Fine-tunable organocatalysts bearing multiple hydrogen-bonding donors for construction of adjacent quaternary and tertiary stereocenters via a Michael reaction.
Fine-tunable organocatalysts bearing multiple hydrogen-bonding donors for construction of adjacent quaternary and tertiary stereocenters via a Michael reaction.
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DOI：
10.1002/chem.200801420
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发表时间：
2008-10
期刊：
影响因子：
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通讯作者：
Zhi-Hai Zhang;Xiuqin Dong;Dong Chen;Chun‐Jiang Wang
中科院分区：
文献类型：
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作者：
Zhi-Hai Zhang;Xiuqin Dong;Dong Chen;Chun‐Jiang Wang
迈克尔加成反应被广泛认为是有机合成中形成CÀC键的最通用和最通用的方法之一因此，这一反应的对映选择性催化方案的发展受到广泛关注也就不足为奇了近年来，通过使用强大的环境友好型有机催化剂来实现不对称迈克尔加成的努力已经得到了广泛的探索。[3,4]特别令人感兴趣的是三取代碳亲核试剂与缺电子烯烃之间的反应，形成含有相邻的季位和叔位立体中心的迈克尔加合物，这是复杂天然产物的关键单元，也是非常有价值的合成单元。尽管它具有巨大的合成潜力，但只有有限的成功方案被报道达到高水平的对映体和/或非对映体选择性与其他不对称催化剂相比，一步反应同时生成相邻的季、叔立体中心的反应还处于起步阶段，开发具有高反应活性、对映选择性和非对映选择性的新型高效催化剂仍然是一个很大的挑战。最近，我们报道了一类新的双功能胺/硫脲催化剂I，它具有多个氢键给体，在催化乙酰内酯与硝基烯烃的不对称加成和高抗选择性硝基-曼尼希反应中表现出优异的性能。[6,7]将这些有机催化剂的兴趣扩展到不对称催化中，本文报道了另一类易于获得的、可调谐的多氢键给体有机催化剂II[8,9]，它们在α-取代β-酮酯对各种硝基烯烃的不对称Michael加成反应中具有高的对映选择性和非对映选择性，并且适用范围广。[5c， e]虽然胺/硫脲I对于各种对称和不对称的1,3 -二酮加成到硝基烯烃上具有很高的效率，但我们最初尝试应用I来促进α-取代β-酮酯加成到硝基烯烃上是不成功的（表1）。在CH2Cl2催化剂I的催化下，2-氧-环戊内酯（1a）与硝基烯烃（2a）的反应在室温下不到0.5 h就完成了，这与1,3 -二酮，[6]的反应一致，但加合物3a的非对映选择性很低，即使在较低温度下，对主要的非对映体也有中等至良好的对映选择性[a] Z.-H。张,X.-Q。董德明，陈志杰教授。武汉大学化学与分子科学学院，430072传真：（+ 86）27-68754067 E-mail: cjwang@ whu。edu。cn
The Michael addition reaction is widely recognized as one of the most general and versatile methods for formation of CÀC bonds in organic synthesis.[1] Therefore, it is not surprising that the development of enantioselective catalytic protocols for this reaction has attracted much attention.[2] Efforts aimed at achieving asymmetric Michael addition by using powerful and environmentally friendly organocatalysts have been explored intensively in recent years.[3, 4] Of particular interest is the reaction between trisubstituted carbon nucleophiles and electron-deficient olefins to form Michael adducts containing adjacent quaternary and tertiary stereocenters, which are key units in complex natural products and highly valuable synthetic building blocks. Despite its great synthetic potential, only limited successful protocols have been reported to achieve high levels of enantio-and/or diastereoselectivity.[5] Compared with other asymmetric catalysis, the reaction simultaneously creating adjacent quaternary and tertiary stereocenters in one step is still in its infancy and the development of novel efficient catalysts showing high reactivity, enantioselectivity and diastereoselectivity still remains a great challenge. Recently, we reported a new class of bifunctional amine/thiourea catalysts I bearing multiple hydrogen-bonding donors, which showed excellent performance in catalytic asymmetric addition of acetylactone to nitroolefins and highly anti-selective nitro-Mannich reaction.[6, 7] Extending the interest of these organocatalyst in asymmetric catalysis, herein we report that another novel family of readily available, fine-tunable multiple hydrogen-bonding donor organocatalysts II [8, 9] results in high enantioselectivity, diastereoselectivity and broad scope in the asymmetric Michael addition of α-substituted β-ketoesters to various nitroolefins.[5c, e] Although amine/thioureas I were shown to be highly efficient for the addition of various of symmetric and asymmetric 1, 3-diketones to nitroolfeins, our initial attempts to apply I to promote the addition of α-substituted β-ketoesters to nitroolefins were unsuccessful (Table1). The reaction of methyl 2-oxo-cyclopentanecaboxylate (1a) to nitroolefin (2a) with catalysts I in CH2Cl2 went to completion at room temperature in less than 0.5 h, which was consistent with the case of 1, 3-diketone,[6] but the adduct 3a was formed in very low diastereoselectivity with moderate to good enantioselectivity for the major diastereomer, even at lower temperature [a] Z.-H. Zhang, X.-Q. Dong, D. Chen, Prof. Dr. C.-J. Wang College of Chemistry and Molecular Sciences Wuhan University, 430072 (PR China) Fax:(+ 86) 27-68754067 E-mail: cjwang@ whu. edu. cn