Suzuki-Miyaura coupling reaction by PdII-catalyzed aromatic C-H bond activation directed by an N-alkyl acetamino group
Suzuki-Miyaura coupling reaction by PdII-catalyzed aromatic C-H bond activation directed by an N-alkyl acetamino group
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DOI：
10.1002/anie.200700590
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Wang, Yang
中科院分区：
文献类型：
--
作者：
Shi, Zhangjie;Li, Bijie;Wang, Yang
C？C键的形成是有机合成中的一个重要过程。[1]在传统的钯催化的Suzuki-Miyaura偶联反应中，需要C±X(X=Br，I，OTf；Tf=三氟甲磺酰基)基团作为底物来引发Pd0的氧化加成反应生成含PdII的中间体。最近的进展允许使用相对便宜和容易获得的有机氯化物，[2]但构建C？C键的理想和环境友好的方法是C？H键的直接官能化。在过去的几十年里，人们已经做出了广泛的努力来开发过渡金属催化的C±H功能化。[3]芳香族C±H键的直接芳基化反应已经被开发出来，无论有没有导向基团来构建联芳基结构基元，这是许多药物相关和生物活性化合物的重要支架。[4]在许多情况下，过渡金属配合物激活C±H键可以提供一条直接获得C±M(M=金属)中间体的途径，这些中间体也可以通过低价过渡金属络合物与有机卤化物的氧化加成来获得。然而，C？H键的直接活化可以得到相同的有价值的产品，但避免了在起始材料中存在卤化物的要求。虽然可以用其他方法通过过渡金属催化芳烃的C±H键活化来构建C±C键，但通过Suzuki-Miyaurat型偶联形成C±C键的过程很少见报道。最近，Yu的研究小组报道了由吡啶和羧基指导的Sp3或Sp2 C±H键的烷基化反应。[6]包括Sams在内的许多研究小组已经报道了由Ru与芳香族硼酸酯和杂环导向基催化的SP3 C±H键的芳基化反应。[7]在这里，我们报道了钯催化的C±C键的形成，在Suzuki-Miyaura类型的偶联反应中，通过乙酰氨基指导的芳香族C±H键的高区域选择性邻位芳基化反应。我们以前利用PdII催化的反应开发了一种高区域选择性的乙酰苯胺卤化反应[式(1)]。[8]在碱性条件下，这种卤化物可以发生由Pd介导的Suzuki-Miyaura偶联反应[式(2)]。[9]在我们的卤化反应中，我们提出了palladacecy5作为关键中间体，与传统的Suzuki-Miyaura偶联反应中4与Pd0的氧化加成生成的中间体相同。这种中间体5如果形成，将与硼酸进行易金属反应，并被还原消除以形成C±C键。因此，我们假设在适当的条件下(方案1)，可以通过乙酰苯胺与芳基硼酸的C±H官能化进行Suzuki-Miyaura偶联。然而，卤化反应和Suzuki-Miyaura偶联的反应条件可能不相容，因为虽然两者可能经过相同的中间体5，但它们由不同的钯物种催化。卤化反应是在酸性条件下进行的，以增强PdII物种的亲电能力，这对环化反应是重要的。然而，大多数Suzuki-Miyaura偶联都是在基本条件下进行的。[1，2]这种差异使得将这两个过程结合起来并从C±H键构造C±C键变得困难。我们必须克服这个问题，如果我们想要直接
CÀC bond formation is an important process in organic synthesis. The Suzuki–Miyaura coupling is one of the most useful methods to construct CÀC bonds and has been broadly applied in syntheses of natural products, synthetic drugs, and materials.[1] In a traditional palladium-catalyzed Suzuki–Miyaura coupling, CÀX (X= Br, I, OTf; Tf= trifluoromethanesulfonyl) groups were required as substrates to initiate the oxidative addition of Pd0 to produce PdII-containing intermediates. Recent advances have allowed the use of the relatively cheap and readily available organic chlorides,[2] but an ideal and environmentally friendly method to construct CÀ C bonds would be the direct functionalization of CÀH bonds. Over the past several decades, extensive efforts have been made to develop a transition-metal-catalyzed CÀH functionalization.[3] Direct arylation of aromatic CÀH bonds has been developed with or without directing groups to construct a biaryl structural motif, which is an important scaffold in many pharmaceutically relevant and biologically active compounds.[4] In many cases, CÀH bond activation by transitionmetal complexes can offer a direct route to CÀM (M= metal) intermediates that are also accessible through the oxidative addition of a low-valent transition-metal complex to organic halides. However, the direct activation of CÀH bonds could lead to the same valuable products but avoid the requirement of the presence of halides in the starting material. Although the CÀC bond could be constructed by transition-metalcatalyzed CÀH bond activation of arenes by using other methods,[5] processes to form CÀC bonds by Suzuki–Miyauratype coupling were rarely reported. Very recently, the research group of Yu reported the alkylation of sp3 or sp2 CÀH bond directed by pyridinyl and carboxylic groups.[6] A number of research groups, including that of Sames, have reported the arylation of sp3 CÀH bonds catalyzed by ruthenium complexes with an aromatic boronic ester and by using a heterocyclic directing group.[7] Herein we report a palladium-catalyzed CÀC bond formation to afford highly regioselective ortho arylation of aromatic CÀH bond in a Suzuki—Miyaura-type coupling reaction with aromatic boronic acids directed by an acetyl amino group. We previously developed a highly regioselective halogenation of acetanilides by using a PdII-catalyzed reaction [Eq.(1)].[8] A Suzuki–Miyaura coupling reaction mediated by Pd could occur from this halide under basic conditions [Eq.(2)].[9] In our halogenation reaction, we proposed the palladacycle 5 as a key intermediate, identical to that generated from the oxidative addition of 4 to Pd0 in the traditional Suzuki–Miyaura coupling. This intermediate 5, if formed, will undergo transmetalation with boronic acids and reductively eliminate to form the CÀC bond. Thus, we hypothesized that a Suzuki–Miyaura coupling by using CÀH functionalization of acetanilides with aryl boronic acids might proceed under the proper conditions (Scheme 1). However, the reaction conditions of the halogenation reaction and Suzuki–Miyaura coupling may not be compatible because, although both may go through the same intermediate 5, they were catalyzed by different palladium species. The halogenation was carried out under acidic conditions to enhance the electrophilic ability of the PdII species that is important for cyclopalladation. However, most Suzuki–Miyaura couplings proceed under basic conditions.[1, 2] This difference makes it difficult to combine these two processes and construct a CÀC bond from a CÀH bond. We have to overcome this problem if we want to directly