Electrochemical α-deuteration of amides

Abstract

Precise deuterium incorporation of bioactive molecules is highly desirable in order to improve ADME properties and monitor pharmacokinetics. Organic electrochemistry offers a powerful tool for molecular editing using electrons as traceless reagents. We herein present an electrochemical deuteration that can specifically modify the α-position of amides via an H/D exchange reaction under mild neutral conditions. This protocol provides an efficient tool for the rapid synthesis of α-deuterated amides in moderate to high yields with excellent levels of deuteration. In addition, the late-stage modification of drug molecules has been well demonstrated. Furthermore, the reduction of amides provides an efficient route to β-bisdeuterated amines, which are difficult to access by the existing methods. We envision that this on-demand deuterium incorporation will provide unique opportunities in biological research and therapeutics.