SusChEM: Mechanism and Discovery of Metal-Catalyzed Fluoroalkylation Reactions

化学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。在这个项目中，Hartwig教授正在对使用过渡金属配合物与含氟烷基键合的催化反应进行机理理解。这些研究回答了一系列关于氟原子对金属结合碳原子的影响的问题。这些研究还评估了几种控制这些过渡金属氟烷基配合物反应性的方法。通过开发控制氟烷基配合物反应性的方法，本研究使得在有机分子中添加氟烷基的新催化反应得以发展。含氟有机分子对材料、农业和医药科学至关重要。例如，超过20%的新药和25%的获批除草剂含有氟。该项目非常适合为博士、科学家和本科生提供广泛的教育，包括那些代表性不足的群体。针对K-12学生、公众和一般科学界的一系列推广活动是Hartwig教授在研究项目中努力的一部分。虽然很大一部分药品和农用化学品含有氟，但氟化结构主要限于由单氟芳烃、三氟甲基芳烃或三氟乙酸酯衍生的结构。许多潜在的合成含氟烷基结构的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。本研究通过结合催化反应的动力学分析和催化中间体的合成，展示了如何在钯的氟烷基配合物中诱导生产反应性，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，目前的化学计量的氟烷基化反应被催化。此外，芳基卤化物的新反应形成具有新结构的氟烷基芳烃，这种新结构很难用其他方法制备。这项研究为材料科学、药物化学和农业科学制备新型氟化分子提供了可能。作为教育计划的一部分，Hartwig教授为那些缺乏正式有机金属催化培训的人教授短期课程，与人合著了一本大二的有机教材，其中包括药用和绿色有机化学中的催化内容，并向普通听众发表演讲，主要是在论坛上，他接触到来自代表性不足的群体的潜在科学家。

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.