Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34075051.
- Also identified by DOI 10.1038/s41467-021-23590-2 and PMC identifier 8169770.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 CF<sub>2</sub>H groups along with complex alkyl or aryl groups into alkenes with regioselectivity opposite to traditional CF<sub>2</sub>H 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 CF<sub>2</sub>H analogues of bioactive molecules. Mechanistic studies and density functional theory calculations suggest a unique ligand effect on the reactivity of the Cu-CF<sub>2</sub>H species.