One-Pot Transition-Metal-Free Synthesis of Weinreb Amides Directly from Carboxylic Acids

Abstract

Weinreb amides were prepared directly from carboxylic acids, <i>N</i>,<i>O</i>-dimethylhydroxylamine, and phosphorus trichloride in one pot at 60 °C in toluene in high yields, thus avoiding the separation of the moisture and air sensitive intermediate P[NMe(OMe)]₃ in advance. Sterically hindered carboxylic acids also give the corresponding Weinreb amides in excellent yields. Various functional groups are tolerated on the carboxylic acid. The method, which is a simple process and gives high yields, is suitable for large-scale production.