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

项目摘要/摘要 治疗药物中常见的结构基序的直接实验室制备 有选择地开发和利用现成的化学品是新能源开发的主要驱动力 合成策略和催化。在我们的实验室，我们采用了合成和催化开发通过 芳香族氮氧化物的非传统单电子转移化学，易于获得，可调，用途广泛 化合物。我们的长期研究目标是开发和了解单电子转移过程 芳香族氮氧化物，可提供新的化学空间和合成和催化途径，使发现成为可能 以及合成和生物系统的创新。五年的研究计划将导致更大的 了解目前不发达的芳香族氮氧化物的单电子转移化学，它是 预计将广泛扩大其用途，作为一种新的实用手段，进入新的化学空间，用于合成 方法论和催化发展。拟议的研究结果将有可能是 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)加快管理和治疗药物的设计、开发和制造 疾病；3)将社会重要性的催化和选择性转变概念化，从而推动 垂直的合成和治疗发展。 基于我们的研究成果和令人振奋的初步数据，我们在1) 用于简单高效地合成复杂分子的乙烯基化学，以及2)氢原子转移 (HAT)催化选择性C-H官能化。在区域1拟议的研究将建立一个原始的 和创新的战略，利用容易获得的炔烃和吡啶氮氧化物来轻松地产生- 氧化吡啶的乙烯基来释放其合成潜力。这一战略将使 各种自由基级联反应导致发现新的转化和合成方法 不能用常规方法来完成。这一贡献预计将广泛扩大 乙烯基介导的反应在合成中的应用，将为新的合成方法提供新的机会 设计和开发用于构建广泛的碳氢化合物的新型临床试剂 杂环和羰基官能团。我们在区域2的拟议研究预计将建立一个 用于区域和立体选择性C-H功能化的创新和模块化催化剂系统 芳香族氮氧化物光诱导HAT催化剂对未活化C(Sp3)−H的有效反应 债券。拟议的多种战略结合了实验和计算研究，包括 催化剂结构开发、合作方法和双功能催化剂，将使一系列现场和 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.