syn-selective and enantioselective direct cross-aldol reactions between aldehydes catalyzed by an axially chiral amino sulfonamide
syn-selective and enantioselective direct cross-aldol reactions between aldehydes catalyzed by an axially chiral amino sulfonamide
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DOI：
10.1002/anie.200604640
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Maruoka, Keiji
中科院分区：
文献类型：
--
作者：
Kano, Taichi;Yamaguchi, Yukako;Maruoka, Keiji
Aldol反应一直被认为是构建新的碳-碳键的最基本的工具之一。[1]在该领域中，已知两种不同醛之间的交叉羟醛缩合反应通常是有问题的，因为存在不期望的副反应，包括产物的脱水、自羟醛缩合反应和烯醇化物向羟醛缩合产物的多次加成。然而，到目前为止，已经报道了几种使用衍生自金属烯醇化物的crossaldol反应，包括作为亲核试剂的甲硅烷基烯醇醚和/或作为亲电试剂的不可烯醇化或缓慢烯醇化的醛，[2-9]并且最近开发了该反应的催化不对称版本的一些罕见实例。[10-16]例如，醛和甲硅烷基烯醇醚之间的非对映体和对映体选择性交叉羟醛缩合反应首先由丹麦等人用手性刘易斯碱催化剂完成，[10]并且最近小林和同事证明了手性刘易斯酸催化的非对映体和对映体选择性反应，其使用衍生的烯氨基甲酸酯作为活化的醛亲核试剂。[11]用这些方法，顺式和反式非对映异构体分别以高度对映选择性的方式形成。另一方面，据我们所知，MacMillan及其同事首次报道的醛的大多数有机催化的直接对映选择性交叉羟醛缩合反应主要提供反羟醛加成物[12-17]，尽管只有少数例外得到顺式加成物。[12d]在这方面，我们一直感兴趣的可能性，开发一个顺式选择性直接交叉醛醇缩合反应两种不同的醛之间使用手性有机催化剂。本文报道了一种轴手性氨基磺酰胺（S）-1催化的顺式选择性和对映选择性的直接交叉羟醛缩合反应。我们的策略是基于最近的观察，即在脯氨酸催化的反应中，轴手性氨基磺酰胺（S）-1催化的直接不对称Mannich反应主要生成反式产物，它是次要的非对映体。[18]由于由供体醛和（S）-1产生的反烯胺A难以与被（S）-1的三氟甲磺酰胺的远端酸性质子活化的受体醛反应，因此预期由（S）-1催化的crossaldol反应将通过顺烯胺中间体B进行，从而得到如方案1所示的所需的不寻常的顺式产物。
The aldol reaction has long been recognized as one of the most fundamental tools for the construction of new carbon–carbon bonds.[1] In this area, the cross-aldol reaction between two different aldehydes is known to be often problematic because of undesired side reactions, including dehydration of the product, self-aldol reaction, and multiple addition of the enolate to the aldol product. To date, however, several crossaldol reactions using aldehyde-derived metal enolates, including silyl enol ethers as nucleophile and/or non-or slowly enolizable aldehydes as electrophile, have been reported,[2–9] and some rare examples of the catalytic asymmetric version of this reaction have recently been developed.[10–16] For example, the diastereo-and enantioselective cross-aldol reaction between aldehydes and silyl enol ethers was first accomplished by Denmark et al. with chiral Lewis base catalysts,[10] and very recently Kobayashi and co-workers demonstrated the chiral Lewis acid catalyzed diastereo-and enantioselective reaction using aldehyde-derived enecarbamates as an activated aldehyde nucleophile.[11] With these methods, both the syn and anti diastereomers, respectively, were formed in a highly enantioselective fashion. On the other hand, to the best of our knowledge, most organocatalytic direct enantioselective cross-aldol reactions of aldehydes, first reported by MacMillan and co-workers, provide predominantly anti aldol adducts,[12–17] albeit with only a few exceptions giving syn adducts.[12d] In this context, we have been interested in the possibility of developing a syn-selective direct cross-aldol reaction between two different aldehydes by using a chiral organocatalyst. Herein we wish to report such a syn-selective and enantioselective direct cross-aldol reaction catalyzed by an axially chiral amino sulfonamide of type (S)-1.Our strategy is based on the recent observation that a direct asymmetric Mannich reaction is catalyzed by the axially chiral amino sulfonamide (S)-1 to give the anti product predominantly, which is a minor diastereomer in the prolinecatalyzed reaction.[18] Since it would be difficult for anti enamine A, which is generated from a donor aldehyde and (S)-1, to react with an acceptor aldehyde that is activated by the distal acidic proton of the triflamide of (S)-1, the crossaldol reaction catalyzed by (S)-1 would be expected to proceed through syn enamine intermediate B, thus giving the desired unusual syn product as shown in Scheme 1.