Conformational energy anomeric effect

The axial-axial arrangement is favored, consistent with expectations based on the anomeric effect. Relative energies (in kcal/mol) are as follows (the first conformation is that relative to the ring incorporating the carbonyl group). 

Keywords Conformational profile Steric effect E2 reaction Elcb reaction Anomeric effect Mutarotation Acetal hydrolysis Acetal formation Carbonyl oxygen exchange in esters Ozonation of acetals Orthoester and hydrolysis Numerical value of anomeric effect Relative energy of acetals 1,4-elimination Mono and dithoacetals Mono and diazaacetals... 

The conformational energies of monosubstituted oxanes studied to date are collected in Table I. In position 2, polar substituents (except NR2) prefer the axial position other substituents prefer the equatorial orientation, which is generally the case for groups in positions 3 and 4. Destabilizing 1,3-diaxial interactions cause the equatorial geometry to be usually favored in the 2-position, the anomeric effect stabilizes the axial conformation. A large purine moiety in position 2 of oxane, for example, prefers the equatorial position because the 1,3-diaxial interactions overcome the anomeric effect (75TL1553). 

Eliel et al. (82JA3635) examined the conformational equilibria of a number of disubstituted oxanes (Table III) by low-temperature C NMR spectroscopy (830MR94) and estimated the AG° values of 3-Me and 2-C=CH substituents (see Table I). The concentration of the axial 2-Me and 4-Me conformers, however, was so small and difficult to detect by NMR spectroscopy that they were forced to employ the use of counterpoised di-2-C=CH and ds-2-CH = CH2 groups to generate equilibria that were sufficiently balanced to measure accurately (AG° values in Table I). Eliel et al. (82JA3635) also discussed the conformational energies in terms of 1,3-diaxial interactions and the anomeric effect. 

Although the conformations of heterocycles are governed by the same principles that apply to carbocycles, where appropriate, additional factors, such as the anomeric effect, can have a significant influence upon the energies of the isomers in equilibrium. 

Quantitatively, the anomeric effect is defined as the difference in conformational free energy for the process shown in Scheme 28 and the corresponding process in cyclohexane. Conformational energies for a range of substituents are available (82JA3635). 

It is to be emphasized that, in the absence of elements of symmetry, as is the case for carbohydrates, determination of the molecular structure should be based on both the experimental, vibrational spectra and the calculated frequencies. In order to minimize the differences between experimental and calculated results, the structure factors utilized in the calculation should take into account the previous conformational studies. The peculiarities of carbohydrate structures, such as anomeric and exo-anomeric effects, are revealed by bond shortening and torsion-angle modifications. These modifications are accompanied by a change in the vibrational-energy level, and hence, by the corresponding information in their infrared or Raman spectra. 

The first precise evaluation (2A, 25) of both the anomeric and the exo-anomeric effects was obtained by studying 1,7-dioxaspiro[5.5]undecane (9) (Fig. 2). With this system, conformational analysis by low temperature nmr spectroscopy was possible because each conformational change involves a chair inversion which has a relatively high energy barrier. The steric effect could also be easily evaluated, and by adding appropriate alkyl substituents, it was theoretically possible to isolate isomeric compounds which would exist in different conformations. 

As we have seen, the anomeric effect confers a double-bond character to each C—0 bond of conformer D the energy barrier for a C —0 bond rotation in acetals must therefore be higher than that observed in simple alkanes. Borgen and Dale (41) may have provided the first evidence for this point by observing that 1,3,7,9-tetraoxacyclododecane (37) has a much higher conformational barrier (11 kcal/mol) than comparable 12-membered rings such as cyclododecane (7.3 kcal/mol (42) or 1,4,7,10-tetraoxacyclododecane (5.5 and 6.8 kcal/mol (43)). It was also shown that the two 1,3-dioxa groupings in 37 exist in a conformation identical to that of dimethoxymethane, i.e. the conformation D. 

Jeffrey et al. have calculated the energy of several conformations of dimethoxymethan as these are representative examples for the glycosidic bonds in a- or P-anomers (cf. Fig. 3) [59]-The calculations were carried out on the RHF/4-31G level. The obtained potential energies for the conformations of 0°, 90°, 180°, and 270° dihedral angles respectively revealed the presence of a strong exo anomeric effect in acetal... 

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