Page 248 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

228 Scheme 2.16. Cyclic Compounds that Exhibit the Anomeric Effect

CHAPTER 2 1 a AcOCH 2 AcOCH 2
AcO O OAc AcO O H
Stereochemistry, AcO AcO
Conformation, AcO AcO
and Stereoselectivity H OAc
o
K = 5 (in 50% HOAc-Ac 2 O, 0.1 H 2 SO 4 at 25 C; ΔH = 1.4 kcal

2 b
O O H
CH 3 Cl CH 3
H Cl
o
K = 32 (pure liquid at 40 C)
CH
CH 3 3
3 c O O
OCH 3 H
H OCH 3
K = 3.4 in CCl ; K = 1.8 in CH CN
4
3
4 d Cl Cl
Crystalline form has all four
O chlorines in axial conformation.
O
Cl Cl
Cl NMR spectrum in CDCl indicates the
3
5 e AcO O Cl OAc all axial conformation is strongly favored.
AcO O
AcO
H
OAc OAc
AcOCH 2
6 f AcOCH 2 OAc Only form observed by NMR
O OAc AcO O
OAc
AcO OAc OAc OAc
a. W. A. Bonner, J. Am. Chem. Soc., 73, 2659 (1951).
b. C. B. Anderson and D. T. Tepp, J. Org. Chem., 32, 607 (1967).
c. E. L. Eliel and C. A. Giza, J. Org. Chem., 33, 3754 (1968).
d. E. W. M. Rutten, N. Nibbering, C. H. MacGillavry, and C. Romers, Rec. Trav. Chim. Pays-Bas, 87, 888 (1968).
e. C. V. Holland, D. Horton, and J. S. Jewell, J. Org. Chem., 32, 1818 (1967).
f. B. Coxon, Carbohydrate Res., 1, 357 (1966).

equilibria are between diastereoisomers and involve reversible dissociation of the
2-substituent. In all cases, the more stable isomer is written on the right. The magnitude
of the anomeric effect depends on the nature of the substituent and decreases with
increasing dielectric constant of the medium. 244 The effect of the substituent can be
seen by comparing the related 2-chloro- and 2-methoxy substituted tetrahydropyrans
in Entries 2 and 3. The 2-chloro compound exhibits a significantly greater preference
for the axial orientation than the 2-methoxy. Entry 3 also provides data relative to the
effect of solvent polarity, where it is observed that the equilibrium constant is larger
in carbon tetrachloride = 2 2 than in acetonitrile = 37 5 .
Compounds in which conformational, rather than configurational, equilibria are
influenced by the anomeric effect are depicted in Entries 4 to 6. X-ray diffraction
studies have unambiguously established that all the chlorine atoms of trans, cis, trans-
2,3,5,6-tetrachloro-1,4-dioxane occupy axial sites in the crystal (Entry 4). Each chlorine

244
K. B. Wiberg and M. Marquez, J. Am. Chem. Soc., 116, 2197 (1994).