Abstract
Wacker oxidations are ubiquitous in the direct synthesis of carbonyl compounds from alkenes. While the reaction mechanism has been widely studied under aerobic conditions, much less is known about such processes promoted with peroxides. Here, we report an exhaustive mechanistic investigation of the Wacker oxidation of styrene using hydrogen peroxide (H(2)O(2)) and tert-butyl hydroperoxide (TBHP) as oxidants by combining density functional theory and microkinetic modeling. Our results with H(2)O(2) uncover a previously unreported reaction pathway that involves an intermolecular proton transfer assisted by the counterion [OTf](-) present in the reaction media. Furthermore, we show that when TBHP is used as an oxidant instead of H(2)O(2), the reaction mechanism switches to an intramolecular protonation sourced by the HOtBu moiety generated in situ. Importantly, these two mechanisms are predicted to outcompete the 1,2-hydride shift pathway previously proposed in the literature and account for the level of D incorporation in the product observed in labeling experiments with α-d-styrene and D(2)O(2). We envision that these insights will pave the way for the rational design of more efficient catalysts for the industrial production of chemical feedstocks and fine chemicals.