Enantioselective Construction of Spiro[2H-pyran-3,4′-indoline] by a Systematic Michael/Reduction/Cyclization Sequence Triggered by the Asymmetric Conjugate Addition of Ketones to Isatylidenemalononitriles
Enantioselective Construction of Spiro[2H-pyran-3,4′-indoline] by a Systematic Michael/Reduction/Cyclization Sequence Triggered by the Asymmetric Conjugate Addition of Ketones to Isatylidenemalononitriles
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DOI：
10.1002/ejoc.201101810
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发表时间：
2012-04
影响因子：
2.8
通讯作者：
Hua Zhao;Yu-Bao Lan;Zhao‐Min Liu;Yong Wang;Xing-Wang Wang-Xing-Wang-Wang-2426252;Jing-chao Tao
中科院分区：
文献类型：
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作者：
Hua Zhao;Yu-Bao Lan;Zhao‐Min Liu;Yong Wang;Xing-Wang Wang-Xing-Wang-Wang-2426252;Jing-chao Tao
杂环螺羟吲哚类化合物广泛存在于许多螺羟吲哚生物碱中，其3位上具有多取代的杂环基和四元立体中心，是一类具有显著生物活性的药物相关化合物。本文报道了一种通过Michael还原环化反应合成对映体富集的螺[2 H-吡喃-3，4 ′-吲哚啉]衍生物的有效方法。以金鸡纳为基础的手性伯胺和L-邻苯二磺酸催化异亚甲基丙二腈与酮的初始Michael加成反应，以高产率（81- 99%）和优异的对映选择性（95-> 99%ee）得到了多功能的光学活性Michael加成物。随后，利用NaBH 4作为级联还原/环化试剂，Michael加成物转化为螺[2 H-吡喃-3，4 ′-吲哚啉]衍生物，产率为52- 93%，非对映体比为1.5：1 - 20：1，ee为90- 99%。
Heterocyclic spirooxindoles that bear a multisubstitutedheterocyclic motif and quaternary stereocenter at the 3-position are prevalent in a large number of spirooxindole alkaloids, which are pharmaceutically relevant compounds with remarkable biological activities. In this paper, we report an efficient method for the construction of enantiomerically enriched spiro[2H-pyran-3,4′-indoline] derivatives by a systematic Michael/reduction/cyclization sequence. The initial Michael addition of isatylidenemalononitriles with ketones was catalyzed by a cinchona-based chiral primary amine and L-camphorsulfonic acid and furnished multifunctional, optically active Michael adducts in high yields (81–99 %) with excellent enantioselectivities (95 to >99 % ee). Subsequently, the Michael adducts were converted into spiro[2H-pyran-3,4′-indoline] derivatives in 52–93 % yields with 1.5:1 to 20:1 diastereomeric ratio and 90–99 % ee by utilizing NaBH4 as a cascade reduction/cyclization reagent.