Photoinduced copper-catalyzed C–N coupling with trifluoromethylated arenes

Abstract

Selective defluorinative functionalization of trifluoromethyl group (–CF3) is an attractive synthetic route to the pharmaceutically privileged fluorine-containing moiety. Herein, we report a strategy based on photoexcited copper catalysis to activate the C–F bond of di- or trifluoromethylated arenes for divergent radical C–N coupling with carbazoles and aromatic amines. The use of different ligands can tune the reaction products diversity. A range of substituted, structurally diverse α,α-difluoromethylamines can be obtained from trifluoromethylated arenes via defluorinative C-N coupling with carbazoles, while an interesting double defluorinative C-N coupling is ready for difluoromethylated arenes. Based on this success, a carbazole-centered PNP ligand is designed to be an optimal ligand, enabling a copper-catalyzed C–N coupling for the construction of imidoyl fluorides from aromatic amines through double C-F bond functionalization. Interestingly, a 1,2-difluoroalkylamination strategy of styrenes is also developed, delivering γ,γ-difluoroalkylamines, a bioisostere to β-aminoketones, in synthetically useful yields. The DFT studies reveal an inner-sphere electron transfer mechanism for Cu-catalyzed selective activation of C(sp3)–F bonds.