Department of Chemistry, Boğaziçi University, Bebek, Istanbul 34342, Turkey.
Org Biomol Chem. 2011 Dec 7;9(23):8079-88. doi: 10.1039/c1ob06285a. Epub 2011 Oct 11.
In this study, the origins of diastereoselectivity in the hydrogen bonding assisted Diels-Alder reactions of chiral dienes with achiral dienophiles have been investigated with density functional methods. The distortion/interaction model has been applied to shed light on the origins of selectivity. C9-Substituted chiral anthracene templates (R = (CH(3))(OCH(3))(H), R = (CH(3))(OH)(H), R = (CH(3))(CH(2)CH(3))(H) and R = (-CH(2)-C(CH(3))(OCH(3))(H)) are used to rationalize the role of a stereogenic center and H-bonding on the product distribution ratio. Even though hydrogen bonding increases the reactivity of the diene, the stereoselectivity is reduced because of the hydrogen bonding capacity of both diastereomeric transition states. The interaction energies of the studied anthracene templates with N-methyl maleimide at the transition state correlate linearly with an increase in reactivity. The selectivity is determined by both favorable distortion and interaction energies. The π-facial selectivity induced by the presence of a chiral auxiliary in 1-substituted 1,3-pentadienes (R1 = (CH(3))(OCH(3))(H) and R1 = (CH(3))(OH)(H)) has also been modeled in order to rationalize the role of the stereogenic center and H-bonding on the stereoselectivity of an aliphatic diene. In both parts, the product distribution ratios calculated from Boltzmann distributions based on Gibbs free energies are in reasonable agreement with the experimental results. Finally the role of OH-substituted five-membered pyrrolidine on C9 of anthracene is investigated since the successful usage of the conformationally rigid pyrrolidines in asymmetric synthesis is well known. Overall, both in the acyclic system and in anthracene, the facilitation due to H-bonding is reflected in the interaction energies: the higher the difference in interaction energies in the transition structures of the two diastereomers, the more selective the H-bonding assisted Diels-Alder reaction is.
在这项研究中，我们应用密度泛函方法研究了手性二烯与非手性双烯反应物氢键辅助的 Diels-Alder 反应中立体选择性的起源。我们应用扭曲/相互作用模型来阐明选择性的起源。使用 C9-取代的手性蒽模板（R = (CH(3))(OCH(3))(H)、R = (CH(3))(OH)(H)、R = (CH(3))(CH(2)CH(3))(H) 和 R = (-CH(2)-C(CH(3))(OCH(3))(H))来合理化手性中心和氢键对产物分布比的作用。尽管氢键增加了二烯的反应活性，但由于两种非对映过渡态的氢键能力，立体选择性降低。研究的蒽模板与 N-甲基马来酰亚胺在过渡态的相互作用能与反应活性呈线性相关。选择性由有利的扭曲和相互作用能决定。在 1-取代的 1,3-戊二烯（R1 = (CH(3))(OCH(3))(H) 和 R1 = (CH(3))(OH)(H)）中存在手性辅助物引起的π-面选择性也被建模，以合理化手性中心和氢键对脂肪族二烯立体选择性的作用。在这两部分中，基于吉布斯自由能的玻尔兹曼分布计算的产物分布比与实验结果吻合良好。最后，研究了蒽 C9 上的 OH 取代的五元吡咯烷的作用，因为众所周知，构象刚性的吡咯烷在手性合成中的成功应用。总的来说，在手性和非手性体系中，氢键的促进作用反映在相互作用能中：两个非对映过渡态的相互作用能差异越大，氢键辅助的 Diels-Alder 反应选择性越高。
