Site‐Selective α─C─H Functionalization of Saturated Heterocycles via Copper‐Photoredox Catalysis

Abstract Site‐selective α─C─H functionalization of saturated heterocycles is of particular importance in synthetic and medicinal chemistry, but the intrinsic chemical inertness of saturated heterocycles renders the transformation difficult. Furthermore, site‐selectivity remains a significant challenge, especially among multiple C(sp 3 )─H bonds with comparable chemical properties. Herein, an unprecedented site‐selective C α ─H functionalization of saturated heterocycles by copper‐photoredox catalysis is described. This undirected approach exploits a novel copper photocatalyst to mediate both substrate activation and photoinduced energy transfer, enabling site‐selective functionalization of cyclic C α ─H bonds in the presence of competitive C(sp 3 )─H bonds. Mechanistic studies reveal that the excellent site‐selectivity stems from the coordination effect between the saturated heterocycle and copper/ligand complex, which makes the cyclic C α ─H bond more acidic and weaker in bond strength, thereby increasing the reactivity differences among similar C(sp 3 )─H bonds. The use of dual‐role air bypasses exogenous HAT reagents and oxidants required in previous methods. This mild and sustainable protocol features broad substrate scope, excellent site‐selectivity, and high functional group compatibility, providing a new and site‐selective reactivity mode for rapid diversification of α─C─H bonds.