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

1Fluoroindan-1carboxylic 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 alpha-methoxy-alpha-(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 Delta delta(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 ASH values was similar to that of MTPA esters. The diastereomers of (R)-(-)-8-phenylmenthyl ester of FICA (5i) was separated and their H-1 NMR analyses revealed that the concept of the modified Mosher's method was successfully applied to 5i. (c) 2006 Elsevier B.V. All rights reserved.