Diphenylprolinol silyl ether as a catalyst in an enantioselective, catalytic, tandem Michael/Henry reaction for the control of four stereocenters
Diphenylprolinol silyl ether as a catalyst in an enantioselective, catalytic, tandem Michael/Henry reaction for the control of four stereocenters
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DOI：
10.1002/anie.200700909
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Hazelard, Damien
中科院分区：
文献类型：
--
作者：
Hayashi, Yujiro;Okano, Tsubasa;Hazelard, Damien
在一次操作中控制多个立体中心形成碳-碳键不仅是一个合成挑战，而且是构建复杂分子的一种有用的方法。串联反应是实现这些目标的方法学的一个非常有力的例子。[1]取代的手性环己烷是有机合成中的重要构件，而相对和绝对构型的控制是制备这些多功能骨架的关键问题。Diels-Alder环加成反应是催化不对称合成环己烷衍生物的一种广泛应用的方法，通常由手性路易斯酸[2]或最近发展起来的手性有机催化剂之一催化。[3]近年来开发了许多有效的有机催化剂，[4]并用具有高对映选择性的有机催化剂合成了手性环己烷和环己烯。[5]二芳基丙醇硅醚最初是由Jørgensen S[5c，d，f，6]和我们的基团[7]独立开发的，最近被用于几个不对称反应。[8]我们发现二苯丙醇硅基醚是醛和硝基烯直接不对称Michael反应的有效有机催化剂，提供具有高合成选择性和良好对映体选择性的Michael加合物。[7A]在我们发现后，发现二苯丙醇甲醚可以促进醛和甲基乙烯基酮的不对称Michael反应，[8a]Enders和他的同事们将我们的反应扩展到一个三级联反应，一步合成手性环己醛。约根森和他的同事们还报道了一种涉及二芳基脯氨醇硅醚的三级联反应。[5F]作为这种有机催化剂在不对称反应中的进一步应用，我们开发了一个高度对映选择性的串联Michael[9]/Henry[10]反应，它在一次操作中提供了具有良好的非对映和对映选择性的取代手性环己烷醛和四个立体中心的控制。我们预计戊烷-1，5-转盘和硝基烯烃将分别作为四碳单元和两碳单元。也就是说，如方案1所示，我们假设烯胺2将由戊烷-1，5-Dial和催化剂1生成，并且根据我们之前的发现，它将在Michael反应中与硝基烯反应生成3。[7A]两性离子3将在分子内Henry反应中与醛部分反应生成4，后者将被水解以提供取代的环己烷甲醛5。这最后两个反应的顺序可能颠倒(即亚胺离子3的水解之后的Henry反应可能提供5)。如果商业上可以获得的2，5-二羟基-3，4-二氢呋喃水溶液[11]可以用作戊烷-1，5-二环己烷的替代品，那将是很方便的。在平衡条件下，2，5-二羟基-3，4-二氢呋喃在水溶液中可以生成戊烷-1，5-二氢呋喃，并且已知有机催化剂介导的Aldol[12，13]和Michael反应[14]可以在水或水的条件下进行。[15]这个反应将在一次操作中产生四个立体中心，形成两个碳-碳键，因此控制相对和绝对构型将是一个重要的问题。我们选择了硝基苯乙烯作为模型的硝基烯烃。我们最初使用水作为溶剂，但由于固体硝基苯乙烯不溶解，反应几乎无法进行。接下来，有机溶剂的使用：…
The formation of carbon–carbon bonds with the control of multiple stereocenters in a single operation is not only a synthetic challenge but also a useful method for the construction of complex molecules. Tandem reactions are a very powerful example of a methodology used to achieve these aims.[1] Substituted chiral cyclohexanes are important building blocks in organic synthesis, and the control of the relative and absolute configurations is a key issue in the preparation of these versatile frameworks. The Diels–Alder cycloaddition is one widely employed method for the catalytic enantioselective synthesis of cyclohexane derivatives, most often catalyzed by either a chiral Lewis acid [2] or one of the recently developed chiral organocatalysts.[3] Many effective organocatalysts have been developed in recent years,[4] and chiral cyclohexanes and cyclohexenes have been synthesized by organocatalysts with high enantioselectivity.[5] Diarylprolinol silyl ether, which was originally developed by Jørgensen s [5c, d, f, 6] and our groups [7] independently, has recently been utilized in several enantioselective reactions.[8] We have found that diphenylprolinol silyl ether is an effective organocatalyst for the direct enantioselective Michael reaction of aldehydes and nitroalkenes to afford the Michael adduct with high syn selectivity and excellent enantioselectivity.[7a] After our discovery, diphenylprolinol methyl ether was found to promote the enantioselective Michael reaction of aldehydes and methyl vinyl ketone,[8a] and Enders and co-workers expanded our reaction to a triple cascade reaction for the synthesis of chiral cyclohexenecarbaldehydes with control of four stereocenters in one operation.[5e] Just recently, Jørgensen and co-workers also reported a triple cascade reaction involving diarylprolinol silyl ether.[5f] As a further application of this organocatalyst in asymmetric reactions, we have developed a highly enantioselective tandem Michael [9]/Henry [10] reaction, which affords, in a single operation, substituted chiral nitrocyclohexanecarbaldehydes with excellent diastereo-and enantioselectivities and control of four stereogenic centers. We anticipated that pentane-1, 5-dial and a nitroalkene would act as a four-carbon unit and a two-carbon unit, respectively. That is, as shown in Scheme 1, we hypothesized that enamine 2 would be generated from pentane-1, 5-dial and catalyst 1 and that it would react with a nitroalkene in a Michael reaction to generate 3, in accordance with our previous findings.[7a] Zwitterion 3 would then react with the aldehyde moiety in an intramolecular Henry reaction to provide 4, which would be hydrolyzed to provide substituted nitrocyclohexanecarbaldehyde 5. The order of these last two reactions might be reversed (that is, hydrolysis of iminium ion 3 followed by the Henry reaction might provide 5). It would be convenient if commercially available aqueous 2, 5-dihydroxy-3, 4-dihydrofuran solution [11] could be used as a surrogate for pentane-1, 5-dial. Pentane-1, 5-dial would be generated from 2, 5-dihydroxy-3, 4-dihydrofuran in aqueous solution under equilibrium conditions, and it is known that organocatalyst-mediated aldol [12, 13] and Michael reactions [14] can proceed in aqueous conditions or in the presence of water.[15] This reaction would generate, in one operation, four stereogenic centers with the formation of two carbon–carbon bonds, and control of the relative and absolute configurations would therefore be an important issue. We chose nitrostyrene as our model nitroalkene. We first used water as the solvent, but the reaction scarcely proceeded because the solid nitrostyrene did not dissolve. Next, the use of organic solvents …