Topic 2.3. The Anomeric Effect in Cyclic Compounds

Crystalline form has all four chlorines in axial conformation. 

Compounds in which conformational, rather than configurational, equilibria are influenced by the anomeric effect are depicted in Entries 4 to 6. X-ray diffraction studies have unambiguously established that all the chlorine atoms of trans, cis, trans-2,3,5,6-tetrachloro-l,4-dioxane occupy axial sites in the crystal (Entry 4). Each chlorine 

Several structural factors have been considered as possible causes of the anomeric effect. In localized valence bond terminology, there is a larger dipole-dipole repulsion between the polar bonds at the anomeric carbon in the equatorial conformation This dipole-dipole interaction is reduced in the axial conformation and this factor contributes to the solvent dependence of the anomeric effect. The preference for the axial orientation is highest in nonpolar solvent effects, where the effect of dipolar 

In general, electrostatic interactions alone do not seem to be sufficient to account for the magnitude of the anomeric effect and do not directly explain the bond length changes that are observed. These factors led to the proposal that the anomeric effect is, at least in part, due to a a hyperconjugation effects. From the molecular orbital viewpoint, the anomeric effect is expressed as resulting from an interaction 

There have also been a number of computational investigations into the nature of the anomeric effect. The axial-equatorial conformational equilibria for 2-fluoro and 2-chlorotetrahydropyran have been investigated with several MO calculations, including the MP2/6-31G level. The MP2/6-31G calculations give values of 3.47 and 2.84 kcal/mol, respectively, for the energy favoring the axial conformer. Solvent effects were also explored computationally and show the usual trend of reduced stability for the axial conformation as solvent polarity increases. Salzner and Schleyer applied 

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