Enantioselective Radical–Radical Cross-Dehydrogenative Coupling of α-Amino C(sp ³ )–H Bonds and Aldehydes Enabled by Photoredox and Nickel Catalysis

Oxidative cross-dehydrogenative coupling (CDC) provides an attractive strategy for direct construction of C–C and C–X bonds by obviating substrate prefunctionalization, offering inherently high step- and atom-economy. However, achieving cross- and enantioselectivity in radical–radical CDC remains a significant challenge, primarily due to the difficulty in precisely controlling and balancing the generation rates of distinct radical species and in leveraging subsequent asymmetric control. Described herein is a catalytic system that merges photoredox with asymmetric nickel catalysis to achieve enantioselective radical–radical CDC between α-amino C(sp 3 )–H bonds and aldehydes under mild conditions, affording enantio-enriched α-amino ketones. Mechanistic studies illuminate a mechanism which leverages a photocatalytic hydrogen atom transfer process to generate two radical species, followed by nickel-catalyzed enantioselective radical–radical coupling event. This decoupled strategy successfully harnesses two transient radicals derived from simple C–H substrates, establishing a paradigm in enantioselective radical–radical cross-coupling.