Harnessing Electrophilic N-Aryl Catalytic Intermediates for Versatile C-N Bond Formation

利用亲电 N-芳基催化中间体形成多功能 C-N 键

• 批准号: 10582239
• 负责人: Tom G Driver
• 金额: $ 5.87万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10582239
• 关键词: Address; African American; Aniline; Anions; Azides; Chemistry; Chicago; Collaborations; Communication; Coupling; Cyclization; Development; Development Plans; Doctor of Philosophy; Drug Industry; Educational workshop; Electron Transport; Electrons; Funding; Generations; Goals; Health; Human; Hydrogen Bonding; Illinois; In Situ; Individual; Indoles; Iodides; Iodine; Leadership; Mentors; Metals; Methods; Nature; Nitrogen; Nitrogen Dioxide; Oxidants; Oxygen; Pattern; Pharmacologic Substance; Planet Earth; Positioning Attribute; Process; Quality of life; Reaction; Reagent; Reducing Agents; Research; Research Support; Research Training; Scheme; Scientist; Silanes; Students; System; Temperature; Training; Transition Elements; Universities; career; career development; career networking; catalyst; cold temperature; design; hydroxyindole; improved; migration; new technology; nitrene; nitroalkene; novel; oxidation; oxindole; pre-doctoral; programs; scaffold; selectfluor; skills; tool; trend

Abstract The ubiquitous nature of N-heterocycles in bioactive molecules that improve the quality of life and health of humans continues to inspire the development of new technology to simplify access to these scaffolds and provides a fertile ground to enable the training of scientists to achieve their professional aspirations. Our research program has been tailored to provide opportunities for the University of Illinois at Chicago's diverse student body to inspire, teach, and mentor them in their professional development by addressing gaps in organic synthetic repertoire through the development of new selective C–N bond forming reactions by exploiting the reactivity of electrophilic N-aryl nitrogen species generated in situ from aryl azides, nitroarenes, or non-activated anilines. Within GM138388, we have leveraged our understanding these N-aryl nitrogen reactive intermediates to develop new transformations that create C–NHAr bonds. To accomplish this, in Aim 1 we will develop new Fe(II)- catalyzed reductive cascade reactions that construct sp3-C–NHAr bonds intra- or intermolecularly from nitroarenes using silane reductants; in Aim 2 we will develop new single-electron transfer processes that generate N-aryl reactive intermediates with tunable oxygen transfer abilities for the synthesis of N- hydroxyindoles and oxindoles; and in Aim 3, we will develop oxidative methods for accessing electrophilic N-aryl nitrenoids from anilines and apply to the intra- and intermolecular synthesis of N-heterocycles. In this diversity supplement request for Jair N. Powell, we request funds to support his research training and career development. Jair will develop new earth abundant metal-catalyzed reductive methods to transform nitroalkenes into N- heterocycles by harnessing the reactivity of nitrosoalkenes to participate in nitroso-ene or C–N cross coupling reactions. His project will exploit the reactivity trends developed in Specific Aim 1 of GM138388 to construct five- or six-membered N-heterocycles through pericyclic or C–N cross-coupling reactions. By establishing that electrophilic nitrogen catalytic intermediates can be accessed from nitro-groups irrespective of their type, Jair will showcase the generality of our tools to construct novel and bioactive N-heterocycles. To help Jair achieve his goal of obtaining a Ph.D. position in the US pharmaceutical industry, his research training will be guided by maintaining an Individual Development Plan and buttressed with activities designed to sharpen his skills in verbal and written communication, and scientific collaboration, leadership, and teamwork. Jair will be given opportunities to participate in career development workshops and cultivate a diverse professional network to support his ambitions.

摘要 N-杂环在生物活性分子中普遍存在的性质，可以改善人类的生活质量和健康 人类继续推动新技术的发展，以简化获得这些支架的途径，并 为培训科学家实现其职业抱负提供了肥沃的土壤。我们的研究 该计划为伊利诺伊大学芝加哥分校的多样化学生群体提供了机会 通过解决有机合成方面的差距来激励、教育和指导他们的专业发展 通过开发新的选择性C-N键形成反应的曲目 由芳基叠氮化合物、硝基芳烃或未活化的苯胺原位生成的亲电N-芳基氮物种。 在GM138388中，我们利用我们对这些N-芳基氮活性中间体的理解来开发 产生C-NHAR键的新转变。为了实现这一目标，在目标1中，我们将开发新的Fe(II)- 从分子内或分子间构建SP3-C-NHAR键的催化还原级联反应 使用硅烷还原的硝基芳烃；在目标2中，我们将开发新的单电子转移工艺 生成氧转移能力可调的N-芳基反应中间体用于合成N-芳基 羟基吲哚和氧吲哚；在目标3中，我们将开发获得亲电N-芳基的氧化方法 芳香族化合物，并应用于N-杂环的分子内和分子间合成。在这种多样性中 对于Jair N.Powell的补充请求，我们请求资金支持他的研究、培训和职业发展。 捷尔公司将开发新的富土金属催化还原方法，将硝基烯烃转化为N- 利用亚硝基烯的反应性参与亚硝基-烯或C-N交叉偶联的杂环 反应。他的项目将利用GM138388的特定目标1中开发的反应性趋势来构建五个- 或六元N-杂环通过周环或C-N交叉偶联反应。通过确立这一点 亲电的氮催化中间体可以从硝基中获得，无论它们的类型是什么 将展示我们用于构建新型生物活性N-杂环的工具的通用性。帮助Jair实现 他的目标是在美国制药业获得博士职位，他的研究培训将由 保持个人发展计划，并通过旨在提高其口语技能的活动来支持 和书面交流，以及科学合作、领导力和团队合作。Jair将被给予 有机会参加职业发展研讨会并培养多样化的专业网络，以 支持他的野心。