Interpretation, of the anomeric effect

In conclusion, we would like to mention that a hyperconjugative interpretation of the anomeric effect has been offered by various workers such as Romers and Altona333, Pople et a/ 43 and Salem et al.344. ... 

Interpretations of the anomeric effect depend on the theory that is applied, and only within a given theory can their correctness be checked. Hence, the number of explanations of the anomeric effect is quite large. They can be divided (23) into two basic groups classical structural theory supplemented with electronic effects (Section III. A) and quantum chemistry (Section III.B). 

The quality of rationalization provided by a given theory can be evaluated with relative ease by its applicability to explain all phenomena caused by the anomeric effect and its ability (if possible) to afford quantitative predictions of conformational equilibria. Following this approach, the description of the most important interpretations of the anomeric effect will be presented. 

The electrostatic interpretation of the anomeric effect has generally been regarded as incomplete because it does not lead to quantitative agreement with experiment (188) and does not account for the observed geometries. In particular, dipole-dipole repulsive interactions have been criticized from the theoretical point of view on the basis of ab initio (189) and semiempirical EHMO and CNDO/2 calculations (190) and recently (191) based on the decreased barrier to ring inversion in 2,2-dimethoxyoxane (98, see Section... 

David S, Eisenstein O, Hehre WJ, Salem L, Hoffman R (1973) Superjacent orbital control. Interpretation of the anomeric effect. J Am Chem Soc 95 3806-3807... 

On the other hand, the stereoelectronic interpretation of the anomeric effect [26] dictates the antiperiplanar orientation of an occupied, high-energy donor orbital and an empty, low-energy acceptor orbital. Such hyperconjugative stabilizing interaction is found in a-sulfinyl carbanions, where the conformation allowing for n. - cr s o two-electron-two-orbital interaction corresponds to the energy minimum (Scheme 3.6). 

Hphe term anomeric effect was introduced by Lemieux in 1958 as a result of a detailed study of the anomerization of acetylated pento-and hexo-pyranoses. The effect is well known to carbohydrate chemists, and refers to the tendency of an electronegative substituent at C-l of a pyranoid ring to assume the axial rather than equatorial orientation, in contrast to predictions based solely on steric grounds. However, the phenomenon is not restricted to carbohydrate systems, but is displayed in many types of heterocyclic compounds. Thus, the investigation of the anomeric effect has been of considerable interest to a variety of chemists, namely, theoreticians, structural chemists, physical organic chemists, and synthetic chemists. Chemists from all of these areas participated in the Symposium on The Origin and Consequences of the Anomeric Effect. This symposium was the first symposium devoted exclusively to a discussion of the anomeric effect, and it provided a mechanism for interactions between the diverse types of chemists. The chapters in this volume are not merely the texts as presented at the symposium, but they also incorporate some new interpretations by the authors resulting from these interactions. 

The paucity of information on the mechanism of reactions, and on the structure of the transition state, and the role of the anomeric effect in its stabilization, constitutes the main reason why qualitative interpretation of reactivity as shown in the aforementioned examples is still very rare. An alternative, more-popular estimation of the relative reaction-rates of con-formers is based on the lone-pair orbital interactions, and their symmetry and energy in the ground state, and could be loosely associated with the perturbation theory of chemical reactivity. ... 

In an attempt to isolate the anomeric effects, analogous phosphonites have been studied. Equilibration of cis- (109) and /ra 5-2-methyl-5-t-butyl-l,3,2-dioxaphosphorinanes(l 10) demonstrated the thermodynamic preference for cis over trans (72% and 28% respectively at 40 °C). This surprising result must mean that axial P-methyl is more stable than equatorial even when no anomeric effects are present, and the authors interpret their n.m.r. results in terms of two equilibrating conformers for trans- 10)... 

The first interpretation of the conformational anomeric effect, given by Edward,2 invoked more favorable electrostatic interactions in the axial anomers than in the equatorial anomers of carbohydrates (Fig. 8). 

Fig. 8 Interpretation of the conformational endo-anomeric effect according to Edwards (hard/hard interactions).

Fig. 10 Stereoelectronic interpretation of the conformational endo- and exo-anomeric effects [ (()) -> a c o hyperconjugation].

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