Enantioselective Radical–Radical Cross-Couplings of β-Hydroxy Amides and <i>N</i>-Hydroxyphthalimide Esters via Ni/Photoredox Catalysis

Enantioselective alkyl-alkyl cross-coupling is a powerful yet challenging strategy for constructing three-dimensional molecular architectures, which are essential in fields such as organic chemistry and pharmaceutical chemistry. While radical-radical cross-coupling offers a promising approach, achieving control over both cross- and enantioselectivity between two distinct alkyl radicals remains a formidable challenge due to their transient nature. In this article, we introduce a practical platform that combines photoredox and chiral nickel catalysis to tame transient primary and secondary alkyl radicals under mild conditions. We also present a one-pot variant wherein the <i>N</i>-hydroxyphthalimide (NHP) ester is generated in situ, enabling the streamlined synthesis of enantioenriched products in a single step from commercially available carboxylic acids and easily accessible alcohols. The utility of this method is demonstrated by diverse transformations to valuable scaffolds and bioactive molecules. A comprehensive mechanistic study has clarified the involvement of a Ni(I)/Ni(II) cycle.