A rationally designed universal catalyst for Suzuki-Miyaura coupling processes
A rationally designed universal catalyst for Suzuki-Miyaura coupling processes
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DOI：
10.1002/anie.200353615
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发表时间：
2004-01-01
影响因子：
16.6
通讯作者：
Buchwald, SL
中科院分区：
文献类型：
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作者：
Walker, SD;Barder, TE;Buchwald, SL
尽管Suzuki-Miyaura交叉耦合过程取得了进展，[1]仍然需要一个操作简单和通用的系统。必须满足的最佳系统的最低标准包括：1）广泛的底物范围，2）制造真正受阻联芳化合物的能力，3）在低催化剂水平下操作一系列底物的能力，而不仅仅是最简单的例子（例如，除苯基硼酸之外），[2]和4）在室温下操作的能力。此外，最希望开发不需要使用手套箱的方案。在此，我们报告了一种基于新配体的催化剂体系，该配体满足上述四个标准，具有前所未有的范围、反应性和稳定性，仅使用市售的、空气稳定的组分，并且实验上易于使用。我们以前的交叉偶联方法的工作表明，二烷基膦基联苯是很好的支持配体。我们已经报道，这些可以通过将芳基格氏试剂添加到原位生成的苯炔中间体中，然后用ClPR 2捕获新形成的有机镁络合物来制备。[3]设计新配体1的思想过程如方案1所示。我们实验室的机理研究表明，消除底环上的邻位氢（不带有二烷基膦基）对催化剂活性和寿命很重要。[4]我们认为这是由于两个效应：1）防止环化[5]（形成钯配体），这减少了催化剂寿命，和2）相对于具有两个邻位氢的络合物增加了空间体积。我们还认为，重要的是，两个甲氧基基团的大小小于两个烷基基团，如在我们以前报道的配体。此外，烷氧基的孤对可能与Pd中心相互作用和/或向配体骨架增加电子密度。后者可能是重要的，因为金属与底环的相互作用是有据可查的[6]，可以帮助稳定中间络合物。[2c此外，1，3-二甲氧基苯部分提供的优点是，它可以通过如下方式安装：
Despite advances in the Suzuki–Miyaura cross-coupling process,[1] the need for an operationally simple and general system remains. The minimum criteria for an optimum system that must be met include: 1) a broad substrate scope, 2) the ability to make truly hindered biaryls, 3) the ability to operate at low levels of catalyst for a range of substrates not just with the most simple examples (eg, other than phenyl boronic acid),[2] and 4) the ability to operate at room temperature. Moreover, it is most desirable to develop protocols that do not necessitate the use of a glovebox. Herein we report a catalyst system based on a new ligand that meets the above four criteria, has unprecedented scope, reactivity, and stability, uses only commercially available, air-stable components, and is experimentally simple to employ. Our previous work on cross-coupling methodology demonstrated that dialkylphosphanylbiphenyls were excellent supporting ligands. We have reported that these can be prepared by the addition of an aryl Grignard reagent to an insitu-generated benzyne intermediate, followed by trapping of the newly formed organomagnesium complex with ClPR2.[3] The thought process that led to the design of the new ligand 1 is shown in Scheme 1.Mechanistic studies in our laboratory indicated that the elimination of ortho hydrogens on the bottom ring (that not bearing the dialkylphosphanyl group) was important for catalyst activity and longevity.[4] We believe that this is due to two effects: 1) prevention of cyclometalation [5](to form a palladacycle), which diminishes catalyst lifetime, and 2) increased steric bulk relative to complexes with two ortho hydrogens. We also feel that it is important that the two methoxy groups are smaller in size than two alkyl groups as in our previously reported ligands. Moreover, the lone pairs of the alkoxy groups might interact with the Pd center and/or add electron density to the ligand backbone. The latter could be important as the interaction of the metal with the bottom ring is well documented [6] and could help stabilize intermediate complexes.[2c, 7] Furthermore, the 1, 3-dimethoxybenzene moiety offers the advantage that it can be installed by means