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The enantioresolution of racemic alcohols as esters of 2-methoxy-2-(1-naphthyl)propionic acid (MalphaNP acid 1) and the determination of their absolute configurations on the basis of (1)H NMR anisotropy effect are described. The enantiopure MalphaNP acid (S)-(+)-1 was allowed to react with racemic 2-alkanols and 1-octyn-3-ol, yielding diastereomeric mixtures of esters, which were easily separated by HPLC on silica gel. To determine the absolute configurations of the first-eluted diastereomeric esters by the (1)H NMR anisotropy method, the general scheme was proposed. Separated esters were reduced with LiAlH(4) or hydrolyzed with KOH/EtOH to recover enantiopure alcohols.

A novel methodology using a chiral molecular tool of MalphaNP acid (1), 2-methoxy-2-(1-naphthyl)propionic acid, useful for preparation of enantiopure secondary alcohols and determination of their absolute configurations by the (1)H NMR anisotropy method was developed; racemic MalphaNP acid (1) was enantioresolved with (-)-menthol, and the enantiopure MalphaNP acid (S)-(+)-(1) obtained was allowed to react with racemic alcohol, yielding a mixture of diastereomeric esters, which was clearly separated by HPLC on silica gel. By applying the sector rule of (1)H NMR anisotropy effect, the absolute configuration of the first-eluted MalphaNP ester was unambiguously determined. Solvolysis or reduction of the first-eluted MalphaNP esters yielded enantiopure alcohols.

[a][ ‡]Keywords: Conformational analysis / 1 H NMR anisotropy effect / MαNP and related esters / Chirality / Aromatic geometry and solvent effectsThe MαNP acid method is very powerful for the preparation of enantiopure alcohols by resolution and the simultaneous determination of their absolute configurations by the 1 H NMR anisotropy effect, where the syn-syn conformation is taken as the preferred conformation of MαNP esters. However, the syn-syn conformation of MαNP esters looks unstable, because two electronegative oxygen atoms (CH 3 O and C=O) are close to each other. To solve the problem of why the MαNP esters take such a syn-syn conformation, the aromatic geometry and solvent effects on the 1 H NMR anisotropy data were studied, leading to the following conclusions: i) the hydrogen-bonding-like interaction among the H-8Ј of the naphthyl group, the ester carbonyl oxygen, and the

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