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: 2350331
• 负责人: John Hartwig
• 金额: $ 80万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2350331&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. 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.

化学部的化学催化计划支持加利福尼亚大学伯克利分校化学系教授约翰·F·哈特维格（John F. Hartwig）教授。在该计划中，Harartwig教授正在发展并寻求理解由催化剂引发和控制的反应（催化剂是化学添加剂，可以通过过渡金属络合物有助于反应发生或更快地进行反应，最终导致键形成碳原子含氟的碳原子。这些研究很重要，因为含有氟的有机分子对于材料，农业和医学科学至关重要。例如，超过30％的新药物和25％的含有氟的许可除草剂。拟议的研究将回答有关氟原子对金属结合碳原子的影响的一系列问题，并将评估多种方法，以诱导和控制过渡金属的这些氟烷基复合物的反应性，从而发现新的催化反应，从而将含氟的碳原子安装到有机分子中。 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 organic catalytic catalysis, the PI will continue extensive mentality of undergraduate students from Berkeley and from outside Institutions who are seeking postgraduate degrees, and the PI will present sewers on catalysis to general audiences, predominantly in他在其中取得了代表性不足的群体的潜在科学家的论坛。尽管大部分的药物和含有氟分子的药物，但在很大程度上仅限于源自简单的氟苯乙烯，三氟甲基苯甲酸苯甲酸苯甲酸或美度氟乙醇的简单含量。合成更多潜水氟烷基结构的方法需要新的方法，包括旨在诱导和控制催化反应中氟烷基过渡金属复合物反应性的新方法。拟议的研究试图通过使用钯，镍和虹膜络合物发现和开发新的氟接亲核和电力的偶联来满足这一需求。其中包括氟接亲核者和电力的对映选择性耦合以及有望揭示氟烷基化中间体结构和反应性的差异的研究。在进行这些基本研究的同时，Hartwig组将针对合成利用过渡金属催化量的氟烷基化反应的几个重要挑战，在含氟的立体生成中心对构型的控制以及芳基卤化反应的发展以及导致新型氟烷基烯丙烯烯的新反应的发展。这是这项研究将影响在材料科学，药物化学和农业科学中很重要的分子的综合。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子和更广泛的影响评估标准来评估，被认为是宝贵的支持。