From Direct to Alternating Current Electrosynthesis: Transition-Metal-Catalyzed Oxidative Cross-Coupling with Hydrogen Evolution

Conspectus

Electrochemical transition-metal catalysis is an effective yet underexplored platform for molecular construction. Combining the advantages of electrochemically driven oxidation processes with the selectivity control afforded by transition-metal catalysis, this field is characterized by a rich variety of reaction types, mild conditions, and high controllability. However, it has long faced major scientific challenges: there is a mismatch between electron transfer on the electrode surface and the rate of catalyst-mediated reactant activation in solution, which complicates precise control over reaction selectivity, and metal catalysts (especially Pd, Ag, and Cu) are prone to reductive deactivation, leading to premature termination of the reactions. To address these challenges, our group has developed three main strategies using oxidative cross-coupling reactions as a representative. First, in direct current (DC) electrosynthesis, we employed a divided cell to prevent the metal catalyst from migrating to the cathode. Second, under specific ligand and solvent combinations, we realized electro-oxidative metal-catalyzed reactions in an undivided cell by precisely controlling the redox potential. To this end, the substrates were equipped with directing groups (DGs) capable of chelating with the metal cation or an extra ligand was introduced into the reaction system, both of which effectively suppressed reductive deactivation. Through this approach, we successfully achieved a series of Pd-, Co-, and Mn-catalyzed oxidative C–H functionalization reactions. Third, we developed an unsymmetrical alternating current (AC)-driven metal catalysis strategy designed to accommodate a broader range of reaction patterns. By precisely adjusting the duty ratio and current of the AC waveform, we ensured smooth reactivation of the metal catalyst. This programmed waveform further enabled the maintenance of a high concentration of the active metal species through a dynamic balance. Consequently, we successfully achieved Cu-, Ag-, and Pd-catalyzed oxidative C–H cross-coupling reactions. The synthetic utility of AC was validated across a diverse set of mechanistic pathways, including C–H activation, radical relay, radical addition, and nucleophilic addition. We propose that AC can serve as a general and robust platform to circumvent the persistent issue of metal catalyst deactivation in electrosynthesis. Overall, we have developed three strategies from DC to AC electrosynthesis to address long-standing issues in electrochemical transition-metal catalysis. In contrast to the well-established DC electrosynthesis, the AC mode demonstrates a greater potential and diversity in transition-metal catalysis. Fully exploiting the unique capabilities of AC to expand the application scenarios is of considerable scientific significance and practical value.