过渡金属催化芳香化合物的氟化反应研究

项目名称： 过渡金属催化芳香化合物的氟化反应研究

项目编号： No.21472219

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 刘国生

作者单位： 中国科学院上海有机化学研究所

项目金额： 100万元

中文摘要： 含氟芳烃是农药、医药和材料领域中非常重要的结构单元，需求日益增加，因此氟代芳香化合物的合成一直是有机合成中非常重要的研究方向。然而有效的合成方法非常有限；发展高效的氟化方法显得非常迫切。本申请就是基于这种现状，基于本课题组前期有关过渡金属催化不饱和烃的氟化反应的研究基础，拟利用过渡金属剂，对芳香化合物的直接氟化展开研究。我们首先利用金属钯、银及廉价金属铜等金属络合物，结合一些配体（如膦配体，双氮配体及卡宾配体等），对卤代芳烃及其类似物的直接氟化转开研究，探索金属活化这些芳烃化合物的活化模式，了解金属氟化物的形成及其规律，发展碳氟键形成的新模式，实现氟代芳烃的高效合成，为一些含氟化合物的合成提供新的思路。

中文关键词： 过渡金属；催化；氟化；氟代芳烃；铜催化

英文摘要： Widespread application of aryl fluorides in pharmaceuticals, agrichemicals, medical diagnosis (positron emission tomography, PET) and material science have provoked general interests in the methodological development for the construction of aryl C-F bonds. Traditional production of aryl fluorides basically relay on two protocols: (1) the Baltz-Schiemman reactions which suffered from harsh acidic condition and (2) Halex process which limited to the electron-deficient aryl substrates. Quite recent, a important breakthrough on transition-mediated fluorination of functionalized aryl reagents have been reported. For examples, Buchwald uncovered the first Pd-catalyzed fluorination of aryl triflate by using steric bulky monophosphine ligands (t-BuBrettPhos) to promote the reductive elimination. However, some limitation was existed in the current transformation, such as substrate limitation in expensive aryl triflate, and small amount of isomers. Thus, exploration of new catalyst system for the efficient synthesis of aryl fluoride is very urgent and important. In the last several years, our group research focused on the transition metal-catalyzed fluorination of unsaturated multi-bonds. And we have developed several catalytic systems, such as palladium, silver and copper catalyst, to achieve fluorination of alkenes, allenes, and alkynes. Based on these results, we'd like to survey the possible of direct fluorination of aromatic compounds. Early studies demonstrated that copper catalyst could applied to conduct fluorination of aryl bromide in the presence of orth-pyridyl group. In this application, the further mechanistic study will be conducted to illustrate the detailed transformation, and explore new efficient catalytic system, we hope, which could be used to catalyze the fluorination of normal aryl bromides, even for aryl chlorides. In addition, investigation of fluorine source is also a key issue, and the inexpensive inorganic fluoride, such as NaF, KF, could be ideal.

英文关键词： Transition Metal;Catalyzed;Fluorination;Aryl Fluoride;Copper catalyzed