Chemoselective Alpha-Deuteration of Amides Via Retro-ene Reaction.

A synthetically convenient approach for the direct α-deuteration of amides is reported. This mechanistically unusual process relies on a retro-ene-type process, triggered by the addition of deuterated dimethyl sulfoxide to an intermediate keteniminium generated through electrophilic amide activation. The transformation displays broad functional-group tolerance and high deuterium incorporation.