NHC催化的分子内S <sub>N</sub> 2'亲核取代的机理和对映选择性的理论研究：NHC和DBU的作用是什么？<a href="#fn1" title="现有电子补充信息（ESI）：此研究涉及的所有结构的绝对能量清单（第1部分），DBPT途径中N9–H5键的扫描曲线（第2部分）以及所有固定点的笛卡尔坐标参与了这项研究（第3部分）。参见DOI：10.1039 / c8qo00129d">†</a>,Organic Chemistry Frontiers

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NHC催化的分子内S _N 2'亲核取代的机理和对映选择性的理论研究：NHC和DBU的作用是什么？†
Organic Chemistry Frontiers ( IF 4.6 ) Pub Date : 2018-03-09 00:00:00 , DOI: 10.1039/c8qo00129d
Huimin Zhang _{1,

2,

3,

4} , Hao Xu _{1,

2,

3,

4} , Huining Bai _{1,

2,

3,

4} , Donghui Wei _{1,

2,

3,

4} , Yanyan Zhu _{1,

2,

3,

4} , Wenjing Zhang _{1,

2,

3,

4}

Affiliation

提出了一种可能的催化机理，并通过使用密度泛函理论（DFT）对最近报道的用三取代的烯丙基溴进行醛的对映选择性分子内S _N 2'亲核取代进行了详细研究。计算结果表明，催化循环应经历四个阶段，包括NHC对底物的亲核攻击，Breslow中间体的生成，S _N 2'亲核取代，以及最终NHC的再生以及产物的释放。。还计算并仔细排除了NHC与一种烯烃碳相互作用以引发副反应的可能性。在S _Ñ2'亲核取代步骤被证明是决定速率和对映体选择性的步骤，并且通过过渡态导致形成R-构型产物的能垒比导致形成S的过程低。-配置的，与实验结果非常吻合。NHC被认为是促进反应发生的催化剂，而我们的计算结果表明，添加剂基DBU也应发挥重要作用，以使NHC催化剂和最重要的Breslow中间体产生。绘制了一些固定点的静电势图（MEP），以帮助我们分析DBU在质子转移过程中的作用。的电和亲核帕尔功能（P _ķ⁺和P _ķ^-）和前沿分子轨道（FMO）理论用于说明NHC如何通过umpolung策略促进反应。我们希望这项工作可以对NHC催化的S _N 2'取代反应的基本机理以及DBU和NHC如何协同促进此类反应的发生提供更深入的了解。

"点击查看英文标题和摘要"

Theoretical study on the mechanism and enantioselectivity of NHC-catalyzed intramolecular SN2′ nucleophilic substitution: what are the roles of NHC and DBU?†

A possible catalytic mechanism was proposed and studied in high detail by using the density functional theory (DFT) for a recently reported enantioselective intramolecular S_N2′ nucleophilic substitution of aldehydes with trisubstituted allylic bromides. The calculated results show that the catalytic cycle should occur through four stages including the nucleophilic attack of an NHC on the substrate, generation of the Breslow intermediate, S_N2′ nucleophilic substitution, and finally regeneration of the NHC along with the release of the product. The possibilities that the NHC interacts with one of the olefin carbons to initiate side reactions were also calculated and carefully excluded. The S_N2′ nucleophilic substitution step was demonstrated to be both the rate- and enantioselectivity-determining steps, and the energy barrier via the transition state leading to the R-configured product was lower than that leading to the S-configured one, which is in good agreement with the experimental results. The NHC was supposed to work as a catalyst to facilitate the reaction to occur, while our calculated results demonstrated that the additive base DBU should also play essential roles to enable the generation of the NHC catalyst and the most important Breslow intermediate. The electrostatic potential maps (MEPs) for some stationary points were plotted to help us analyze the roles DBU plays in the proton transfer process. The electrophilic and nucleophilic Parr functions (P_k⁺ and P_k⁻) and frontier molecular orbital (FMO) theory were applied to illustrate how NHCs could promote the reaction through the umpolung strategy. We hope this work could give deeper insight into the fundamental mechanisms of the NHC-catalyzed S_N2′ substitution reactions and how DBU and NHCs cooperatively promote these sorts of reactions to occur.

更新日期：2018-03-09

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