Carboxylic Acids as Traceless Directing Groups for Formal meta-Selective Direct Arylation
Carboxylic Acids as Traceless Directing Groups for Formal meta-Selective Direct Arylation
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DOI：
10.1002/anie.201103720
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Larrosa, Igor
中科院分区：
文献类型：
--
作者：
Cornella, Josep;Righi, Marika;Larrosa, Igor
联芳基化合物的合成非常重要，因为这些结构形成许多天然产物、药物和有机材料的一部分。[1，2]它们的合成最常用的方法是传统的交叉偶联反应，这需要使用有机金属芳基给体。这导致大量的浪费以及低原子和步骤经济性，特别是当需要间位取代的芳基给体时，因为它们的制备通常涉及几个步骤。[3]近年来，出现了直接C13 H芳基化方法，其中简单的芳烃在C13 H键处芳基化，从而避免了使用有机金属芳基供体。[4]然而，控制取代苯芳基化反应的区域选择性仍然是一个巨大的挑战。这一领域的最新进展表明，几种类型的取代基，包括2-吡啶基，酰胺和羧酸等，可以作为直接芳基化邻位上的导向基团。[4]另一方面，间位选择性芳基化更难以实现。2009年，Gaunt及其同事的一份开创性报告描述了第一种间位选择性直接芳基化的方法。[5]然而，该系统仅限于使用2-氧代取代的导向基团和非市售的Ar 2 IOTf物质作为偶联配偶体。控制直接芳基化的区域选择性的所有这些策略依赖于有限数量的导向基团，如果靶分子中存在不同的取代基，则需要随后的修饰。相反，理想的直接芳基化体系将允许区域选择性偶联，而不管芳烃上存在的取代基的性质如何。这是特别重要的情况下，metaselective直接arylations，迄今为止，只有一类的指导组已被报道。它应该是可能的访问间位取代的加合物通过使用一个战略性放置的可移动的邻位导向基团，最近审查的Breit的概念。[6]实际上，Satoh、Miura等人已经成功地将该方法应用于芳烃的正式Meta烯烃化，其通过苯甲酸的邻位乙烯基化，然后脱羧。[7]然而，这一概念的应用，间位取代的联芳基化合物的合成尚未实现。在本文中，我们报告了我们的策略，用于在Meta位直接芳基化为各种吸电子和给电子取代基，从而绕过这些取代基的任何电子偏好（方案1）。通过使用该串联方法，邻位取代的苯甲酸1变成Meta阴离子I的合成等价物，因此允许合成否则难以获得的间位取代的联芳基化合物（4）。这种一锅法操作简单，需要低催化剂负载，使用容易获得的碘代芳烃作为偶联配偶体，并且重要的是，与各种各样的取代基相容。我们的小组和Goossen最近报道了许多苯甲酸在银催化下可以很容易地脱羧，只要它们在邻位带有吸电子或供电子取代基。[8]这些结果将羧酸取代基作为我们的间位选择性直接芳基化策略的理想候选者。Daugulis和同事以及Yu和同事报道了两种通过Pd/Ag体系介导的苯甲酸与碘代芳烃的邻位选择性直接芳基化的方法。[9]然而，只有一个报道的实施例含有取代基（Me）邻位的羧酸，从而表明一般缺乏兼容性。尽管如此……
The synthesis of biaryl compounds is of high importance as these structures form part of numerous natural products, pharmaceuticals, and organic materials.[1, 2] The most commonly used method for their synthesis is the traditional crosscoupling reaction, and this requires the use of organometallic aryl donors. This results in large amounts of waste as well as low atom and step economy, especially when meta-substituted aryl donors are required as their preparation usually involves several steps.[3] In recent years, direct CÀH arylation methods have emerged, in which a simple arene is arylated at a CÀH bond, thus avoiding the use of an organometallic aryl donor.[4] However, controlling the regioselectivity of arylation in substituted benzenes is still a great challenge. Recent advances in this area have shown that several types of substituents, including 2-pyridyls, amides, and carboxylic acids among others, can act as directing groups for the direct arylation on the ortho position.[4] meta-Selective arylation, on the other hand, is much more difficult to achieve. In 2009, a pioneering report by Gaunt and coworkers described the first method for meta-selective direct arylation.[5] This system, however, is limited exclusively to the use of 2-oxo-substituted directing groups, and the noncommercially available Ar2IOTf species as the coupling partner. All of these strategies to control the regioselectivity of direct arylation rely on a limited number of directing groups, which require subsequent modification if a different substituent is present in the target molecule. On the contrary, the ideal direct arylation system would allow regioselective coupling regardless of the nature of the substituents present on the arene. This is particularly important in the case of metaselective direct arylations as, to date, only one class of directing group has been reported. It should be possible to access meta-substituted adducts by the use of a strategically placed removable ortho-directing group, a concept recently reviewed by Breit.[6] Indeed, this approach has been successfully applied by Satoh, Miura et al. to the formal meta olefination of arenes by ortho vinylation of benzoic acids followed by decarboxylation.[7] However, the application of this concept to the synthesis of meta-substituted biaryl compounds has not been achieved. Herein we report our strategy for performing direct arylation in the meta position to a variety of electron-withdrawing and electrondonating substituents, thus bypassing any electronic preferences from such substituents (Scheme 1). Through the use of this tandem process, ortho-substituted benzoic acid 1 becomes a synthetic equivalent of the meta anion I, therefore allowing the synthesis of meta-substituted biaryl compounds (4) that would otherwise be difficult to obtain. This one-pot method is operationally simple, requires low catalyst loadings, uses readily available iodoarenes as coupling partners, and, importantly, is compatible with a wide variety of substituents. Our group, as well as Goossen s, have recently reported that a wide variety of benzoic acids can be easily protodecarboxylated under Ag catalysis provided that they bear an electron-withdrawing or electron-donating substituent in the ortho position.[8] These results place carboxylic acid substituents as the ideal candidates for our meta-selective direct arylation strategy. Daugulis and co-workers, and Yu and coworkers have reported two methods for the ortho-selective direct arylation of benzoic acids with iodoarenes mediated by a Pd/Ag system.[9] However, only one of the reported examples contained a substituent (Me) ortho to the carboxylic acid, thus suggesting general lack of compatibility. Despite this …