Structure and Conformation of Carbohydrates
1.1
7
The relative stabilities of the two chair conformers of 1,1-geminally disubstituted cyclohexanes are additive based on A values [39,40] unless the populations of rotamers present for one
of the two substituents are different to when in the monosubstituted cyclohexane [8,41] or
unless there is differential solvation of one of the substituents in this compound as opposed
to the cyclohexane derivative [39]. The latter situation applies with 1-methylcyclohexanol (7),
where G is 1.3 kJ mol −1 in carbon disulfide in favor of the methyl equatorial conformation, whereas subtraction of A values gives 3.2 kJ mol −1 [39]. In contrast, for 1-methoxy-1methylcyclohexane, the observed and calculated G values are 3.1 and 3.7 kJ mol −1 , respectively [40], a difference that will not have large conformational consequences. The difference
between observed and calculated Gs for 7 presumably arises because the difference in the
aggregation of the equatorial and axial oriented hydroxyl conformers through hydrogen bonding is much larger for the tertiary alcohol 7 than for the corresponding conformers of cyclohexanol. This effect could be important for conformational equilibria of ketoses or branched
chain sugars but is probably negligible in hydroxylic solvents.
1.2.2 Conformations of Tetrahydropyran Derivatives
The replacement of a CH 2 group by an oxygen atom to give tetrahydropyran or oxane alters the
shape of the chair conformation slightly by replacing two 153 pm C–C bonds by two 142 pm
C–O bonds [42,43]. This has little effect on the barrier to ring reversal [8,44]. However, the
substituent A-values now depend on position. The A-values for a methyl group at positions 2,
3, and 4 are 12.0, 5.98, and 8.16 kJ mol −1 , respectively [45], compared to ∼7.5 kJ mol −1
for methylcyclohexane. The value at position 2 is significantly increased relative to that for
methylcyclohexane because the shorter bond lengths increase steric repulsion, while that
at position-3 is decreased because one of the CH 3 /H synaxial interactions is replaced by
a CH 3 /lone pair interaction ( > Fig. 3).
A methoxy group at position-2 of tetrahydropyran is much more stable in the axial orientation than would be expected based on its A value, a manifestation of the anomeric effect [46,47,48,49,50,51,52,53], originally observed with carbohydrate derivatives by
1.1
7
The relative stabilities of the two chair conformers of 1,1-geminally disubstituted cyclohexanes are additive based on A values [39,40] unless the populations of rotamers present for one
of the two substituents are different to when in the monosubstituted cyclohexane [8,41] or
unless there is differential solvation of one of the substituents in this compound as opposed
to the cyclohexane derivative [39]. The latter situation applies with 1-methylcyclohexanol (7),
where G is 1.3 kJ mol −1 in carbon disulfide in favor of the methyl equatorial conformation, whereas subtraction of A values gives 3.2 kJ mol −1 [39]. In contrast, for 1-methoxy-1methylcyclohexane, the observed and calculated G values are 3.1 and 3.7 kJ mol −1 , respectively [40], a difference that will not have large conformational consequences. The difference
between observed and calculated Gs for 7 presumably arises because the difference in the
aggregation of the equatorial and axial oriented hydroxyl conformers through hydrogen bonding is much larger for the tertiary alcohol 7 than for the corresponding conformers of cyclohexanol. This effect could be important for conformational equilibria of ketoses or branched
chain sugars but is probably negligible in hydroxylic solvents.
1.2.2 Conformations of Tetrahydropyran Derivatives
The replacement of a CH 2 group by an oxygen atom to give tetrahydropyran or oxane alters the
shape of the chair conformation slightly by replacing two 153 pm C–C bonds by two 142 pm
C–O bonds [42,43]. This has little effect on the barrier to ring reversal [8,44]. However, the
substituent A-values now depend on position. The A-values for a methyl group at positions 2,
3, and 4 are 12.0, 5.98, and 8.16 kJ mol −1 , respectively [45], compared to ∼7.5 kJ mol −1
for methylcyclohexane. The value at position 2 is significantly increased relative to that for
methylcyclohexane because the shorter bond lengths increase steric repulsion, while that
at position-3 is decreased because one of the CH 3 /H synaxial interactions is replaced by
a CH 3 /lone pair interaction ( > Fig. 3).
A methoxy group at position-2 of tetrahydropyran is much more stable in the axial orientation than would be expected based on its A value, a manifestation of the anomeric effect [46,47,48,49,50,51,52,53], originally observed with carbohydrate derivatives by