SusChEM: Mechanism and Discovery of Metal-Catalyzed Fluoroalkylation Reactions

SusChEM：金属催化氟烷基化反应的机理和发现

• 批准号: 1565886
• 负责人: John Hartwig
• 金额: $ 68万
• 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: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1565886&HistoricalAwards=false
• 关键词: SusChEM; Mechanism; Discovery; Metal; Catalyzed

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. In this program, Professor Hartwig is developing a mechanistic understanding of catalytic reactions that use transition metal complexes bonded to fluorine-containing alkyl groups. These studies answer a series of questions about the impact of fluorine atoms on the metal-bound carbon atom. The studies also assess several approaches to control the reactivity of these fluoroalkyl complexes of transition metals. By developing methods to control the reactivity of fluoroalkyl complexes, this research enables the development of new catalytic reactions that add fluoroalkyl groups into organic molecules. Organic molecules containing fluorine are vital to materials, agricultural, and medicinal sciences. For example, over 20% of new pharmaceuticals and 25% of licensed herbicides contain fluorine. The project is well suited for providing a broad education to Ph.D. scientists and undergraduates, including those of underrepresented groups. A series of outreach activities for K-12 students, the general public, and the general scientific community are part of Professor Hartwig's efforts resulting from the research program.Although a large fraction of pharmaceuticals and agrochemicals contain fluorine, fluorinated structures are largely limited to those derived from simple fluoroarenes, trifluoromethylarenes or trifluoroacetates. Many of the potential methods to synthesize more diverse structures containing fluoroalkyl groups require new approaches to induce and control the reactivity of fluoroalkyl transition-metal complexes in catalytic reactions. This research creates these capabilities by demonstrating, by a combination of kinetic analysis of catalytic reactions and synthesis of catalytic intermediates, how to induce productive reactivity in fluoroalkyl complexes of palladium. This project also creates new catalytic reactions that couple partially fluorinated alkyl groups to aromatic and heteroaromatic molecules to form products that are difficult to access by current synthetic methods. With this information, fluoroalkylation reactions that are currently stoichiometric are being made catalytic. Additionally, new reactions of aryl halides that form fluoroalkylarenes with novel structures that are difficult to prepare by alternative methods are being created. This research enables the preparation of new classes of fluorinated molecules for materials science, medicinal chemistry, and agroscience. As part of the educational plan, Professor Hartwig teaches short-courses for those lacking formal training in organometallic catalysis, co-authors a sophomore organic text that includes content on catalysis in medicinal and green organic chemistry, and delivers lectures to general audiences, predominantly in forums in which he reaches potential scientists from underrepresented groups.

化学部化学催化项目支持加州大学伯克利分校化学系 John F. Hartwig 教授的项目。在该项目中，Hartwig 教授正在对使用与含氟烷基键合的过渡金属配合物进行催化反应的机理进行理解。这些研究回答了一系列有关氟原子对金属结合碳原子影响的问题。 这些研究还评估了控制这些过渡金属氟烷基配合物反应性的几种方法。通过开发控制氟烷基配合物反应性的方法，这项研究能够开发将氟烷基添加到有机分子中的新催化反应。含氟有机分子对于材料、农业和医学科学至关重要。例如，超过 20% 的新药品和 25% 的许可除草剂含有氟。该项目非常适合为博士提供广泛的教育。科学家和本科生，包括代表性不足的群体。为 K-12 学生、公众和一般科学界开展的一系列外展活动是 Hartwig 教授在该研究项目中所做努力的一部分。尽管大部分药物和农用化学品都含有氟，但氟化结构很大程度上仅限于这些衍生自简单的氟代芳烃、三氟甲基芳烃或三氟乙酸酯。许多合成含有氟烷基的更多样化结构的潜在方法需要新的方法来诱导和控制催化反应中氟烷基过渡金属配合物的反应性。这项研究通过结合催化反应动力学分析和催化中间体合成，展示了如何诱导钯氟烷基配合物的生产反应性，从而创造了这些能力。 该项目还创造了新的催化反应，将部分氟化的烷基与芳香族和杂芳香族分子偶联，形成目前合成方法难以获得的产物。有了这些信息，目前化学计量的氟烷基化反应正在被催化。 此外，正在创建新的芳基卤化物反应，形成具有新结构的氟代烷基芳烃，而这些新结构难以通过替代方法制备。这项研究能够为材料科学、药物化学和农业科学制备新型氟化分子。作为教育计划的一部分，哈特维格教授为那些缺乏有机金属催化方面正规培训的人讲授短期课程，与人合着了一本大二有机课本，其中包括医药和绿色有机化学中的催化内容，并向普通观众提供讲座，主要是在他通过论坛接触来自代表性不足群体的潜在科学家。