Investigation of the Yamaguchi esterification mechanism. Synthesis of a lux-s enzyme inhibitor using an improved esterification method.

[reaction: see text] A one-pot procedure for the regioselective synthesis of aliphatic esters is described. This was a result of a study on mixed aliphatic-aromatic anhydrides. The data suggest that during the Yamaguchi esterification reaction, a symmetric aliphatic anhydride is produced in situ, which upon reaction with an alcohol yields the ester. We confirmed that benzoyl chloride could be used instead of the sterically hindered Yamaguchi acid chloride. This method was successfully applied in the synthesis of Lux-S aspartic acid inhibitor.