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Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay.

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.

SUBMITTER: Cai A

PROVIDER: S-EPMC8169770 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay.

Cai Aijie A Yan Wenhao W Zeng Xiaojun X Zacate Samson B SB Chao Tzu-Hsuan TH Krause Jeanette A JA Cheng Mu-Jeng MJ Liu Wei W

Nature communications 20210601 1

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 ad ...[more]

PMID: 34075051

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