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.

在化学合成计划的支持下，加利福尼亚大学（UCLA）的Abigail G. Doyle教授正在研究使用可见光作为能量来源的化学反应，以将易于使用的起始材料转化为更有价值的药用性产品，用于药用药用，治疗方法和聚合物化学。由于大多数有机分子没有吸收可见光，因此需要催化剂。在这个项目中，Doyle团队正在设计可见的光吸收催化剂，使我们能够访问多功能，高能量中间体，称为碳和碳酸化。以前，这些中间体仅使用有害反应条件（例如在高温和/或腐蚀性试剂下）才能进入。这种条件的使用使将敏感的官能团纳入前体是挑战，从而限制了可以在化学中使用的分子。相反，Doyle组对这些中间体的方法允许访问和操纵更高度功能化和敏感的前体。为了最好地探索这项科学，Doyle教授和她的团队正在将现代数据科学技术整合到催化剂设计，反应优化和发展科学理解的工作流程中。因此，该项目正在提供化学博士学位的潜水员群体。学生和本科生通过跨学科的培训和扩大技能集，这些技能越来越有助于为STEM（科学，技术，工程和数学）劳动力做出贡献。 Doyle博士和她的同事从事各种各样的教育和外展活动，包括为UCLA化学的每周一次的每周“多样性”共同撰写每月的“多样性”，通过STEMPREP为当地小学生提供教育化学表演，这些演示是在当地的小学生中属于当地社区研究员，并在本地社区中占有不足的群体，并在夏季研究员伙伴关系，并将其统治成果，并在本地社区的陪伴下，并将其居住在夏季的研究中，并依靠夏季研究员，并将其重新培训。 UCLA的Abigail G. Doyle教授正在开发合成反应，使用可见光和光催化剂访问高能，极性反应性中间体。对于广泛的合成策略，碳和碳是有价值的反应性中间体。但是，这些中间体的产生通常需要强酸或碱，强的氧化物或降低或高温，只能访问稳定的中间体，并且/或需要使用前体，这些前体从原料化学物质中以多个合成步骤制备。这些限制排除了在晚期合成中碳酸化或碳酸化的应用，并限制了访问许多理想但相对敏感的基序的能力。该程序通过使用光催化自由基偏移跨界剂来解决这些挑战，从而从丰富和稳定的C（SP3） - H，羧酸和酒精前体中获取碳化或碳化。 Doyle团队正在开发一种机械新颖的疾病反应，该反应具有完整的现场选择性，使用数据科学指导性的催化剂发现和优化工作流程，通过化学选择性催化剂的平台通过化学选择性交叉偶联到两种羧酸和催化性去毒性的酒精反应。这些策略将在综合药用，农业和聚合物化学中潜在效用的功能分子的背景下进行审查。此外，这些研究旨在揭示机械理解，以促进对可见光的促进化学反应的基本知识，并在催化中应用数据科学工具。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛的影响审查标准来评估来获得的支持。