| Abstract
| - The so-called reverse anomeric effect is the preference of cationic substituents for the equatorialposition on a pyranose ring, but it is not consistent with current theories of molecular structure or withprevious studies designed to test it. To probe this further, the N-protonation-induced shifts of the anomericequilibrium in a series of N-(tetra-O-methylglucopyranosyl)anilines have been measured with high precisionthrough an NMR titration method that compares basicities of α and β anomers in a mixture of the two. Forcomparison, the N-protonation-induced shifts of the cis/trans equilibrium in N-(4-tert-butylcyclohexyl)anilineshave also been measured by this same method. In both series, there is a shift of the equilibrium towardequatorial upon N-protonation, consistent with steric hindrance to ionic solvation. This shift is smaller forthe glucosylanilines than for the cyclohexylanilines, consistent with an enhancement of the normal anomericeffect that counters the steric hindrance and reduces the shift toward the equatorial β anomer. Moreover,the shift toward equatorial increases slightly but detectably with electron-withdrawing substituents on thecyclohexylaniline, which fine-tune the steric hindrance to ionic solvation. In contrast, the shift decreasesfor the glucosylanilines. This is consistent with an enhancement of the normal anomeric effect due to amore localized positive charge, rather than with a reverse anomeric effect. These results thus define thesubstituent dependence of the anomeric effect.
|
