Abstract
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(sp3)–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(sp3)–C(sp3) or C(sp3)–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.
Keywords
Regiodivergent synthesis - Asymmetric synthesis - Hydrogen atom transfer - Chiral
copper catalysis - C(sp
3)–H functionalization
