Cu-Promoted <i>ipso</i>-Hydroxylation of sp² Bonds with Concomitant Aromatic 1,2-Rearrangement Involving a Cu-oxyl-hydroxo Species

Herein, we report the first example of Cu-promoted β <i>ipso</i>-hydroxylation of substituted benzophenones using a bidentate directing group (DG) and H₂O₂ as an oxidant. In addition to the new C-O bond formed, the <i>ipso</i>-oxidation induces a very unusual 1,2-rearrangement of the iminyl group to the vicinal γ position. This transformation is highly dependent on the substrate utilized (favored for 4-methoxy-substituted benzophenones) and on the DG used (2-picolylamine leads to selective γ-C-H functionalization, while β <i>ipso</i>-oxidation requires 2-(2-aminoethyl)pyridine). An analysis of the oxidation of substrate-ligands derived from 2-(2-aminoethyl)pyridine and unsymmetrical 4-MeO-substituted benzophenones indicates high regioselectivity (up to 89:11 for the MeO-substituted arene ring and up to 92:8 for β <i>ipso</i>- vs γ-C-H hydroxylation). Mechanistic studies (which include spectroscopic characterization of reaction intermediates, kinetics, and calculations) suggest the formation of a mononuclear Cu^IIOOH species before the rate-determining step (rds) of the reaction. DFT calculations suggest that the γ-C-H hydroxylation pathway involves a one-step concerted O-O cleavage and electrophilic aromatic attack. Conversely, β <i>ipso</i>-hydroxylation occurs in a stepwise fashion, in which O-O bond cleavage produces a Cu^III(O·)(OH) before electrophilic aromatic attack. Calculations also shed light on the mechanism of the 1,2-rearrangement step, which involves strain release from a spiro 5-membered to a 6-membered Cu chelate.