Origin of anomeric effect: A density functional steric analysis

Abstract

The anomeric effect (the tendency of heteroatomic substituents adjacent to a heteroatom within the cyclohexane ring to prefer the axial orientation instead of the sterically less hindered equatorial position) is traditionally explained through either the dipole moment repulsion or the hyperconjugation effect. In this work, by employing our recent work in density functional steric analysis, we provide a novel two-component explanation, which is consistent with the common belief in chemistry that the effect has a stereoelectronic origin. With α-D-glucopyranose as the prototype, we systematically explore its conformational space and generate 32 isomers, leading to a total of 80 axial-equatorial conformation pairs. The energy difference analysis of these pairs shows that while statistically speaking the tendency is valid, the anomeric effect is not always true and can be violated. Three energy components, exchange-correlation, classical electrostatic, and density functional steric, are found to be directly proportional to the total energy difference between axial and equatorial isomers. We also found that the total dipole moment change, not the hyperconjugation effect, is a reasonable indicator of the total energy difference. However, all these correlations alone are not strong enough to provide a compellingly convincing explanation for the general validity of the effect. With the help of strong correlations between energy components, an explanation with two energy components, steric and electrostatic, was proposed in this work. We show that the axial-equatorial energy difference in general, with the anomeric effect as a special case, is dictated by two factors of the stereoelectronic origin, steric hindrance and classical electrostatic interactions, synchronously working together. Another explanation in terms of exchange-correlation and electrostatic interactions has also been obtained in this work.

Origin of molecular conformational stability: Perspectives from molecular orbital interactions and density functional reactivity theory

“…This result, meanwhile, confirms the validity of the Walsh rule. Also, this result is consistent with our other recent studies, [10][11][12][13][14][15][16][17][18][19][20][21][22][23] where we found that the electrostatic interaction is the major determinant in many chemical effects and processes such as bond rotation, and chemical reactions.…”

“…Notice that there is also a kinetic counterpart of the dynamic correlation effect, [29][30][31][32][33][34][35][36] This DFT approach to partition energies has been applied to a number of systems, such as conformational changes of small molecules, S N 2 reactions, chained and branched alkanes, and other systems. [10][11][12][13][14][15][16][17][18][19][20][21][22] Reasonably, good trends and linear relationships between theoretical and experimental scales of the steric effect have recently been observed by Taft at both group and entire molecular levels.…”

“…To that end, the total energy difference is partitioned in a couple of different ways in terms of different energetic contributions accounting for different physiochemical effects, such as kinetic, exchange-correlation, electrostatic, steric, and fermionic quantum. 9 The new analysis has recently been applied to a number of systems, [10][11][12][13][14][15][16][17][18][19][20][21][22] such as bond rotation barriers, cis-effect, anomeric effect, SN 2 reaction barriers, and water clusters. A clear picture has seemingly merged from these different studies, showing that for all systems considered thus far, the electrostatic interaction plays the predominant role, whereas other effects such as those from the steric and exchange-correlation interactions play minor but indispensable roles.…”

Computational Study of Chemical Reactivity Using Information-Theoretic Quantities from Density Functional Reactivity Theory for Electrophilic Aromatic Substitution Reactions

“…[19][20][21][22][23][24][25][26][27][28][29][30][31] In this work, we will examine the role of these quantities and relationships for a number of electrophilic aromatic substitution reactions. In particular, we are interested to see (i) what the performance of applying Hirshfeld charge and information gain in predicting the reaction barrier height of these reactions is; (2) whether the electrostatic component is still the dominant contributor to the barrier height; and (3) if there exist similar strong linear correlations from the information-theoretic quantities for these systems with transition state involved.…”

Complete basis set, hybrid-DFT study and NBO interpretation of conformational analysis of 2-methoxytetrahydropyran and its thiopyran and selenopyran analogues in relation to the anomeric effect

“…In 2011, Liu and co-workers have looked into the validity of the AE from an energetic point of view by the use of the energy decomposition within the framework of density functional theory (DFT) [24,25]. Based on their results, the energy decomposition analysis shows three energy components (exchange-correlation, classical electrostatic and density functional steric) are directly proportional to the total energy difference between the axial and equatorial isomers.…”