TEMPO–Me: An Electrochemically Activated Methylating Agent

Bench- and air-stable 1-methoxy-2,2,6,6-tetramethylpiperidine (TEMPO–Me) is relatively unreactive at ambient temperature in the absence of an electrochemical stimulus. In this report, we demonstrate that the one-electron electrochemical oxidation of TEMPO–Me produces a powerful electrophilic methylating agent in situ. Our computational and experimental studies are consistent with methylation proceeding via a SN2 mechanism, with a strength comparable to the trimethyloxonium cation. A protocol is developed for the electrochemical methylation of aromatic acids using TEMPO–Me.