CONFORMATIONAL PREFERENCES OF THE O-C-C-C UNIT IN ACYCLIC AND CYCLIC SYSTEMS - THE EXO-DEOXOANOMERIC EFFECT AND RELATED PHENOMENA

The origin of the observation by Kishi et al. that C-glycosides have a gauche O-C1-C(exo)-C torsional arrangement was investigated by ab initio quantum mechanics. In propanol, 2-butanol, 2-ethyltetrahydropyran, and 2-ethyl-3-hydroxytetrahydropyran models for C-glycosides, the gauche O-C-C-C conformation is lower in energy than the anti. By contrast, in 3-methyltetrahydropyran and 5-methyl-1,3-dioxane, the equatorial forms (anti O-C-C-C) are more stable than the axial forms (gauche O-C-C-C). These apparently conflicting preferences are rationalized on the basis of electrostatic and steric arguments. The gauche O1-C2-C3-C4 preference of 0.3 kcal/mol in simple systems becomes an anti preference when C2 and C3 are part of a ring or when C3 is alkyl substituted. The hypothesis was tested by developing bond dipole parameters for MM2; these parameters mimic experimental differences. A simple torsional parameter was developed and was also used in MM2 to predict the conformations of a series of acyclic alcohols. The results compare favorably with the experimental values derived from C-13 NMR spectra.