Radical Hydro‐Ethoxycarbonyldifluoromethylation of Alkenes with BrCF<sub>2</sub>CO<sub>2</sub>Et
The difluoromethylene (CF₂) group, valued for its unique electronic and steric properties, plays a critical role in pharmaceutical and agrochemical design, as exemplified by drugs like lubiprostone, which requires ethyl 2,2-difluorohexanoate as a key intermediate for its synthesis. Consequently, developing efficient methods to incorporate the ethoxycarbonyldifluoromethyl group into alkanes is highly desirable. Herein, we describe a mild, versatile, and efficient radical hydro-ethoxycarbonyldifluoromethylation of alkenes with BrCF<sub>2</sub>CO<sub>2</sub>Et. This process is applicable to both unactivated alkyl alkenes and active aryl alkenes. The protocol is characterized by mild reaction conditions, the absence of expensive reagents, and the elimination of transition metals.
Authors
- Jin‐Hong Lin (ORCID: https://orcid.org/0000-0002-7000-9540)
- Guoqing Dong (ORCID: https://orcid.org/0000-0003-1850-6774)
- Xing Zheng (ORCID: https://orcid.org/0000-0002-2918-5497)
- Xiao Ming Yang (ORCID: https://orcid.org/0000-0002-0311-8915)
- Xu Yao (ORCID: https://orcid.org/0009-0000-4984-4069)
- Yu Meng (ORCID: https://orcid.org/0000-0002-9743-9882)
- Ji‐Chang Xiao (ORCID: https://orcid.org/0000-0001-9679-3292)
Institutions
- Shanghai University (CN)
- Shanghai Innovative Research Center of Traditional Chinese Medicine (CN)
- Shanghai Institute of Organic Chemistry (CN)
- Sino Biological (China) (CN)
- Hunan Vocational Institute of Technology (CN)
- Department of Science and Technology of Hunan Province (CN)
- University of South China (CN)
Publication Details
- Journal
- Chemistry - A European Journal
- Published
- 2025-06-06
- DOI
- https://doi.org/10.1002/chem.202501414
- Primary Topic
- Fluorine in Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Science and Technology Commission of Shanghai Municipality