Department of Chemistry , Yale University , 275 Prospect Street , New Haven , Connecticut 06520-8107 , United States.
Department of Chemistry , University of Connecticut , 55 North Eagleville Road , Storrs , Connecticut 06269-3060 , United States.
J Org Chem. 2018 May 4;83(9):5242-5255. doi: 10.1021/acs.joc.8b00707. Epub 2018 Apr 12.
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.
我们通过一项协同的实验和计算研究重新考察了端基效应的起源。这些研究的结果表明，有许多不同但相关的相互作用共同导致了端基效应。没有任何单一因素可以单独解释取代基的轴向偏好，这种偏好是端基效应的标志。我们已经通过实验证明，在杂环中，极性轴向取代基（G）与顺轴向氢原子（s）之间存在 CH···G 非键相互作用。涉及从环杂原子到轴向 C-G 键的激发态的电子转移的超共轭模型被证明只是一个次要贡献者，因为环杂原子上的电荷密度变化非常小：主要的电荷转移是从 H-C-G 单元中的氢到 G。这似乎是由于 C-G 键的延长，以最小化与环原子孤对电子的排斥，并利用更正的氢，从而与环杂原子（s）产生稳定的库仑相互作用。简而言之，端基效应主要来自两个单独的 CH···G 非键库仑吸引力。
