Facile and general electrochemical deuteration of unactivated alkyl halides

Abstract

Herein, a facile and general electroreductive deuteration of unactivated alkyl halides (X = Cl, Br, I) or pseudo-halides (X = OMs) using D₂O as the economical deuterium source was reported. In addition to primary and secondary alkyl halides, sterically hindered tertiary chlorides also work very well, affording the target deuterodehalogenated products with excellent efficiency and deuterium incorporation. More than 60 examples are provided, including late-stage dehalogenative deuteration of natural products, pharmaceuticals, and their derivatives, all with excellent deuterium incorporation (up to 99% D), demonstrating the potential utility of the developed method in organic synthesis. Furthermore, the method does not require external catalysts and tolerates high current, showing possible use in industrial applications.

Deuterium-labelled compounds are useful for mechanistic studies and pharmaceutical science, but syntheses are not trivial. Here, the authors report deuteration of unactivated alkyl (pseudo)halides driven by electrochemical force, using deuterium oxide as the source of the isotope.