Catalysis

Iminium

Electrochemistry

Photochemistry

Cyclic voltammetry

Pyrazine

Protonation

Alkyl

Electron transfer

Stereochemistry

Physical chemistry

Combinatorial chemistry

Physics

Organic chemistry

Pyridinium

Astronomy

Amine gas treating

Trifluoromethyl

Alkyne

Proton-coupled electron transfer

Primary (astronomy)

Pyrimidine

Radical

Chemistry

Electrode

Ether

Amide

Pyridine

Journal of the American Chemical Society

Accessing hindered amines, particularly primary amines α 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 α-amino radicals and radicals derived from cyanoheteroarenes.

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