Ex Situ Generation of D2 for Reductive Deuteration: Scope and Application to Late-Stage Functionalization

An efficient deuteration method through the ex situ generation of D2 for the reductive deuteration of biologically significant α-substituted acrylic acids and enamide derivatives is reported. This method was successfully applied to the synthesis of deuterated analogs of marketed NSAIDs such as ibuprofen, flurbiprofen, and naproxen. Additionally, it facilitates late-stage deuteration of enamides and N-vinylated drugs. Moreover, the method was extended to N-viny azoles, cinnamic acid derivatives, and other unsaturated substrates toward deuteration reaction. This technique utilizes D2O as a safe and economical deuterium source. Notably, the reaction is performed in a standard fume hood setup, ensuring ease of handling and enhanced practicality.