(E)-Ethyl-2-cyano-2-(((2,4,6-trichlorobenzoyl)oxy)imino)acetate: A Modified Yamaguchi Reagent for Enantioselective Esterification, Thioesterification, Amidation, and Peptide Synthesis

Here, the synthesis and applications of ( E )-ethyl-2-cyano-2-(((2,4,6-trichlorobenzoyl)oxy)imino)acetate as a racemization suppressing and easily recyclable version of the Yamaguchi reagent that can be used for amide and peptide synthesis are reported. We demonstrated its application in racemization-free esterification, thioesterification, amidation, and peptide bond formation. We successfully synthesized oligopeptides on the solid support in dimethylformamide as well as in solution (dichloromethane) by applying this coupling reagent. It is important to note that a mixed-anhydride-based method provides peptide-forming reactions as good as the current methods using built-in coupling reagents. Mechanism investigation, racemization suppression, and recyclability are also discussed.