Molecular orbital calculations anomeric effect

Theoretical studies of tetrahedral carbon species have played an important role in the formulation of ALPH and the anomeric effect. Similarly, molecular-orbital calculations have been the touchpaper for development of the stereoelectronic effect in phosphorus chemistry. Early theoretical calculations indicated the influence of the anomeric and gauche effects in phosphates (Newton, 1973). But without doubt, the foray of Lehn and Wipff (1975) into this field provided the inceptive piece of research that was the impetus for a series of studies resulting in the proposition of a stereoelectronic theory with a far-reaching impact on nucleophilic substitution reactions at phosphorus. 

Additional experimental evidence is sparse [78, 79]. The geometric changes are consistent with an enhanced anomeric effect, not a reverse one [68, 80] Molecular orbital calculations are not conclusive because it is difficult to separate the RAE from steric effects and hydrogen bonding, which also favor the equatorial con-former [70, 81-84]. 

Tvaroska, L, Carver, J. P. (1996). Ab Initio Molecular Orbital Calculation of Carbohydrate Model Compounds. 5. Anomeric, xo-Anomeric, and Reverse Anomeric Effects in C-, N-, and S-Glycosyl Compounds. Journal of Physical Chemistry, 100, 11305-11313. 

Calculated rotamer states for the acetoxymethyl group at C-5 of gluco-and galacto-pyranosyl rings have been compared with those obtained from A"-ray crystallography and found to be in good agreement. Molecular orbital calculations on dimethoxymethane, a model for the anomeric centre of methyl pyranosides, have produced results consistent with the anomeric and the exn-anomeric effects. The results were compared with evidence obtained by neutron diffraction. Dynamic H n.m.r. methods applied to the... 

Molecular orbital calculations have been carried out on 2-fluoro- and 2-chloro-tetrahydropyrans as models for examining the anomeric effect in gtycosyl halides. The calculated population of the axial conformer decreased as the solvent polarity increased, which indicated a consequent decrease in the anomeric effect.The synthesis of a series of 2-(perfluoroall yl) ethyl glycosides is mentioned in Chapter 3, and some 3 -fluorinated ribonucleosides are covered in Chapter 20. The syntheses of 2-fluoro-L-daunosaniine and 2-fluoro-D-ristosamine are discussed in Chapter 9, while 2 -fluorocarminontydn is described in Chapter 19, and some fluorinated 2-deoxy KDO analogues are covered in Chapter 16. 

Ab Initio molecular orbital calculations on methanedithiol and thiolmethanol have been used as models for the anomeric effect in S-C-S and 0-C-S carbohydrate systems. The lower anomeric effect in sulphur systems was attributed to lower dipolar contributions to the total energy compared to the oxygen systems. 

Definitions based on Eqs. 1,3, and 4 should, in principle, also apply for the exo-anomeric and reverse anomeric effects. There are, however, some problems with the practical application of Eq. 1 in the case of the exo-anomeric effect, because the AG values are largely not available. For the exo-anomeric effect, the conformational equiUbrium is specified by two dihedral angles, 6 and d>, and the value of AG° is needed for all six individual con-formers shown in Fig. 3. Because rotation around the exocychc bond by angle O is much less restricted in comparison with rotation by angle 6, a mixture of conformers was experimentally observed, with a difficult resolution of AG2 into individual components. If the exo-anomeric effect is treated by Eq. 3, the extra term AE(AE2) should be redefined for the whole range of values of the torsional angle O. Due to the lack of experimental data on AG or AE , for each conformer in Fig. 3, the energy values calculated correctly , for example by some molecular orbital method, are used, instead of... 

The balance of electrostatic and delocalization interactions in an isolated molecule may be perturbed by the influence of the solvent. In calculations based on Eq. 7, the analysis of solvation-energy terms suggested that the electrostatic contribution stabilizing the ap orientation of the acetal s ment is the conformationally dominant term. For example, in 2-methoxyoxane, the difference in energy of the (ap, ap) and (ap, sc) conformers in water, compared to that in the isolated molecule, caused by solute-solvent electrostatic interactions alone, amounts to 4 kJ.mor. Accordingly, the inter-and intra-molecular, electrostatic interactions operate in reverse directions in acetals. Whereas the intramolecular, electrostatic interactions are responsible, together with delocalization interactions, for the aiq)earance of the anomeric, reverse anomeric, and exo-anomeric effects, the solute-solvent electrostatic interactions lessen their im nitude, and may even cancel them. Of course, the solvent may also influence the electron distribution and energy of MO s in a molecule. In this way, the orbital interactions of lone-pairs and delocalization contributions to the anomeric effect may be scaled by the solvent, but this mechanism of the environmental effect is, in most cases, of only minor importance. 

Scientists performing molecular orbital (MO) calculations usually consider the magnitude A g of the anomeric effect as the positive difference of the potential energy of antiperiplanar (ap) and of synclinal (sc) conformers (36) ... 

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