Asymmetric synthesis of ( S)-ibuprofen by esterification with amides of ( S)-lactic acid as chiral auxiliaries: experimental and theoretical results

Abstract

A novel synthesis of chiral ibuprofen by a dynamic kinetic resolution process is described. The racemic ibuprofen was converted into the corresponding diastereomeric mixtures of esters with amides of ( S)-lactic acid as chiral auxiliaries, using dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) as condensation agents. The reactions afforded predominantly one of the two diastereomers with good diastereomeric ratios. The reasons of the stereoselectivity were also investigated by molecular mechanic calculations, using MM2 force fields.