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

alpha-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in natural products and pharmaceuticals. We report the alpha-acetylation of C(sp3)-H substrates R-H with arylmethyl ketones ArC(O)Me to provide alpha-alkylated ketones ArC(O)CH2R at RT with tBuOOtBu as oxidant via copper(I) beta ${\beta }$ -diketiminato catalysts. Proceeding via alkyl radicals R center dot, this method enables alpha-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 center dot to give R-CH2C(O)Ar outcompeting dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH2CH2C(O)Ar.