Electrocatalytic Reductive Deuteration of (Hetero)Arenes

Abstract

The incorporation of deuterium to organic molecules have widespread applications in medicinal chemistry and material science1,2. For example, deuterated drugs e.g. Austedo3, Donafenib4 and Sotyktu5 have been approved, recently. Because of all these applications, developing methodologies for the synthesis of deuterated compounds with high deuterium ratios is highly desirable6. However, reductive deuteration of aromatic hydrocarbons, which are ubiquitous skeletal features in inert chemical feedstocks, to saturated cyclic compounds, including heterocyclic skeletons has been rarely achieved. So far, only few methods have been reported for direct reductive deuteration using stoichiometric strong reducing agents or D2. Here, we describe a scalable and general electrocatalytic method for the reductive deuteration and deuterodefluorination of (hetero)arenes using a prepared nitrogen doped electrode and D2O, giving perdeuterated and saturated deuterocarbons. This protocol has been successfully applied to the high incorporation of deuterium in 13 drugs.