Repurposing amine and carboxylic acid building blocks with an automatable esterification reaction

New methodologies to unite amines and carboxylic acids that complement the popular amide coupling can significantly expand accessible chemical space because they yield products distinct from the classic R–NHC(O)–R’ amide arrangement. Here we have developed an amine–acid esterification reaction based on pyridinium salt activation of amine C–N bonds to create products of type R–OC(O)–R’ upon reaction with alkyl and aryl carboxylic acids. The protocol is robust and facile, as demonstrated by automation on open-source robotics.