Directed Hydroxylation of sp² and sp³ C–H Bonds Using Stoichiometric Amounts of Cu and H₂O₂

Abstract

The use of copper for C-H bond functionalization, compared to other metals, is relatively unexplored. Herein, we report a synthetic protocol for the regioselective hydroxylation of sp² and sp³ C-H bonds using a directing group, stoichiometric amounts of Cu and H₂O₂. A wide array of aromatic ketones and aldehydes are oxidized in the carbonyl γ-position with remarkable yields. We also expanded this methodology to hydroxylate the β-position of alkylic ketones. Spectroscopic characterization, kinetics, and density functional theory calculations point toward the involvement of a mononuclear LCu^II(OOH) species, which oxidizes the aromatic sp² C-H bonds via a concerted heterolytic O-O bond cleavage with concomitant electrophilic attack on the arene system.