Photocatalytic Radical Polar Crossover for C-H, C-O, and C-C Functionalization

用于 C-H、C-O 和 C-C 官能化的光催化自由基极性交叉

• 批准号: 2349315
• 负责人: Abigail Doyle
• 金额: $ 57.5万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2349315&HistoricalAwards=false
• 关键词: Photocatalytic; Radical; Polar; Crossover; Functionalization

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Abigail G. Doyle at the University of California, Los Angeles (UCLA) is studying chemical reactions that use visible light as an energy source to transform readily available starting materials to more valuable products of potential utility in medicinal, agrochemical and polymer chemistry. Because most organic molecules do not absorb visible light, a catalyst is necessary. In this project, the Doyle team is designing visible light-absorbing catalysts that enable us to access versatile, high energy intermediates known as carbocations and carbanions. Previously, these intermediates were only accessible using harsh reaction conditions, such as at high temperatures and/or corrosive reagents. The use of such conditions makes it challenging to incorporate sensitive functional groups into the precursors, thus limiting the molecules that can be used in the chemistry. In contrast, the Doyle group’s approach to these intermediates allows for access to and manipulation of more highly functionalized and sensitive precursors. To best explore this science, Professor Doyle and her team are integrating modern data science techniques into the workflow for catalyst design, reaction optimization, and advancing scientific understanding. As such, this project is providing a diverse group of chemistry Ph.D. students and undergraduates with the interdisciplinary training and broadened skill sets that are becoming increasingly necessary to contribute to the STEM (science, technology, engineering, and mathematics) workforce. Dr. Doyle and her coworkers engage in an extensive range of educational and outreach activities, including co-writing monthly “diversity highlights” for UCLA chemistry’s weekly departmental newsletter, delivering educational chemistry table demos through StemPrep for local elementary school students who belong to groups underrepresented in STEM, and partnering with local community colleges to host summer Research Experiences for Undergraduates (REU) students.Under this award, the team led by Professor Abigail G. Doyle at UCLA is developing synthetic reactions that access high-energy, polar reactive intermediates using visible-light and photocatalysts. Carbocations and carbanions are valuable reactive intermediates for a broad range of synthetic strategies. However, the generation of these intermediates typically requires strong acid or base, strong oxidants or reductants, or high temperatures, only affords access to stabilized intermediates, and/or requires the use of precursors that are prepared in multiple synthetic steps from feedstock chemicals. These restrictions preclude the application of carbocations or carbanions in late stage synthesis and limit the ability to access a number of desirable but relatively sensitive motifs. This program is addressing these challenges by using photocatalytic radical-polar crossover to access carbocations or carbanions under mild and selective conditions from abundant and stable C(sp3)–H, carboxylic acid and alcohol precursors. The Doyle team is developing a mechanistically novel desaturation reaction that features complementary site selectivity, enantioselective C(sp3)–H oxidation reactions using a data-science guided catalyst discovery and optimization workflow, a platform for the synthesis of esters by chemoselective cross-coupling of two carboxylic acids, and a catalytic direct deoxygenative alkylation reaction of alcohols. These strategies will be vetted in the context of the synthesis of functional molecules of potential utility in medicinal, agrochemical and polymer chemistry. Moreover, these studies aim to uncover mechanistic understanding that will advance fundamental knowledge of visible-light promoted chemical reactions and the application of data science tools in catalysis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学系化学合成项目的支持下，加州大学洛杉矶分校 (UCLA) 的 Abigail G. Doyle 教授正在研究使用可见光作为能源的化学反应，将现成的起始材料转化为更多的化学反应。由于大多数有机分子不吸收可见光，因此在该项目中需要催化剂，Doyle 团队正在设计可吸收可见光的催化剂，使我们能够获得多功能、高效的产品。活力以前，这些中间体只能在恶劣的反应条件下获得，例如在高温和/或腐蚀性试剂下，因此将敏感的官能团掺入前体中具有挑战性。相比之下，Doyle 小组对这些中间体的方法允许获取和操纵功能更高、更敏感的前体，为了更好地探索这门科学，Doyle 教授和她的团队正在整合现代数据科学。因此，该项目为不同的化学博士生和本科生提供了跨学科培训和拓宽的技能组合，这些技能对于做出贡献越来越必要。 Doyle 博士和她的同事参与了广泛的教育和外展活动，包括为加州大学洛杉矶分校化学系的每周部门新闻通讯撰写每月“多样性亮点”，提供教育信息。化学表演示通过为属于 STEM 中代表性不足群体的当地小学生提供 StemPrep，并与当地社区学院合作，为本科生 (REU) 学生举办暑期研究体验活动。在该奖项下，加州大学洛杉矶分校 (UCLA) 的 Abigail G. Doyle 教授领导的团队进行了合成反应使用可见光和光催化剂获得高能反应性极性中间体是用于多种合成策略的有价值的反应性中间体。需要强酸或碱、强氧化剂或还原剂或高温，只能获得稳定的中间体，和/或需要使用由原料化学品在多个合成步骤中制备的前体。这些限制排除了碳阳离子或碳负离子的应用。该项目正在通过使用光催化自由基-极性交叉在温和和选择性条件下获取配位或碳负离子来解决这些挑战。 Doyle 团队正在开发一种机制新颖的去饱和反应，该反应采用数据科学引导的催化剂发现和互补位点选择性、对映选择性 C(sp3)-H 氧化反应。优化工作流程，通过两种羧酸的化学选择性交叉偶联合成酯的平台，以及醇的催化直接脱氧烷基化反应。此外，这些研究旨在揭示机械理解，从而推进可见光促进的化学反应和数据应用的基础知识。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。