Enantioselective Desymmetrization of<i>para</i>-Quinamines through an Aminocatalyzed Aza-Michael/Cyclization Cascade Reaction

Abstract

An unprecedented organocatalytic asymmetric desymmetrization of para-quinamines leading to functionalized hydroindoles, a common motif in many alkaloids, has been reported. The ability of diarylprolinol silyl ethers to promote iminium and enamine activation of α,β-unsaturated aldehydes in one catalytic cycle is the centerpiece of the strategy involving a challenging aza-Michael/intramolecular cyclization cascade reaction. A range of prochiral para-quinamines and α,β-unsaturated aldehydes were investigated to afford 16 examples of hydroindoles possessing four contiguous stereocenters including one quaternary carbon. The hydroindole structures include multiple orthogonal functionalities, which underwent various transformations.