Oxidative Biaryl Coupling of Thiophenes and Thiazoles with Arylboronic Acids through Palladium Catalysis: Otherwise Difficult C4-Selective C-H Arylation Enabled by Boronic Acids
Oxidative Biaryl Coupling of Thiophenes and Thiazoles with Arylboronic Acids through Palladium Catalysis: Otherwise Difficult C4-Selective C-H Arylation Enabled by Boronic Acids
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DOI：
10.1002/anie.201007060
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Itami, Kenichiro
中科院分区：
文献类型：
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作者：
Kirchberg, Sylvia;Tani, Satoshi;Itami, Kenichiro
带有芳基的杂芳烃（杂二芳基）通常存在于生物活性化合物、有机材料和药品中。近年来，由过渡金属配合物催化的杂芳烃直接CÀH芳基化[1,2]已成为一种替代已建立的pd催化交叉偶联反应的实用方法。尽管包括我们的团队在内的合成界做出了巨大的努力[3-5]，最终获得了大量有用的高活性催化剂，但仍有相当大的研究空间。特别是，从科学和实践的角度来看，开发一种独特的催化体系，可以优先激活和芳化杂芳烃上的其他活性较低的CÀH键，这是至关重要的例如，已知pd催化的噻吩与卤代芳烃CÀH键的芳化反应优先发生在α到硫原子（C2和/或C5）的位置，遵循噻吩环的典型反应性（方案1，顶部反应）。[6,7]除了非常罕见的情况，[4,8]在β到硫原子（C3和/或C4）的位置上不会发生选择性和优先芳基化。对于噻唑的芳基化也是如此，而且一种能够优先芳基化活性最低的C4位点的催化体系还没有出现。[6,9]我们在此报道了pd催化的噻吩和噻唑与芳基硼酸的氧化CÀH芳基化反应，表现出其他困难的C4区域选择性（方案1，底部反应）目前的发现是重要的，不仅因为区域选择性的结果是互补的，利用卤代芳烃，[2]芳化，而且因为它证明了这两个看似相关的pd催化的直接芳化过程之间显着的机制差异。在早期的实验中，我们发现2-乙基噻吩（1a）与苯硼酸（2a）在2,2,6,6 -四甲基哌啶- n -氧基[11](TEMPO), Pd (OAc) 2和2,2 ' -联吡啶（bipy）存在于1,2 -二氯乙烷（DCE）中，温度为808C的情况下发生CÀH芳基化（表1，输入1）。令人惊讶的是，我们发现在这些条件下，2-乙基-4-苯基噻吩（3aa）是唯一的偶联产物（收率为69%）。未发现相应的c5 -苯基化产物（4aa）。
Heteroarenes equipped with aryl groups (heterobiaryls) are often found in biologically active compounds, organic materials, and pharmaceuticals. In recent years, the direct CÀH arylation of heteroarenes catalyzed by a transition-metal complex [1, 2] has emerged as a practical alternative to the wellestablished Pd-catalyzed cross-coupling reactions. Although tremendous efforts in the synthetic community including our groups [3–5] have culminated in a wealth of useful and highly active catalysts,[2] considerable room remains for further investigations. In particular, the development of a unique catalytic system that can preferentially activate and arylate an otherwise less reactive CÀH bond on heteroarenes is critically important from both scientific and practical points of view.[6] For example, the Pd-catalyzed arylation of CÀH bonds of thiophenes with haloarenes is known to occur preferentially at the positions α to the sulfur atom (C2 and/or C5) following the typical reactivity profile of the thiophene ring (Scheme 1, top reaction).[6, 7] Except for very rare cases,[4, 8] selective and preferential arylation at the positions β to the sulfur atom (C3 and/or C4) does not take place. This is also true for the arylation of thiazoles, and a catalytic system that can preferentially arylate the least reactive C4 positions has not been forthcoming.[6, 9] We herein report that the Pd-catalyzed oxidative CÀH arylation of thiophenes and thiazoles with arylboronic acids manifests the otherwise difficult C4 regioselectivity (Scheme 1, bottom reaction).[10] The present finding is significant not only because the regioselective outcome is complementary to that of the arylation using haloarenes,[2] but also because it demonstrates the remarkable mechanistic difference between these two seemingly related Pd-catalyzed direct arylation processes.In early experiments, we found that the CÀH arylation of 2-ethylthiophene (1a) with phenylboronic acid (2a) took place in the presence of 2, 2, 6, 6-tetramethylpiperidine-N-oxyl radical [11](TEMPO), Pd (OAc) 2, and 2, 2’-bipyridyl (bipy) in 1, 2-dichloroethane (DCE) at 808C (Table 1, entry 1). Very surprisingly, we identified 2-ethyl-4-phenylthiophene (3 aa) to be the sole coupling product under these conditions (69% yield). The corresponding C5-phenylation product (4 aa) was not identified.