Aromatic C−H Hydroxylation Reactions with Hydrogen Peroxide Catalyzed by Bulky Manganese Complexes
Eduard Masferrer‐Rius, Margarida Borrell, Martin Lutz, Miguel Costas, Robertus J. M. Klein Gebbink
Abstract
Abstract The oxidation of aromatic substrates to phenols with H 2 O 2 as a benign oxidant remains an ongoing challenge in synthetic chemistry. Herein, we successfully achieved to catalyze aromatic C−H bond oxidations using a series of biologically inspired manganese catalysts in fluorinated alcohol solvents. While introduction of bulky substituents into the ligand structure of the catalyst favors aromatic C−H oxidations in alkylbenzenes, oxidation occurs at the benzylic position with ligands bearing electron‐rich substituents. Therefore, the nature of the ligand is key in controlling the chemoselectivity of these Mn‐catalyzed C−H oxidations. We show that introduction of bulky groups into the ligand prevents catalyst inhibition through phenolate‐binding, consequently providing higher catalytic turnover numbers for phenol formation. Furthermore, employing halogenated carboxylic acids in the presence of bulky catalysts provides enhanced catalytic activities, which can be attributed to their low pK a values that reduces catalyst inhibition by phenolate protonation as well as to their electron‐withdrawing character that makes the manganese oxo species a more electrophilic oxidant. Moreover, to the best of our knowledge, the new system can accomplish the oxidation of alkylbenzenes with the highest yields so far reported for homogeneous arene hydroxylation catalysts. Overall our data provide a proof‐of‐concept of how Mn(II)/H 2 O 2 /RCO 2 H oxidation systems are easily tunable by means of the solvent, carboxylic acid additive, and steric demand of the ligand. The chemo‐ and site‐selectivity patterns of the current system, a negligible KIE, the observation of an NIH‐shift, and the effectiveness of using t BuOOH as oxidant overall suggest that hydroxylation of aromatic C−H bonds proceeds through a metal‐based mechanism, with no significant involvement of hydroxyl radicals, and via an arene oxide intermediate. magnified image