Vinylation of aromatic halides using inexpensive organosilicon reagents. Illustration of design of experiment Protocols
Vinylation of aromatic halides using inexpensive organosilicon reagents. Illustration of design of experiment Protocols
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DOI：
10.1021/ja7100888
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发表时间：
2008-03-19
影响因子：
15
通讯作者：
Butler, Christopher R.
中科院分区：
文献类型：
--
作者：
Denmark, Scott E.;Butler, Christopher R.
本文报道了在廉价的硅烷醇盐活化剂存在下，钯催化芳香族碘和溴与二乙烯基四甲基二硅氧烷（DFDS）的偶联反应制备苯乙烯的方法。为了便于发现最佳反应条件，使用实验设计（DoE）方案。通过指导选择试剂、化学计量、温度和溶剂，乙烯基化反应快速优化为三个阶段，包括约。175个实验（可能的1440种组合）。在室温下，在三甲基硅酸钾存在下，使用Pd（dba）（2）在DMF中以良好的产率进行各种芳香族碘化物的交叉偶联。需要三苯基氧化膦来延长催化剂寿命。这些条件的芳基溴的应用程序完成了两个互补的协议的发展。首先，在升高的温度下在THF中使用芳基碘直接实施成功的反应条件以良好至优异的产率提供了相应的苯乙烯。或者，使用三乙基硅烷醇钾和大体积的“Buchwald型”配体允许乙烯基化反应在室温或略高于室温下发生。对于所描述的每个方案，广泛的溴化物以良好的产率进行偶联。
The preparation of styrenes by palladium-catalyzed cross-coupling of aromatic iodides and bromides with divinyltetramethyldisiloxane (DVDS) in the presence of inexpensive silanolate activators has been developed. To facilitate the discovery of optimal reaction conditions, Design of Experiment (DoE) protocols were used. By the guided selection of reagents, stoichiometries, temperatures, and solvents, the vinylation reaction was rapidly optimized with three stages consisting of ca. 175 experiments (of a possible 1440 combinations). A variety of aromatic iodides undergo cross-coupling at room temperature in the presence of potassium trimethylsilanoate using Pd(dba)(2) in DMF in good yields. Triphenylphosphine oxide is needed to extend catalyst lifetime. Application of these conditions to aryl bromides was accomplished by the development of two complementary protocols. First, the direct implementation of the successful reaction conditions using aryl iodides at elevated temperature in THF provided the corresponding styrenes in good to excellent yields. Alternatively, the use of potassium triethylsilanolate and a bulky "Buchwald-type" ligand allows for the vinylation reactions to occur at or just above room temperature. A wide range of bromides underwent coupling in-good yields for each of the protocols described.