Cooperative Organocatalysis for the Asymmetric γ Alkylation of α-Branched Enals
Cooperative Organocatalysis for the Asymmetric γ Alkylation of α-Branched Enals
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DOI：
10.1002/anie.201004761
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发表时间：
2010-01-01
影响因子：
16.6
通讯作者：
Melchiorre, Paolo
中科院分区：
文献类型：
--
作者：
Bergonzini, Giulia;Vera, Silvia;Melchiorre, Paolo
羰基化合物在g位的直接、催化和立体选择性功能化是不对称合成中一个极具挑战性和持久性的问题。[1,2]所有解决这一问题的尝试都必须解决位点选择性和立体选择性的挑战最近，我们的研究小组通过利用手性胺催化剂在与g烯化不饱和羰基化合物的缩合过程中原位形成亲核二胺中间体的能力，假设二胺催化是否可以为设计直接的葡萄制程提供一个通用平台。二胺催化是由Jørgensen及其同事[5]于2006年提出的，用于促进a， b不饱和醛的直接、对端选择性氨基化反应。然而，它的应用却很有限最近发表的关于有机催化出现的观点并没有将二胺催化列为一般的激活和诱导模式这可能是因为烯醛的氨基化最初被认为遵循特定的[4+ 2]环加成路径，而不是更普遍的亲核加成流形。最近，我们证明了二胺催化可以被利用来促进Michael加成模式下的葡萄亲核性，通过伯胺催化剂选择性激活未修饰的环a， b不饱和酮在此，我们报告了由二胺催化引起的葡萄树反应性也具有合成亲核取代反应的潜力。具体来说，我们描述了a取代的线性a不饱和醛通过SN1途径直接不对称烷基化。这种前所未有的转化[9]是通过一个交织的激活途径完成的，该途径成功地同时整合了二胺催化和Brønsted酸催化[10]。
The direct, catalytic, and stereoselective functionalization of carbonyl compounds at the g position represents a highly challenging and persistent problem for asymmetric synthesis.[1, 2] All attempts to solve this problem must address the challenge of site selectivity as well as stereoselectivity.[3] Recently, our research group hypothesized whether dienamine catalysis could provide a general platform for designing direct vinylogous processes,[4] by exploiting the ability of chiral amine catalysts to form a nucleophilic dienamine intermediate insitu in the condensation with g-enolizable unsaturated carbonyl compounds. Dienamine catalysis was introduced in 2006 by Jørgensen and co-workers [5] to promote the direct, enantioselective g amination of a, b-unsaturated aldehydes. However, it has since found limited application.[6] A recently published perspective on the advent of organocatalysis did not number dienamine catalysis among the generic modes of activation and induction.[7] This was probably a result of the fact that g amination of enals was originally thought to follow a particular [4+ 2] cycloaddition path,[5] instead of a more general nucleophilic addition manifold.Recently, we documented that dienamine catalysis can be exploited to promote vinylogous nucleophilicity within Michael addition patterns, upon selective activation of unmodified cyclic a, b-unsaturated ketones by primary amine catalysts.[8] Herein, we report that vinylogous reactivity induced by dienamine catalysis also has synthetic potential for nucleophilic substitution reactions. Specifically, we describe the direct asymmetric g alkylation of a-substituted linear a, bunsaturated aldehydes through an SN1 pathway. This unprecedented transformation [9] has been accomplished using an interwoven activation pathway that successfully integrates dienamine catalysis and Brønsted acid catalysis [10] simultaneously.