The electrosynthetic deethylation of tertiary amides, commonly encountered moieties in pharmaceuticals and agrochemicals, is an analogue of the function of cytochrome P450 enzymes, a major oxidant metabolic pathway for xenobiotics. The ability to tractably synthesise, in a late‐stage manner, drug metabolites from the parent drug is currently unsolved. We report the first study, mechanistic rationale, and synthetic scope of an undivided controlled current electrosynthetic method that selectively mono deethylates tertiary amides without over‐reaction. An optimisation survey found that changing the electron input from controlled voltage to controlled current conditions led to deethylation rather than the expected dehydrogenative coupling. The scope and limitations of the method were interrogated with 14 examples with the parent benzamide reaction optimised (86 % yield) and the scalable production of the major human metabolite of the insect repellent DEET was achieved from the parent molecule in one step.
- tertiary amide