Synthesis of 1-fluoroindan-1-carboxylic acid (FICA) and its properties as a chiral derivatizing agent

Abstract

1-Fluoroindan-1-carboxylic acid (FICA) ( 1) was designed and synthesized as its methyl ester (FICA Me ester) ( 4) in order to develop an efficient chiral derivatizing agent (CDA) which excels α-methoxy-α-(trifluoromethyl)phenylacetic acid (MTPA) in capability. FICA Me ester ( 4) was prepared by fluorination of methyl 1-hydroxyindan-1-carboxylate ( 3) with (diethylamino)sulfur trifluoride (DAST) and derived to the esters of racemic secondary alcohols by ester exchange reaction. The resulting Δ δ F value was large in the case of 2-butyl ester of FICA ( 5a), whereas not detectable in the case of the corresponding MTPA ester ( 6a). The magnitude of the Δ δ H values was similar to that of MTPA esters. The diastereomers of ( R)-(−)-8-phenylmenthyl ester of FICA ( 5i) was separated and their 1H NMR analyses revealed that the concept of the modified Mosher's method was successfully applied to 5i.