基于碳氟键和碳氢键活化的碳碳偶联反应

It is of great significance to activate and functionalize carbon-fluorine bond for the construction of novel useful (or fluorine-containing) compounds. The carbon-hydrogen is the most simple and basic chemical bond in organic compounds. The activation and controlled transformation of the carbon-hydrogen have been extensively researched. Base on our previous research on the activation of C-F bond - - - - hydrodefluorination and functionalization, and utilizing the results and experience of the activation of C-H in aromatic ring or heterocyclic ring which were obtained by other researchers, in this project, we focuses on the more significant and difficult studies on the activation of C-F bond and C-H bond simultaneously in the same reaction (catalytic) system to realize the cross-coupling between carbon-carbon atom. We try to use palladium, nickel or ruthenium, which are usually used to activate C-F or C-H bond in literatures, as catalyst. The several novel highly efficient and practical metal catalytic systems will be obtained via the selectivity of suitable solvents, additives, ligands and oxidants. And subsequently, by using those novel catalytic systems, different type C-F bonds such as C-F bonds in electron-rich arenes, polyfluoroarenes, directing group-bearing arenes will be reacted with the C-H bond in the directing group bearing arenes to undergo carbon-carbon cross-coupling reactions. Finally, several series of novel diversity of structural (or fluorine-containing) compounds will be efficiently constructed via the new strategy. The common of point of the concurrent C-F/C-H activation will be studied and the new research area and application of the activation and functionaliztion of inert chemical bonds will be promoted by the implement this project.

将碳氟键活化并进一步官能团化对于构建结构新颖的、功能化的含(氟)小分子具有重要的意义。碳氢键作为有机化合物中最简单、最基本的化学键，其活化已得到广泛的研究。本项目在我们前期碳氟键的活化- - -碳氢化和官能团化的研究工作基础上，借鉴国内外在芳(杂)环上碳氢键活化已取得的成果，拟开展难度较大、应用前景更广的在同一个催化反应体系中活化/断裂碳氟键和碳氢键的研究,实现碳碳偶联反应。金属盐催化剂拟采用常用于能活化碳氟键或碳氢键的钯、镍或钌类催化剂，通过选择配体、碱、氧化剂和溶剂，筛选出各种高效的在金属盐催化下的反应体系，将不同类型的碳氟键(如富电子芳烃的碳氟键、多氟芳烃的碳氟键、含有诱导基团芳烃的碳氟键活化，并与含导向基团的芳(杂)环上碳氢键发生偶联反应，以构建结构新颖的功能化的(含氟)小分子。通过本项目实施，为碳氟键和碳氢键在同一体系活化探索共同点，为惰性化学键活化增加新的研究内容并扩大其应用范围。

本项目以当前研究热点碳氟键活化或断裂为研究对象，开展了多氟芳烃以及偕二氟烯烃的碳氟键在不同反应条件下与不同的碳氢键的各种官能团化反应的研究。同时，也开展了其它与含氟化合物相关的新方法和新反应的研究。取得主要研究成果包括以下几个方面：1. 氟代物的碳氟键与不同的sp3、sp2以及sp杂化的碳氢键的偶联反应：(1) 铜催化偕二氟烯烃与活泼亚甲基环化反应合成多取代呋喃；(2) LDA介导的室温下以芳基氟与二芳基甲烷反应合成三芳基甲烷；(3) 碱促进的无金属催化的偕二氟烯烃与杂环的碳氢键直接偶联的反应；(4) HMPA促进的用芳基氟芳基化茚来合成3-芳基茚；(5) 用三氟甲基苯乙烯直接对二芳基甲烷的C(sp3)−H进行二氟烯丙基化；(6) 三氟甲基苯乙烯与末端炔反应合成二氟甲基烯炔；(7) HMPA-促进以Prakash试剂将二、三芳基甲烷进行硅二氟甲基化；(8) LDA-介导的用芳基氟与芳基乙腈合成邻位氰基化的二芳基甲烷；(9) 以偕二氟烯烃与羰基硫酰胺成环反应合成N,N-二取代2-氨基噻吩；(10) 由偕二氟烯烃与末端炔合成-氟烯炔。2. 氟代物的碳氟键与格氏试剂或芳基硼酸的反应：(11) 铜或镍催化的立体选择性用叔、仲、伯格氏试剂烷基化单氟烯烃；(12) 立体控制的铜催化或无金属催化的偕二氟烯烃与叔、仲、伯格氏试剂的偶联反应；(13) 钯或镍催化偕二氟烯烃或单氟烯烃与格氏试剂的Kumada交叉偶联反应；(14) 镍催化的Suzuki类型的2,2-二氟烯基苯与苯硼酸的交叉偶联反应；(15) 经由镍催化Kumada类型的偕二氟烯烃与双格氏试剂的偶联反应合成环外三取代烯烃。3. 偕二氟烯烃参与的其它新反应：(16) 以苄基为氰基化试剂温和的无铜参与的立体选择性氰基化偕二氟烯烃；(17) 铜催化的以B2pin2立体选择性硼化偕二氟烯烃；(18) 以N,N-二甲基甲酰胺、伯胺和仲胺直接胺化-水解偕二氟烯烃；(19) 由偕二氟烯烃和吡唑啉酮(硫酮)反应合成氟烯基吡唑(硫)醚；(20) 由偕二氟烯烃与芳基硼酸、氧气三组分合成氟烯基芳基醚；(21) 近期偕二氟烯烃的合成和碳氟键官能团化的研究进展。通过对这些新反应的研究，进一步理解碳氟键的本质及其活化的关键问题；推动了碳氟键活化理论和方法研究及应用。项目实施期间，以项目负责人为通讯作者共发表相关SCI论文33篇。