General Access to N-CF3 Secondary Amines and Their Transformation to N-CF3 Sulfonamides.

Abstract

The synthesis of N-CF3 compounds through fluorination or trifluoromethylation of N-containing compounds has been extensively investigated. However, general access to N-CF3 compounds simply from N-CF3 secondary amines is hampered by the challenging preparation and instability of these amines, as well as a much lower reactivity due to the strong electron-withdrawing nature and steric bulk of the trifluoromethyl moiety. Herein, we report a general and highly efficient synthesis of N-CF3 secondary amines with excellent isolated yields via the addition of the in situ generated difluoromethyl imine (R-N=CF2 ) intermediates with hydrogen fluoride, which is mildly produced by triethylsilane and silver fluoride. N-CF3 sulfonamides, highly desirable but scarce at present, are easily accessible from these valuable building blocks through an unprecedented route. This study will bring new vitality to the synthesis of N-CF3 compounds.