Copper-Catalyzed Regio- and Enantioselective Hydroamination of <i>gem</i>-Difluoroalkenes to Access Chiral Difluoromethyl Amines
The difluoromethyl group (CF<sub>2</sub>H) is an important motif in medicinal chemistry. We report the efficient synthesis of a range of optically pure α-difluoromethyl amines via copper-catalyzed regio- and enantioselective hydroamination of <i>gem</i>-difluoroalkenes. The application of a chiral pyridine-derived ligand inhibits β-F elimination from the chiral α-CF<sub>2</sub>H organocopper intermediate. The proposed chiral Cu catalyst promotes the production of chiral α-difluoromethyl amines by an enantioselective Cu-H insertion and a reductive C-N bond elimination using readily available materials. The findings of this study establish a new synthetic strategy to access chiral α-difluoromethyl motifs.
Authors
- Dachang Bai (ORCID: https://orcid.org/0000-0001-7342-2966)
- Ming Yu Jin (ORCID: https://orcid.org/0000-0003-0434-3548)
- Mengqi Cui (ORCID: https://orcid.org/0009-0003-8141-9961)
- Hao Wu (ORCID: https://orcid.org/0000-0002-0767-4177)
- Yuanyuan Guo (ORCID: https://orcid.org/0000-0001-6470-1963)
Institutions
- Henan Normal University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-05-27
- DOI
- https://doi.org/10.1021/acs.orglett.5c01680
- Citations
- 5
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 3.95
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Henan Province
- Education Department of Henan Province
- Henan Postdoctoral Science Foundation
- Henan Key Laboratory of Organic Functional Molecules and Drug Innovation