EnantioselectiveAlkyl–Acyl Radical Cross-CouplingEnabled by Metallaphotoredox Catalysis

Radical–radical cross-coupling (RCC) offers a promising approach for carbon–carbon bond formation in organic synthesis, particularly for creating complex, three-dimensional molecules. However, achieving both cross- and enantioselectivity in RCC reactions has remained a significant challenge. Here, we report a novel metallaphotoredox platform that enables highly enantioselective decarboxylative coupling of carboxylic acid derivatives with aldehydes. Our strategy leverages independent control over radical generation and subsequent enantioselective bond formation through fine-tuning of a common photocatalyst and a simple chiral bis(oxazoline) nickel catalyst. This redox-neutral protocol requires no exogenous oxidants or reductants and demonstrates broad substrate scope and functional group compatibility in the synthesis of enantioenriched α-aryl and α-amino ketones. The α-amino ketone products can be readily transformed into valuable β-amino alcohols, streamlining access to these important motifs. Furthermore, we showcase the potential of this approach for more challenging enantioselective C(sp³)–C(sp³) alkyl–alkyl RCC reactions. This unified platform for enantioselective alkyl–acyl radical cross-coupling represents a significant advance in asymmetric catalysis and underscores the potential for metallaphotoredox catalysis to exploit new mechanisms to solve long-standing synthetic problems.