PdII-catalyzed monoselective ortho halogenation of C-H bonds assisted by counter cations:: A complementary method to directed ortho lithiation
PdII-catalyzed monoselective ortho halogenation of C-H bonds assisted by counter cations:: A complementary method to directed ortho lithiation
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DOI：
10.1002/anie.200705613
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Yu, Jin-Quan
中科院分区：
文献类型：
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作者：
Mei, Tian-Sheng;Giri, Ramesh;Yu, Jin-Quan
过渡金属催化的失活C-H键转化为C-杂原子和C-C键，通过将C-H活化作为一种战略反应，在许多全合成中得到了广泛的应用。[1，2]最近，钯催化的C-H活化反应在底物范围和实用性方面取得了进展。[3，4]然而，两大障碍阻碍了C-H官能化反应的广泛合成应用。首先，从合成效用和原子经济性的角度来看，对底物中含氮的导向基团的需要施加了基本的限制。第二，缺乏能够调节反应活性的外部试剂，特别是区域、立体和化学选择性。这些试剂是广泛使用的Pd0催化偶联反应成功的关键。在此，我们报道了四烷基铵阳离子有效地促进了C-H活化和提高了芳基羧酸的邻位碘化的单选择性。以前已经报道了一些用于C-H键的邻位卤化的步骤。[5-7]最近还发展了一种非常有趣的无金属的芳烃与I(吡啶)2BF4的亲电碘化反应。[8]由于芳基羧酸的选择性邻位卤代反应在合成和药物化学中广泛应用，特别是对于制备要求很高的一类1，2，3-取代芳烃，我们决定测试我们之前报道的PdII催化的C/H活化/碘化[6b]是否可以扩展到芳烃羧酸。在这个碘化反应中，IOAc将芳基钯(II)氧化成PdIV物种[9]，该物种经过还原消除得到碘化产物。我们研究组的另一项研究表明，羧酸钠和羧酸钾是C-H活化的活性底物。因此，我们进行了邻甲苯甲酸(1)和邻甲苯甲酸钠的碘化反应
The transition-metal-catalyzed transformation of inactivated CĀH bonds into CĀheteroatom and CĀC bonds has found synthetic utility in a number of total syntheses through the use of CĀH activation as a strategic reaction.[1, 2] Recently, progress has been made in Pd-catalyzed CĀH activation reactions in terms of substrate scope and practicality.[3, 4] However, two major obstacles prevent the broad synthetic application of CĀH-functionalization reactions. First, the need for a nitrogen-containing directing group in the substrate imposes a fundamental limitation from the viewpoint of synthetic utility and atom economy. Second, external reagents capable of modulating the reactivity, especially the regio-, stereo-, and chemoselectivity, are lacking. Such reagents are key to the success of the widely used Pd0-catalyzed coupling reactions. Herein, we report that tetraalkyl ammonium cations are effective in promoting CĀH activation and enhancing the monoselectivity of the ortho iodination of aryl carboxylic acids.A number of procedures for the ortho halogenation of CĀH bonds have been reported previously.[5–7] A very interesting metal-free electrophilic iodination of arenes with I (pyridine) 2BF4 was also developed recently.[8] As the selective ortho halogenation of aryl carboxylic acids is broadly useful in synthesis and medicinal chemistry, particularly for the preparation of a demanding class of 1, 2, 3-substituted arenes, we decided to test whether our previously reported PdII-catalyzed CĀH activation/iodination [6b] could be extended to arene carboxylic acids. In this iodination reaction, IOAc oxidizes the aryl palladium (II) intermediate to a PdIV species,[9] which undergoes reductive elimination to give the iodinated products. Another study by our research group showed that sodium and potassium carboxylates are reactive substrates for CĀH activation.[10] Thus, we carried out iodination reactions of o-toluic acid (1) and sodium o-toluate