TEMPO-catalyzed electrochemical dehydrogenative cyclocondensation of o-aminophenols: synthesis of aminophenoxazinones as antiproliferative agents

The aminophenoxazinone core is widely prevalent in natural products, dyes and pharmaceutical molecules. We report here a TEMPO-catalyzed electrosynthetic method allowing the dehydrogenative cyclocondensation of o-aminophenols. This mild and sustainable method proceeds in the absence of stoichiometric oxidants and uses an easily available organo-electrocatalyst to access pharmaceutically valuable 2-aminophenoxazinones. Mechanistic studies indicate that the electrochemically generated TEMPO+ enables the oxidative radical homo-dimerization of o-aminophenols. The application of electrosynthesis provides an approach for the synthesis of pseudo-aminophenoxazinone alkaloids with improved structural diversification and bioactivities.

Automated summary

The study presents a TEMPO-catalyzed electrosynthetic method for the dehydrogenative cyclocondensation of o-aminophenols to access pharmaceutically valuable 2-aminophenoxazinones. The method is mild, sustainable, and does not require stoichiometric oxidants, providing a new approach for the synthesis of bioactive compounds with improved structural diversity. Mechanistic studies show that electrochemically generated TEMPO+ enables the oxidative radical homo-dimerization of o-aminophenols.