Synthesis of Methyl-d(3) Arene via Electrochemical Deuterodefluorination of Trifluoromethyl Arene

The methyl-d(3) group is anew isotopicfunctional group for medicine design. In this work, we report an electrochemicaldeuteration approach for converting aromatic trifluoromethyl to methyl-d(3) groups with deuterium water in commonDMF. Yields up to 94%, D ratio up to 97%, and CD3 incorporationup to 90% were achieved. A basic additive is the key factor enablingthe highly chemoselective reaction.

Automated summary

In this study, an electrochemical deuteration method using deuterium water in DMF was used to convert aromatic trifluoromethyl to methyl-d(3) groups. The addition of a basic additive was crucial for achieving highly selective reaction, resulting in yields up to 94%, D ratio up to 97%, and CD3 incorporation up to 90%.