Orthogonal Relay Organocatalysis for Stereodivergent Sequential Michael Reactions

Stereodivergent synthesis via sequential organocatalysis remains challenging due to competing stereocontrol and catalyst interference. Herein, we report a stereodivergent one-pot process combining iminium-and enamine-mediated Michael reactions using structurally related diarylprolinol silyl ether catalysts. Switching the second catalyst selectively affords either anti or syn products with high enantioselectivity. Mechanistic studies reveal distinct reactivity profiles that enable catalyst orthogonality. This strategy provides an efficient approach to stereodivergent synthesis using closely related organocatalysts.