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.