Electrochemical synthesis of phosphorus-containing glycines and peptides via triarylamine-catalyzed dehydrogenative C(sp3)–P coupling

Abstract

Herein, we described an atom-economical and sustainable electrochemically driven triarylamine-catalyzed dehydrogenative phosphorylation coupling of glycine derivatives with phosphine oxides, affording the corresponding phosphorus-containing products in moderate to excellent yields. This green protocol employing recyclable triarylamine as a redox mediator was found to offer excellent atom economy and low E-factor scores. The reaction could be conducted in an undivided cell under mild conditions without the use of metal catalysts or stoichiometric oxidants. The substrate scope was wide, encompassing functionalized glycine esters, amides and peptides bearing various functional groups. Mechanism investigation suggested that triarylamine played a crucial role as a redox mediator in the reaction, and a plausible reaction mechanism was proposed. Notably, scale-up reactions and modifications of drugs and peptides demonstrate the potential of this green and sustainable approach for applications in drug discovery.