Chiral synthetic unprecedented spiro[indoline-2,3′-thiophen]-3-ones via an organocatalytic asymmetric sulfa-Michael/aldol cascade reaction

Abstract

An asymmetric sulfa-Michael/aldol cascade reaction of 2-ylideneoxindoles with 1,4-dithiane-2,5-diol catalyzed by squaramide derived from cinchona was first developed to realize the chiral synthesis of unprecedented C2-spirooxindoles with a 3-amine-tetrahydrothiophene moiety incorporated into a spiro hetero-quaternary carbon center and three consecutive chiral centers (30 examples; up to 95% yield, >20 : 1 dr and 99% ee). For some examples of poor enantioselectivity, the optical purity of spiro[indoline-2,3′-thiophene]-3-ones can be further improved by cocrystallization without the addition of other pure cocrystallization additives. In addition, DFT calculations offered a mechanistic explanation for this high stereoselectivity of the sulfa-Michael/aldol cascade reaction.