Page 176 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

156

CHAPTER 2
Stereochemistry,
Conformation,
and Stereoselectivity

Fig. 2.15. 60-MHz 1 H-NMR spectrum for the C(1)H in chlorocyclohexane:

(a) axial-equatorial equilibrium at −115 C; (b) axial-enriched mixture at −150 C;

(c) pure equatorial conformer at −150 C. Reproduced from J. Am. Chem. Soc.,

91, 3223 (1969), by permission of the American Chemical Society.
Crystallization of chlorocyclohexane at low temperature provided crystals
containing only the equatorial isomer. When the solid is dissolved at −150 C, the

NMR spectrum of the solution exhibits only the signal characteristic of the equatorial
conformer. When the solution is warmed to −115 , the conformation equilibrium is

reestablished. The appearance of the 60-MHz spectrum of the H-C−Cl hydrogen is
shown in Figure 2.15.
The free-energy difference between conformers is referred to as the conforma-
tional free energy. For substituted cyclohexanes it is conventional to specify the value
of − G for the equilibrium:
c
axial equatorial

As G is negative when the equatorial conformation is more stable than the axial,
c
the value of − G is positive for groups that favor the equatorial position. The larger
c
the − G , the greater the preference for the equatorial position.
c
The case of iodocyclohexane provides an example of the use of NMR spectroscopy
to determine the conformational equilibrium constant and the value of − G .
c

At −80 C, the NMR shows two distinct peaks in the area of the CHI signal as shown
in Figure 2.16. 53 The multiplet at higher field is a triplet of triplets with coupling
constants of 3.5 and 12 Hz. This pattern is characteristic of a hydrogen in an axial
position with two axial-axial couplings and two axial-equatorial couplings. The broader
peak at lower field is characteristic of a proton at an equatorial position and reflects
the four equatorial-equatorial couplings of such a proton. The relative area of the two
peaks is 3.4:1 in favor of the conformer with the axial hydrogen. This corresponds to
a − G value of 0.47 kcal/mol for the iodo substituent.
c
Another method for measuring conformational free energies involves establishing
an equilibrium between diastereomers differing only in the orientation of the desig-
nated substituent group. The equilibrium constant can then be determined and used
to calculate the free-energy difference between the isomers. For example, cis- and
trans-t-butylcyclohexanol can be equilibrated using a nickel catalyst in refluxing
benzene to give a mixture containing 28% cis-4-t-butylcyclohexanol and 72% trans-
t-butylcyclohexanol. 54

53 F. R. Jensen, C. H. Bushweller, and B. H. Beck, J. Am. Chem. Soc., 91, 334 (1969).
54
E. L. Eliel and S. H. Schroeter, J. Am. Chem. Soc., 87, 5031 (1965).