Hydroxylamine-Mediated C(sp2)-H Trifluoromethylation of Terminal Alkenes

Chemistry. 2024 Apr 10:e202400995. doi: 10.1002/chem.202400995. Online ahead of print.

Abstract

Introduction of the trifluoromethyl (CF3) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine-mediated radical process for C(sp2)-H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late-stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway.

Keywords: Addition-elimination; Alkene; Hydroxylamine; Radical; Trifluoromethylation.