Exo-anomeric effects

Three staggered conformations are possible for the rotation about the C2-02 bond in both equatorial and axial conformers of 2-methoxy-tetrahydropyran (Fig. 2.14). These are referred to as E1-E3 (34, 36, and 38) and A1-A3 (35, 37, 39) conformers. In the El conformer (34) there are no iyn-axial steric 

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It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

In 1991, an important paper was published by Bock et a/.84 that described the steric and electronic effects on the formation of the dispiroketal dihexulose dianhydrides. The authors described the conformation of six dihexulose dianhydrides, as determined by X-ray crystallography or NMR spectroscopy. They concluded that these conformations are dictated by the anomeric and exo-anomeric effects. Thus, the dihexulose dianhydrides are disposed to adopt conformations that permit operation of these effects—even if this results in the dioxane ring having a boat conformation or all three substituents on one pyranose ring being axial. 

Consequences of the conformational anomeric effect are largely expressed in monosaccharides and their derivatives. One recognizes the conformational endo-anomeric effect for pyranosides with a polar X group at C(l) (contrasteric electronic stabilization effect Fig. 7A) and conformational exo-anomeric effect for glycosides (acetals) in which the alkyl group of the exocyclic moiety is synclinal (Fig. 7B, C). 

Fig. 7 (A) Conformational endo-anomeric effect (B) conformational exo-anomeric effect in axial O-pyranosides (X = OR) (C) conformational exo-anomeric effect in equatorial O-pyranosides (X = OR).

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

The turning of the key once the complex has formed is a separate issue. In this regard, Lemieux (47) has pointed out that rotation about the glycosidic bond must weaken the exo-anomeric effect and thereby importantly activate the anomeric carbon to nucleophilic attack. Therefore, it seems likely that the role of the key hydroxyl group of the aglycon is to accommodate the rotation prior to the attack by water to form / -D-glucopyranose, which is the first product of the reaction. 

Anhydrous hydrogen fluoride, application of for the structural analysis of polysaccharides, 47, 167-202 Anomeric and exo-anomeric effects in carbohydrate chemistry, 47, 45-123 Anomeric-oxygen activation for glycoside synthesis, trichloroacetimidate method, 50,21-123... 

Carba-sugars (pseudo-sugars) and their derivatives, chemistry of, 48, 21 - 90 Carbohydrate chemistry anomeric and exo-anomeric effects in, 47, 45-123... 

No data were reported on 1,2-frans-thioglycosides. However, in accordance with a weaker exo-anomeric effect in thiooligosaccharides than in the O-glycosides, these compounds should also be more flexible. 

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