Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay

Aijie Cai, Wenhao Yan, Xiaojun Zeng, Samson B. Zacate, Tzu Hsuan Chao, Jeanette A. Krause, Mu Jeng Cheng, Wei Liu

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1 Citation (Scopus)

Abstract

Organic molecules that contain alkyl-difluoromethyl moieties have received increased attention in medicinal chemistry, but their synthesis in a modular and late-stage fashion remains challenging. We report herein an efficient copper-catalyzed radical relay approach for the carbo-difluoromethylation of alkenes. This approach simultaneously introduces CF2H groups along with complex alkyl or aryl groups into alkenes with regioselectivity opposite to traditional CF2H radical addition. We demonstrate a broad substrate scope and a wide functional group compatibility. This scalable protocol is applied to the late-stage functionalization of complex molecules and the synthesis of CF2H analogues of bioactive molecules. Mechanistic studies and density functional theory calculations suggest a unique ligand effect on the reactivity of the Cu-CF2H species.

Original languageEnglish
Article number3272
JournalNature communications
Volume12
Issue number1
DOIs
Publication statusPublished - 2021 Dec

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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