Enantioselective Cupraelectrocatalyzed C−H Activation for C−Het Bond Formation

Chiral aryl phosphorus compounds are key motifs in medicinal chemistry, materials science, and agrochemistry. Electrochemical, transition-metal-catalyzed C−H activation offers an economical route to these structures. However, enantioselective C−H phosphorylation of ferrocenyl derivatives catalyzed by earth-abundant metals has remained elusive. Here we disclose the enantioselective cupraelectrocatalyzed C−H phosphorylation of ferrocenyl amides, providing planar chiral ferrocenylphosphorus compounds in up to 71% yield and 97% ee. This strategy operates under mild electrochemical conditions without external oxidants and is characterized by a broad substrate scope. Notably, electrochemistry enables high efficiency and high enantioselectivity, while conventional oxidants give poor performance. The same strategy even allows for C−H sulfonylations in an enantioselective manner, hence reflecting its versatility. Mechanistic studies reveal the dual role of the anodic oxidation in that (S)-BINOL mediates copper(III) formation through SET. Detailed mechanistic studies by experiment, high-resolution mass spectrometry, and electroanalysis provides strong evidence for the key role of initial naphthol anodic oxidation for electrocatalyst generation.