Umpolung Amide Synthesis Using Free Amino Acids

Abstract

Traditional amide synthesis employs a nucleophilic amine, which is reacted with an electrophilic activated carboxylic acid or carboxylic acid surrogate. Recently, colleagues in the Johnston lab introduced an unconventional approach to amide synthesis. In contrast to the standard approach, this new method utilizes an electrophilic amine and nucleophilic carboxylic acid equivalent. This approach, referred to as Umpolung Amide Synthesis (UmAS), was extended to the synthesis of amides from free amino acids. The products of these reactions bear one less protecting group than the analogous products of standard amide forming reactions. In addition, prior work has shown that epimerization does not occur with UmAS reactions. A library of stereochemically pure or enriched dipeptides was synthesized using this approach. In addition, the discovery of a novel reaction that converts α-bromonitroalkanes to carboxylic acids is reported.