The Anomeric Effect: It’s Complicated

Abstract

The origin of the anomeric effect has been reexamined in a coordinated experimental and computational investigation. The results of these studies implicate a number of different, but correlated, interactions that in the aggregate are responsible for the anomeric effect. No single factor is uniquely responsible for the axial preference of a substituent that is the hallmark of the anomeric effect. A CH···G nonbonded attraction between a polar axial substituent (G) and the syn-axial hydrogen(s) in the heterocycle has been demonstrated experimentally. The hyperconjugation model involving electron transfer from a ring heteroatom to an excited state of an axial C-G bond was shown to be, at most, a minor contributor because of the very small changes in charge density at the ring heteroatom(s): the main charge transfer is from hydrogen to G in the H-C-G unit. This appears to result from lengthening the C-G bond to minimize repulsion with the ring atom lone pair(s) and the advantage of having a more positive hydrogen that leads to a stabilizing Coulombic interaction with the ring heteroatom(s). In short, the anomeric effect arises mainly from two separate CH···G nonbonded Coulombic attractions.

The endo‐ and exo‐Anomeric Effects in Furanosides. A Computational Study

“…For instance, in the case of pyranoses, the anomeric effect and its magnitude may result from the combined influence of non-bonded interactions between ring substituent and the synaxial aliphatic hydrogens, hyperconjugation effect, steric interactions, solute-solvent interactions, etc. [28,29] The detailed analy-sis of the origins of the anomeric effect in furanoses is not the aim of this paper; however, one may note that the high pyranose vs. furanose correlation of the associated energies speaks for the conclusion that the same factors play a role for both furanoses and pyranoses.…”

Hyperconjugation

“…The consequences of σ CH → σ* CH hyperconjugation are made apparent via the use of v C–H is method . For example, C–H frequencies in ethane are 42 cm −1 redshifted in comparison with those in methane (Figure ).…”

“…Selected effects of CH/CX hyperconjugation on C–H IR‐stretching frequencies (app = antiperiplanar. ) Redshifted H‐bonds are shown in red…”

“…An extreme version of this effect is observed upon Lewis acid coordination at the carbonyl. Such coordination shifts the C–H stretch back to higher frequencies, as the lone pair cannot participate in the n O → σ* interactions anymore (Figure ) …”

“…Values from Ref. . Insert at the bottom: Deactivation of n O → σ* CH interactions by coordination of a Lewis acid at the carbonyl…”