Insights into the mechanism, selectivity, and substituent effects in the Diels-Alder reaction of azatrienes with electron-rich dienophiles: An MEDT study

IF 2.7 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling Pub Date : 2024-07-14 DOI:10.1016/j.jmgm.2024.108819

Amine Rafik , Abdeljabbar Jaddi , Mohammed Salah , Najia Komiha , Miguel Carvajal , Khadija Marakchi

{"title":"Insights into the mechanism, selectivity, and substituent effects in the Diels-Alder reaction of azatrienes with electron-rich dienophiles: An MEDT study","authors":"Amine Rafik , Abdeljabbar Jaddi , Mohammed Salah , Najia Komiha , Miguel Carvajal , Khadija Marakchi","doi":"10.1016/j.jmgm.2024.108819","DOIUrl":null,"url":null,"abstract":"<div><p>The reactivity and mechanistic intricacies of azatrienes in Diels-Alder reactions have been relatively unexplored despite their intriguing potential applications. In this study, we employ Molecular Electron Density Theory to theoretically investigate the hetero-Diels–Alder reaction involving azatrienes with ethyl vinyl ether and allenyl methyl ether. Analysis of Conceptual Density Functional Theory, energetic profiles, and the topological characteristics is conducted to elucidate the reactions. The revealed mechanism manifests as a polar one-step two-stages process under kinetic control. We establish a clear relationship of between the periselectivity, regioselectivity, and stereoselectivity on one hand and the characteristics of the reactions mechanism on the other hand. The influence of weak interactions on reaction activation barriers and bonding evolution are discussed in detail. We demonstrate that substituents enhancing the reverse electron density flux facilitate the feasibility of the reactions. The results lay ground for a meticulous control of the reaction of azatriene in similar synthetic scenarios.</p></div>","PeriodicalId":16361,"journal":{"name":"Journal of molecular graphics & modelling","volume":"132 ","pages":"Article 108819"},"PeriodicalIF":2.7000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of molecular graphics & modelling","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1093326324001190","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}

引用次数: 0

Abstract

The reactivity and mechanistic intricacies of azatrienes in Diels-Alder reactions have been relatively unexplored despite their intriguing potential applications. In this study, we employ Molecular Electron Density Theory to theoretically investigate the hetero-Diels–Alder reaction involving azatrienes with ethyl vinyl ether and allenyl methyl ether. Analysis of Conceptual Density Functional Theory, energetic profiles, and the topological characteristics is conducted to elucidate the reactions. The revealed mechanism manifests as a polar one-step two-stages process under kinetic control. We establish a clear relationship of between the periselectivity, regioselectivity, and stereoselectivity on one hand and the characteristics of the reactions mechanism on the other hand. The influence of weak interactions on reaction activation barriers and bonding evolution are discussed in detail. We demonstrate that substituents enhancing the reverse electron density flux facilitate the feasibility of the reactions. The results lay ground for a meticulous control of the reaction of azatriene in similar synthetic scenarios.

Abstract Image

查看原文本刊更多论文

揭示氮杂三烯与富电子亲二烯的 Diels-Alder 反应的机理、选择性和取代基效应：MEDT 研究

尽管氮杂三烯在 Diels-Alder 反应中具有引人入胜的潜在应用价值，但其反应性和机理的复杂性相对而言尚未得到研究。在本研究中，我们采用分子电子密度理论，从理论上研究了氮杂三烯与乙烯基乙醚和烯丙基甲醚的杂环-Diels-Alder 反应。通过对概念密度泛函理论、能量曲线和拓扑特征的分析，阐明了反应的机理。所揭示的机理表现为动力学控制下的极性一步两阶段过程。我们在过选择性、区域选择性和立体选择性与反应机理特征之间建立了明确的关系。我们详细讨论了弱相互作用对反应活化障碍和键合演化的影响。我们证明，增强反向电子密度通量的取代基有助于提高反应的可行性。这些结果为在类似的合成方案中细致地控制偶氮三烯的反应奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of molecular graphics & modelling 生物-计算机：跨学科应用

CiteScore

5.50

自引率

6.90%

发文量

216

审稿时长

35 days

期刊介绍： The Journal of Molecular Graphics and Modelling is devoted to the publication of papers on the uses of computers in theoretical investigations of molecular structure, function, interaction, and design. The scope of the journal includes all aspects of molecular modeling and computational chemistry, including, for instance, the study of molecular shape and properties, molecular simulations, protein and polymer engineering, drug design, materials design, structure-activity and structure-property relationships, database mining, and compound library design. As a primary research journal, JMGM seeks to bring new knowledge to the attention of our readers. As such, submissions to the journal need to not only report results, but must draw conclusions and explore implications of the work presented. Authors are strongly encouraged to bear this in mind when preparing manuscripts. Routine applications of standard modelling approaches, providing only very limited new scientific insight, will not meet our criteria for publication. Reproducibility of reported calculations is an important issue. Wherever possible, we urge authors to enhance their papers with Supplementary Data, for example, in QSAR studies machine-readable versions of molecular datasets or in the development of new force-field parameters versions of the topology and force field parameter files. Routine applications of existing methods that do not lead to genuinely new insight will not be considered.