Proline-catalyzed direct asymmetric aldol reactions
Proline-catalyzed direct asymmetric aldol reactions
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DOI：
10.1021/ja994280y
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发表时间：
2000-03-15
影响因子：
15
通讯作者：
Barbas, CF
中科院分区：
文献类型：
--
作者：
List, B;Lerner, RA;Barbas, CF
大多数酶转化都有一个合成的对应物。然而，通常情况下，天然催化剂和合成催化剂的作用机制明显不同。催化不对称醛醇反应是化学和生物学中一个基本的CC键形成反应，在这方面是一个有趣的例子。在化学上，这种反应主要是利用预先形成的烯酸酯等价物与手性催化剂结合的方法。典型地，一种金属参与了反应机制。然而，大多数酶使用一种根本不同的策略，催化两种未经修饰的羰基化合物的直接醛化。第一类醛缩酶利用基于烯胺的机制2，而第二类醛缩酶通过锌辅助因子介导这一过程。利用烯胺机制和接受疏水有机底物的醛缩酶抗体的发展已经证明了胺催化的不对称醛缩反应的内在潜力。最近，首次以锌、镧和钡配合物的形式描述了小分子不对称II类醛缩酶模拟物。然而，基于胺的不对称I类醛缩酶模拟物尚未在文献中描述。在这里，我们报告了我们的发现，氨基酸脯氨酸是一种有效的不对称催化剂，用于未修饰的丙酮和各种醛之间的直接醛醇反应。
Most enzymatic transformations have a synthetic counterpart. Often though, the mechanisms by which natural and synthetic catalysts operate differ markedly. The catalytic asymmetric aldol reaction as a fundamental CC bond forming reaction in chemistry and biology is an interesting case in this respect. Chemically, this reaction is dominated by approaches that utilize preformed enolate equivalents in combination with a chiral catalyst. 1 Typically, a metal is involved in the reaction mechanism. 1d Most enzymes, however, use a fundamentally different strategy and catalyze the direct aldolization of two unmodified carbonyl compounds. Class I aldolases utilize an enamine based mechanism, 2 while Class II aldolases mediate this process by using a zinc cofactor. 3 The development of aldolase antibodies that use an enamine mechanism and accept hydrophobic organic substrates has demonstrated the potential inherent in amine-catalyzed asymmetric aldol reactions. 4 Recently, the first small-molecule asymmetric class II aldolase mimics have been described in the form of zinc, lanthanum, and barium complexes. 5, 6 However, amine-based asymmetric class I aldolase mimics have not been described in the literature. 7 Here we report our finding that the amino acid proline is an effective asymmetric catalyst for the direct aldol reaction between unmodified acetone and a variety of aldehydes.