Department Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, Haus F, 81377 München, Germany.
Nat Chem. 2010 Feb;2(2):125-30. doi: 10.1038/nchem.505. Epub 2010 Jan 17.
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.
立体选择性的有机分子功能化在现代合成中具有重要意义。为了确保适当的生物活性，通常需要对具有药理活性的分子进行立体选择性制备。因此，非对映选择性方法是高效构建多个立体中心的有价值工具。本文报道了各种环烷基锌试剂与芳基卤化物的高非对映选择性 Csp(3)Negishi 交叉偶联。在所有情况下，均获得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-取代的环状体系有效，而且对 1,3-和 1,4-取代的环己基锌试剂也有效。通过 NMR 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。根据这些实验和理论数据提出了一个详细的反应机制。
