Absence of reverse anomeric effect in glycosylimidazoles

The so-called reverse anomeric effect is the preference of cationic substit uents for the equatorial position on a pyranose ring, but it is not consist ent with theories of molecular structure. To reinvestigate this, we have me asured the N-protonation-induced shifts of the anomeric equilibrium in N-(g lycopyranosyl)imidazoles and their tetra-O-acetyl derivatives 1-3 with high precision through an NMR titration method that is applicable to a mixture of alpha and beta anomers. We find a Delta Delta G degrees(beta-->alpha) th at is almost always negative, corresponding to a greater preference for the axial position of a protonated imidazolyl group than of an unprotonated gr oup. This preference counters asmall steric effect, arising from hindrance to ionic solvation, that has been measured independently in N-(4-tert-butyl cyclohexyl)imidazoles 4. These results are exactly opposite to what is expe cted from the reverse anomeric effect. We conclude that there is no firm ev idence for this effect.