Electrochemical Trideuteromethylation with AcOD-d₄: A Route to CD₃-Labeled Building Blocks

Deuterium substitution (CH₃ → CD₃) can enhance metabolic stability via the kinetic isotope effect and enable bioanalytical mass shifts. We report an electrochemical Kolbe heterocoupling that installs CD₃ at aliphatic positions by coupling carboxylic acids with AcOD-d₄. The reaction proceeds at room temperature under constant current with Pt electrodes and base. Diverse CD₃-labeled building blocks are obtained in moderate to good yields, and the method avoids CD₃I and deuterated solvents.