Anomeric effect

In organic chemistry, the anomeric effect or Edward-Lemieux effect is a stereoelectronic effect that describes the tendency of heteroatomic substituents adjacent to a heteroatom within a cyclohexane ring to prefer the axial orientation instead of the less hindered equatorial orientation that would be expected from steric considerations. This effect was originally observed in pyranose rings by J. T. Edward in 1955 when studying carbohydrate chemistry.

The term "anomeric effect" was introduced in 1958. The name comes from the term used to designate the C-1 carbon of a pyranose, the anomeric carbon. Isomers that differ only in the configuration at the anomeric carbon are called anomers. The anomers of glucopyranose are diastereomers, with the beta anomer having an OH group pointing up equatorially, and the alpha anomer having that OH group pointing down 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 about 1–2 kcal/mol in the case of sugars, but is different for every molecule.

In the above case, the methoxy group 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= OMe.

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.

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