Synthesis of α-Deuterated Trifluoromethylated Amines through Isomerization-Deuteration Reaction of Imines

Deuterated compounds are of significant interest in chemistry, medicinal chemistry, and the pharmaceutical industry. Herein, we report organocatalytic isomerization-deuteration reactions of trifluoromethyl imines via a deprotonation-H/D exchange-deuteration sequence, providing a new strategy for the effective synthesis of chiral and racemic α-deuterated trifluoromethylated amines with excellent deuterium incorporation using D₂O as the deuterium source. High enantioselectivity could be achieved for aliphatic trifluoromethyl imine using as low as 0.2 mol % of new cinchonium betaine catalysts.