SusChEM: Copper-Catalyzed Radical Reactions of Nitroso Compounds for the Synthesis of Carbon-Nitrogen Bonds

SusChEM：铜催化亚硝基化合物的自由基反应合成碳氮键

• 批准号: 1566614
• 负责人: Javier Read de Alaniz
• 金额: $ 42万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1566614&HistoricalAwards=false
• 关键词: SusChEM; Copper; Catalyzed; Radical; Reactions

The Chemical Catalysis Program of the Chemistry Division supports the project by Professor Read de Alaniz. Professor Read de Alaniz is a faculty member in the Department of Chemistry at University of California Santa Barbara (UCSB). He is developing new strategies for the direct incorporation of nitrogen and oxygen atoms into structurally diverse molecules using earth abundant metals. The goal of this research is to develop a general and versatile strategy to expedite the discovery of therapeutic agents. The molecular diversity of nitrogen containing therapeutic agents and the strong influence nitrogen substituents have on both pharmacokinetics and pharmacodynamics mandates the development of new methodologies for installing these functional groups into small therapeutic organic molecules. In addition, the methodology has potential applications in material science, as well as for the construct of agrochemical compounds. The project is well suited for the education of scientists at all levels. The educational plan includes training of underrepresented groups in outstanding professional development and research training programs at UCSB's California NanoSystems Institute and Materials Research Lab (notably the RISE, SIMS, UC LEADS, CAMP, and MARC programs), as well as developing a new multi-layered mentoring program for graduate students. While the value of amines and the synthetic utility of radical reactions are well-established, exploration of the strategy for constructing carbon (C) - nitrogen (N) and C-oxygen (O) bonds by merging radical reactions with nitroso compounds is almost completely unknown. Through these studies, new opportunities in C-N bond-forming reactions that are mild, functional group tolerant, and use earth abundant copper are under development. These new transformations reduce the number of synthetic steps required to access nitrogen containing molecules that are otherwise difficult to prepare. The transformations also give chemists access to new synthetic bond disconnections. Specifically, the goals of the proposed work are: 1) extend the scope of the recently developed copper-catalyzed radical addition with nitroso compounds to include heterocycles, benzyl bromides and alpha-bromo nitriles; 2) develop the reaction with commercially available aryl and heteroaryltrifluoroborates using nitrite salts to generate the nitroso reagent in situ; 3) apply this strategy to the concise total synthesis of pyrroloindoline alkaloid natural products; 4) develop a new intramolecular radical based N-O transfer process that provides spatial control of the nitrogen and oxygen heteroatoms over a range of architectures. Professor Read de Alaniz's group is well positioned to provide the highest level of education and training for students underrepresented in science. Outreach activities involving a new multi-layered mentoring program are part of the project.

化学系的化学催化计划支持Read de Alaniz教授的项目。Read de Alaniz教授是加州大学圣巴巴拉分校（UCSB）化学系的教员。 他正在开发新的策略，利用地球上丰富的金属，将氮原子和氧原子直接结合到结构多样的分子中。本研究的目标是开发一种通用的策略，以加快治疗药物的发现。含氮治疗剂的分子多样性和氮取代基对药代动力学和药效学的强烈影响要求开发用于将这些官能团安装到小的治疗性有机分子中的新方法。此外，该方法在材料科学以及农用化合物的构建中具有潜在的应用。该项目非常适合各级科学家的教育。 该教育计划包括在UCSB的加州纳米系统研究所和材料研究实验室（特别是RISE，西姆斯，UC LEADS，CAMP和MARC计划）的优秀专业发展和研究培训计划中培训代表性不足的群体，以及为研究生开发新的多层指导计划。虽然胺的价值和自由基反应的合成效用是公认的，但通过将自由基反应与亚硝基化合物合并来构建碳（C）-氮（N）和C-氧（O）键的策略的探索几乎完全未知。通过这些研究，在C-N键形成反应的新的机会，是温和的，功能团宽容，并使用地球丰富的铜正在开发中。这些新的转化减少了获得含氮分子所需的合成步骤的数量，否则这些分子很难制备。 这种转变也使化学家们能够获得新的合成键断开。具体而言，本工作的目标是：1）将最近开发的铜催化的亚硝基化合物的自由基加成反应的范围扩展到包括杂环、苄基溴和α-溴代腈; 2）开发利用亚硝酸盐与市售芳基和杂芳基三氟硼酸酯的反应以原位生成亚硝基试剂; 3）将此策略应用于吡咯并吲哚啉生物碱天然产物的简明全合成; 4）开发一种新的基于分子内自由基的N-O转移过程，该过程提供了在一系列结构上的氮和氧杂原子的空间控制。Read de Alaniz教授的小组有能力为科学领域代表性不足的学生提供最高水平的教育和培训。涉及新的多层次指导方案的外联活动是该项目的一部分。

项目成果

Copper-Mediated Single-Electron Approach to Indoline Amination: Scope, Mechanism, and Total Synthesis of Asperazine A

• DOI: 10.1021/acs.joc.2c00923
• 发表时间: 2022-07-25
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: Shaum，James B.;Nikolaev，Andrei;de Alaniz，Javier Read
• 通讯作者: de Alaniz，Javier Read