Alternating Current-Driven Diol Epimerization via a Deplete–Regenerate Strategy

Epimerization is a powerful strategy for stereochemical editing, granting access to under-represented isomers without altering molecular connectivity. Although photocatalytic methods have recently expanded the epimerization toolkit, electrocatalytic alternatives have remained limited by redox incompatibilities that preclude simultaneous oxidation and reduction under direct current (DC) electrolysis. Here we report a general electrocatalytic epimerization enabled by alternating-current (AC) electrolysis. A deplete-regenerate strategy enables temporal separation of redox events: the thiol mediator is exhaustively oxidized during the anodic half-cycle (depletion prior to substrate activation), and subsequent polarity reversal regenerates the thiol in situ to quench the radical intermediate. This time-domain control allows the oxidative and reductive steps to occur in distinct phases. The method accommodates a broad range of functional groups and is compatible with complex bioactive molecules. Mechanistic investigations (kinetic analysis, cyclic voltammetry, and deuterium labeling) support a model wherein the AC waveform sustains catalytic turnover by resolving the redox incompatibility through this time-separated deplete-regenerate sequence.