Organocatalytic asymmetric conjugate addition of 1,3-dicarbonyl compounds to maleimides
Organocatalytic asymmetric conjugate addition of 1,3-dicarbonyl compounds to maleimides
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DOI：
10.1002/anie.200600370
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Melchiorre, Paolo
中科院分区：
文献类型：
--
作者：
Bartoli, Giuseppe;Bosco, Marcella;Melchiorre, Paolo
与环状和非环状β-酮酯以及与环状β-二酮的对映体选择性（高达98%ee）和非对映体选择性（dr=高达> 98：2）。此外，该策略是基于一个操作简单的程序，其中使用未经修改的廉价和商业上可获得的起始原料和催化剂。不对称共轭加成的碳中心的亲核试剂的马来酰亚胺应该提供一个实用的路线合成和生物学上重要的手性α-取代琥珀酰亚胺。[10]因此，令人惊讶的是，据我们所知，迄今为止只有一种有效的不对称策略被描述。[11]我们的有机催化不对称方法的可行性首先通过在催化量的金鸡纳生物碱衍生物（10mol%）的存在下将2-氧代-1-茚满羧酸甲酯（1a）和马来酰亚胺（2a）在二氯甲烷（0.5 m）中混合来测试;使用方案1中所示的生物碱广泛筛选反应条件的代表性结果列于表1中。天然金鸡纳生物碱奎宁（Q）被证明是最有前途的催化剂，并提供了相对良好的非对映体和对映体选择性的1，4-加合物（表1，条目2）。合成的金鸡纳生物碱衍生物A和B是几种不对称C12 C键形成反应的广泛有效的双功能有机催化剂，[12]结果不佳（表1，条目3和4）。刚性酚类奎尼丁衍生物β-异铜精（C;示意图1）[13]以令人满意的选择性促进了共轭加成（表1，条目5），但当反应在208 ℃下进行时获得的结果表明Q和C之间在催化活性方面存在显著差异（表1，条目6/7和8/9）。
of both enantio-(up to 98% ee) and diastereoselectivity (dr= up to> 98: 2) with both cyclic and acyclic β-ketoesters and with cyclic β-diketones. Furthermore, the strategy is based on an operationally simple procedure in which unmodified cheap and commercially available starting materials and catalysts are used.The asymmetric conjugate addition of carbon-centered nucleophiles to maleimides should provide a practical route to synthetically and biologically important chiral α-substituted succinimides.[10] Therefore, it is surprising that, to our knowledge, just one effective asymmetric strategy has been described to date.[11] The feasibility of our organocatalytic asymmetric approach was first tested by mixing methyl-2-oxo-1-indanecarboxylate (1a) and maleimide (2a) in dichloromethane (0.5 m) in the presence of a catalytic amount of a cinchona alkaloid derivative (10mol%); representative results of the extensive screen of reaction conditions using the alkaloids shown in Scheme 1 are listed in Table 1. The natural cinchona alkaloid quinine (Q) proved to be the most promising catalyst and afforded the 1, 4-adduct with relatively good diastereo-and enantioselectivity (Table 1, entry 2). The synthetic cinchona alkaloid derivatives A and B, which are broadly effective bifunctional organocatalysts for several asymmetric CÀC bond-forming reactions,[12] gave poor results (Table1, entries3 and 4). The rigid phenolic quinidine derivative β-isocupreidine (C; Scheme1)[13] promoted the conjugate addition with satisfactory selectivity (Table1, entry5), but the results obtained when the reaction was performed at À208C indicated a significant difference between Q and C in terms of catalytic activity (Table1, entries 6/7 and 8/9).