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

Inorg Chem. 2019 Jun 3;58(11):7584-7592. doi: 10.1021/acs.inorgchem.9b00901. Epub 2019 May 14.


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 LCuII(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.