2-fluoro-2 phenylacetic acid as a chiral derivatizing agent: configurational determination from 19F NMR chemical shifts measurements of esters and amides of this C.D.A. and theoretical calculations of conformers in these series.

Abstract

2-Fluoro-2 phenylacetic acid was synthetized from phenylglycine through a fluorodeamination reaction in a HF-pyridine mixture (1). This acid can be used as a derivatizing chiral agent: the enantiomeric excess of secondary alcohols (or of primary amines whose NH 2 group was born by a chiral carbon) can be easily measured by 19F NMR spectra of the corresponding esters (or amides). More detailed studies relative to correlations between the configuration of the esters and proton and particularly fluorine chemical shifts were undertaken. For instance, the 19F NMR chemical shifts (δF) of the (p-Z)PhC*HFCO 2CH*L(p-YPh) esters showed a linear correlation of the δF with the σ + Brown-Okamoto Z substituent parameters and of the δF with the σ Hammett Y substituents parameters. The difference for the two different esters configurations were observed mostly on the y-intercept of the δF=f(σ +) correlation. We therefore were able to use this observation for determination of the configuration (pMeO)PhC*HFCO 2C*HL 1L 2 (electrochemically prepared by french colleagues) from that of PhC*HFCO 2C*HL 1L 2 (2,3). Other configurational determinations were made on other series. The origin of this δF high sensitivity to structural effects were researched from evaluation of contbrmers. AM1 (or PM3) semi-empirical theoretical calculations were undertaken for quantitative evaluation of preferential conformations versus appropriate dihedral angles. As five atoms (benzylic carbon, CO 2 group and the chiral atom of the alcohol or amine) were shown to be coplanar, a discussion using the following Newman-like projection will be made. ▪ The benzylic hydrogen atom was substituted with a methyl group. The influence of this replacing on the relative stabilities of the previous conformers will be presented.