Anomeric effects group

It IS not possible to tell by inspection whether the a or p pyranose form of a par ticular carbohydrate predominates at equilibrium As just described the p pyranose form IS the major species present m an aqueous solution of d glucose whereas the a pyranose form predominates m a solution of d mannose (Problem 25 8) The relative abundance of a and p pyranose forms m solution depends on two factors The first is solvation of the anomeric hydroxyl group An equatorial OH is less crowded and better solvated by water than an axial one This effect stabilizes the p pyranose form m aqueous solution The other factor called the anomeric effect, involves an electronic interaction between the nng oxygen and the anomeric substituent and preferentially stabilizes the axial OH of the a pyranose form Because the two effects operate m different directions but are com parable m magnitude m aqueous solution the a pyranose form is more abundant for some carbohydrates and the p pyranose form for others... 

Anomeric effect (Section 25 8) The preference for an elec tronegative substituent especially a hydroxyl group to oc cupy an axial orientation when bonded to the anomeric carbon m the pyranose form of a carbohydrate Anti (Section 3 1) Term describing relative position of two substituents on adjacent atoms when the angle between their bonds is on the order of 180° Atoms X and Y m the structure shown are anti to each other... 

Compounds in which conformational, rather than configurational, equilibria are influenced by the anomeric effect are depicted in entries 4—6. Single-crystal X-ray dilfiaction studies have unambiguously established that all the chlorine atoms of trans, cis, ira j-2,3,5,6-tetrachloro-l,4-dioxane occupy axial sites in the crystal. Each chlorine in die molecule is bonded to an anomeric carbon and is subject to the anomeric effect. Equally striking is the observation that all the substituents of the tri-0-acetyl-/ -D-xylopyranosyl chloride shown in entry 5 are in the axial orientation in solution. Here, no special crystal packing forces can be invoked to rationalize the preferred conformation. The anomeric effect of a single chlorine is sufficient to drive the equilibrium in favor of the conformation that puts the three acetoxy groups in axial positions. 

Anomeric effect (Section 25.8) The preference for an electronegative substituent, especially a hydroxyl group, to occupy an axial orientation when bonded to the anomeric carbon in the pyranose form of a carbohydrate. 

For oxathiane 1, lone pair selectivity is controlled by steric interactions of the gem-dimethyl group and an anomeric effect, which renders the equatorial lone pair less nucleophilic than the axial lone pair. Of the resulting ylide conformations, 25a will be strongly preferred and will react on the more open Re face, since the Si face is blocked by the gem-dimethyl group (Scheme 1.9) [3, 15]. 

Hall et al.1 s estimated the conformational equilibrium for the structural units in the polymer of 2 using the numerical parameters determined for carbohydrates16. For a frans-l,3-tetrahydropyranoside, conformer 8 is calculated to be more stable than 7 by 9.2 kJmol-1 and would therefore occur almost exclusively (ca. 98%) at equilibrium. For a m-1,3-tetrahydropyranoside unit, the anomeric effect favors con-former 9, but its severe syn-axial interaction between alkoxy and alkyl groups would highly favor 10 (ca. 99%). 

Polymerization of 4-bromo-6,8-dioxabicyclo[3.2.1 ]octane 2 7 in dichloromethane solution at —78 °C with phosphorus pentafluoride as initiator gave a 60% yield of polymer having an inherent viscosity of 0.10 dl/g1. Although it is not described explicitly, the monomer used seems to be a mixture of the stereoisomers, 7 7a and 17b, in which the bromine atom is oriented trans and cis, respectively, to the five-membered ring of the bicyclic structure. Recently, the present authors found that pure 17b was very reluctant to polymerize under similar conditions. This is understandable in terms of a smaller enthalpy change from 17b to its polymer compared with that for 17a. In the monomeric states, 17b is less strained than 17a on account of the equatorial orientation of the bromine atom in the former, whereas in the polymeric states, the polymer from 17b is energetically less stable than that from 17a, because the former takes a conformation in which the bromine atom occupies the axial positioa Its flipped conformation would be even more unstable, because the stabilization by the anomeric effect is lost, in addition to the axial orientation of the methylene group. 

The configuration of each anomeric hydroxyl group that forms a polymer linkage is fixed, and the type of linkage has a significant effect on the physical properties of the polymer, as will be seen. 

Similar results were obtained from a study of 2-phenyl-5-t-butyl-l,3 2-dioxaphosphorinane (111) in that the cw-isomer was thermodynamically more stable than the trans. However, in this case even the trans-isomer adopts a conformation (112) with the P-phenyl group and, perforce, the t-butyl group axial. A similar situation has already been noted in the phosphite (108), and it may be that the special case of a phenyl group produces some type of pseudo anomeric effect. 

FIERON reactions of 7V-acyloxy-7V-alkoxyamides would be expected to favour migration of acyloxyl groups since anomeric effects are strongest in this direction... 

Alternatively, lactols react with benzenesulfinic acid in the presence of CaCl2 to yield the sulfones, again at room temperature [307,309]. In the axial series, the bulk of the sulfone group is such that the 4Cj chair is not always the preferred conformation, and it has been shown that a twist-boat conformer is adopted in at least one instance [305]. Nevertheless, equilibration studies have shown that the sulfonyl group has a small anomeric effect and that the axial anomer is preferred [310],... 

Taken from NIST Chemistry Webbook. b Estimated from CH2(CN)2 adding -7 kcal/mol (exchange of a CH2 group by a CHMe group). c Enthalpy difference indicates a destabilization effect for gem-disubstitution with respect to alkanes. d Enthalpy difference shows a stabilization effect for gem-dialkoxy-disubstitution with respect to alkanes. c Enthalpy difference shows increases of enthalpic anomeric effect for tertiary acetals compared to secondary acetals. 

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). 

---