Asymmetric Desymmetrizing Sulfonylation of Diarylmethanes via Peptidyl-Cu(I)-Catalysis with Remote Stereocontrol

An asymmetric catalytic desymmetrizing cross-coupling of diarylmethanes with organosulfinates has been developed. Permutations of proteinogenic and noncanonical amino acids allow access to guanidinylated peptide-based ligands that may be tuned for distal stereocontrol under copper catalysis. Noncovalent attractive interactions are likely significant in organizing the geometry of substrate-copper-peptide ternary complexes, modulated by countercation effects, for effective enantioselective oxidative addition; further enantioenrichment of the sulfone products occurs via secondary kinetic resolution, corroborated by mechanistic studies. The mild protocols disclosed herein expand asymmetric and site-selective catalysis mediated by peptides first to enable C-S bond-forming cross-coupling reactions with remote stereocontrol.