Mechanism and Discovery of Metal-Catalyzed Fluoroalkylation Reactions

化学系的化学催化项目支持约翰·F·史密斯教授的项目。哈特维希在加州大学伯克利分校化学系。Hartwig正在开发和寻求理解由催化剂（催化剂是化学添加剂，有助于反应发生或更快地进行）通过过渡金属络合物引发和控制的反应，最终导致形成与碳原子的键含氟。这些研究很重要，因为含氟有机分子对材料、农业和医学科学至关重要。例如，超过30%的新药和25%的许可除草剂含有氟。拟议的研究将回答一系列关于氟原子对金属结合碳原子的影响的问题，并将评估诱导和控制这些过渡金属氟烷基络合物反应性的几种方法，从而能够发现将含氟碳原子安装到有机分子中的新催化反应。作为教育计划的一部分，PI的研究团队将访问K-12教室，介绍催化课程，PI将为那些缺乏有机金属催化正规培训的人教授短期课程，PI将继续为伯克利和外部机构的本科生提供广泛的指导谁正在寻求研究生学位，PI将向普通观众介绍催化研讨会，尽管大部分药物和农用化学品都含有氟，但氟化分子主要限于由简单的氟代芳烃、三氟甲基芳烃或三氟乙酸酯衍生的那些。合成更多样化的氟烷基结构的方法需要新的方法，包括旨在诱导和控制氟烷基过渡金属络合物在催化反应中的反应性的新方法。拟议的研究旨在通过发现和开发使用钯，镍和铱的络合物的氟化亲核试剂和亲电试剂的新偶联来解决这一要求。包括氟化亲核试剂和亲电子试剂的对映选择性偶联，以及有望揭示氟代烯丙基中间体结构和反应性差异的研究。在进行这些基础研究的同时，Hartwig小组将解决氟化分子目标合成的几个重要挑战，包括利用催化量的过渡金属的氟烷基化反应的开发，含氟立体中心的构型控制，以及导致新型氟烷基芳烃的芳基卤化物的新反应的开发。因此，该研究将影响在材料科学、药物化学和农业科学中具有重要意义的分子的合成。该奖项反映了NSF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。

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, Prof. Hartwig is developing and seeking to understand reactions that are initiated and controlled by catalysts (catalysts are chemical additives that help a reaction to occur or to proceed more rapidly) through transition-metal complexes that ultimately result in the formation of bonds to carbon atoms bearing fluorine. These studies are important because organic molecules containing fluorine are vital to materials, agricultural, and medicinal sciences. For example, over 30% of new pharmaceuticals and 25% of licensed herbicides contain fluorine. The proposed research will answer a series of questions about the impact of fluorine atoms on the metal-bound carbon atom and will assess several approaches to induce and control the reactivity of these fluoroalkyl complexes of transition metals, thereby enabling the discovery of new catalytic reactions that install fluorine-bearing carbon atoms into organic molecules. As part of the educational plan, the PI’s research team will visit K-12 classrooms to present lessons on catalysis, the PI will teach short-courses for those lacking formal training in organometallic catalysis, the PI will continue extensive mentorship of undergraduate students from Berkeley and from outside institutions who are seeking postgraduate degrees, and the PI will present seminars on catalysis to general audiences, predominantly in forums in which he reaches potential scientists of underrepresented groups.Although a large fraction of pharmaceuticals and agrochemicals contain fluorine, fluorinated molecules are largely limited to those derived from simple fluoroarenes, trifluoromethylarenes or trifluoroacetates. Methods to synthesize more diverse fluoroalkyl structures require new approaches including new methods aimed at inducing and controlling the reactivity of fluoroalkyl transition-metal complexes in catalytic reactions. The proposed research seeks to address this requirement by discovering and developing new couplings of fluorinated nucleophiles and electrophiles using complexes of palladium, nickel, and iridium. Included are enantioselective couplings of fluorinated nucleophiles and electrophiles and studies that promise to reveal the differences in structures and reactivities of fluoroallyl intermediates. While carrying out these fundamental studies, the Hartwig group will address several important challenges for the synthesis of fluorinated molecular targets including the development of fluoroalkylation reactions that utilize catalytic quantities of transition metals, the control of the configuration at fluorine-containing stereogenic centers, and the development of new reactions of aryl halides that lead to novel fluoroalkylarenes. Thus, this research will impact the synthesis of molecules that are important in materials science, medicinal chemistry, and agroscience.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.