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

芳香族氮氧化物的单电子氧化选择性化学合成和催化

• 批准号: 10714856
• 负责人: Yongming Deng
• 金额: $ 33.77万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714856
• 关键词: Adopted; Alkynes; Architecture; Area; Catalysis; Chemicals; Chemistry; Clinical; Complex; Data; Development; Disease; Electron Transport; Electrons; Future; Generations; Goals; Hydrogen; Hydrogen Bonding; Laboratories; Mediating; Medicine; Methodology; Methods; Molecular; Outcome; Oxides; Preparation; Process; Reaction; Research; Series; Site; Structure; System; Technology; Therapeutic Agents; biological systems; catalyst; chemical synthesis; computer studies; design; driving force; experimental study; innovation; manufacture; novel; oxidation; programs; pyridine; therapeutic development

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.

项目摘要/摘要 在A 选择性时尚和使用易于使用的化学品是开发新的主要推动力 合成策略和催化。在我们的实验室中，我们通过 芳族N-氧化物的非常规单电子转移化学，易于访问，可调且通用 化合物。我们的长期研究目标是开发和理解 可以提供新的化学空间并获得合成和催化的芳香族氧化物 以及跨合成系统和生物系统的创新。五年的研究计划将导致更大的 了解当前不发达的芳族N-氧化物的单电子转移化学，这是 预计将广泛扩展其作为访问合成的新化学空间的一种新的实用方法 方法论和催化发育。拟议研究的结果将有可能 变革性的是，它们将1）帮助未来开发单电子化学的发展 芳香族氧化物； 2）加快药物的设计，开发和制造来管理和治疗 疾病； 3）概念化社会重要性的催化和选择性转变，从而移动 垂直合成和热发育。 根据我们的研究成就和令人兴奋的初步数据，我们在1的领域获得了） 乙烯基自由基化学，用于复杂分子的简洁有效合成，2）氢原子转移 （HAT）选择性C-H功能化的催化。第1区提议的研究将建立原始的 以及利用易于使用的炔烃和吡啶n-氧化物的创新策略，可轻松产生- 乙烯基乙烯基自由基释放其合成潜力。这样的策略将使一个发展 各种根治性的级联反应，导致发现新的转化和合成方法 传统方法无法完成。预计这一贡献将广泛扩展 乙烯基自由基介导的反应的合成应用，它将为 使用酒精的新临床剂的设计和开发用于建造各种碳水化合物和 杂种和羰基功能。我们在第2区提议的研究有望建立 通过开发区域和立体选择性C-H功能化的创新和模块化催化剂系统 基于N-氧化物的光诱导的HAT催化剂，对未激活C（SP3）-H有效反应性 债券。提出的多种策略与实验和计算研究合并，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站点和 简单和复杂的分子体系结构的区域选择性脂肪族C-H功能化反应。