Trienamines in Asymmetric Organocatalysis: Diels-Alder and Tandem Reactions
Trienamines in Asymmetric Organocatalysis: Diels-Alder and Tandem Reactions
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不对称有机催化中的三烯胺：Diels-Alder 和串联反应
DOI：
10.1021/ja1112194
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发表时间：
2011-04-06
影响因子：
15
通讯作者：
Jorgensen, Karl Anker
中科院分区：
文献类型：
--
作者：
Jia, Zhi-Jun;Jiang, Hao;Jorgensen, Karl Anker
发现了有机催化提供的一种新的活化方式。研究表明，光学活性的仲胺和多烯的结合生成了反应性的三烯胺中间体，这些中间体很容易与不同类别的亲双烯分子发生Diels-Alder反应，从而以良好的立体控制提供了进入高度复杂的分子框架的便捷途径。对于与3-烯烃氧吲哚的Diels-Alder反应，生成的螺环氧化产物产率高，对映体选择性在94-98%ee范围内。结果表明，部分产物可转化为六氢呋喃并[2，3-b]吲哚碎片。有机催化三烯胺的概念已经扩展到还包括氰基乙酸酯取代的烯烃的Diels-Alder反应，提供了高产率和良好的立体控制的具有三个连续立体中心的多官能环己烯。这种激活策略的新奇之处在于最多八个键的距离上的完美手性继电器。此外，我们还提出了三烯胺催化和烯胺活化相结合的第一个三烯胺串联反应。除了实验结果外，还提供了详细的机理综述，包括核磁共振波谱研究和活性三烯胺中间体的计算，合理地解释了立体化学的起源。
The discovery of a novel activation mode provided by organocatalysis is presented. It is demonstrated that the merger of optically active secondary amines and polyenals generates reactive trienamine intermediates, which readily participate in Diels-Alder reactions with different classes of dienophiles, hence, providing a facile entry to highly complex molecular frameworks with excellent stereocontrol. For the Diels-Alder reactions with 3-olefinic oxindoles, spirocyclic oxidoles are formed in high yields, and with enantioselectivities in the range of 94-98% ee. It is demonstrated, that some of these products can be transformed into the hexahydrofuro[2,3-b]indole fragment. The organocatalytic trienamine concept has been extended to also include Diels-Alder reactions of olefins substituted with cyanoacetates providing multifunctional cyclohexenes with three contiguous stereocenters in high yield and good stereocontrol. The novelty of this activation strategy lies within the perfect chirality relay over a distance of up to eight bonds. Moreover, we also present the first trienamine tandem reaction by combining trienamine catalysis with enamine activation. In addition to the experimental results, a detailed mechanistic survey is also provided including NMR spectroscopic studies and calculations of the reactive trienamine intermediates, rationalizing the origin of stereochemistry.