Redox-Controlled Selectivity of C-H Activation in the Oxidative Cross-Coupling of Arenes
Redox-Controlled Selectivity of C-H Activation in the Oxidative Cross-Coupling of Arenes
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DOI：
10.1002/anie.201209007
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发表时间：
2013-01-01
影响因子：
16.6
通讯作者：
Larrosa, Igor
中科院分区：
文献类型：
--
作者：
Cambeiro, Xacobe C.;Boorman, Tanya C.;Larrosa, Igor
C2 H4活化在合成联芳基化合物中的最终应用是两个非预官能化芳烃交叉偶联的反应。[1，2]这种氧化交叉偶联将大大简化合成策略，从而产生更环保的方法。迄今为止，这些氧化偶联几乎完全由Pd催化，最近的一些例子使用Cu。[3，4]然而，在这些方法可以广泛应用之前，仍有一些缺点有待解决。首先，通常需要苛刻的反应条件，需要强酸作为溶剂和/或温度通常超过1108 ℃。第二，用取代芳烃通常获得差的区域选择性。最后，在大多数氧化偶联中，两种偶联配偶体都被具有非常相似选择性的PdII或PdIV物质活化，这导致需要使用30- 300当量的两种芳烃之一以确保实现交叉偶联，而不是同质偶联。[5]我们假设，过渡金属能够根据其氧化态呈现正交C1 H2活化选择性，这将允许一种新的方法来合理设计具有高选择性的氧化交叉偶联方法。在这里，我们证明了Au物种呈现出这种独特的氧化还原控制的选择性，并强调其潜在的用途，设计新的交叉耦合，涉及氧化双CNOH活化。这些Au介导的转化在比当前Pd系统更低的温度下进行，并且显示出优异的区域选择性、高的交叉偶联选择性（crossversus homo-coupling selectivities）（从而避免了对大量过量的芳烃的需要），并且与Pd敏感基团（例如I和Br）相容。[6]我们最近报道了AuI盐能够在508 ℃介导缺电子芳烃的C3 OH活化（方案1a）。[7]这与众所周知的Au III盐即使在室温下也能进行富电子芳烃的C3 OH活化的能力形成对比（方案1b）。[8，9]因此，我们假设，如果AuI和（III）盐分别对贫电子和富电子芳烃具有完全选择性，则可以利用Au的这种有趣的性质来提供完全选择性的基于双C3 OH活化的交叉偶联方法（方案2）。在我们假设的过程中，贫电子芳烃（1）和富电子芳烃（3）的混合物最初会与AuI盐反应，导致1的选择性C2 H4活化。在添加氧化剂后，芳基-AuI物质I将被氧化为AuIII络合物II，这反过来又会对富电子芳烃进行选择性的C3 OH活化，在还原消除后形成联芳基4。这种方法的开发提出了许多挑战：1）尽管最近提出了几种通过AuI/III氧化还原循环进行的方法，[10，11]迄今为止没有涉及芳基-AuI物质I的氧化。2)CNOH激活芳基-金III物种II从未被证明，虽然它可能是一个步骤，在homocoupling的富电子芳烃。[12]3）芳基-Au III物种已被建议通过金属转移进行配体混乱，产生同源偶联产物。[9，10]最初，我们探索了邻碘苯甲醚与芳基-AuI 2a的偶联（表1），其在我们的标准C2 H4活化条件下制备（方案1a）[7]，产率为99%。氧化剂优化显示，尽管在不存在氧化剂的情况下没有获得产物，但可以观察到所需的交叉偶联产物，尽管产率低，
The ultimate application of CÀH activation to the synthesis of biaryl compounds is a reaction in which two non-prefunctionalized arenes are cross-coupled.[1, 2] Such an oxidative crosscoupling would substantially streamline synthetic strategies, resulting in greener methods. To date, these oxidative couplings have been catalyzed almost exclusively by Pd, with some recent examples using Cu.[3, 4] However, several drawbacks remain to be addressed before these methods can be widely applied. First, harsh reaction conditions are commonly needed, with strong acids required as solvents and/or temperatures typically exceeding 1108C. Second, poor regioselectivities are generally obtained with substituted arenes. Finally, in most oxidative couplings, both coupling partners are activated by PdII or PdIV species that have very similar selectivities, which results in the need for using 30–300equiv of one of the two arenes to ensure that crosscoupling, rather than homo-coupling, is achieved.[5] We hypothesized that a transition metal capable of presenting orthogonal CÀH activation selectivities depending on its oxidation state would allow a new approach towards the rational design of oxidative cross-coupling methods with high selectivities. Herein, we demonstrate that Au species present this unique redox-controlled selectivity and highlight their potential use for the design of novel cross-couplings involving oxidative double CÀH activation. These Au-mediated transformations proceed at lower temperatures than current Pd systems, and display excellent regioselectivities, high crossversus homo-coupling selectivities (thus avoiding the need for vast excesses of the arenes), and are compatible with Pdsensitive groups, such as I and Br.[6] We have recently reported that AuI salts are able to mediate the CÀH activation of electron-poor arenes at just 508C (Scheme 1 a).[7] This contrasts with the well-known ability of AuIII salts to perform CÀH activation of electronrich arenes, even at room temperature (Scheme 1b).[8, 9] We thus hypothesized that, if AuI and (III) salts are completely selective for electron-poor and-rich arenes, respectively, this interesting property of Au could be exploited to provide a completely selective double CÀH activation-based crosscoupling method (Scheme 2). In our hypothetical process, a mixture of an electron-poor (1) and an electron-rich (3) arene would initially react with a AuI salt, leading to selective CÀH activation of 1. Upon addition of an oxidant, aryl–AuI species I would be oxidized to AuIII complex II, which in turn would perform selective CÀH activation on the electron-rich arene, forming biaryl 4 upon reductive elimination. The development of such a process presents a number of challenges: 1) Despite the few recent methods suggested to proceed by a AuI/III redox cycle,[10, 11] to date none involve the oxidation of aryl–AuI species I. 2) CÀH activation by aryl–AuIII species II has never been demonstrated, although it may be a step in the homocoupling of electron-rich arenes.[12] 3) Aryl–AuIII species have been suggested to undergo ligand scrambling by transmetalation, giving rise to homocoupling products.[9, 10]Initially, we explored the coupling of o-iodoanisole with aryl–AuI 2a (Table1), which was prepared under our standard CÀH activation conditions (Scheme 1a)[7] in 99% yield. Oxidant optimization revealed that, whereas in the absence of oxidant no product was obtained, the desired cross-coupling product could be observed, albeit in low yields,