Synthesis of α-Deuterioalcohols by Single-Electron Umpolung Reductive Deuteration of Carbonyls Using D2O as Deuterium Source

Abstract

AbstractDeuterium incorporation can effectively stabilize the chiral centers of drug and agrochemical candidates that hampered by rapid in vivo racemization. In this work, the synthetically challenging chiral-center deuteration of alcohols has been achieved via a single-electron umpolung reductive-deuteration protocol using benign D2O as deuterium source and mild SmI2 as electron donor. The broad scope and excellent functional group tolerance of this method has been showcased by the synthesis of 43 respective α-deuterioalcohols in high yields and ≥98% deuterium incorporations. The potential application of this versatile method has been exemplified in the synthesis of 6 deuterated drug derivatives, 1 deuterated human hormone, and 3 deuterated natural products. This method using D2O is greener and more efficient compared to traditional pyrophoric-metal-deuteride-mediated reductive deuterations.