Cu-Promoted <i>ipso</i>-Hydroxylation of\nsp<sup>2</sup> Bonds with Concomitant Aromatic 1,2-Rearrangement Involving\na Cu-oxyl-hydroxo Species

Herein, we report the first example of Cu-promoted β <i>ipso</i>-hydroxylation of substituted benzophenones using a\nbidentate directing group (DG) and H<sub>2</sub>O<sub>2</sub> as an\noxidant. In addition to the new C–O bond formed, the <i>ipso</i>-oxidation induces a very unusual 1,2-rearrangement\nof the iminyl group to the vicinal γ position. This transformation\nis highly dependent on the substrate utilized (favored for 4-methoxy-substituted\nbenzophenones) and on the DG used (2-picolylamine leads to selective\nγ-C–H functionalization, while β <i>ipso</i>-oxidation requires 2-(2-aminoethyl)pyridine). An analysis of the\noxidation of substrate–ligands derived from 2-(2-aminoethyl)pyridine\nand unsymmetrical 4-MeO-substituted benzophenones indicates high regioselectivity\n(up to 89:11 for the MeO-substituted arene ring and up to 92:8 for\nβ <i>ipso</i>- vs γ-C–H hydroxylation).\nMechanistic studies (which include spectroscopic characterization\nof reaction intermediates, kinetics, and calculations) suggest the\nformation of a mononuclear Cu<sup>II</sup>OOH species before the rate-determining\nstep (rds) of the reaction. DFT calculations suggest that the γ-C–H\nhydroxylation pathway involves a one-step concerted O–O cleavage\nand electrophilic aromatic attack. Conversely, β <i>ipso</i>-hydroxylation occurs in a stepwise fashion, in which O–O\nbond cleavage produces a Cu<sup>III</sup>(O·)(OH) before electrophilic\naromatic attack. Calculations also shed light on the mechanism of\nthe 1,2-rearrangement step, which involves strain release from a spiro\n5-membered to a 6-membered Cu chelate.