Visible Light-Triggered Regiodivergent and Enantioselective Alkylation of Glycine Derivatives

Regiodivergent asymmetric synthesis provides a powerful strategy for generating structurally diverse chiral molecules from common starting materials. However, achieving precise control over both regio- and stereoselectivity in radical-mediated processes remains a formidable challenge, largely due to the transient nature and flexibility of radical intermediates. To tackle this longstanding issue, we have developed a cooperative catalytic platform that integrates photoinduced hydrogen atom transfer (HAT) with chiral copper catalysis. This dual-catalyst system enables regiodivergent and enantioselective C(sp(3))-H functionalization of N-aryl glycine derivatives using simple hydrocarbons as alkylating agents. Through systematic modulation of chiral ligands, additives, and other reaction parameters, we have achieved switchable formation of either C(sp(3))-C(sp(3)) or C(sp(3))-N bonds, leading to the selective synthesis of C- or N-alkylated products. The reactions proceed with high efficiency (up to 92% yield), excellent regiocontrol (>20:1 rr), and outstanding enantioselectivity (up to 96% ee). Importantly, this methodology facilitates site-selective alkylation of biologically relevant scaffolds and demonstrates tunable regioselectivity under mild photochemical conditions. Thus, it establishes a new paradigm for stereocontrolled bond construction in complex molecular architectures.