Novel Chiral Molecular Tools for Preparation of Enantiopure Alcohols by Resolution and Simultaneous Determination of Their Absolute Configurations by the 1H NMR Anisotropy Method

Abstract

The development and applications of novel chiral molecular tools, (S) - (+) -2-methoxy-2- (l-naphthyl)propionic acid (MαNP acid (2)) and (S) - (+) -2-methoxy-2- (9-phenanthryl) propionic acid (M9PP acid (3)), useful for preparation of enantiopure secondary alcohols and simultaneous determination of their absolute configurations by the 1H NMR anisotropy method are explained. Racemic MαNP acid 2 was enantioresolved with (-) -menthol, and the enantiopure MαNP acid (S) - (+) -2 obtained was allowed to react with racemic alcohols yielding diastereomeric esters, which were easily and clearly separated by HPLC on silica gel. By applying the sector rule of 1H NMR anisotropy effect, the absolute configurations of the first-eluted MαNP esters were unambiguously determined. MαNP acid (S) - (+) -2 has thus a great power to discriminate the chirality of various alcohols, especially that of aliphatic alcohols, in both HPLC and 1H NMR. The solvolysis or reduction of the first-eluted MαNP esters yielded enantiopure alcohols, whose absolute configurations were simultaneously determined. Another chiral molecular tool, M9PP acid (S) - (+) -3, was similarly applied to prepare both enantiomers of sulcatol, an insect pheromone, in enantiopure forms.