The [Cu(OH)•TMEDA]2Cl2-catalyzed coupling of arylboronic acids with imidazoles in water
The [Cu(OH)•TMEDA]2Cl2-catalyzed coupling of arylboronic acids with imidazoles in water
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DOI：
10.1021/jo0016780
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发表时间：
2001-02-23
影响因子：
3.6
通讯作者：
Costanzo, S
中科院分区：
文献类型：
--
作者：
Collman, JP;Zhong, M;Costanzo, S
建立构建n -芳基咪唑亚基的有效方法是目前有机合成的一个活跃领域。n -芳基咪唑不仅是生物系统中的重要结构，也是药物研究中常见的基团。大量的n -芳基咪唑衍生物已被报道具有生物医学应用，作为环AMP磷酸二酯酶抑制剂、1种AMPA受体拮抗剂、2种强心剂、3种血栓素合成酶抑制剂、1b、4和局部抗青光眼药物。此外，最近的高分辨率x射线分析显示，在细胞色素c氧化酶（CcO）的活性位点上，有一个N-（2-羟基苯基）咪唑基序，由组氨酸（His240）和酪氨酸（Tyr244）残基通过CN连锁形成。CcO是一种血红素-铜氧化酶，是线粒体和需氧细菌的终末呼吸酶。据推测，这种酚功能化的咪唑参与了氧还原成水循环过程中的质子和电子转移步骤。我们的CcO长期项目需要n -芳基咪唑中间体来构建新的CcO活性位点模型。9,10因此，我们对通过咪唑与活化的芳基底物直接偶联来开发n -芳基咪唑的新方法产生了兴趣。n-芳咪唑是通过亲核芳香族取代2、3b、c、4b、11和ullman型偶联两种直接偶联方式制备的。1、3a、3c、4a、5、12前一种方法要求衬底含有吸电子取代基，后一种方法通常在高温下进行耦合。在温和的反应条件下，用芳基铅、芳基硼烷和芳基硅烷代替芳基卤化物生成n -芳基咪唑的其他有效方法也已建立。例如，López-Alvarado13和Konopelski14报道了在催化量的Cu (OAc) 2存在下芳香三乙酸铅与咪唑的偶联；然而，这种方法会产生有毒的有机铅副产品。Chan和Lam15描述了Cu-(OAc) 2促进的市售芳基硼酸与咪唑在室温下的n -芳基化。最近，我们证明了在室温下，在不添加任何碱的情况下，在催化量[Cu (OH)， TMEDA] 2Cl2的存在下也可以实现相同的偶联。17另外，Lam18最近描述了苯基三甲氧基硅烷与苯并咪唑在四丁基氟化铵（TBAF）和等摩尔量的铜（OAc） 2的促进下偶联成n -苯基苯并咪唑。虽然这种方法相当温和，但芳基三甲氧基硅烷并不容易获得，而且它们的制备涉及剧毒的三甲氧基硅烷。近年来，人们在利用水作为有机合成的反应介质方面做了很多努力。许多研究表明，许多传统上只在有机溶剂中进行的有机反应也可以在水介质中进行。硼酸介导的铃木型交叉偶联形成CC键是成功的方法之一
Establishing efficient methods for constructing the N-arylimidazole subunit is currently an active area in organic synthesis. N-Arylimidazoles are not only important structures in biological systems but also common moieties in pharmaceutical research. A significant number of N-arylimidazole derivatives have been reported to have biomedical applications, serving as cyclic AMP phosphodiesterase inhibitors, 1 AMPA receptor antagonists, 2 cardiotonic agents, 3 thromboxane synthase inhibitors, 1b, 4 and topical antiglaucoma agents. 5 Furthermore, recent high-resolution X-ray analyses have shown a N-(2-hydroxyphenyl) imidazole motif, formed by histidine (His240) and tyrosine (Tyr244) residues through a CN linkage, in the active site of cytochrome c oxidase (CcO). 6 CcO is a heme-copper oxidase and the terminal respiratory enzyme of mitochondria and aerobic bacteria. 7 This phenol-functionalized imidazole is speculated to participate in the proton and electron-transfer steps during the reduction cycle of oxygen to water. 8 Our long-term program on CcO required N-arylimidazole intermediates for the construction of new CcO active-site models. 9, 10 Accordingly, we became interested in developing new approaches to N-arylimidazoles by directly coupling imidazoles with activated aryl substrates. N-Arylimidazoles have been prepared by two types of direct-coupling, ie nucleophilic aromatic substitution2, 3b, c, 4b, 11 and Ullman-type coupling. 1, 3a, 3c, 4a, 5, 12 The former method requires substrates bearing electronwithdrawing substituents and the latter coupling is usually carried out at high temperatures. Other efficient methods for generating N-arylimidazoles using aryllead, arylborane, and arylsilane reagents instead of aryl halides under mild reaction conditions have also been established. For instance, López-Alvarado13 and Konopelski14 have reported the coupling of aryllead triacetate with imidazoles in the presence of a catalytic amount of Cu (OAc) 2; however, this method produces toxic organolead byproducts. Chan and Lam15 have described a Cu-(OAc) 2-promoted N-arylation of commercially available arylboronic acids with imidazoles at room temperature. 16 Recently, we demonstrated that the same coupling can be accomplished in the presence of a catalytic amount of [Cu (OH)‚TMEDA] 2Cl2 without the addition of any base at room temperature. 17 Alternatively, Lam18 has recently described the coupling of phenyl trimethoxysilane with benzimidazole to N-phenylbenzimidazole, promoted by tetrabutylammoniun fluoride (TBAF) and an equimolar amount of Cu (OAc) 2. Although this method is quite mild, aryl trimethoxysilanes are not readily available and their preparation involves highly toxic trimethoxysilane. In recent years, much effort has been devoted to the use of water as a reaction medium for organic synthesis. 19 A number of studies have shown that many organic reactions that are traditionally carried out exclusively in organic solvents can be also performed in aqueous media. Ayrlboronic acid mediated Suzuki-type cross coupling for forming CC bonds is one of the successful