Photoinduced Chemo-, Site- and Stereoselective alpha-C(sp(3))-H Functionalization of Sulfides

The ubiquity of sulfur-containing molecules in biologically active natural products and pharmaceuticals has long attracted synthetic chemists to develop efficient strategies towards their synthesis. The strategy of direct alpha-C(sp(3))-H modification of sulfides provides a streamlining access to complex sulfur-containing molecules. Herein, we report a photoinduced chemo-, site- and stereoselective alpha-C(sp(3))-H functionalization of sulfides using isatins as the photoredox reagent and coupling partner catalyzed by a chiral gallium(III)-N,N '-dioxide complex. The reaction proceeds through a verified single-electron transfer (SET) mechanism with high efficiency, excellent functional group tolerance, as well as a broad substrate scope. Importantly, this cross-coupling protocol is highly selective for the direct late-stage functionalization of methionine-related peptides, regardless of the inherent structural similarity and complexity of diverse residues.