Anomeric effect

The α- and β-anomers of D-glucopyranose.

In organic chemistry, the anomeric effect or Edward-Lemieux effect (after J. T. Edward and Raymond Lemieux) 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.[1] 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.[2] The name comes from the term used to designate the lowest-numbered ring carbon of a pyranose, the anomeric carbon. Isomers that differ only in the configuration at the anomeric carbon are called anomers. The anomers of D-glucopyranose are diastereomers, with the beta anomer having a hydroxyl (−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.[3] 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.[4] The exact method by which the anomeric effect causes stabilization is a point of controversy, and several hypotheses have been proposed to explain it.

  1. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (1996) "Anomeric Effect". doi:10.1351/goldbook.A00372
  2. ^ Juaristi, E.; Cuevas, G. (1992). "Recent studies of the anomeric effect". Tetrahedron. 48 (24): 5019–5087. doi:10.1016/S0040-4020(01)90118-8.
  3. ^ Bauerfeldt, Glauco F.; Cardozo, Thiago M.; Pereira, Márcio S.; da Silva, Clarissa O. (1 January 2013). "The anomeric effect: the dominance of exchange effects in closed-shell systems". Organic & Biomolecular Chemistry. 11 (2): 299–308. doi:10.1039/c2ob26818c. PMID 23172415.
  4. ^ Kirby, Anthony J. (1983). The anomeric effect and related stereoelectronic effects at oxygen; with 24 tables. Berlin [u.a.]: Springer. ISBN 978-0-387-11684-6.