Deaminative Trifluoromethylation of Alkyl Amines Enabled by Photoexcited Copper Complexes

Abstract

The direct conversion of abundant alkyl amines to high-value motifs remains highly desirable yet challenging in chemical synthesis. Herein, we disclose a photoinduced copper-mediated protocol for the deaminative trifluoromethylation of alkyl amines via crude isonitrile intermediates. This reaction proceeds through the photoexcitation of both high-valent Cu(III)(CF3)3 and low-valent (isonitrile)Cu(CF3)n species, enabling the homolytic cleavage of C(sp 3 )-N bonds and subsequent C(sp 3 )-CF3 bond formation under mild conditions. This photoactivation protocol enables the conversion of a broad range of primary alkyl amines into trifluoromethylated products with excellent functional group tolerance. The utility of this method is further demonstrated by the late-stage functionalization of complex bioactive molecules. In addition, detailed mechanistic studies were carried out to elucidate the potential reaction pathway.