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

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教授正在研究化学反应，利用可见光作为能量源，将现成的起始材料转化为更有价值的产品，在医药、农业化学和聚合物化学中具有潜在的用途。因为大多数有机分子不吸收可见光，所以催化剂是必要的。在这个项目中，Doyle团队正在设计可见光吸收催化剂，使我们能够获得多用途的高能量中间体，即碳阳离子和碳离子。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。在这种条件下，将敏感官能团纳入前体是一项挑战，从而限制了化学中可使用的分子。相比之下，Doyle小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。为了更好地探索这门科学，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、反应优化和推进科学理解的工作流程中。因此，该项目为化学博士生和本科生提供了跨学科的培训和扩展的技能组合，这些技能对于STEM（科学、技术、工程和数学）劳动力的贡献越来越必要。多伊尔博士和她的同事参与了广泛的教育和推广活动，包括为加州大学洛杉矶分校化学每周部门通讯共同撰写每月“多样性亮点”，通过StemPrep为属于STEM中代表性不足的群体的当地小学生提供教育化学表演示，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。在该奖项下，UCLA的Abigail G. Doyle教授领导的团队正在开发利用可见光和光催化剂获取高能极性反应中间体的合成反应。碳正离子和碳正离子是有价值的反应中间体，用于广泛的合成策略。然而，这些中间体的生成通常需要强酸或强碱，强氧化剂或还原剂，或高温，只能提供稳定的中间体，和/或需要使用从原料化学品中经过多个合成步骤制备的前体。这些限制排除了碳正离子或碳离子在后期合成中的应用，并限制了获得一些理想但相对敏感的基序的能力。该项目通过光催化自由基-极性交叉，在温和和选择性的条件下，从丰富和稳定的C(sp3) -H、羧酸和醇前体中获得碳阳离子或碳离子，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，其特点是互补位点选择性，对映选择性C(sp3) -H氧化反应，使用数据科学指导的催化剂发现和优化工作流程，通过化学选择性交叉偶联两种羧酸合成酯的平台，以及催化直接脱氧烷基化反应醇。这些策略将在药物、农化和聚合物化学中潜在用途的功能分子合成的背景下进行审查。此外，这些研究旨在揭示机制理解，这将推进可见光促进化学反应的基础知识和数据科学工具在催化中的应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.