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

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-d4.