Anomeric effect
In organic chemistry, the anomeric effect or Edward-Lemieux effect (after J. T. Edward and Raymond Lemieux) is a stereoelectronic effect describing the tendency for vicinal heteroatomic substituents of a cyclic heteroatom – e.g., oxygen in a tetrahydropyran ring – to assume the relative axial orientation, rather than a less sterically-hindered equatorial orientation. This effect was first observed in pyranose rings by J. T. Edward in 1955, while studying carbohydrate chemistry.
The term "anomeric effect" gained common usage by 1958, derived from the stereochemical designation for the lowest-numbered ring-carbon of a pyranose ring – the anomeric carbon. Anomeric molecules are isomers differing only in their configuration at the anomeric carbon; D-glucopyranose anomers are diastereomers, where the β-anomer is oriented such that the hydroxyl (−OH) group is pointed upwards equatorially, while the α-anomer hydroxyl points downward axially.
The anomeric effect can also be generalized to any cyclohexyl or linear system with the general formula C−Y−C−X, where Y is a heteroatom with one or more lone pairs, and X is an electronegative atom or group. The magnitude of the anomeric effect is estimated at 4–8 kJ/mol in the case of sugars, but is different for every molecule.
In the above case, the methoxy group (−O−CH3) on the cyclohexane ring (top) prefers the equatorial position. However, in the tetrahydropyran ring (bottom), the methoxy group prefers the axial position. This is because in the cyclohexane ring, Y = carbon, which is not a heteroatom, so the anomeric effect is not observed and sterics dominates the observed substituent position. In the tetrahydropyran ring, Y = oxygen, which is a heteroatom, so the anomeric effect contributes and stabilizes the observed substituent position. In both cases, X = methoxy group.
The anomeric effect is most often observed when Y = oxygen, but can also be seen with other lone pair bearing heteroatoms in the ring, such as nitrogen, sulfur, and phosphorus. The exact method by which the anomeric effect causes stabilization is a point of controversy, and several hypotheses have been proposed to explain it.