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

在化学系化学合成计划的支持下，加州大学洛杉矶分校(UCLA)的阿比盖尔·G·道尔教授正在研究利用可见光作为能源的化学反应，将现成的原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中间体，即碳正离子和碳负离子。以前，这些中间体只能在苛刻的反应条件下获得，例如在高温和/或腐蚀性试剂下。这些条件的使用使得将敏感官能团加入到前体中具有挑战性，从而限制了可以用于化学的分子。相比之下，多伊尔小组对这些中间体的研究方法允许获得和操纵更高功能化和更敏感的前体。为了更好地探索这门科学，Doyle教授和她的团队正在将现代数据科学技术整合到催化剂设计、反应优化和促进科学理解的工作流程中。因此，该项目正在为不同的化学博士生和本科生提供跨学科培训和更广泛的技能集，这些技能对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一系列广泛的教育和推广活动，包括为加州大学洛杉矶分校的每周院系通讯共同撰写每月的“多样性亮点”，通过StemPrep为属于STEM代表性不足群体的当地小学生提供教育化学表格演示，以及与当地社区大学合作为本科生举办暑期研究体验(REU)。在这个奖项下，加州大学洛杉矶分校的阿比盖尔·G·道尔教授领导的团队正在开发利用可见光和光催化剂访问高能、极性反应中间体的合成反应。碳正离子和碳负离子是一系列合成策略的有价值的活性中间体。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，只能获得稳定的中间体，和/或需要使用以原料化学品为原料的多个合成步骤制备的前体。这些限制排除了碳正离子或碳负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。该计划正在解决这些挑战，通过使用光催化自由基-极性交叉来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正离子或碳负离子。Doyle团队正在开发一种机械上新颖的减饱和反应，该反应具有互补的位置选择性，使用数据科学指导的催化剂发现和优化工作流程的对映选择性C(SP3)-H氧化反应，通过两个羧酸的化学选择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。这些策略将在合成在医药、农用化学和聚合物化学中具有潜在用途的功能分子的背景下进行审查。

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.