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.

项目概要/摘要 治疗剂中常见的结构基序的直接实验室制备 选择性时尚和利用现成的化学品是开发新产品的主要驱动力 在我们的实验室，我们采用了合成和催化开发。 芳香族氮氧化物的非常规单电子转移化学，易于获取、可调且用途广泛 我们的长期研究目标是开发和理解单电子转移过程。 芳香族氮氧化物可以提供新的化学空间以及合成和催化的途径，从而实现发现 跨合成和生物系统的创新和创新将带来更大的五年研究计划。 了解目前尚未开发的芳香族氮氧化物的单电子转移化学， 预计将广泛扩大其用途，作为进入新的合成化学空间的新的实用手段 拟议研究的结果将有可能成为现实。 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 3）概念化具有社会重要性的催化和选择性转变，从而推动 垂直合成和治疗开发。 基于我们的研究成果和我们在以下领域获得的令人兴奋的初步数据：1) 用于简洁有效地合成复杂分子的乙烯基自由基化学，以及2）氢原子转移 选择性 C-H 官能化的 (HAT) 催化 区域 1 中拟议的研究将建立一种原创的方法。 以及利用现成的炔烃和吡啶氮氧化物轻松生成-的创新策略 oxypyridinium 乙烯基自由基释放其合成潜力将有助于开发一种新的方法。 各种自由基级联反应导致新转化和合成方法的发现 传统方法无法实现这一贡献，预计将广泛扩展。 乙烯基自由基介导反应的合成应用，将为乙烯基自由基介导反应的合成提供新的机会 使用炔烃设计和开发新的临床制剂，用于构建各种碳和 我们在区域 2 中提出的研究预计将建立一个 通过开发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 对未活化的 C(sp3)−H 具有有效反应活性的芳香族 N-氧化物基光诱导 HAT 催化剂 所提出的多种策略结合了实验和计算研究，包括 催化剂结构的开发、合作方法和双功能催化剂，将使一系列的位点和 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。