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Copper Catalyzed sp3 C-H α-Acetylation

preprint
submitted on 19.12.2019 and posted on 23.12.2019 by Otome Okoromoba, Eun Sil Jang, Claire McMullin, Thomas Cundari, Timothy H. Warren

α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in in natural products and pharmaceuticals. We report the sp3 C-H α-acetylation of sp3 C-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-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 under competing dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH2CH2C(O)Ar.

Funding

NSF CHE-1665348

History

Email Address of Submitting Author

thw@georgetown.edu

Institution

Georgetown University

Country

USA

ORCID For Submitting Author

0000-0001-9217-8890

Declaration of Conflict of Interest

none

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