Mechanism and Discovery of Metal-Catalyzed Fluoroalkylation Reactions

金属催化氟烷基化反应的机理和发现

• 批准号: 1955635
• 负责人: John Hartwig
• 金额: $ 71万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955635&HistoricalAwards=false
• 关键词: Mechanism; Discovery; Metal; Catalyzed; Fluoroalkylation

The Chemical Catalysis Program of the Chemistry Division supports the project by Professor John F. Hartwig in the Department of Chemistry at the University of California, Berkeley to improve catalytic processes that form organic molecules containing fluorine atoms. These studies are important because fluorinated organic molecules are vital to material, agricultural, and medicinal sciences. For example, over 30% of new pharmaceuticals and 25% of licensed herbicides contain fluorine. This project answers a series of questions to understand how these catalytic systems work. This knowledge is then being used to design solutions to overcome catalytic bottlenecks that will increase the availability of fluorinated organic molecules. The program also includes outreach activities for K-12 students on chemical catalysis topics, short training courses for the chemical workforce, and presentations to general audiences to reach future scientists from underrepresented groups.Although a large fraction of pharmaceuticals and agrochemicals contain fluorine, available fluorinated molecules are largely limited to those derived from simple fluoroarenes, trifluoromethylarenes, or trifluoroacetates. In order to reliably synthesize molecules with fluoroalkyl groups, new ways to induce and control the reactivity of fluoroalkyl transition-metal complexes in catalytic processes are needed. These studies are improving catalytic capabilities for forming fluorinated organic compounds by preparing fluoroalkyl complexes of palladium and fluoroallylic complexes of iridium and determining the factors that promote carbon-carbon bond formation with these intermediates. This fundamental work is revealing how to turnover catalytic processes involving these transition metal intermediates to advance the synthesis of fluorinated organic molecules. In addition, these studies are determining how to control the formation of stereogenic centers and how to tolerate a larger array of functional groups. This project is impacting the catalytic synthesis of molecules that are important in materials science, medicinal chemistry, and agroscience. Simultaneously, this program is providing training for a diverse group of graduate and undergraduate students, as well as outreach activities to K-12 students to motivate the next generation of scientists.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.

化学部的化学催化计划支持加州大学伯克利分校化学系约翰·F·哈特威格教授的项目，该项目旨在改善形成含有氟原子的有机分子的催化过程。这些研究很重要，因为氟化有机分子对材料、农业和医药科学至关重要。例如，超过30%的新药和25%的特许除草剂含有氟。这个项目回答了一系列问题，以了解这些催化系统是如何工作的。然后，这些知识被用来设计解决方案，以克服催化瓶颈，从而增加氟化有机分子的可用性。该计划还包括针对K-12学生的化学催化主题的推广活动，为化学工作者举办的短期培训课程，以及向普通观众介绍来自代表性不足群体的未来科学家。尽管很大一部分药品和农用化学品含有氟，但可用的氟化分子主要限于从简单的氟芳烃、三氟甲基芳烃或三氟乙酸酯中衍生出来的分子。为了可靠地合成含氟烷基的分子，需要新的方法来诱导和控制氟烷基过渡金属络合物在催化过程中的反应活性。这些研究正在通过制备含氟烷基的钯配合物和含氟烯丙基的Ir络合物，并确定促进这些中间体形成碳-碳键的因素，来提高形成含氟有机化合物的催化能力。这项基础性工作揭示了如何利用这些过渡金属中间体的催化过程来促进含氟有机分子的合成。此外，这些研究正在确定如何控制立体生成中心的形成，以及如何容忍更大数量的官能团。该项目正在影响材料科学、药物化学和农业科学中重要的分子的催化合成。同时，该计划正在为不同的研究生和本科生群体提供培训，以及面向K-12学生的外联活动，以激励下一代科学家。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

gem-Difluoroallylation of Aryl Halides and Pseudo Halides with Difluoroallylboron Reagents in High Regioselectivity

高区域选择性二氟烯丙基硼试剂对芳基卤化物和拟卤化物进行偕二氟烯丙基化

• DOI: 10.1002/anie.202111476
• 发表时间: 2021
• 期刊: Angewandte Chemie
• 作者: Sakamoto, Shu;Butcher, Trevor W.;Yang, Jonathan L.;Hartwig, John F.
• 通讯作者: Hartwig, John F.