6
1
General Principles
⊡ Figure 2
The 1,3-diaxial interaction in cis-1,3-disubstituted cyclohexanes
vent [8,22,23]), for methoxyl (2.3–3.1 kJ mol −1 [23,24]), for carboxyl (5.7 kJ mol −1 [25]), for
carboxylate (7.9–8.2 kJ mol −1 [25,26]), and for methoxycarbonyl (4.6–5.5 kJ mol −1 [24,25,
26,27]). On the basis of the lack of change in geometry of the syn axial CH bonds on addition
of an axial methyl, it was concluded [20] that the cause of the equatorial preference is repulsive
steric interactions between the axial group and the ring carbons including the gauche torsional
interaction rather than the traditional [8] explanation of steric interactions with the 1,3-related
axial hydrogens (synaxial interaction). However, see below.
The interactions between substituents are important for the stabilities of the conformations of
carbohydrates. Non-geminally disubstituted cyclohexanes can exist as cis- and trans-isomers.
The relative stabilities of cis- and trans-1,4-disubstituted cyclohexanes or the relative stabilities
of the diaxial versus the diequatorial conformers of trans-1,4-disubstituted cyclohexanes can
be predicted successfully from the A values of the two substituents [8]. Another factor arises
when cis-1,3-disubstituted-1,3-cyclohexanes are considered: the interaction between syn-1,3diaxially related substituents, as shown in > Fig. 2. Corey and Feiner summarized values for
this interaction [28]. For carbohydrates, the most important of those available are: the OH / OH
interaction (7.9 kJ mol −1 [29]), the CH 3 / OH interaction (7.9–11.3 kJ mol −1 [30,31,32]) and
the OAc / OAc interaction (8.4 kJ mol -1 [33]).
The two chair conformers of cis-1,2-disubstituted cyclohexanes both have additional gauche
interactions between substituents (5). One might expect that the stability differences between
the diequatorial and diaxial conformers of the trans-isomer would be the sum of the A-values
for the axial substituents minus the value of the gauche interaction for the equatorial substituents (6). For methyl substituents, where the gauche interaction is that of butane, this
has been shown to be approximately true [34,35]. Corey and Feiner [28] found that gauche
interactions between substituents other than methyl could not be estimated by averaging
1/2 the substituent’s A values but have tabulated these gauche interaction values. Those
involving polar groups are highly dependent on solvent because the diaxial and diequatorial conformers have very different dipole moments. Direct determination by measurement
of the difference in stability between the diequatorial and diaxial conformers requires the
subtraction of the substituent A values from the total stability difference. These latter values
may be uncertain or have large solvent dependencies, leading to large uncertainties in the
interaction energies. The most relevant values are the OH:OH interaction (1.5 kJ mol −1 in
water [29], the OH:OMe interaction (2.7 kJ mol −1 in carbon disulfide [36], 1.9 kJ mol −1 in
pentane [37], 1.9 kJ mol −1 in methanol [37]), the OMe:OMe interaction (5.3 kJ mol −1 in
pentane, 2.3 kJ mol −1 in methanol [37]), and the OH:CH 3 interaction (1.6 kJ mol −1 [38]).
1
General Principles
⊡ Figure 2
The 1,3-diaxial interaction in cis-1,3-disubstituted cyclohexanes
vent [8,22,23]), for methoxyl (2.3–3.1 kJ mol −1 [23,24]), for carboxyl (5.7 kJ mol −1 [25]), for
carboxylate (7.9–8.2 kJ mol −1 [25,26]), and for methoxycarbonyl (4.6–5.5 kJ mol −1 [24,25,
26,27]). On the basis of the lack of change in geometry of the syn axial CH bonds on addition
of an axial methyl, it was concluded [20] that the cause of the equatorial preference is repulsive
steric interactions between the axial group and the ring carbons including the gauche torsional
interaction rather than the traditional [8] explanation of steric interactions with the 1,3-related
axial hydrogens (synaxial interaction). However, see below.
The interactions between substituents are important for the stabilities of the conformations of
carbohydrates. Non-geminally disubstituted cyclohexanes can exist as cis- and trans-isomers.
The relative stabilities of cis- and trans-1,4-disubstituted cyclohexanes or the relative stabilities
of the diaxial versus the diequatorial conformers of trans-1,4-disubstituted cyclohexanes can
be predicted successfully from the A values of the two substituents [8]. Another factor arises
when cis-1,3-disubstituted-1,3-cyclohexanes are considered: the interaction between syn-1,3diaxially related substituents, as shown in > Fig. 2. Corey and Feiner summarized values for
this interaction [28]. For carbohydrates, the most important of those available are: the OH / OH
interaction (7.9 kJ mol −1 [29]), the CH 3 / OH interaction (7.9–11.3 kJ mol −1 [30,31,32]) and
the OAc / OAc interaction (8.4 kJ mol -1 [33]).
The two chair conformers of cis-1,2-disubstituted cyclohexanes both have additional gauche
interactions between substituents (5). One might expect that the stability differences between
the diequatorial and diaxial conformers of the trans-isomer would be the sum of the A-values
for the axial substituents minus the value of the gauche interaction for the equatorial substituents (6). For methyl substituents, where the gauche interaction is that of butane, this
has been shown to be approximately true [34,35]. Corey and Feiner [28] found that gauche
interactions between substituents other than methyl could not be estimated by averaging
1/2 the substituent’s A values but have tabulated these gauche interaction values. Those
involving polar groups are highly dependent on solvent because the diaxial and diequatorial conformers have very different dipole moments. Direct determination by measurement
of the difference in stability between the diequatorial and diaxial conformers requires the
subtraction of the substituent A values from the total stability difference. These latter values
may be uncertain or have large solvent dependencies, leading to large uncertainties in the
interaction energies. The most relevant values are the OH:OH interaction (1.5 kJ mol −1 in
water [29], the OH:OMe interaction (2.7 kJ mol −1 in carbon disulfide [36], 1.9 kJ mol −1 in
pentane [37], 1.9 kJ mol −1 in methanol [37]), the OMe:OMe interaction (5.3 kJ mol −1 in
pentane, 2.3 kJ mol −1 in methanol [37]), and the OH:CH 3 interaction (1.6 kJ mol −1 [38]).