A general and efficient method for the Suzuki-Miyaura coupling of 2-pyridyl nucleophiles
A general and efficient method for the Suzuki-Miyaura coupling of 2-pyridyl nucleophiles
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DOI：
10.1002/anie.200801465
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Buchwald, Stephen L.
中科院分区：
文献类型：
--
作者：
Billingsley, Kelvin L.;Buchwald, Stephen L.
Suzuki-Miyaura反应已成为构建碳-碳键的最有价值的合成工艺之一，[1]我们的实验室开发了许多高活性催化剂系统，可有效处理具有挑战性的芳基卤化物和硼酸组合。[2]最近，我们已经能够将我们的方法扩展到杂芳基硼酸和酯的交叉偶联，其作为生物活性分子组装的重要构件。[3]-[4]然而，对于构建许多天然产物和药学上感兴趣的化合物具有重要意义的2-取代的含氮杂芳基有机硼烷[5]使用我们的标准条件不能有效偶联。对文献的进一步研究表明，仅开发了几种允许2-吡啶基亲核试剂与芳基卤化物的Suzuki-Miyaura反应的方法，并且在这些实施例中，仅芳基碘化物被证明是合适的偶联配偶体。[3][6]-[10]这一困难可归因于几个因素：（1）缺电子杂芳基硼衍生物以相对缓慢的速率进行金属转移（2）这些试剂通过原脱硼途径快速分解。我们发现基于亚磷酸酯或氧化膦配体（1-4）的催化剂对2-吡啶基硼衍生物与1-溴-4-丁基苯的Suzuki-Miyaura反应具有高活性（方案1）。[6]李的工作开创了这些的使用，最近出现了Ackermann和Wolf的优雅应用。然而，该反应仍然对亲核试剂和碱的性质敏感。例如，市售试剂如2-吡啶基硼酸、[7]频哪醇硼酸酯[8]或N-苯基二乙醇胺硼酸酯[9]与4-正丁基溴苯的反应产生低收率的所需联芳基产物（表1，表1-3）。类似地，尝试使用有机三氟硼酸盐导致芳基溴的低转化率（表1，条目4）。[10]虽然在Suzuki-Miyaura反应中已经使用了2-吡啶基硼酸酯，但是交叉偶联方法仅导致所需联芳基产物的差至中等产率。[11]然而，当使用三异丙基2-吡啶基硼酸锂（A）作为亲核试剂时，
The Suzuki-Miyaura reaction has become one of the most valuable synthetic processes for the construction of carbon-carbon bonds,[1] and our laboratories has developed many highly active catalyst systems that efficiently process challenging combinations of aryl halides and boronic acids.[2] Recently, we have been able to extend our methodology to the cross-coupling of heteroaryl boronic acids and esters, which serve as important building blocks for the assembly of biologically active molecules.[3]-[4] However, 2-substituted nitrogen-containing heteroaryl organoboranes, which are of importance for the construction of numerous natural products and pharmaceutically interesting compounds,[5] were not effectively coupled using our standard conditions. Further examination of the literature indicated that only a few methods have been developed that allow for the Suzuki-Miyaura reaction of 2-pyridyl nucleophiles with aryl halides, and in these examples, only aryl iodides have been demonstrated as suitable coupling partners.[3],[6]-[10] The difficulty can be attributed to several factors:(1) electron-deficient heteroaryl boron derivatives undergo transmetallation at a relatively slow rate (2) these reagents rapidly decompose via a protodeboronation pathway. The lack of an efficient method to process this class of nucleophiles led us to develop a technique specifically designed to accomplish this transformation.We found that catalysts based upon phosphite or phosphine oxide ligands (1-4) were highly active for the Suzuki-Miyaura reaction of 2-pyridyl boron derivatives with 1-bromo-4-butylbenzene (Scheme 1).[6] The use of these has been pioneered by the work of Li, and elegant applications by Ackermann and Wolf have appeared more recently. However, the reaction remained sensitive to the nature of the nucleophile and base. For example, the reaction of commercially-available reagents, such as 2-pyridyl boronic acid,[7] pinacol boronate ester [8] or N-phenyl diethanolamine boronate ester,[9] with 4-n-butylbromobenzene produced low yields of the desired biaryl product (Table 1, Entries 1-3). Similarly, attempts to use organotrifluoroborates resulted in a low conversion of the aryl bromide (Table 1, Entry 4).[10] Although 2-pyridylboronates have been employed in Suzuki-Miyaura reactions, the crosscoupling processes result in only poor to modest yields of the desired biaryl product.[11] However, when lithium triisopropyl 2-pyridyl boronate (A) was employed as the nucleophile,