A generalized electrochemical dehydrogenation approach en route to α-phosphorylated amines

Abstract

Given the widespread use of organophosphorus scaffolds in several disciplines, the formation of C(sp³)–P bonds is of fundamental importance. Direct access to α-phosphorylated amines still remains challenging, though, because conventional methods frequently call for substrate-specific photocatalytic conditions, stoichiometric oxidants, or prefunctionalized substrates. Here, we provide a broad electrochemical approach for the direct phosphorylation of feedstock amines and peptides. Under ambient conditions, the reaction proceeds via anodic oxidation, producing an α-amino radical and cationic intermediates that are efficiently coupled with secondary phosphine oxide-, phosphonate-, and phosphinate-based nucleophiles. Overall, this platform's redox-neutral characteristics, broad substrate range, functional group tolerance, and scalability enable the efficient synthesis of a variety of α-phosphorylated amines. A generic and sustainable solution for C–P bond formation is provided by incorporating electrochemical activation into organophosphorus chemistry, opening new possibilities for the creation of organophosphorus ligands and bioactive compounds.