Endo-anomeric effect

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. 8 Interpretation of the conformational endo-anomeric effect according to Edwards (hard/hard interactions).

In the case of 2-hydroxytetrahydropyran, the axial conformer 22 is calculated to be more stable than its equatorial conformer 23 in vacuum (Fig. 12). Solvent effects change the equilibrium constant and the equatorial form 23 is favored in aqueous solution, in agreement with data. The magnitude of the conformational endo-anomeric effect in 22 is estimated to 2.0 kcal/mol (gas phase stereoelectronic effects overwhelming the steric... 

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). 

E. Bidirectionality of Anomeric Effect Exo and Endo Anomeric Effects... 

When the C—Y bond is a part of a ring, then describes the exo anomeric effect (6a) and AG g y the endo anomeric effect following a suggestion by Booth and Khedhair (50). It must be noted, however, that Booth et al. (68) also extended the latter term to cases where both X and Y are members of the same ring, for example, in cis-decahydroquinazoline IS note that for this compound the term exo anomeric effect does not apply. 

I. 46 (see Section II.F). Therefore, the observed equatorial preference of X = COOMe in a tetrahydropyran ring ( — 7.1 kJ/mol) is smaller than that expected based on steric interactions (- 7.59 kJ/mol), in qualitative agreement with the results of Tschierske et al. (38). The difference, equal to —7.1 — (-7.59) = 0.5 kJ/mol, reflects the magnitude of the endo anomeric effect in the O—C—COOMe system in terms (see Eq. [17], Section II.F). By the same token we calculated other values and placed them in the last column of Table 4 values for 31, 33, and 34 were taken from Section... 

II. F). It is evident that the endo anomeric effect involving Y = NH as a donor is stronger than that for Y = O, as expected (see Section III.B.4). A comparison of compounds 30 with 33 and 31 with 34 shows that the cyano group participates in the anomeric interactions more effectively than the carbo-methoxy group. 

Soon, it was pointed out by Fuchs et al. (89) that the equivalence of oxygen lone electron pairs is not consistent with X-ray structures of carbohydrates. They scrutinized 111 structures and found torsion angles O in Oendo—C—O—R fragments appreciably larger than 60°. If lone pairs were equivalent, one might expect 0 = 60° to be preferred whereas nonequivalence implies 0 > 60°. Indeed, Cosse-Barbi et al. (69,257) have recently shown that the endo anomeric effect is stronger in furanoses than in pyranoses. They... 

Based upon the results of the studies of VaseUa et al. [85] and Franck et al. [95], it can be concluded that the reverse anomeric effect does not exist. The electropositive substituent at the anomeric carbon produces the enhanced endo-snometic effect but not a reverse anomeric effect [97]. Non-solvated electropositive axial anomeric substituents such as nitro and sulfone groups show the ent/o-anomeric effect to be much larger than the oxygen anomeric effect, namely, 2.35 kcal/mol for the nitro group and 3.05 kcal/mol for the sulfone group, as opposed to the endo-anomeric effect for the oxygen atom of 0.85-1.54 kcal/mol. 

This result can be used to shed some light on the exo-lendo-momenc effect in the 2-aminotetrahydropyrans studied extensively by Booth et al. [100-102]. Because nitrogen is less electronegative than oxygen, it is a better donor, and the antibonding o C—N orbital a weaker acceptor of electrons than the antibonding o C—O orbital. Consequently it could be expected that 2-methylaminotetrahydropyran exhibits a stronger exo-anomeric effect (n —o c o) than endo-anomeric effect (no—o c-n)-Thus, as shown by Booth et al. [100-102], 2-methylaminotetrahydropyran prefers the equatorial conformation (Fig. 2.42). 

To further examine hyperconjugation, NBO analysis [30, 57] was carried out on stmctures I-IV of both fluoropi-peridine and trifluoromethylpiperidine. The key results at the (oB97X-D/aug-cc-pVTZ level are summarized in Table 6. The nitrogen lone pair occupancy, n, is lowest for stmcture IV at 1.872 electrons for FP and 1.908 electrons for TP. Since the nitrogen lone pair population is less than two, we conclude that the endo-anomeric effect is operative for stmcture IV, and we will show below that this is due to hyperconjugation in the NBO analysis framework. 

Magaud D, Dohnazon R, Anker D, Doutheau A, Dtuy YL, Deslongchamps P (2000) Differential reactivity of a- and P-anomers of gfycosyl accepters in glycosylations. A remote consequence of the endo-anomeric effect Org Lett 2 2275-2277... 

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