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教授正在研究利用化学反应制备环状分子的方法，这种化学反应可以被正式地描述为“电环化”。正在探索的过程处于定义明确的反应类别之间的边缘，这些反应类别通常被认为是彼此分离的，并且根据不同的原理进行操作。该项目的一个中心目标是通过研究分子的反应性来更多地了解这些模糊的、很少被探索的转化，这些分子被专门设计成在公认范式的“边缘”表现出行为。该研究结合了从实验和计算化学中获得的见解，除了预期的理论进展之外，这项工作有望为合成含有多个环的复杂分子提供新的实用方法，这些分子具有明确的三维结构。这些化合物作为新型药剂、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用途。随着Frontier教授继续开发和维护她于2004年创建的创新的“Not Voodoo”网站，该奖项的广泛影响将扩展到化学教育所带来的好处。该网站，现在辅以有用的社会媒体为基础的外展，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窍门或技巧的高级科学家。“非巫术”在促进化学品安全方面也发挥着宝贵的作用。罗切斯特大学前沿小组的这项研究将专注于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，这种反应是在已知电环化学的边缘通过不明确的机制途径发生的。在项目1中，一种模棱两可的五环化，即“异纳扎罗夫”环化的范围正在扩大，并通过实验和计算技术的结合来研究这些边缘反应的电环和离子性质。在项目2中，通过对精心设计的不饱和底物的研究，电环反应性的界限被扩展到以前未知的高阶阳离子电环反应（例如，6 - pi选择过程导致7元环）。最后，项目3的目标是发现一条路线，或一座桥梁，允许从自由基到电环化学的有效通道。在此，一种基于1,5-氢原子转移的自由基-极性交叉策略正在被探索，作为一种产生阳离子和阴离子中间体的手段，从而有可能以一种新的方式进入电环化学。预计这三个项目将导致合成不寻常多环的重要新方法，包括含有环庚烷环、螺环基序和氮氧杂环的例子。对Not Voodoo网站的改进也在进行中，包括：(1)增加化学信息资源；(2)利用从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，随着用户的输入不断演进；(4)扩大了实用技术内容的范围。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.