Potassium tert-Butoxide Promoted Proton Transfer-Electron Transfer in Aerobic C(sp³)-H Hydroxylations

Aerobic C(sp³)-H hydroxylation is a crucial chemical process, where alkali-metal reagents act as key mediators that profoundly influence the reaction mechanism. However, the mechanistic understanding of such a reaction remains limited, probably due to the complex electronic structure of the reaction involving the O₂ and the formed clusters of alkali metal reagent aggregations. Herein, we propose a new Alkali Metal Reagent Promoted Proton Transfer-Electron Transfer (A-PTET) mechanism in aerobic C(sp³)-H hydroxylations by density functional theory (DFT) calculations to understand the different radical detection outcomes depending on the amount of KO^tBu. With catalytic KO^tBu, the reaction proceeds through the carbanion pathway, and thus, radical species are undetected experimentally. In contrast, when 3 equiv of KO^tBu are employed, the positive electrostatic field generated by K⁺ cations stabilizes radical intermediates that induce the single electron transfer in the A-PTET mechanism, leading to the experimentally observed radical species. This study establishes a theoretical foundation for the development of aerobic reactions, and the A-PTET mechanism may extend to other reactions based on new insights into alkali-metal reagents.