Catalysis

Materials science

Receptor

Alkyl

Biochemistry

Combinatorial chemistry

Physics

Tandem

Ligand (biochemistry)

Organic chemistry

Hydroamination

Photoredox catalysis

Astronomy

Amine gas treating

Trifluoromethyl

Primary (astronomy)

Catalytic cycle

Composite material

Radical

Oxime

Chemistry

Photocatalysis

Steric effects

Journal of the American Chemical Society

Primary amines are an important structural motif in active pharmaceutical ingredients (APIs) and intermediates thereof, as well as members of ligand libraries for either biological or catalytic applications. Many chemical methodologies exist for amine synthesis, but the direct synthesis of primary amines with a fully substituted α carbon center is an underdeveloped area. We report a method which utilizes photoredox catalysis to couple readily available O-benzoyl oximes with cyanoarenes to synthesize primary amines with fully substituted α-carbons. We also demonstrate that this method enables the synthesis of amines with α-trifluoromethyl functionality. Based on experimental and computational results, we propose a mechanism where the photocatalyst engages in concurrent tandem catalysis by reacting with the oxime as a triplet sensitizer in the first catalytic cycle and a reductant toward the cyanoarene in the second catalytic cycle to achieve the synthesis of hindered primary amines via heterocoupling of radicals from readily available oximes.

Synthesis of Sterically Hindered Primary Amines by Concurrent Tandem Photoredox Catalysis