STEREOSELECTIVE ACETALIZATION OF 1,3-ALKANEDIOLS CONTROLLED BY INTRAMOLECULAR VAN-DER-WAALS ATTRACTIVE INTERACTIONS AND ITS APPLICATION TO AN ENANTIODIFFERENTIATING TRANSFORMATION OF SIGMA-SYMMETRICAL 1,3,5-PENTANETRIOLS

Acetalization reactions of racemic bis(trimethylsilyl) ethers (R1R2CHCH(OTMS)CH(R3)CH2OTMS) with racemic menthone, under thermodynamically controlled conditions, stereoselectively give spiroacetal 2 (in which the substituent R1R2CH- is attached to the carbon adjacent to the axial oxygen atom with respect to the menthane ring) in preference to the diastereomeric spiroacetal 3 (in which the substituent is attached to the carbon adjacent to the equatorial oxygen atom). Correlation between the stereoselectivities and the structures of the spiroacetals as well as the higher stereoselectivities observed in the related acetalization with 7,7,7-trimethylmenthone indicates that the preferential formation of spiroacetal 2 of a folded structure is a result of intramolecular attractive interactions between the menthane moiety and the substituent attached to the 1,3-dioxane ring. Molecular mechanics (MM2) calculations give satisfactory agreement with experiments and provide support for the operation of the van der Waals attractive interaction as the most important factor determining the stereoselectivities. The stereoselective acetalization with l-menthone is successfully applied to a novel enantiodifferentiating transformation of sigma-symmetric 1,3,5-pentanetriols (HOCH2CHRCH(OH)CHRCH2OH; R = Me or H). The reaction provides an efficient and straightforward route to chiral menthonide derivatives 13a-c, which can be utilized as versatile chiral building blocks.