Entry to heterocycles based on indium-catalyzed Conia-ene reactions: Asymmetric synthesis of (-)-salinosporamide A
Entry to heterocycles based on indium-catalyzed Conia-ene reactions: Asymmetric synthesis of (-)-salinosporamide A
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DOI：
10.1002/anie.200801967
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Hatakeyama, Susumi
中科院分区：
文献类型：
--
作者：
Takahashi, Keisuske;Midori, Michiko;Hatakeyama, Susumi
含氮杂环作为药物和其他化学实体的重要性继续激励着合成它们的战术方法的发展。在一个旨在合成具有高度官能化的吡咯烷酮核团的耐人寻味的天然产物[1]的项目[1]中，如盐孢子胺A、乳糖菌素[2]和恶唑霉素类化合物，[3]我们开始对开发一种新的方法感兴趣，该方法依赖于酰胺丙二酸酯1经2的柯尼亚-烯反应得到3-吡咯烷酮(方案1)。最近，代替最初的热柯尼亚-烯反应，[4]设计了许多在温和条件下进行的金属催化反应来制备碳环[5，6]和杂环，[7，6]8]尽管后者主要限于3-亚甲基吡咯烷和四氢呋喃。然而，尚不清楚金属催化版本的Conia-Ene反应是否适用于我们设想的转化(方案1)。在这里，我们报道了一条合成吡咯烷酮和其他杂环化合物的新路线，该路线是基于铟催化的含氮和含氧的乙酰丙二酸酯的锥烯环化反应。我们还通过将该反应应用于合成海洋放线菌Salinispora tropica产生的一种高效的20S蛋白酶体抑制剂(±)-盐孢子胺A来证明了该反应的有效性。[9-12]我们研究了AUI-，[5a]NiII-，[5c]和InIII催化的1a的[5f，6]反应(表1)。In(OTf)3含量最高
The importance of nitrogen-containing heterocycles as drugs and other chemical entities continue to inspire the development of tactical methods for their synthesis. In connection with a project directed towards the synthesis of intriguing natural products [1] having a highly functionalized pyrrolidinone core, such as salinosporamideA, lactacyctin,[2] and oxazolomycins,[3] we became interested in developing a novel approach which relied upon the Conia-ene reaction of amidomalonate 1 to give pyrrolidinone 3 via 2 (Scheme 1).Recently, in place of the original thermal Conia-ene reaction,[4] a number of metal-catalyzed reactions that are carried out under mild conditions have been devised for the preparation of carbocycles [5, 6] and heterocycles,[7, 8] although the latter are largely limited to 3-methylene pyrrolidines and tetrahydrofurans. However, it was unknown whether metalcatalyzed versions of the Conia-ene reaction would be applicable to our envisaged transformation (Scheme1). Herein, we report a new route to pyrrolidinones and other heterocycles based on the indium-catalyzed Conia-ene-type cyclization of nitrogen-and oxygen-tethered acetylenic malonic esters. We also demonstrate the utility of this reaction by its application to the synthesis of (À)-salinosporamide A, a highly potent 20S proteasome inhibitor produced by the marine actinomycete Salinispora tropica.[9–12] We examined AuI-,[5a] NiII-,[5c] and InIII-catalyzed [5f, 6] reactions of 1a (Table 1). In (OTf) 3 was found to most