Orbital orientation, anomeric effects

Second-row heteroatoms are known to show a substantial anomeric effect. There appears to be evidence for a reverse anomeric effect in 2-aminotetrahydro-pyrans. ° It has been called into question whether a reverse anomeric effect exists at all. ° In 94, the lone-pair electrons assume an axial conformation and there is an anomeric effect. In 95, however, the lone-pair electron orbitals are oriented gauche to both the axial and equatorial oc-CH bond and there is no anomeric effect. ... 

Anomeric effects are cumulative, and can cause a potentially flexible ring to adjust to a more rigid conformation in order to maximize the overlap of suitable lone pair and a orbitals. It has been particularly instructive in explaining anomalous preferences for substituent orientations in tetrahydropyrans and related compounds. In the case of 2-methoxytetrahydropyran, for example, the axial conformer is three times more populated than the equatorial form (Scheme 1.2). 

Anomeric effect - The stabilization ( x—>ocz ) of a ring conformation by interaction of a lone pair of electrons ( x)on a ring heteroatom with an antibonding c orbital (oCz ) of an adjacent electron-withdrawing substituent Z is known as the anomeric effect. This type of stabilization (i.e., o >°cz ) was first invoked to explain the preference for the axial orientation of electronegative substituents Z at the 2-position (anomeric position) of tetrahydropyrans. For examples see Sections 2.2.3.1, 2.2.4.3, and 2.4.4.4. 

The theoretical requirement for a maximum exo-anomeric effect is that the aglycon be so oriented as to place a p-orbital of 01... 

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. 

The observation that L-arabinal adopted the conformation exclusively and that the and conformations of o-glucal were comparably populated led Curran and Suh" to propose a vinylogous anomeric effect , similar to the anomeric effect. Additional stabilisation of an electronegative substituent in an axial orientation was available from a p-type lone pair on oxygen, separated by a double bond, via overlap of the C X a orbital and v /2 of the enol ether (Figure 6.70). No experimental estimates of its magnitude are available, but it is likely to be smaller than the anomeric effect itself, not least because any electrostatic component is much smaller. 

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