Direct 1,6-Difluoromethylation of 3-Methyl-4-nitro-5-styryl Isoxazoles by Photoredox-Promoted Radical Addition

Jianli Zheng; Yingqian Xu; Shaorui Song; Ling Huang; Dongdong Cao; Aiguo Zhong; Jianguo Yang; Dingben Chen

doi:10.1021/acs.joc.3c00529

Direct 1,6-Difluoromethylation of 3-Methyl-4-nitro-5-styryl Isoxazoles by Photoredox-Promoted Radical Addition

J Org Chem. 2023 Jul 21;88(14):10206-10211. doi: 10.1021/acs.joc.3c00529. Epub 2023 Jul 12.

Authors

Jianli Zheng^{1

2}, Yingqian Xu¹, Shaorui Song¹, Ling Huang¹, Dongdong Cao¹, Aiguo Zhong¹, Jianguo Yang¹, Dingben Chen^{1

2

3}

Affiliations

¹ School of Pharmaceutical and Chemical Engineering, Taizhou University, 1139 Shifu Road, Taizhou 318000, China.
² Department of Chemistry, Zhejiang Sci-Tech University, Xiasha West Higher Education District, Hangzhou 310018, China.
³ Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.

PMID: 37436148
DOI: 10.1021/acs.joc.3c00529

Abstract

The photoredox-catalyzed 1,6-difluoromethylation of 3-methyl-4-nitro-5-styrylisoxazole with HCF₂SO₂Na has been developed. Structurally diverse difluoromethylated products were obtained in good yields, and their further transformations were also investigated. The di-, tri-, and monofluoromethylation of the substrates were compared, and the yield of the difluoromethylation was the highest. DFT calculations revealed that in the difluoromethylation reaction the CF₂H radical was nucleophilic, and the transition state activation energy was the lowest.