Direct enantioselective C(sp³)-H coupling of N-alkyl anilines via metallaphotoredox catalysis

Amine functionalization is crucial in pharmaceutical and agrochemical synthesis yet direct enantioselective α-C(sp³)-H functionalization of N-alkyl anilines remains challenging. Here we show a metallaphotoredox-catalysed radical approach for α-C(sp³)-H arylation of N-alkyl anilines, introducing a simple, sterically hindered aryl ketone photocatalyst. This key innovation slows undesired back-electron transfer, enabling efficient α-anilinoalkyl radical generation. Our strategy uses a sequential single-electron transfer and proton transfer process, thereby overcoming multiple limitations of existing methods. In conjunction with a chiral nickel catalyst, we have achieved site-selective, enantioselective arylation of diverse N-alkyl anilines with various (hetero)aryl halides. The method exhibits exceptional functional group tolerance, enabling modular functionalization of complex molecular structures. This approach provides an effective route to valuable α-aryl amines, offering significant possibilities for drug discovery and streamlining challenging synthetic sequences.