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的普遍存在性质，可改善人类的生活质量和健康， 人类继续激发新技术的发展，以简化对这些支架的访问， 提供了一个肥沃的土壤，使科学家的培训，以实现他们的专业愿望。我们的研究 该计划已量身定制，为伊利诺伊大学芝加哥分校的多元化学生提供机会 通过解决有机合成方面的差距，激励，教导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， 由芳基叠氮化物、硝基芳烃或未活化的苯胺原位产生的亲电N-芳基氮物质。 在GM 138388中，我们利用对这些N-芳基氮反应性中间体的了解，开发了 产生C-NHAr键的新转化。为了实现这一目标，在目标1中，我们将开发新的Fe（II）- 催化的还原级联反应，其在分子内或分子间构建sp3-C-NHAr键 硝基芳烃使用硅烷还原剂;在目标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，用于合成N- 在目标3中，我们将开发获得亲电N-芳基的氧化方法， 从苯胺类nitrenoids和适用于分子内和分子间的N-杂环的合成。在这种多样性中 Jair N的补充请求。鲍威尔，我们要求资金支持他的研究培训和职业发展。 Jair将开发新的地球丰富的金属催化还原方法，将硝基烯烃转化为N- 通过利用亚硝基烯烃的反应性参与亚硝基-烯或C-N交叉偶联， 反应.他的项目将利用GM 138388的具体目标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。通过确定， 亲电氮催化中间体可以从硝基获得，而不管它们的类型，Jair 将展示我们的工具，以构建新的和生物活性的N-杂环的一般性。帮助杰尔实现 他获得博士学位的目标在美国制药行业的地位，他的研究培训将指导 保持个人发展计划，并通过旨在提高语言技能的活动来支持 书面交流，科学合作，领导力和团队合作。杰尔将被赐予 有机会参加职业发展讲习班，并培养多样化的专业网络， 支持他的野心。