Metallaphotoredox‐Catalyzed Enantioselective Cross‐Electrophile Coupling Using Alcohols as Reducing Agents

Abstract The cross‐electrophile coupling (XEC) represents a powerful strategy for C−C bond formation. However, controlling the enantioselectivity in these processes remains a challenge. Here, we report an unprecedented enantioselective XEC of α‐amino acid derivatives with aryl bromides, enabled by alcohols as reducing agents via Ni/photoredox catalysis. This mechanistically distinct approach exploits the ability of photocatalytically generated α‐hydroxyalkyl radicals to convert alkyl electrophiles to the corresponding alkyl radicals that are then enantioselectively coupled with aryl bromides. The readily scalable protocol allows modular access to valuable enantioenriched benzylic amines from abundant and inexpensive precursors, and is applicable to late‐stage diversification with broad functional group tolerance. Mechanistic studies rationalize the versatility of this alcohol‐based reactivity for radical generation and subsequent asymmetric cross‐coupling. We expect that this alcohol‐based cross‐coupling will render a general platform for the development of appealing yet challenging enantioselective XECs.