Microwave-assisted ester formation using O-alkylisoureas: a convenient method for the synthesis of esters with inversion of configuration.
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 S(N)2 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.
Chighine
Alessandra
A
School of Chemistry, University of Edinburgh, Joseph Black Building, West Mains Road, Edinburgh EH9 3JJ, United Kingdom.
Crosignani
Stefano
S
Arnal
Marie-Claire
MC
Bradley
Mark
M
Linclau
Bruno
B
D000438:Alcohols / Q000737:chemistry; D000473:Alkanes / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis; D008872:Microwaves; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism; D014508:Urea / Q000737:chemistry*
D000438:Alcohols; D000473:Alkanes; D002264:Carboxylic Acids; D004952:Esters; D014508:Urea