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.