The elusive reaction mechanism of Mn(II)-mediated benzylic oxidation of alkylarene by H 2 O 2 : a gem -diol mechanism or a dual hydrogen abstraction mechanism?

The direct oxygenation of alkylarenes at the benzylic position employing bioinspired nonheme catalysts has emerged as a promising strategy for the production of bioactive arene ketone scaffolds in drugs. However, the structure-activity relationship of the active species and the mechanism of these reactions remain elusive. Herein, the reaction mechanism of the Mn(II)-mediated benzylic oxygenation of phenylbutanoic acid (PBA) to 4-oxo-4-phenylbutyric acid (4-oxo-PBA) by H 2 O 2 was investigated using density functional theory calculations. The calculated results demonstrated that the Mn III -OOH species (1) is a sluggish oxidant and needs to be converted to a high-valent manganese-oxo species (2). The conversion of PBA to 4-oxo-PBA by 2 occurs via the consecutive hydroxylation of PBA to 4-hydroxyl-4-phenylbutyric acid (4-OH-PBA) and the alcohol oxidation of 4-OH-PBA to 4-oxo-PBA. The hydroxylation of PBA proceeds via a novel hydride transfer/hydroxyl-rebound mechanism and the alcohol oxidation of 4-OH-PBA occurs via three pathways ( gem -diol, dual hydrogen abstraction (DHA), and reversed-DHA pathways). The regio-selectivity of benzylic oxidations was caused by a strong π-π stacking interaction between the pyridine ring of the nonheme ligand and the phenyl ring of the substrate. These mechanistic findings enrich the knowledge of biomimetic alcohol oxidations and play a positive role in the rational design of new non-heme catalysts.