Alternating Current-Driven Hydrogen Isotope Labeling of Aliphatic Amines Using 1,3-Propanedithiol as an Efficient Hydrogen Atom Transfer Reagent

generate a potent HAT agent─a mercaptothiyl radical─via alternating current electrolysis. This radical benefits from a significantly weakened effective S-H bond dissociation energy of 34 kcal/mol compared to conventional monothiol HAT catalysts (∼80 kcal/mol), driven by exothermic disulfide ring formation. Mechanistic studies and computational analyses reveal a strong structure-activity relationship among dithiols, identifying 1,3-propanedithiol as the optimal catalyst, which is uniquely suited to balance fast HAT kinetics with efficient regeneration of the dithiol. The application of this method to over 30 pharmaceutically relevant compounds achieved up to 3.7 D per molecule. This work addresses a long-standing challenge in electrochemical HIE and introduces a new HAT platform with broad potential in synthetic and biological chemistry.