Three-Component Synthesis of Perfluoroalkyl- or Perfluoroaryl-Substituted 4-Hydroxypyridine Derivatives and Their Palladium-Catalyzed Coupling Reactions
Three-Component Synthesis of Perfluoroalkyl- or Perfluoroaryl-Substituted 4-Hydroxypyridine Derivatives and Their Palladium-Catalyzed Coupling Reactions
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DOI：
10.1021/jo9022183
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发表时间：
2010-02-05
影响因子：
3.6
通讯作者：
Reissig, Hans-Ulrich
中科院分区：
文献类型：
--
作者：
Lechel, Tilman;Dash, Jyotirmayee;Reissig, Hans-Ulrich
以锂化的烷氧基丙二烯、腈和全氟羧酸为前体，通过三组分反应合成了一系列全氟烷基或全氟芳基取代的4-羟基吡啶衍生物。将这些化合物转化为4-吡啶基九氟丁磺酸酯，其可用作使用钯催化偶联合成π-共轭化合物的通用结构单元。在吡啶环的C-4和C-3处的Suzuki反应以中等至高的产率进行。此外，还研究了Suzuki-miyaura，Stille，Buchwald-Hartwig偶联反应，得到了相应的高取代吡啶衍生物。从芳基化的炔丙基醚开始的三组分反应导致五取代的4-羟基吡啶衍生物，其也可以在吡啶核的C-4和C-3处用于钯催化过程。用这种简单的方法可以制备空间高度拥挤的3，4，5-三苯基取代的吡啶衍生物37 a，并通过X射线分析进行研究。以乙腈为前体，当该组分过量使用时，发现不同的反应途径，从而产生具有新取代模式的吡啶衍生物。总之，本文所述的方法允许灵活且相当有效地进入各种带有全氟化烷基或芳基的高度取代的吡啶衍生物。
A three-component reaction with lithiated alkoxyallenes, nitriles, and perfluorinated carboxylic acids as precursors led to a series of perfluoroalkyl- or perfluoroaryl-substituted 4-hydroxypyridine derivatives. These Compounds were converted into 4-pyridyl nonaflates which can be employed as versatile building blocks for the synthesis of pi-conjugated compounds with use of palladium-catalyzed couplings. Suzuki reactions at C-4 and C-3 of the pyridine ring proceeded with moderate to high yields. In addition, Suzuki-miyaura, Stille, or Buchwald-Hartwig coupling reactions have also been studied and afforded the corresponding highly substituted pyridine derivatives. Starting from an arylated propargylic ether the three-component reaction led to a pentasubstituted 4-hydroxypyridine derivative that could also be employed in palladium-catalyzed processes at C-4 and at C-3 of the pyridine core. With this simple approach the sterically highly crowded 3,4,5-triphenyl-substituted pyridine derivative 37a could be prepared and studied by an X-ray analysis. With acetonitrile as precursor a different reaction pathway was found when this component was used in excess resulting in a pyridine derivative with a new substitution pattern. In summary, the methods described here allow a flexible and fairly efficient entry to a variety of highly substituted pyridine derivatives bearing perfluorinated alkyl or aryl groups.