Synthesis and Reactivity at the Edges of Electrocyclic Chemistry

在化学系化学合成项目的支持下，罗切斯特大学的Alison J. Frontier教授正在研究使用化学反应制备环状分子，这种化学反应可以正式描述为“电环化”。“正在探索的过程位于定义明确的反应类别之间的边界，这些反应类别通常被认为是相互独立的，并且根据不同的原理运行。该项目的一个中心目标是通过研究专门设计用于在公认范式的“边缘”表现行为的分子的反应性，更多地了解这些模糊和很少探索的转化。除了从研究中预期的理论进展之外，该研究结合了从实验和计算化学中获得的联合收割机见解，预计这项工作将为合成含有多个环的复杂分子提供新的实用方法，并具有明确的三维结构。这些化合物作为新药剂、农用化学品和其他对社会有价值的先进化学材料的前体具有潜在的实用性。该奖项的更广泛的影响将扩展到化学教育的好处，因为Frontier教授继续开发和维护她在2004年创建的创新的“Not Voodoo”网站。该网站现在得到了有用的社交媒体推广的补充，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者提供服务，从刚刚开始独立研究的学生到寻找技巧或技巧的更高级的科学家。罗切斯特大学前沿小组的这项研究将集中在三种新的合成方法的开发上，每种方法都涉及一种不发达的反应类型，这种反应是通过已知电循环化学边缘的一种不明确的机械途径发生的。在项目1中，一种模糊的pentannulation类型的范围，“iso-Nazarov”环化，正在扩大，这些边界反应的电循环与离子性质的实验和计算技术的结合询问。 在项目2中，电环化反应性的边界被扩展到以前未知的高阶阳离子电环化（例如，6 π选举过程导致7元环）的精心设计的不饱和底物的研究。最后，项目3的目标是发现一条路线或一座桥梁，允许从自由基到电循环化学的有效通道。在本文中，正在探索一种基于1，5-氢原子转移的自由基-极性交叉策略作为产生阳离子和阴离子中间体的手段，从而可能以新的方式进入电环化学。所有这三个项目预计将导致显着的新方法合成不寻常的多环，包括例子含有环庚烷环，螺环基序，氮和氧杂环。目前还在改进非巫毒网站，包括：（1）增加化学品信息资源;（2）利用从化学品安全图书馆收集的信息引入新的化学品安全内容;（3）网站维护，随着用户的投入不断发展;以及（4）该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的学术价值和更广泛的影响评审标准。

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.