Control of four stereocentres in a triple cascade organocatalytic reaction
Control of four stereocentres in a triple cascade organocatalytic reaction
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DOI：
10.1038/nature04820
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发表时间：
2006-06-15
期刊：
影响因子：
64.8
通讯作者：
Raabe, Gerhard
中科院分区：
文献类型：
--
作者：
Enders, Dieter;Hüettl, Matthias R. M.;Raabe, Gerhard
具有多个立体中心的复杂有机分子的高效和优雅的合成在学术和工业实验室中仍然很重要（1）。特别地，在天然产物和合成结构单元的全合成期间使用的催化不对称多组分"多米诺"反应是高度期望的（2，3）。这些反应避免了耗时和昂贵的过程，包括中间体的纯化和涉及官能团保护和脱保护的步骤，并且它们是环境友好的，并且通常以优异的立体选择性进行（4，5）。因此，设计新的催化和立体选择性级联反应是合成化学前沿的一个持续挑战（6）。此外，催化级联反应可以被描述为仿生，因为它们让人想起复杂天然产物生物合成过程中可能发生的串联反应（7，8）。在这里，我们报告了一个不对称的有机催化三重级联反应的发展，用于合成四取代环己烯甲醛。这一三组分多米诺反应通过催化的迈克尔/迈克尔/羟醛缩合顺序进行，产物产率较高至中等（25 - 58%）。在该序列中，形成了四个具有高非对映选择性和完全对映选择性的立体中心。此外，原料的变化可用于获得不同的多官能环己烯衍生物，其可用作有机合成中的结构单元。
Efficient and elegant syntheses of complex organic molecules with multiple stereogenic centres continue to be important in both academic and industrial laboratories(1). In particular, catalytic asymmetric multi-component 'domino' reactions, used during total syntheses of natural products and synthetic building blocks, are highly desirable(2,3). These reactions avoid time-consuming and costly processes, including the purification of intermediates and steps involving the protection and deprotection of functional groups, and they are environmentally friendly and often proceed with excellent stereoselectivities(4,5). Therefore, the design of new catalytic and stereoselective cascade reactions is a continuing challenge at the forefront of synthetic chemistry(6). In addition, catalytic cascade reactions can be described as biomimetic, as they are reminiscent of tandem reactions that may occur during biosyntheses of complex natural products(7,8). Here we report the development of an asymmetric organocatalytic triple cascade reaction for the synthesis of tetra-substituted cyclohexene carbaldehydes. This three-component domino reaction proceeds by way of a catalysed Michael/Michael/aldol condensation sequence affording the products with good to moderate yields (25-58 per cent). During this sequence, four stereogenic centres are formed with high diastereoselectivity and complete enantioselectivity. In addition, variation of the starting materials can be used to obtain diverse polyfunctional cyclohexene derivatives, which can be used as building blocks in organic synthesis.