Exploiting Vinylogy in Iminium-Catalyzed Desymmetrization of Cyclohexadienones

Abstract

Desymmetrization of cyclohexadienones via a vinylogous Michael reaction, promoted by a cinchona alkaloid derived 9-amine catalyst, has been developed. The reaction proceeds through the iminium activation and leverages intermolecular addition, where a nucleophile attacks the β-position of the enone system, breaking the molecular symmetry with high enantioselectivity. The reaction led to a coumarin-derived 3,4-disubstituted cyclohexyl skeleton with the creation of two contiguous chiral centers in good yield with high stereocontrol. The asymmetric desymmetrization displays a broad substrate scope, stereodivergence, and diverse postsynthetic modification without erosion in selectivity.