Structure and Conformation of Carbohydrates
1.1
9
⊡ Figure 5
Newman projections of lone pair orbitals on one oxygen atom in a COCOR unit. Left: the geometry of an axial OR
group in a tetrahydropyran ring with sp 3 orbitals on the endocyclic oxygen. Center: the geometry of an axial OR
group in a tetrahydropyran ring with n p and n σ orbitals on the endocyclic oxygen. Right: the geometry has been
altered to show the best overlap of the n p orbital with the σ * orbital of the OR bond. This results in the COCC
torsional angle closing from about staggered to ∼30°
atom [48,50,52]. This description has somewhat different stereochemical consequences for
n → σ * overlap ( > Fig. 5). In the traditional description, the most favorable overlap from
the n orbital of O1 occurs when the C–O1–C–O2 torsional angle is 60°, which matches that
present for the axial OR group in a 2-substituted tetrahydropyran. The correct description leads
to the most favorable overlap at a torsional angle of 90° where the intra-ring COCC torsional
angle has been reduced to 30°. Considerable overlap is still present at the tetrahydropyran
intra-ring torsional angle but Dubois et al. have suggested that this type of overlap explains
the larger anomeric effect present in furanoses [61]. The recent conclusion that acyclic acetals
RCH(OR 1 )(OR 2 ) increasingly adopt conformations with the smaller of R 1 or R 2 eclipsed with
the acetal H as the two other R groups increase in size is in accord with this description of the
oxygen lone pairs [62].
Evidence for the importance of the first explanation includes changes in bond lengths about
the anomeric center. In the axial conformer, a lone pair on the endocyclic oxygen atom is
aligned with the exocyclic C–O bond leading to orbital interaction and bond shortening and
concomitant bond lengthening of the exocyclic C–O bond, the endo anomeric effect. In both
conformers, if the methoxy methyl is gauche to the endocyclic C–O bond and anti to the C1–
C2 bond, a lone pair will interact with the aligned endocyclic C–O bond leading to exocyclic
C–O bond shortening. The preference for these conformers is termed the exo anomeric effect.
This bond shortening has been clearly observed for the central C–O bonds in the favored
+gauche,+gauche (+g,+g) or -gauche,-gauche (−g,−g) (8) conformers of dimethoxymethane,
both in the gas phase [63] and recently in the solid [64]. In this conformation, there are two
possible n → σ * interactions that compete. The C–O bond arrangements in this conformation
correspond to those in the axial conformer of 2-methoxytetrahydropyran while those in the
gauche,anti (g,a) conformer of dimethoxymethane (9) are similar to those in the equatorial
conformer of 2-methoxytetrahydropyran. Where only one oxygen atom is the source of the n
electrons, it is calculated using high level ab initio methods that greater bond shortening of
the a C–O bond occurs, as in the g,a conformer [65,66]. These calculations also support the
contention that n → σ * interactions are very important for the anomeric effect. Similar bond
shortening is observed for the appropriate conformers of ClCH 2 OH [67]. Statistical analyses of bond length data from X-ray diffraction studies support the bond shortening due to
n → σ * interactions [61,68,69] and are in agreement with greater bond shortening in the a,p
conformer. In addition, electron withdrawing groups in 2-alkoxytetrahydropyrans [70,71] or
1.1
9
⊡ Figure 5
Newman projections of lone pair orbitals on one oxygen atom in a COCOR unit. Left: the geometry of an axial OR
group in a tetrahydropyran ring with sp 3 orbitals on the endocyclic oxygen. Center: the geometry of an axial OR
group in a tetrahydropyran ring with n p and n σ orbitals on the endocyclic oxygen. Right: the geometry has been
altered to show the best overlap of the n p orbital with the σ * orbital of the OR bond. This results in the COCC
torsional angle closing from about staggered to ∼30°
atom [48,50,52]. This description has somewhat different stereochemical consequences for
n → σ * overlap ( > Fig. 5). In the traditional description, the most favorable overlap from
the n orbital of O1 occurs when the C–O1–C–O2 torsional angle is 60°, which matches that
present for the axial OR group in a 2-substituted tetrahydropyran. The correct description leads
to the most favorable overlap at a torsional angle of 90° where the intra-ring COCC torsional
angle has been reduced to 30°. Considerable overlap is still present at the tetrahydropyran
intra-ring torsional angle but Dubois et al. have suggested that this type of overlap explains
the larger anomeric effect present in furanoses [61]. The recent conclusion that acyclic acetals
RCH(OR 1 )(OR 2 ) increasingly adopt conformations with the smaller of R 1 or R 2 eclipsed with
the acetal H as the two other R groups increase in size is in accord with this description of the
oxygen lone pairs [62].
Evidence for the importance of the first explanation includes changes in bond lengths about
the anomeric center. In the axial conformer, a lone pair on the endocyclic oxygen atom is
aligned with the exocyclic C–O bond leading to orbital interaction and bond shortening and
concomitant bond lengthening of the exocyclic C–O bond, the endo anomeric effect. In both
conformers, if the methoxy methyl is gauche to the endocyclic C–O bond and anti to the C1–
C2 bond, a lone pair will interact with the aligned endocyclic C–O bond leading to exocyclic
C–O bond shortening. The preference for these conformers is termed the exo anomeric effect.
This bond shortening has been clearly observed for the central C–O bonds in the favored
+gauche,+gauche (+g,+g) or -gauche,-gauche (−g,−g) (8) conformers of dimethoxymethane,
both in the gas phase [63] and recently in the solid [64]. In this conformation, there are two
possible n → σ * interactions that compete. The C–O bond arrangements in this conformation
correspond to those in the axial conformer of 2-methoxytetrahydropyran while those in the
gauche,anti (g,a) conformer of dimethoxymethane (9) are similar to those in the equatorial
conformer of 2-methoxytetrahydropyran. Where only one oxygen atom is the source of the n
electrons, it is calculated using high level ab initio methods that greater bond shortening of
the a C–O bond occurs, as in the g,a conformer [65,66]. These calculations also support the
contention that n → σ * interactions are very important for the anomeric effect. Similar bond
shortening is observed for the appropriate conformers of ClCH 2 OH [67]. Statistical analyses of bond length data from X-ray diffraction studies support the bond shortening due to
n → σ * interactions [61,68,69] and are in agreement with greater bond shortening in the a,p
conformer. In addition, electron withdrawing groups in 2-alkoxytetrahydropyrans [70,71] or