Synthesis and Reactivity at the Edges of Electrocyclic Chemistry

环电化学边缘的合成和反应性

• 批准号: 2154854
• 负责人: Alison Frontier
• 金额: $ 52.5万
• 依托单位: University of Rochester
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154854&HistoricalAwards=false
• 关键词: Synthesis; Reactivity; Edges; Electrocyclic; Chemistry

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Alison J. Frontier of the University of Rochester is studying the preparation of cyclic molecules using chemical reactions that can be formally characterized as "electrocyclizations." The processes being explored lie on the borderline between well-defined reaction classes that are typically considered to be separate from one another and which operate according to different principles. A central goal of the project is to learn more about these ambiguous and little explored transformations by investigating the reactivity of molecules specially designed to exhibit behavior at the "edges" of an accepted paradigm. Beyond the theoretical advances anticipated from the research, which combine insights gained from both experimental and computational chemistry, the work is expected to provide new practical approaches for the synthesis of complex molecules containing multiple rings and that possess well-defined three-dimensional structures. Such compounds are of potential utility as precursors to new pharmaceutical agents, agrochemicals, and other advanced chemical materials of value to society. The broader impacts of this award will extend to the benefits to chemical education accrued as Professor Frontier continues to develop and maintain the innovative "Not Voodoo" website that she created in 2004. The site, which is now complemented by useful social media-based outreach, is designed to help practitioners of synthetic organic chemistry to demystify laboratory techniques and procedures. It serves hundreds of experimentalists each day, from students just beginning their independent research, to more advanced scientists looking for tips or tricks. "Not Voodoo" also plays a valuable role in promoting chemical safety.This research in the Frontier group at the University of Rochester will focus on the development of three new synthetic methods, each involving an underdeveloped reaction type that occurs by an ill-defined mechanistic pathway at the edges of known electrocyclic chemistry. In Project 1, the scope of an ambiguous type of pentannulation, the "iso-Nazarov" cyclization, is being expanded upon and the electrocyclic vs. ionic nature of these borderline reactions interrogated by a combination of experimental and computational techniques. In Project 2, the boundaries of electrocyclic reactivity are being extended to previously unknown higher-order cationic electrocyclizations (e.g., 6 pi-election processes leading to 7-membered rings) by studies of carefully designed unsaturated substrates. Finally, Project 3 has as its aim the discovery of a route, or a bridge, allowing efficient passage from radical to electrocyclic chemistry. Herein, a 1,5-hydrogen atom transfer-based radical-polar crossover strategy is being explored as a means to generate both cationic and anionic intermediates, thereby potentially accessing electrocyclic chemistry in a novel way. All three projects are anticipated to lead to significant new methods for the synthesis of unusual polycycles, including examples containing cycloheptane rings, spirocyclic motifs, and nitrogen and oxygen heterocycles. Improvements to the Not Voodoo website are also underway, including: (1) addition of chemical information resources; (2) introduction of new chemical safety content using information collected from the Chemical Safety Library; (3) site maintenance, which evolves continuously with user input; and (4) expanding the scope of the practical technical content.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系化学合成项目的支持下，罗切斯特大学的 Alison J. Frontier 教授正在研究利用化学反应制备环状分子，这种化学反应可以正式称为“电环化”。正在探索的过程位于明确定义的反应类别之间的边界，这些反应类别通常被认为是彼此独立的，并且根据不同的原理进行操作。该项目的中心目标是通过研究专门设计用于在公认范式的“边缘”表现出行为的分子的反应性，来更多地了解这些模糊且很少探索的转变。除了该研究预期的理论进展（结合了从实验和计算化学中获得的见解）之外，这项工作预计将为合成含有多个环并具有明确的三维结构的复杂分子提供新的实用方法。这些化合物具有作为新药剂、农用化学品和其他对社会有价值的先进化学材料的前体的潜在用途。随着 Frontier 教授继续开发和维护她于 2004 年创建的创新型“Not Voodoo”网站，该奖项的更广泛影响将延伸到化学教育所带来的好处。该网站现在得到了有用的基于社交媒体的宣传的补充，旨在帮助合成有机化学从业者揭开实验室技术和程序的神秘面纱。它每天为数百名实验人员提供服务，从刚刚开始独立研究的学生，到寻找技巧或窍门的高级科学家。 “Not Voodoo”在促进化学安全方面也发挥着重要作用。罗切斯特大学前沿小组的这项研究将重点开发三种新的合成方法，每种方法都涉及一种不发达的反应类型，该反应类型是由不明确的机制发生的已知电循环化学边缘的途径。在项目 1 中，正在扩大一种模糊类型的五环化（“iso-Nazarov”环化）的范围，并通过实验和计算技术的结合来探讨这些边界反应的电环与离子性质。 在项目2中，通过对精心设计的不饱和底物的研究，电环反应性的边界正在扩展到以前未知的高阶阳离子电环化（例如，导致7元环的6π选举过程）。最后，项目 3 的目标是发现一条路线或一座桥梁，允许从自由基化学到电循环化学的有效过渡。在此，人们正在探索一种基于 1,5-氢原子转移的自由基-极性交叉策略，作为生成阳离子和阴离子中间体的一种手段，从而有可能以一种新颖的方式进入电环化学。预计这三个项目将带来合成不寻常多环的重要新方法，包括含有环庚烷环、螺环基序以及氮和氧杂环的例子。 Not Voodoo网站的改进也在进行中，包括：（1）增加化学信息资源； （二）利用化学品安全图书馆收集的信息介绍新的化学品安全内容； (3) 站点维护，随着用户的输入而不断发展； (4) 扩大实用技术内容的范围。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，认为值得支持。

项目成果

Approach to High-Nitrogen Materials with Dual-Use Properties via Tetraaza-Nazarov Cyclization

通过四氮杂-纳扎罗夫环化制备具有双重用途的高氮材料

• DOI: 10.1021/acs.inorgchem.2c02649
• 发表时间: 2022-11
• 期刊: Inorganic Chemistry
• 影响因子: 4.6
• 作者: Thoenen, Michael;Gettings, Matthew;Holt, Connor;Frontier, Alison J.;Caruana, Patrick A.;Zeller, Matthias;Byrd, Edward F.;Piercey, Davin G.
• 通讯作者: Piercey, Davin G.

Alkynyl Prins carbocyclization cascades for the synthesis of linear-fused heterocyclic ring systems

用于合成线性稠合杂环系统的炔基 Prins 碳环化级联

• DOI: 10.1039/d2sc04750k
• 发表时间: 2022-11-30
• 期刊: Chemical Science
• 影响因子: 8.4
• 作者: Hernandez, Jackson J.;Frontier, Alison J.
• 通讯作者: Frontier, Alison J.

Divergent Reactivity of Triaryldivinyl Ketones: Competing 4π and Putative 6π Electrocyclization Pathways

三芳基二乙烯基酮的不同反应性：竞争的 4Ï 和假定的 6Ï 电环化途径

• DOI: 10.1021/acs.joc.2c01294
• 发表时间: 2022-11
• 期刊: The Journal of Organic Chemistry
• 作者: Yadykov, Anton V.;Eremchenko, Artem E.;Milosavljevic, Aleksa;Frontier, Alison J.;Shirinian, Valerii Z.
• 通讯作者: Shirinian, Valerii Z.

Nitrogen-interrupted halo -Prins/ halo -Nazarov fragment coupling cascade for the synthesis of indolines

氮中断 halo -Prins/ halo -Nazarov 片段偶联级联用于合成二氢吲哚

• DOI: 10.1039/d3sc00986f
• 发表时间: 2023-05-24
• 期刊: Chemical Science
• 影响因子: 8.4
• 作者: Milosavljevic, Aleksa;Holt, Connor;Frontier, Alison J.
• 通讯作者: Frontier, Alison J.