Synthesis of Trifluoromethylated Aziridines Via Photocatalytic Amination Reaction

Abstract

Trifluoromethylated aziridines are the smallest fluorinated N-heterocycle and represent important strategic building blocks with broad application in drug discovery for the synthesis of functionalized, fluorinated amines via ring-opening reactions. Their catalytic synthesis represents even today a major challenge in organic chemistry, and methods relying on classic nitrene transfer reactions of electron-poor, fluorinated olefins are significantly hampered. Herein, we demonstrate that iodinanes undergo oxidative quenching in the presence of the simple Ru(bpy)3Cl2 catalyst and release a nitrene radical anion, which serves as a reactive intermediate in direct aziridination reactions of fluorinated olefins. We have demonstrated the applicability of this photocatalytic synthesis platform to access fluorinated aziridines in a generalized fashion, allowing for different substitution patterns of the fluorinated aziridine core, including difluoromethyl and perfluoroalkylated aziridines. Experimental and computational studies indicate the importance of an unusual nitrene radical anion to access the trifluoromethylated aziridine.