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.

抽象的 n-杂环在生物活性分子中的无处不在，可以改善生活质量和健康 人类继续激发新技术的发展，以简化对这些脚手架的访问和 提供肥沃的基础，使科学家的培训能够实现其专业愿望。我们的研究 计划量身定制，以为芝加哥潜水员学生团体的伊利诺伊大学提供机会 通过解决有机合成的差距来激发，教学和男人的职业发展 通过开发新的选择性C – N键反应，曲目通过利用的反应性来形成反应 由芳基叠氮，硝酸或未激活的苯胺原位产生的亲电N-芳基氮种。 在GM138388中，我们利用了这些N-芳基氮反应性中间体的理解 创建C – NHAR债券的新转换。为此，在AIM 1中，我们将开发新的Fe（II） - 从 使用硅烷还原的氮气；在AIM 2中，我们将开发新的单电子转移过程 生成具有可调氧转移能力的N-芳基反应性中间体，以合成N- 羟基吲哚和氧吲哚；在AIM 3中，我们将开发用于访问亲电n- Aryl的氧化方法 来自苯胺的硝酸盐，并应用于N-杂环的分子内和分子间合成。在这种多样性中 补充杰尔·鲍威尔（Jair N. Powell）的请求，我们要求资金支持他的研究培训和职业发展。 Jair将开发富含新地球的金属催化的减少方法，以将硝基烷烃转化为n- 通过利用硝基烯烃的反应性参与硝基烯或C – N交叉耦合，杂环 反应。他的项目将利用GM138388特定目的1中发展的反应性趋势来构建五个 或通过周环或C-N交叉偶联反应的六元N-近地循环。通过确定 无电氮催化中间体可以从硝基群中访问，而不论其类型Jair 将展示我们构建新颖和生物活性N-核时环的工具的普遍性。帮助杰尔实现 他获得博士学位的目标在美国制药行业的职位，他的研究培训将由 维持个人发展计划，并进行旨在提高他口头技能的活动 以及书面交流以及科学合作，领导和团队合作。杰尔将被给予 参加职业发展研讨会并培养潜水专业网络的机会 支持他的野心。