetrahydrothiophenes bearing three contiguous stereocenters, one of them quaternary, can be achieved by reacting trans-α-cyano-α,β-unsaturated ketones and trans-tert-butyl 4-mercapto-2-butenoate in the presence of a readily available amine thiourea. The products are obtained in high yield, good diastereoselectivity, and excellent enantioselectivity. The overall formation of tetrahydrothiophenes occurs via a cascade double Michael reaction involving a highly efficient process of dynamic kinetic resolution.