Highly diastereoselective Csp3-Csp2 Negishi cross-coupling with 1,2-, 1,3-and 1,4-substituted cycloalkylzinc compounds
Highly diastereoselective Csp3-Csp2 Negishi cross-coupling with 1,2-, 1,3-and 1,4-substituted cycloalkylzinc compounds
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DOI：
10.1038/nchem.505
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发表时间：
2010-02-01
期刊：
影响因子：
21.8
通讯作者：
Knochel, Paul
中科院分区：
文献类型：
--
作者：
Thaler, Tobias;Haag, Benjamin;Knochel, Paul
有机分子的立体选择性官能化对现代合成具有重要意义。通常需要药物活性分子的立体选择性制备以确保适当的生物活性。因此，非对映选择方法是有效建立多个立体中心的有价值的工具。本文报道了各种环烷基锌试剂与芳基卤化物具有高度非对映选择性的Csp(3)根岸交联反应。在所有情况下，得到了热力学最稳定的立体异构体。值得注意的是，这种非对映选择性偶联不仅对1,2取代的环体系，而且对1,3-和1,4取代的环己基锌试剂也是成功的。通过核磁共振实验和密度泛函理论计算，研究了这种远程立体控制的起源。基于这些实验和理论数据，提出了一个详细的机理。
Stereoselective functionalizations of organic molecules are of great importance to modern synthesis. A stereoselective preparation of pharmaceutically active molecules is often required to ensure the appropriate biological activity. Thereby, diastereoselective methods represent valuable tools for an efficient set-up of multiple stereocentres. In this article, highly diastereoselective Csp(3) Negishi cross-couplings of various cycloalkylzinc reagents with aryl halides are reported. In all cases, the thermodynamically most-stable stereoisomer was obtained. Remarkably, this diastereoselective coupling was successful not only for 1,2-substituted cyclic systems, but also for 1,3- and 1,4-substituted cyclohexylzinc reagents. The origin of this remote stereocontrol was investigated by NMR experiments and density functional theory calculations. A detailed mechanism based on these experimental and theoretical data is proposed.