Anomeric effect definition

These results clearly indicate that barriers to all isomerisation processes are at least less than about 8kcalmol 1. In /V-benzyloxy-7V-chlorobenzamide 44 the amide isomerisation was not observable but the anomeric overlap resulted in diastereotopic benzylic hydrogens, which at coalescence afforded a barrier for rotation about the N-OBn bond of around 10.3 kcalmol-1.32 Like its /V-chloro analogue, the amide isomerisation barrier in 43 is too low to be observed by 3H NMR and even though there is definitive X-ray and theoretical evidence for anomeric effects in /V-acyloxy-/Y-alkoxyamidcs, the barrier to isomerisation about the N-OBn bond must be lower than 10.3 kcalmol-1. The n0-CN ci anomeric interaction in 44 is predicted to be stronger than the n0-CN OAc interaction in 43 on purturbation arguments.32... 

By definition, a generalized anomeric effect is observed at carbon of an XCY system when a molecule preferentially adopts a conformation that optimizes a secondary, stabilizing electronic interaction involving overlap between the lone pair on one heteroatom with the a orbital of the bond between the central carbon atom and the second heteroatom . Figure 5a illustrates that in XNY systems, as with anomeric carbon centres, two anomeric interactions are possible and involve either an ny-CT x ° nx-o NY overlap where nx and ny represent the p-type lone pairs on X and Y and NX and NY represent the N—X and N—Y a orbitals. In either case, the result is a net stabilization of the lone pair of electrons (Figure 5b). Except where the nitrogen is symmetrically substituted, one of these interactions will be strongest. 

The bases are in syn or anti orientation. The orientation of the base relative to the sugar moiety is defined by torsion angle x which is constrained by steric interactions, and by the anomeric effect. The main conformations are referred to as syn and anti (see Fig. 17.5). In syn, j X is close to 0° (sp for torsion angle definition, see Box 13.3 Fig. 13.12), and the base is I oriented "above the ribose ring causing steric interactions which in the anti conformation with x close to 180° (ap) are avoided. The anti conformation is therefore preferred and is the j only form observed in double-helical DNA and RNA. An exception is the left-handed Z-DNA with alternating purine/pyrimidine nucleotide sequence where the purines are in the syn conformation. 

Unfortunately, Aj at position 2 of an oxane is not measurable for a substituent with an anomeric effect because steric repulsion cannot be separated experimentally from this effect. Let us look at the CFE in cyclohexane. The example of the methyl group, without the anomeric effect (see Section 2.5), leads us to suppose that the repulsion is greater at this position. We obtain values lower than they are in reality. There are other definitions, but none can escape criticism. 

Fig. 5.—The Standard Equilibrium in (a) Substituted Oxanes and (b) Substituted Cyclohexanes Used in the Definition of the Anomeric Effect by Eq. I.

The term A parameter is also used in the literature for the Gibbs energy —AGg. According to the definition in Eq. 7, the anomeric effect AG(AEl) depends on the A value of the substituent, and on the temperature and solvent used in measurement of equilibria in Eq. 7. This definition can be extended to multisubstituted pyran derivatives, and simple, additivity schemes of steric interactions of substituents are used for the estimation ofAG(AEl). 

This definition does not take into account the usual preference of bulky substituents for the equatorial position in cyclic compounds, and, with the assumption of the same entropy and volume for the a and the e isomer, corresponds to the AG° value in Eq. 1. In this case, a molecule exhibits the anomeric effect if the axial position sc orientation) is more stable than the equatorial position ap orientation). 

Ail three definitions of the anomeric effect are interrelated, but as the data required for direct recalculation of one definition into another are frequently lacking, a substituent can be characterized by the diverse data about the energy of the anomeric effect Their comparison for various groups needs caution, and inspection as to how they were originally calculated. 

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... 

A. Classical Definition of Anomeric Effect by Lemieux Generalized Anomeric Effect... 

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