School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, China.
J Chem Phys. 2011 Feb 28;134(8):084103. doi: 10.1063/1.3555760.
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.
端基效应（杂原子在环己烷环内相邻的杂原子附近的取代基优先采用轴向取向而不是空间位阻较小的平伏键取向的趋势）传统上通过偶极矩排斥或超共轭效应来解释。在这项工作中，我们通过采用最近在密度泛函立体分析方面的工作，提供了一种新的双组分解释，这与化学界普遍认为该效应具有立体电子起源的观点一致。以 α-D-吡喃葡萄糖为原型，我们系统地探索了其构象空间，生成了 32 个异构体，导致总共 80 个轴向-平伏构象对。这些对的能量差分析表明，虽然从统计学上讲这种趋势是有效的，但端基效应并不总是成立的，也可能会被违反。发现交换相关、经典静电和密度泛函立体三个能量分量与轴向和平伏异构体之间的总能量差直接成正比。我们还发现总偶极矩变化而不是超共轭效应是总能量差的合理指标。然而，所有这些相关性本身都不足以提供令人信服的解释来说明该效应的普遍有效性。在能量分量之间的强相关性的帮助下，这项工作提出了用两个能量分量（立体和静电）来解释的方法。我们表明，一般来说，轴向-平伏能量差，包括端基效应作为一个特殊情况，是由两个立体电子起源因素决定的，即空间位阻和经典静电相互作用，它们协同作用。在这项工作中还获得了另一种基于交换相关和静电相互作用的解释。
