Deciphering the Synchronization of Alternating Current Frequency with the Nickel Catalytic Cycle in Selective C-N...

Alternating current (AC) electrolysis offers a promising strategy for modulating redox states in metal-catalyzed reactions, yet its mechanistic basis remains poorly understood. Here, we uncover how AC frequency synchronizes with key steps in a Ni-catalyzed cross-coupling cycle to control product selectivity between C-N and C-C coupling. We show that optimal C-N selectivity arises from minimizing the exposure of a key intermediate, Ni^II(Ar)Br, to reducing conditions that otherwise promote off-cycle Ni^I species and undesired C-C homocoupling. By developing a simple cyclic voltammetry-based method, we accurately predict the optimal AC frequency across diverse aryl bromides and amines, eliminating the need for time-consuming trial-and-error reaction optimization. The predicted values align well with experimentally determined frequencies, validating the approach. This work establishes a mechanistic foundation for integrating AC waveform control into metal catalysis and highlights its potential for advancing selective electrochemical transformations in synthetic and medicinal chemistry.