10
1
General Principles
2-phenoxytetrahydropyrans [72,73,74], which lower the energy of the σ * orbital and increase
the interaction, were found to increase the preference for the axial conformer. A similar effect
was seen in substituted 2,2-diphenyl-1,3-dioxanes where the phenyl rings bearing electronwithdrawing substituents preferred the axial orientation and vice versa [75]. The smaller magnitude of the 1 J C,H value at anomeric centers for axial CH bonds than for equatorial CH bonds
has been interpreted in terms of n → σ * overlap [76,77], but recently it has been shown that
the calculated dependence of the size of this value on the HCOC torsional angle is incompatible with this explanation [78]. The effects of replacing hydrogen by deuterium atoms on the
positions of anomeric equilibria for the D-glucopyranoses were interpreted in terms of n → σ *
overlap [79].
The alternative explanation for the anomeric effect involves destabilizing dipole-dipole repulsion between the two oxygen atoms and their lone pairs [33,54] (see > Fig. 6). This explanation was reexamined by Box [80,81], who suggested that the bond shortening evidence can be
explained by n orbital repulsion. Persuasive support for this position has come from ab initio
calculations on 2-methoxytetrahydropyran conformers by da Silva and coworkers, performed
using the generalized valence bond-perfect wave function at the GVB-PP/6–31G(d,p) level [52]. This approach only uses a localized description of bonding which inherently excludes
n → σ * overlap. These calculations were able to fully account for the relative conformer energies and bond length shortening and lengthening previously explained by n → σ * overlap. The
changes in bond lengths with geometry are caused by differences in the % s character in the
local orbitals and the contribution of n → σ * overlap was considered to be insignificant [52].
In agreement, Perrin et al. showed how dipole-dipole repulsion could also lead to bond length
alteration [82]. Wiberg and Marquez demonstrated that there was a significant solvent effect
on the axial-equatorial equilibrium of 4,6-dimethyl-2-methoxytetrahydropyran and suggested
that the reduction of electrostatic interaction between dipoles with increasing solvent polarity
⊡ Figure 6
Approximate representation of the geometries of the n p and n s orbitals on oxygen atoms at the anomeric center.
In the equatorial conformer, the n s orbital on the exocyclic oxygen atom is aligned with one lobe of the n p orbital
on the endocyclic oxygen atom and one lobe of the n p orbital on the exocyclic oxygen atom is aligned with the
n p orbital on the endocyclic oxygen atom, leading to repulsive destabilization. In the axial conformer, only one
pair of orbitals is aligned, leading to less repulsion
1
General Principles
2-phenoxytetrahydropyrans [72,73,74], which lower the energy of the σ * orbital and increase
the interaction, were found to increase the preference for the axial conformer. A similar effect
was seen in substituted 2,2-diphenyl-1,3-dioxanes where the phenyl rings bearing electronwithdrawing substituents preferred the axial orientation and vice versa [75]. The smaller magnitude of the 1 J C,H value at anomeric centers for axial CH bonds than for equatorial CH bonds
has been interpreted in terms of n → σ * overlap [76,77], but recently it has been shown that
the calculated dependence of the size of this value on the HCOC torsional angle is incompatible with this explanation [78]. The effects of replacing hydrogen by deuterium atoms on the
positions of anomeric equilibria for the D-glucopyranoses were interpreted in terms of n → σ *
overlap [79].
The alternative explanation for the anomeric effect involves destabilizing dipole-dipole repulsion between the two oxygen atoms and their lone pairs [33,54] (see > Fig. 6). This explanation was reexamined by Box [80,81], who suggested that the bond shortening evidence can be
explained by n orbital repulsion. Persuasive support for this position has come from ab initio
calculations on 2-methoxytetrahydropyran conformers by da Silva and coworkers, performed
using the generalized valence bond-perfect wave function at the GVB-PP/6–31G(d,p) level [52]. This approach only uses a localized description of bonding which inherently excludes
n → σ * overlap. These calculations were able to fully account for the relative conformer energies and bond length shortening and lengthening previously explained by n → σ * overlap. The
changes in bond lengths with geometry are caused by differences in the % s character in the
local orbitals and the contribution of n → σ * overlap was considered to be insignificant [52].
In agreement, Perrin et al. showed how dipole-dipole repulsion could also lead to bond length
alteration [82]. Wiberg and Marquez demonstrated that there was a significant solvent effect
on the axial-equatorial equilibrium of 4,6-dimethyl-2-methoxytetrahydropyran and suggested
that the reduction of electrostatic interaction between dipoles with increasing solvent polarity
⊡ Figure 6
Approximate representation of the geometries of the n p and n s orbitals on oxygen atoms at the anomeric center.
In the equatorial conformer, the n s orbital on the exocyclic oxygen atom is aligned with one lobe of the n p orbital
on the endocyclic oxygen atom and one lobe of the n p orbital on the exocyclic oxygen atom is aligned with the
n p orbital on the endocyclic oxygen atom, leading to repulsive destabilization. In the axial conformer, only one
pair of orbitals is aligned, leading to less repulsion