Rate-accelerated nonconventional amide synthesis in water: A practical catalytic aldol-surrogate reaction
Rate-accelerated nonconventional amide synthesis in water: A practical catalytic aldol-surrogate reaction
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DOI：
10.1002/anie.200604358
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Chang, Sukbok
中科院分区：
文献类型：
--
作者：
Cho, Seung Hwan;Chang, Sukbok
羟醛缩合反应是一种强有力的β-羟基羰基单元的合成方法，β-羟基羰基单元是有机合成中用途非常广泛的结构单元。[1]尽管在过去的几十年中，在高度立体选择性的羟醛缩合反应的发展方面取得了巨大的进展，但它们通常依赖于类似的基本策略：在促进剂的存在下，将可烯醇化的羰基化合物加成到醛或酮上。[2]因此，含有不稳定官能团的底物在烯醇形成的条件下是不适合的。[3]最近，我们报道了高效的Cu催化的末端炔、磺酰叠氮和胺或醇的三组分反应，以提供脒或亚胺酯。[4]目前认为，该反应是通过常见的乙烯酮亚胺中间体进行的，该中间体是由铜介导的叠氮化物和炔的分子间环加成反应，然后释放N2产生的。[5]在此假设的基础上，一种新的非传统的酰胺合成可以实现通过允许合理的烯酮亚胺中间体与水反应。[6]我们随后设想，将该方案应用于炔丙醇底物可能会在温和和实用的条件下产生β-羟基N-磺酰胺。由于这些组分不容易通过传统的羟醛过程获得，[7]我们预计我们的方法将是制备这些合成通用化合物的优秀羟醛替代物。我们的结果在本文中进行了描述（方案1）。[8]在最初的研究中，我们计划研究在水性溶剂体系中进行Cu催化的水合酰胺合成的可行性，因为这些天对在水性溶剂中的有机反应的开发有强烈的需求。此外，经常观察到反应在水性溶剂体系中比在有机溶剂中更快。[9]首先在CuI催化剂和三乙胺存在下，在4-叔丁基苯乙炔与对甲苯磺酰叠氮的测试反应中仔细检查各种反应介质（表1）。我们
The aldol reaction is a powerful method for installing βhydroxycarbonyl units, which are extremely versatile building blocks in organic synthesis.[1] Although tremendous progress has been made during the last few decades in the development of highly stereoselective aldol reactions, they usually rely on a similar basic strategy: the addition of enolizable carbonyl compounds to an aldehyde or ketone in the presence of promoters.[2] Accordingly, substrates containing labile functional groups are not amenable under conditions for enol formation.[3]Recently, we reported the highly efficient Cu-catalyzed three-component reactions of terminal alkynes, sulfonyl azides, and amines or alcohols to afford amidines or imidates.[4] It is believed at present that the reaction proceeds via a common ketenimine intermediate, which is generated from the copper-mediated intermolecular cycloaddition of azides and alkynes followed by the release of N2.[5] On the basis of this postulate, a novel nonconventional amide synthesis could be realized by allowing the plausible ketenimine intermediate to react with water.[6] We subsequently envisioned that application of this protocol to propargyl alcohol substrates might lead to β-hydroxy N-sulfonamides under mild and practical conditions. Since these components are not easily accessed through traditional aldol processes,[7] we anticipated that our approach would be an excellent aldol surrogate for the preparation of these synthetically versatile compounds. Our results are described herein (Scheme 1).[8] In initial studies we planned to examine the feasibility of performing the Cu-catalyzed hydrative amide synthesis in aqueous solvent systems, as the development of organic reactions in aqueous solvents is in strong demand these days. Additionally, reactions are frequently observed to be faster in aqueous solvent systems than in organic solvents.[9] Various reaction media were first scrutinized in a test reaction of 4-tert-butylphenylacetylene with p-toluenesulfonyl azide in the presence of CuI catalyst and triethylamine (Table1). We