Selective Chemical Synthesis and Catalysis Enabled by Single-Electron Oxidation of Aromatic N-oxides

项目总结/摘要 简单的实验室制备的结构基序常见于治疗剂中， 选择性的方式和利用容易获得的化学品是开发新的 合成策略和催化。在我们的实验室里，我们已经通过合成和催化发展， 芳香族N-氧化物的非传统单电子转移化学，易于获得、可调且用途广泛 化合物.我们的长期研究目标是开发和理解的单电子转移过程的 芳香族氮氧化物，可以提供新的化学空间，并获得合成和催化，使发现 以及在合成和生物系统中的创新。这项为期五年的研究计划将导致更大的 了解目前不发达的单电子转移化学的芳香族N-氧化物，它是 预计将广泛扩大其使用，作为进入合成新化学空间的新的实用手段。 方法学和催化剂开发。拟议研究的成果将有可能成为 变革性的，因为它们将1）帮助引领单电子化学的未来发展， 芳香族氮氧化物; 2）加快药物的设计，开发和制造，以管理和治疗 疾病; 3）概念化社会重要性的催化和选择性转变，从而移动 纵向上是综合和治疗开发。 基于我们在以下领域取得的研究成果和令人兴奋的初步数据： 乙烯基自由基化学，用于简洁有效地合成复杂分子，以及2）氢原子转移 (HAT)用于选择性C-H官能化的催化。在第一区的拟议研究将建立一个原始的 和创新的策略，利用容易获得的炔和吡啶N-氧化物， oxypyridinium乙烯基自由基，以释放其合成潜力。这一战略将有助于发展一个 各种自由基级联反应，导致发现新的转化和合成方法， 这是传统方法无法实现的。预计这一贡献将广泛扩大 乙烯基自由基介导的反应的合成应用，它将提供新的合成机会， 设计和开发新的临床药物，使用炔类构建广泛的碳- 杂环和羰基官能团。我们在第二区的拟议研究预计将建立一个 用于区域和立体选择性C-H官能化的创新和模块化催化剂系统， 对未活化的C（sp3）−H具有有效反应性的芳族N-氧化物基光诱导HAT催化剂 债券所提出的多种策略结合了实验和计算研究，包括 催化剂结构的发展，合作的方法，和双功能催化剂，将使一系列的网站-和 简单和复杂分子结构的区域选择性脂肪族C-H官能化反应。

Project Summary/Abstract The straightforward laboratory preparation of structural motifs commonly found in therapeutic agents in a selective fashion and utilizing readily available chemicals is a major driving force in the development of new synthetic strategies and catalysis. In our laboratory, we have adopted synthesis and catalysis development via unconventional single-electron transfer chemistry of aromatic N-oxides, readily accessible, tunable, and versatile compounds. Our long-term research goal is to develop and understand the single-electron transfer process of aromatic N-oxides that could offer new chemical space and access to synthesis and catalysis enabling discovery and innovation across synthetic and biological systems. The five-year research program will lead to a greater understanding of the currently underdeveloped single-electron transfer chemistry of aromatic N-oxides, and it is expected to broadly expand its use as a new and practical means of accessing new chemical space for synthetic methodology and catalysis development. The outcomes of the proposed research will have the potential to be transformational in that they will 1) aid in ushering in the future development of single-electron chemistry of aromatic N-oxides; 2) expedite the design, development and manufacture of medicines to manage and treat diseases; 3) conceptualize catalytic and selective transformations of societal importance, thereby moving synthesis and therapeutic development vertically. Based on our research accomplishments and exciting preliminary data we have obtained in the arenas of 1) vinyl radical chemistry for concise and efficient synthesis of complex molecules, and 2) hydrogen-atom transfer (HAT) catalysis for selective C-H functionalization. The proposed research in Area 1 will establish an original and innovative strategy utilizing readily available alkynes and pyridine N-oxides for the facile generation of - oxypyridinium vinyl radical to unleash its synthetic potential. Such a strategy will enable the development of a variety of radical cascade reactions leading to the discovery of new transformations and synthetic methods that could not be accomplished by conventional methods. This contribution is expected to broadly expand the synthetic applications of vinyl radical mediated reactions and it will provide new synthetic opportunities for the design and development of new clinical agents using alkynes for the construction of a wide range of carbo- and hetero-cycles, and carbonyl functionalities. Our proposed research in Area 2 is expected to establish an innovative and modular catalyst system for regio- and stereoselective C-H functionalization by developing aromatic N-oxide based photoinduced HAT catalysts with effective reactivity towards unactivated C(sp3)−H bonds. The proposed multiple strategies incorporated with experimental and computational studies, including catalyst structure development, cooperative approach, and bifunctional catalysts, will enable a series of site- and regio-selective aliphatic C-H functionalization reactions of simple and complex molecular architectures.