Page 247 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

OH 227
N CH 2 F
TOPIC 2.3
Cl The Anomeric Effect in
Eliprodil Cyclic Compounds

Entry 5 is an interesting example that entails both enzymatic and hydrolytic
epoxide conversion. In the first step, an enzymatic hydrolysis proceeds with retention of
the configuration at the tertiary center. This reaction is selective for the S-epoxide. The
remaining R-epoxide is then subjected to acid-catalyzed hydrolysis, which proceeds
with inversion at the center of chirality (see p. 186). The combined reactions give an
overall product yield of 94%, having 94% e.e. 242

A. niger EH OH O
O +
CH 3
CH 3 HO CH 3 R-enantiomer
S-enantiomer H +
H O
2

Entry 6 is one of several examples demonstrating enantioselectivity for both the cis
and trans isomers of heptane-2,3-epoxide. Entry 7 shows the kinetic resolution of
an exocyclic cyclohexane epoxide. The two stereoisomeric monomethyl analogs were
only partially resolved and the 3-methyl isomer showed no enantioselectivity. This
shows that the steric or hydrophobic effect of the dimethyl substituents is critical for
selective binding.

Topic 2.3. The Anomeric Effect in Cyclic Compounds

The incorporation of heteroatoms into rings can result in stereoelectronic effects
that significantly affect conformation and, ultimately, reactivity. It is known from many
examples in carbohydrate chemistry that pyranose (six-membered oxygen-containing
rings) sugars substituted with an electron-withdrawing group such as halogen or alkoxy
at C(2) are often more stable when the substituent has an axial rather than an equatorial
orientation. This tendency is not limited to carbohydrates but carries over to simpler
ring systems such as 2-substituted tetrahydropyrans. The phenomenon is known as the
anomeric effect, since it involves a substituent at the anomeric position in carbohydrate
pyranose rings. 243 Scheme 2.16 lists several compounds that exhibit the anomeric
effect, along with some measured equilibrium compositions. In Entries 1 to 3, the

242 R. V. Orru, I. Osprian, W. Kroutil, and K. Faber, Synthesis, 1259 (1998).
243 For reviews, see R. U. Lemieux, Pure Appl. Chem. 25, 527 (1971); W. A. Szarek and D. Horton.
eds., Anomeric Effects, ACS Symposium Series, No. 87, American Chemical Society, Washington,
DC, 1979; A. J. Kirby, The Anomeric Effect and Related Stereoelectronic Effects at Oxygen, Springer-
Verlag, Berlin, 1983; P. Deslongchamps, Stereoelectronic Effects in Organic Chemistry, Pergamon
Press, Oxford, 1983; M. L. Sinot, Adv. Phys. Org. Chem., 24, 113 (1988); P. R. Graczyk and M.
Mikolajczyk, Top. Stereochem., 21, 159 (1994); E. Juraisti and G. Cuevas, The Anomeric Effect, CRC
Press, Boca Raton, FL, 1995; C. J. Cramer, Theochem, 370, 135 (1996).