Chemoselective Alpha-Deuteration of Amides via Retro-ene Reaction

Chemistry. 2020 Dec 1;26(67):15509-15512. doi: 10.1002/chem.202004103. Epub 2020 Nov 17.

Abstract

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 a keteniminium intermediate, generated through electrophilic amide activation. The transformation displays broad functional-group tolerance and high deuterium incorporation.

Keywords: amide activation; chemoselectivity; deuteration; sulfoxide isotopic labelling.