Tandem H/D Exchange-SET Reductive Deuteration Strategy for the Synthesis of α,β-Deuterated Amines Using D₂O

Abstract

α,β-Deuterated amines are crucial for the development of deuterated drugs. We intend to introduce the novel tandem H/D exchange-single electron transfer (SET) reductive deuteration strategy with high pot- and reagent-economy by the synthesis of α,β-deuterated amine using nitrile as the precursor. The H/D exchange of the -CH₂CN group was achieved by D₂O/Et₃N, which were also the required reagents in the tandem SmI₂-mediated SET reductive deuteration of the α-deuterated nitrile. The potential application of this method was further showcased by the synthesis of bevantolol-<i>d</i>₄.