Progressive Chemoselective Reductive Deuteration and Deuterodefluorination of Fluoroalkyl Ketones Using D 2 O

By applying an umpolung strategy, we present a convenient metal-free protocol for the reductive deuteration of trifluoromethyl ketone derivatives, delivering α-deuterated CF3-substituted alcohols as novel deuterated building blocks using D2O as the deuterium source in the presence of diphenylphosphine oxide and tBuOLi. This method efficiently transforms a wide range of fluoroalkyl ketones into their corresponding α-deuterated trifluoromethylated alcohols in good to excellent yields and attains remarkable deuteration efficiency (99% D). Furthermore, for the first time, transition-metal-free deuterodefluorination of trifluoromethyl ketones can also be achieved under slightly modified reaction conditions. Control experiments and mechanistic studies indicate that the combination of tBuOLi and the polar aprotic solvent NMP plays a crucial role in governing the reaction pathway.