Copper-Photocatalyzed Enantioselective S‑Alkylation of Sulfenamides Enabled by Amino-Acid-Derived N,N,N‑Tridentate Ligand

Chiral sulfilimines are valuable sulfur-stereogenic motifs in medicinal chemistry and serve as versatile precursors to sulfoximines and sulfondiimines. Despite their importance, enantioselective S-alkylation of sulfenamides accessing to sulfilimines from abundant alkyl feedstocks remains largely unexplored, particularly via radical pathways. Herein, we report the enantioselective copper-photoredox-catalyzed S-alkylation of sulfenamides enabled by a family of amino-acid-derived N,N,N-tridentate ligands. This strategy allows the use of alkyl carboxylic acids via decarboxylative radical sulfilimination to afford enantioenriched sulfilimines in high yields and enantioselectivities. Importantly, the platform is further extended to alkyl iodides through an XAT-induced radical pathway, demonstrating the generality of this enantioselective S-alkylation manifold. A broad range of primary, secondary, and tertiary alkyl radicals, diverse sulfenamides, and complex bioactive substrates are well tolerated. Mechanistic studies support a radical process involving a stereoinvertive SH2-type substitution at a copper-sulfenamide intermediate. Gram-scale synthesis and downstream oxidation to pharmaceutically relevant sulfoximines underscore the synthetic utility of this method.