Electrochemical Synthesis of Hindered Primary and Secondary Amines via Proton-Coupled Electron Transfer

Accessing hindered amines, particularly primary amines alpha to a fully substituted carbon center, is synthetically challenging. We report an electrochemical method to access such hindered amines starting from benchtop-stable iminium salts and cyanoheteroarenes. A wide variety of substituted heterocycles (pyridine, pyrimidine, pyrazine, purine, azaindole) can be utilized in the cross-coupling reaction, including those substituted with a halide, trifluoromethyl, ester, amide, or ether group, a heterocycle, or an unprotected alcohol or alkyne. Mechanistic insight based on DFT data, as well as cyclic voltammetry and NMR spectroscopy, suggests that a proton-coupled electron-transfer mechanism is operational as part of a hetero-biradical cross-coupling of a-amino radicals and radicals derived from cyanoheteroarenes.