SOLVATION EFFECTS ON THE CONFORMATION OF ESTERS OF CHIRAL SECONDARY ALCOHOLS AND 2-FLUORO-2-PHENYL ACETIC ACID USED AS A FLUORINE-SUBSTITUTED CHIRAL D ERIVATIZING AGENT : AN EXPERIMENTAL AND QUANTUM MECHANICAL STUDY

Solvation effects on the conformation of esters of three p-substituted 1-phenylethanols with 2-fluoro-2-phenyl acetic acid (FCDA) were studied both experimentally (in five solvents ranging from CDCl3 to DMSO) and quantum mechanically. Semi-empirical (AM1 of MJS Dewar and PM3 of JJP Stewart) and ab initio (RHF/3-21 G) calculations were undertaken. Energy maps for the conformers of the esters as a function of the dihedral angles alpha (F-C-alpha acid-C=O) and beta (CO-O-C-alcohol-H) were obtained. Solvent effect calculations, through the self-consistent reaction field, on the most stable conformers were also carried out. All the results justify our previously suggested working hypothesis: the conformation generating the fluorine NMR chemical shift difference between the two diastereoisomers(1) has the C-phenyl (of the FCDA) bond in the atoms C-alpha(acid)-CO-O-C-(alcohol)-H plane.