Catalytic enantioselective synthesis of α-C chiral sulfones enabled by merging photoactive electron donor–acceptor complexes with nickel catalysis

Abstract

α-C chiral sulfones are privileged building blocks widely found in pharmaceuticals, agrochemicals, natural products, and ligands. Although many nucleophilic or electrophilic protocols have been developed for their construction, radical-based asymmetric catalysis, especially that involving photoactive electron donor–acceptor (EDA) complexes, remains a significant unmet challenge. Herein, we present the first catalytic asymmetric production of α-C chiral sulfones enabled by merging a photoactive EDA complex with a chiral Ni catalyst. With this cooperative asymmetric catalysis system, a wide range of α-C chiral sulfones are achieved in good yields with excellent enantioselectivities (53 examples, up to 99% yield, 99 : 1 er). The synthetic utility of this protocol is further demonstrated by the first asymmetric synthesis of the selective MMP-3 (stromelysin-1) inhibitor. Detailed mechanistic and spectroscopic studies suggest that a newly identified type of EDA complex generated from sulfonyl chlorides and Hantzsch esters (HEs) is crucial to the success as a precursor of sulfonyl radicals.