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.