Microwave-assisted ester formation using O-alkylisoureas: a convenient method for the synthesis of esters with inversion of configuration

Chighine, Alessandra, Crosignani, Stefano, Arnal, Marie-Claire, Bradley, Mark and Linclau, Bruno (2009) Microwave-assisted ester formation using O-alkylisoureas: a convenient method for the synthesis of esters with inversion of configuration. Journal of Organic Chemistry, 74 (13), 4753-4762. (doi:10.1021/jo900476y).

Abstract

The formation of carboxylic esters via reaction of carboxylic acids with O-alkylisoureas proceeds in excellent yields with very short reaction times when conducted in a monomode microwave synthesizer. Efficient processes were developed using preformed or commercially available isoureas derived from primary and secondary alcohols, with a reaction time of only 5 min or less. It was demonstrated that under these microwave conditions, ester formation proceeded in good yields with clean inversion of configuration where appropriate. The process was validated using menthol, a hindered substrate for SN2 reactions. In addition, starting from primary alcohols, ester formation was successfully accomplished using an in situ isourea formation procedure. A polymer-assisted solution-phase procedure was also developed by employing preformed solid-supported isoureas and by an efficient “catch and release” ester formation procedure whereby primary alcohols were caught on resin as isoureas by reaction with immobilized carbodiimide and released as esters by subsequent treatment with a carboxylic acids.

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Contributors

Author: Bruno Linclau

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