CONFORMATIONAL-ANALYSIS OF GLUCOPYRANOSYLAMMONIUM IONS - DOES THE REVERSE ANOMERIC EFFECT EXIST

Despite the generality of the anomeric effect (the axial tendency exhibited by many electronegative groups at Cl of a tetrahydropyran), some cationic substituents prefer the equatorial position. This preference is claimed to exceed that due to steric repulsion, and it has been called a ''reverse anomeric effect''. Such an effect is sometimes invoked to account for relative reactivities and stereoselectivities when there are cationic leaving groups. However, all such substituents have been bulky aromatic rings whose steric factors are difficult to judge, and it is advantageous to compare NHR and NH2R+ groups of known axial preference. Therefore the proportions of axial anomers of glucopyranosylamine and some of its N-alkyl, tetra-O-acetyl, and 4,6-benzylidene derivatives were determined by H-1 NMR in a variety of solvents, including acidic media. This proportion is small, and the assignments were confirmed by coupling constants, saturation transfer, reequilibration, and decoupling difference spectroscopy. The data indicate that the shift in the position of equilibrium that occurs upon N-protonation is small and can be accounted for on the basis of steric effects and a small normal anomeric effect. Therefore we conclude that the reverse anomeric effect does not exist.