Direct synthesis of N-trifluoromethyl amides via photocatalytic trifluoromethylamidation

Abstract

N-CF3 amides are promising targets for pharmaceutical and agrochemistry. Unfortunately, there is a defluorination problem of N-CF3 amine starting materials when using common amide bond formation method. Recently, elegant alternative approaches emerged. However, none have used the well known amidyl radical chemistry to directly prepare N-CF3 amides. We describe here a convenient preparation of N-(N-CF3 imidoyloxy) pyridinium salts and their applications as efficient trifluoromethylamidyl radical precursors in photocatalytic trifluoromethylamidations of (hetero)arenes, alkenes, alkynes, silylenol ethers, and isocyanides. The rapid construction of diverse N-CF3 amides, particularly the synthesis of cyclic N-CF3 amides, demonstrates the uniqueness and flexibility of the method. This method is expected to provide a platform for directly synthesizing N-CF3 amides and to inspire the discovery of more redox molecular systems that can handle challenging trifluoromethylamidations. The synthesis of N-CF3 amides is of great interest, but the direct preparation of these compounds via established amidyl radical chemistry remains underexplored. Here, the authors report the synthesis of N-(N-CF3 imidoyloxy) pyridinium salts and demonstrate their utility as trifluoromethylamidyl radical precursors in photocatalytic trifluoromethylamidation reactions.

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