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

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.