Bioinspired Aerobic Oxidation of Secondary Amines and Nitrogen Heterocycles with a Bifunctional Quinone Catalyst

Copper amine oxidases
are a family of enzymes with quinone cofactors
that oxidize primary amines to aldehydes. The native mechanism proceeds
via an iminoquinone intermediate that promotes high selectivity for
reactions with primary amines, thereby constraining the scope of potential
biomimetic synthetic applications. Here we report a novel bioinspired
quinone catalyst system consisting of 1,10-phenanthroline-5,6-dione/ZnI2 that bypasses these constraints via an abiological pathway
involving a hemiaminal intermediate. Efficient aerobic dehydrogenation
of non-native secondary amine substrates, including pharmaceutically
relevant nitrogen heterocycles, is demonstrated. The ZnI2 cocatalyst activates the quinone toward amine oxidation and provides
a source of iodide, which plays an important redox-mediator role to
promote aerobic catalytic turnover. These findings provide a valuable
foundation for broader development of aerobic oxidation reactions
employing quinone-based catalysts.