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Updated: Jun 9, 2025
Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
Copper-Catalyzed C(sp3)-H α-Acetylation: Generation of Quaternary Centers
Otome E Okoromoba1, Ting-An Chen1,2, Eun Sil Jang1
1Department of Chemistry, Georgetown University, Box 571227, 20057-1227, Washington, DC, USA.
Abstract:
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) -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.
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