FICA, a new chiral derivatizing agent for determining the absolute configuration of secondary alcohols by 19F and 1H NMR spectroscopies

Optically active 1-fluoroindan-1-carboxylic acid (FICA) was designed and prepared as its methyl ester for determining the absolute configuration of chiral molecules by both H-1 and F-19 NMR spectroscopies. Enantiomerically pure isomers of FICA methyl esters (FICA Me esters) were obtained by chromatographic separation using HPLC with a Daicel Chiralcel OJ-H column. The absolute configuration of the (+)-FICA Me ester was deduced to be (S) by X-ray crystallographic analysis of the (+)-FICA amide of (R)-alpha-phenethylamine. Both enantiomers were derived to the diastereomeric esters of chiral secondary alcohols by an ester exchange reaction. In the H-1 NMR spectra, the signs of Delta delta(H) (delta(R) - delta(S)) were consistent on each side of the FICA molecular plane. Therefore, the concept of the modified Mosher's method could be successfully applied to the FICA-based procedure. Moreover, the consistency in the signs of Delta delta(F) (delta(R) - delta(S)) values suggests that the FICA method would be reliable in assigning the absolute configurations of secondary alcohols based on F-19 NMR spectroscopy. (C) 2013 Elsevier Ltd. All rights reserved.