The Orbital-Effect-Myth

Abstract

In the cyclohexane derivatives, the equatorial conformer, having less steric repulsion of hydrogen atoms adjacent to substituent, is dominant over the axial conformer. This is a normal stereochemical requirement. In hexose, containing oxygen atoms in the ring, however, α-anomer (with axial substituent) is more stable than β-anomer (with equatorial substituent) and it is called the anomeric effect. Why does this phenomenon, which is not compatible with the stereochemical intuition (but still widely accepted), happen at all? It has been more than 60 years since Edward reported it, but the root cause has not yet become clear. At present, the most popular explanation for the anomeric effect is that it is due to the interaction between a lone pair of electrons on oxygen and the anti-bonding orbital (σ*) of C-R bond. Contrary to popular belief, we demonstrate that this explanation does not hold.