Quinidine thiourea-catalyzed aldol reaction of unactivated ketones: highly enantioselective synthesis of 3-alkyl-3-hydroxyindolin-2-ones.
Quinidine thiourea-catalyzed aldol reaction of unactivated ketones: highly enantioselective synthesis of 3-alkyl-3-hydroxyindolin-2-ones.
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DOI：
10.1002/anie.201004161
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发表时间：
2010-12-03
影响因子：
16.6
通讯作者：
Zhao, Cong-Gui
中科院分区：
文献类型：
--
作者：
Guo, Qunsheng;Bhanushali, Mayur;Zhao, Cong-Gui
Aldol反应是最重要的碳-碳键形成反应之一，因此，过去已经开发了许多该反应的不对称变体。1自从List和Barbas发现了酮和醛的不对称交叉Aldol反应以来，人们已经开发出了许多用于不对称交叉Aldol反应的胺类化合物，主要是Pro类化合物。3从机理上讲，这些催化剂通过形成烯胺中间体来活化酮或可烯化的醛(方案1，上式)。3反应机理通常是共价和非共价催化剂的组合，因为大多数催化剂还含有氢键部分，以引导烯胺受体的接近。相反，尽管烯醇和烯醇(方案1，下式)是原始羟醛反应中的活性中间体，4未活化酮通过烯醇机理进行的有机催化的对映选择性直接羟醛反应是非常困难的，因为这些酮中的α-质子的酸性很低。据我们所知，还没有这样的报道。然而，烯化机制确实有一定的优点，特别是当烯胺难以形成时。在我们使用活化酮类化合物作为烯胺受体进行有机催化的Aldol反应的研究中，8我们设想，如果烯醇受体被充分激活，这种有机催化的烯醇介导的Aldol反应应该是可能的，因为平衡有利于与这样的底物形成产物。本文报道了首次涉及烯醇化反应的未活化酮的不对称Aldol反应，该反应可用于3-烷基-3-羟基吲哚-2-酮的高对映选择性合成。9.
Aldol reaction is one of the most important carbon-carbon bond formation reactions1 and, therefore, many asymmetric variants of this reaction have been developed in the past. 1 Since List and Barbas discovered the proline-catalyzed cross aldol reaction of ketones and aldehydes, 2 many amine derivatives, mainly proline derivatives, have been developed for the asymmetric cross aldol reactions. 3 Mechanistically, these catalysts activate the ketones or enolizable aldehydes through the formation of an enamine intermediate (Scheme 1, upper equation). 3 The mechanism is usually a combination of both covalent and noncovalent catalyses since most of these catalysts also contain a hydrogen bonding moiety to direct the approach of the enamine acceptor. In contrast, although enol and enolate (Scheme 1, lower equation) are the active intermediates in the original aldol reactions, 4 organocatalyzed enantioselective direct aldol reaction of unactivated ketones via the enolate mechanism is very difficult, because the acidity of the α-proton in these ketones is very low. To our knowledge, there has been no such report. 5, 6, 7 Nevertheless, the enolate mechanism does have certain advantages, especially when the formation of an enamine is difficult. During our study of using activated ketone compounds as the enamine acceptors for the organocatalyzed aldol reactions, 8 we envisioned such an organocatalyzed enolate-mediated aldol reaction should be possible if the enolate acceptor is sufficiently activated, because the equilibrium favors the formation of the product with such a substrate. Herein we wish to report the first enantioselective aldol reaction of unactivated ketones involving the enolate mechanism, which may be used for the high enantioselective synthesis of 3-alkyl-3-hydroxyindolin-2-ones. 9
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影响因子：
15
作者：
Li, Le;Klauber, Eric G.;Seidel, Daniel
通讯作者：
Seidel, Daniel
影响因子：
1.8
作者：
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通讯作者：
Tomasini, Claudia
影响因子：
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作者：
Dodda, Rajasekhar;Zhao, Cong-Gui
通讯作者：
Zhao, Cong-Gui
影响因子：
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作者：
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通讯作者：
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影响因子：
4.3
作者：
Connon, Stephen J.
通讯作者：
Connon, Stephen J.