Nickel-Catalyzed α‑Arylation and Alkenylation of α‑Trifluoromethyl Amines via 1,2-HAT Assisted by DMSO.

α-Trifluoromethyl amines are privileged scaffolds in pharmaceuticals and bioactive compounds, serving as metabolically stable amide bioisosteres. However, conventional synthetic approaches often suffer from multistep reactions, limited functional group tolerance, and instability of imine precursors. To overcome these limitations, we report a nickel-catalyzed cross-electrophilic coupling constructing diverse α-trifluoromethylamines via a mechanistically distinct pathway involving solvent-enabled 1,2-hydrogen atom transfer (HAT). In this process, the N-O bond is activated by Ni(0)-promoted SET to form transient N-centered radicals, which undergo DMSO-promoted 1,2-HAT to generate nucleophilic C-(sp3)-centered radicals. These radicals then participate in nickel-catalyzed coupling with a wide range of commercially available aryl halides and vinyl bromides. This strategy suppresses competing C-N bond formation and offers several advantages: the use of bench-stable radical precursors, high chemoselectivity, broad substrate scope, mild reaction conditions, and applicability to the late-stage functionalization of natural products and drug derivatives. Furthermore, the method relies exclusively on earth-abundant nickel and commercially available feedstocks. By leveraging polar solvent-assisted HAT to circumvent traditional intermediates, this methodology enables efficient and scalable synthesis of high-value α-aryl- or alkenyl-substituted α-trifluoromethyl amines.