Conformational analysis of MαNP esters, powerful chiral resolution and 1H NMR anisotropy tools -: Aromatic geometry and solvent effects on Δδ values

The M alpha NP acid method is very powerful for the preparation of enantiopure alcohols by resolution and the simultaneous determination of their absolute configurations by the H-1 NMR anisotropy effect, where the syn-syn conformation is taken as the preferred conformation of M alpha NP esters. However, the syn-syn conformation of M alpha NP esters looks unstable, because two electronegative oxygen atoms (CH3O and C=O) are close to each other. To solve the problem of why the M alpha NP esters take such a syn-syn conformation, the aromatic geometry and solvent effects on the H-1 NMR anisotropy data were studied, leading to the following conclusions: i) the hydrogen-bonding-like interaction among the H-8' of the naphthyl group, the ester carbonyl oxygen, and the methoxy oxygen supports a triangular intramolecular force to stabilize the syn-syn conformation; ii) triangular hydrogen bonding among a hydrogen atom of protic solvents, the ester carbonyl oxygen, and the methoxy oxygen also supports the syn-syn conformation. This hydrogen bonding, as the solvation effect implies, suggests that a similar hydrogen bonding between a M alpha NP ester and a hydroxy group of the silica gel surface would make a dominant contribution to the excellent discrimination of diastereomeric M alpha NP esters observed in the HPLC on silica gel. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007.