Pentafluorophenyl Group as Activating Group: Synthesis of α-Deuterio Carboxylic Acid Derivatives via Et₃N Catalyzed H/D Exchange

We discovered that highly regioselective H/D exchange can be achieved on the α-position of the pentafluorophenyl (Pfp) ester using Et₃N as the catalyst and D₂O as the deuterium source. Our computational and experimental results showed that the Pfp group can significantly increase the acidity of the α-hydrogen of the ester. This mild reaction condition tolerated a variety of functional groups. 90%∼98% yields and 91%∼98% deuterium incorporations were obtained with all the tested Pfp esters. Taking advantage of the high reactivity of Pfp esters, a series of valuable α-deuterio carboxylic acid derivatives, including herbicide, drugs and drug intermediates, have been synthesized using α-deuterio Pfp esters as precursors. (Figure presented.).