Electrocatalytic Reductive Deuteration of (Hetero)Arenes

The incorporation of deuterium to organic molecules have widespread applications in medicinal chemistry and material science^1,2. 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.