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.