Copper‐Catalyzed C(sp3)−H α‐Acetylation: Generation of Quaternary Centers

α‐substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in natural products and pharmaceuticals. We report the α‐acetylation of C(sp3)−H substrates R−H with arylmethyl ketones ArC(O)Me to provide α‐alkylated ketones ArC(O)CH2R at RT with tBuOOtBu as oxidant via copper(I) β ${\beta }$ ‐diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α‐substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [CuII](CH2C(O)Ar) that capture alkyl radicals R• to give R−CH2C(O)Ar outcompeting dimerization of the copper(II) enolate to give the 1,4‐diketone ArC(O)CH2CH2C(O)Ar. We demonstrate a new C(sp3)−H acetylation methodology for the synthesis of α‐substituted ketones that enables the construction of quaternary C centers via copper catalysis. A t‐butoxy radical derived from tBuOOtBu engages in H‐atom ion of an C(sp3)−H bond in substrates R−H to generate radicals R• captured by copper(II) enolates [CuII](CH2C(O)Ph) formed through acid‐base exchange between [CuII]−OtBu intermediates and ketones CH3C(O)Ar to give α‐functionalized ketones R−CH2C(O)Ar.