Conformational analysis anomeric effect

Fernandez, B., M. A. Rios, and L. Carballeira. 1991. Molecular Mechanics (MM2) and Conformational Analysis of Compounds with N-C-O Units. Parametrization of the Force Field and Anomeric Effect. J. Comput. Chem. 12, 78-90. 

In following the temperature dependence of AG°, Booth et al. [85JC-S(CC)467 87T4699]also determined A/f° and AS° for the conformational equilibria of 2-C1-, 2-OMe-, 2-OH-, and 2-NHMe-oxanes (see Table II) and discussed the results in terms of exo- or endo-anomeric effects (Section III,C,8). Employing the NOE and a number of H,H- and C,H-coupling constants as a means of analysis, the preferred rotamers of axial/equatorial-2-OMe-oxane were found to be in the conformations az and 2, respectively, as given in Scheme 1 (90T1525). 

Substituents can play important roles in determining conformation. It is clear from microwave analysis of fiuorinated and alkoxy substituted 1,2,4-trioxolanes, where the substituents are mostly axial and C—O bonds in the rings are shorter, that the anomeric effect is dominant (Section... 

The nature of the anomeric effect in the bicyclic /ra r-fused octahydro-l-methyl-l//-2,l-benzothiazine 2,2-dioxide 37 has been examined by single crystal X-ray structure analysis (Figure 5) <1998CJC164>. The crystal structure of 37 shows that the A -Me group assumes an axial position in the solid state. The authors suggest that this conformation is also the most stable in solution and propose that this hyperconjugation effect is >2.0 kcal mol . ... 

M. A. Fabian, C. L. Perrin, and M. L. Sinnott, Absence of reverse anomeric effect Conformational analysis of glucosylimidazolium and glucosylimidazole, J. Am. Chem. Soc. 776 8398... 

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. 

This analysis was confirmed by the cyclization studies of hydroxyketone thiols 69 and 72. Compound 69 gave on cyclization the isomer 70 rather than the isomer 71 which has an equatorial oxygen. Similarly, cyclization of 72 gave 73 only the isomer 74 was not observed. It was further shown that compounds 70 and 73 exist in a conformation equivalent to 68A, which has two anomeric effects. 

The detailed analysis of these conformers showed that 66 exists in a conformation equivalent to 64A only. Similarly, 67 would also exist in a conformation equivalent to 64B only. This analysis further predicted that 66 is more stable than 67 by 2.4 kcal/mol and since these isomers can be inter-converted by equilibration under acidic conditions, isomer 66 should be the major isomer formed under thermodynamically controlled conditions. Cy-clization of 65 under equilibrating conditions gave 66 and 67 in a 98 2 ratio and 66 was shown to exist in a conformation equivalent to 64A. The fact that a small percentage of 67 was detected at room temperature shows that, at sufficiently low temperature, less than 0.1% of 67 would be present. This result confirms that, at low temperature, l,7-dithiaspiro[5.5]-undecane exists essentially in the conformation 64A only. The anomeric effect for a sulfur atom in the dithioacetal function must therefore be of the order of 1.4 kcal/mol. 

We will first examine what miqht occur when stereoelectronic effects are taken into account. An analysis of the conformations D, A, and (Fig. 17) of dimethoxymethane which have two, one, and zero anomeric effects respec-... 

In a detailed analysis of the 13C-NMR chemical shifts of several l-l -glycosides Pavia et al [105] have demonstrated the importance of the exo anomeric effect to rule also the conformations of these non reducing disaccharides. 

Further Justification for the Exo-anomeric Effect. Conformational Analysis Based in Nuclear Magnetic Resonance Spectroscopy of the B Human Blood Group Determinant, H. Thogersen, R. U. Lemieux, K. Bock, and B. Meyer, Can. J. Chem., 60 (1982) 44-57. 

NMR analysis indicated that the O-disaccharide derivative of 11, exists primarily in the exo-syn/exo-syn conformation (93%), corresponding to the operation of two exo-anomeric effects (38). By comparison the C-glycoside 11... 

Thogersen H, Lemieux RU, Boch K, Meyer B (1982) Further justification for the exo-anomeric effect. Conformational analysis based on nuclear magnetic resonance spectroscopy of oligosaccharides. Can J Chem 60 44-57... 

The conformational analysis of the perhydro-imidazo[l,5-n]pyridines (465) (Section VI), the perhydro-oxazolo[3,4-a]pyridines (466) (Section VII), and the perhydrothiazolo[3,4-a]pyridines (467) (Section VIII) may best be considered together since the conformational preferences of these systems are dominated by the generalized anomeric effect [83MI1 ... 

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