Page 251 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

Table 2.7. Solvent Dependence of Conformational 231
Equilibrium for 2-Methoxytetrahydropyran
TOPIC 2.3
Solvent Dielectric % Axial
The Anomeric Effect in
constant conformer
Cyclic Compounds
2 2 83
CCl 4
Benzene 2 3 82
Chloroform 4 7 71
Acetone 20 7 72
Methanol 32 6 69
Acetonitrile 37 5 68
Water 78 5 52

between the lone-pair electrons on the pyran oxygen and the orbital associated
∗
with the bond to the electronegative substituent. 250 When the C−X bond is axial,
an interaction between an occupied p-type orbital on oxygen (unshared electrons)
∗
and the antibonding orbital of the C−X combination is possible. This interaction
permits delocalization of the unshared electrons and would be expected to shorten
and strengthen the C−O bond while lengthening and weakening the C−X bond, as
is observed. These are the same structural factors identified in Topic 1.2, where the
effect of hyperconjugation on conformation of acyclic compounds is discussed.

+
O O

O –

There have been various studies aimed at determining the energy differences
associated with the anomeric effect. Temperature-dependent 13 C-NMR chemical shift
studies of 2-methoxytetrahydropyran determined G values ranging from 0.5 to
0.8 kcal/mol, depending on the solvent. 251 Wiberg and Marquez measured a difference
of 1.2 kcal/mol between the axial and equatorial methoxy group in the conforma-
tionally biased 3,5-dimethyltetrahydropyran ring. 244 The energy difference decreased
in more-polar solvents; the equatorial isomer is preferred in water.
There have also been a number of computational investigations into the nature
of the anomeric effect. The axial-equatorial conformational equilibria for 2-fluoro
and 2-chlorotetrahydropyran have been investigated with several MO calculations,
∗
∗
including the MP2/6-31G level. The MP2/6-31G calculations give values of 3.47
and 2.84 kcal/mol, respectively, for the energy favoring the axial conformer. 252 Solvent
effects were also explored computationally and show the usual trend of reduced stability
for the axial conformation as solvent polarity increases. Salzner and Schleyer applied
250 S. Wolfe, A. Rauk, L. M. Tel, and I. G. Csizmaida, J. Chem. Soc. B, 136 (1971); S. O. David,
O. Eisenstein, W. J. Hehre, L. Salem, and R. Hoffmann, J. Am. Chem. Soc. 95, 306 (1973); F. A.
Van-Catledge, J. Am. Chem. Soc., 96, 5693 (1974).
251 H. Booth, J. M. Dixon, and S. A. Readshaw, Tetrahedron, 48, 6151 (1992).
252
I. Tvaroska and J. P. Carver, J.Phys.Chem., 98, 6452 (1994).