Palladium-catalyzed alkene carboamination reactions for the synthesis of substituted piperazines
Palladium-catalyzed alkene carboamination reactions for the synthesis of substituted piperazines
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DOI：
10.1016/j.tet.2009.04.017
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发表时间：
2009-08-15
期刊：
影响因子：
2.1
通讯作者：
Wolfe, John P.
中科院分区：
文献类型：
--
作者：
Nakhla, Josephine S.;Schultz, Danielle M.;Wolfe, John P.
描述了从氨基酸前体立体选择性制备对映体富集的顺式-2,6-二取代哌嗪的策略。使用钯催化的芳基或烯基卤化物与取代的乙二胺衍生物之间的碳胺化反应形成杂环，生成的目标化合物具有 95-99% ee，具有良好至优异的非对映选择性（通常为 14:1 至 >20:1）。该合成仅需要 4-5 个市售氨基酸步骤，并且允许模块化构建在 N-1、N-4、C-2 和 C-6 处带有不同取代基的哌嗪。还报道了使用该策略构建 2,3-二取代哌嗪、稠合双环哌嗪和四氢喹喔啉。此外，还讨论了关键碳胺化反应的机制，并提出了预测和解释这些转化的立体化学结果的新模型。 (C) 2009 Elsevier Ltd. 保留所有权利。
A strategy for the stereoselective preparation of enantiomerically enriched cis-2,6-disubstituted piperazines from amino acid precursors is described. The target compounds are generated in 95-99% ee with good to excellent levels of diastereoselectivity (Usually 14:1 to >20:1) using Pd-catalyzed carboamination reactions between aryl or alkenyl halides and substituted ethylenediamine derivatives to form the heterocyclic rings. The synthesis requires only 4-5 steps from commercially available amino acids, and allows for the modular construction of piperazines bearing different substituents at N-1, N-4, C-2, and C-6. The use of this strategy for the construction of 2,3-disubstituted piperazines, fused bicyclic piperazines, and tetrahydroquinoxalines is also reported. In addition, the mechanism of the key carboamination reactions is discussed, and new models that predict and explain the stereochemical outcome of these transformations are presented. (C) 2009 Elsevier Ltd. All rights reserved.