An Asymmetric Aromatic Finkelstein Reaction: A Platform for Remote Diarylmethane Desymmetrization

A first-of-its-kind
enantioselective aromatic Finkelstein reaction
is disclosed for the remote desymmetrization of diarylmethanes. The
reaction operates through a copper-catalyzed C–I bond-forming
event, and high levels of enantioselectivity are achieved through
the deployment of a tailored guanidinylated peptide ligand. Strategic
use of transition-metal-mediated reactions enables the chemoselective
modification of the aryl iodide products; thus, the synthesis of a
diverse set of otherwise difficult-to-access diarylmethanes with excellent
levels of selectivity is realized from a common intermediate. A mixed
experimental/computational analysis of steric parameters and substrate
conformations identifies the importance of remote conformational effects
as a key to achieving high enantioselectivity in this desymmetrization
reaction.