School of Chemistry, University of Melbourne, VIC 3010, Australia.
Acc Chem Res. 2013 Apr 16;46(4):979-89. doi: 10.1021/ar3000794. Epub 2012 Jul 24.
This Account describes how attractive interactions of aromatic rings with other groups can influence and control the stereoselectivity of many reactions. Recent developments in theory have improved the accuracy in the modeling of aromatic interactions. Quantum mechanical modeling can now provide insights into the roles of these interactions at a level of detail not previously accessible, both for ground-state species and for transition states of chemical reactions. In this Account, we show how transition-state modeling led to the discovery of the influence of aryl groups on the stereoselectivities of several types of organic reactions, including asymmetric dihydroxylations, transfer hydrogenations, hetero-Diels-Alder reactions, acyl transfers, and Claisen rearrangements. Our recent studies have also led to a novel mechanistic picture for two classes of (4 + 3) cycloadditions, both of which involve reactions of furans with oxyallyl intermediates. The first class of cycloadditions, developed by Hsung, features neutral oxyallyl intermediates that contain a chiral oxazolidinone auxiliary. Originally, it was thought that these cycloadditions relied on differential steric crowding of the two faces of a planar intermediate. Computations reveal a different picture and show that cycloaddition with furan takes place preferentially through the more crowded transition state: the furan adds on the same side as the Ph substituent of the oxazolidinone. The crowded transition state is stabilized by a CH-π interaction between furan and Ph worth approximately 2 kcal/mol. Attractive interactions with aromatic rings also control the stereoselectivity in a second class of (4+3) cycloadditions involving chiral alkoxy siloxyallyl cations. Alkoxy groups derived from chiral α-methylbenzyl alcohols favor crowded transition states, where a stabilizing CH-π interaction is present between the furan and the Ar group. The cationic cycloadditions are stepwise, while the Hsung cycloadditions are concerted. Our results suggest that this form of CH- π-directed stereocontrol is quite general and likely controls the stereoselectivities of other addition reactions in which one face of a planar intermediate bears a pendant aromatic substituent.
该账户描述了芳香环与其他基团的吸引力相互作用如何影响和控制许多反应的立体选择性。理论上的最新发展提高了对芳香相互作用建模的准确性。量子力学建模现在可以提供对这些相互作用在以前无法获得的细节水平上的作用的深入了解，无论是对于基态物种还是对于化学反应的过渡态。在本说明中，我们展示了过渡态建模如何导致发现芳基基团对几种类型的有机反应的立体选择性的影响，包括不对称二羟化反应、转移氢化反应、杂 Diels-Alder 反应、酰基转移反应和 Claisen 重排反应。我们最近的研究还为两类（4+3）环加成反应提供了一个新的机理图，这两类反应都涉及呋喃与氧杂丙二烯中间体的反应。Hsung 开发的第一类环加成反应以包含手性恶唑烷酮助剂的中性氧杂丙二烯中间体为特征。最初，人们认为这些环加成反应依赖于平面中间体两个面的差分空间拥挤度。计算表明了不同的情况，并表明呋喃与 furan 加成主要通过更拥挤的过渡态进行：呋喃与恶唑烷酮的 Ph 取代基在同一侧添加。拥挤的过渡态通过呋喃和 Ph 之间的 CH-π 相互作用稳定，其值约为 2 kcal/mol。芳香环的吸引力相互作用还控制涉及手性烷氧基硅氧基丙二烯阳离子的第二类（4+3）环加成反应的立体选择性。来源于手性α-甲基苄醇的烷氧基基团有利于拥挤的过渡态，其中呋喃和 Ar 基团之间存在稳定的 CH-π 相互作用。阳离子环加成是逐步进行的，而 Hsung 环加成是协同的。我们的结果表明，这种形式的 CH-π 定向立体控制是相当普遍的，并且可能控制其他加成反应中平面中间体的一个面带有附加芳基取代基的立体选择性。
