Copper-Mediated Coupling of 1,1-Dibromo-1-alkenes with Nitrogen Nucleophiles: A General Method for the Synthesis of Ynamides
Copper-Mediated Coupling of 1,1-Dibromo-1-alkenes with Nitrogen Nucleophiles: A General Method for the Synthesis of Ynamides
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DOI：
10.1002/anie.200901099
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Evano, Gwilherm
中科院分区：
文献类型：
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作者：
Coste, Alexis;Karthikeyan, Ganesan;Evano, Gwilherm
由于其上级的热稳定性相比，甜菜碱在过去的十年中受到了相当大的关注，显然是新兴的关键和多功能的合成中间体。[1]仅在最近，已证明双酰亚胺是闭环复分解、[2]钯介导的偶联反应或重排、[3]环异构化反应[4]和[2+ 2]环加成、[5]自由基转化、[6] Pauson-Khand环化、[7]非对映选择性σ迁移重排、[8]炔羰基复分解、[9]碳酰化、[10]以及许多其他有用的转换。它们也被用作制备各种分子的有效的双氢吡喃，如酮酰亚胺，[11]氨基吲哚，[12]恶唑酮，[13]咔唑，[14]三唑，[15]和苯并呋喃。[16]除了一些通常缺乏通用性的传统方法外，[1]最近出现了两种合成阿托奈德的方法。第一个依赖于使用高价炔基碘鎓盐[4 b，7]，而第二个，可能是迄今为止应用最广泛的，是铜催化的炔基溴与酰胺的偶联，[17]这是Goldberg反应的现代变体，最近已扩展到使用末端炔。[18]尽管取得了这些进展，但仍然需要一般的方法来制备酰胺类化合物，特别是因为现有的方法要么受到底物范围的限制，要么需要形成炔基化剂，要么使用大量过量的酰胺。用于制备二苯甲酰胺的有吸引力的替代方案将依赖于从容易获得的1，1-二溴-1-烯烃开始生成sp2类卡宾中间体，以及它们与氮亲核试剂的进一步反应（方案1）。如果成功的话，这一过程将特别方便和直接用于制备双酰亚胺。从铜催化的交叉偶联反应领域的最新经验中吸取，[19，20]我们想知道这样的反应是否可以使用催化量的铜（I）盐进行。两个重要的先例为我们研究这种转变提供了基础：
As a result of their superior thermal stability compared to ynamines, ynamides have received considerable attention over the past decade and are clearly emerging as key and versatile synthetic intermediates.[1] Only recently ynamides have been shown to be excellent substrates for ring-closing metathesis,[2] palladium-mediated coupling reactions or rearrangements,[3] cycloisomerization reactions [4] and [2+ 2] cycloadditions,[5] radical transformations,[6] Pauson–Khand cyclization,[7] diastereoselective sigmatropic rearrangements,[8] ynecarbonyl metathesis,[9] carbometalations,[10] as well as many other useful transformations. They have also been used as efficient synthons for the preparation of a wide array of molecules such as keto-imides,[11] amino-indoles,[12] oxazolones,[13] carbazoles,[14] triazoles,[15] and benzofurans.[16] In addition to a number of traditional approaches that often lack generality,[1] two methods for the synthesis of ynamides have recently emerged. The first one relies on the use of hypervalent alkynyliodonium salts [4b, 7] while the second one, perhaps the most widely applicable to date, is the coppercatalyzed coupling of alkynyl bromides with amides,[17] a modern variant of the Goldberg reaction which has recently been extended to the use of terminal alkynes.[18] Despite these advances, general methods are still needed for the preparation of ynamides, particularly because existing procedures suffer either from limited substrate scope, require the formation of the alkynylating agent, or use a large excess of the amide. An attractive alternative for the preparation of ynamides would rely on the generation of sp2 carbenoid intermediates starting from readily available 1, 1-dibromo-1-alkenes and their further reaction with nitrogen nucleophiles (Scheme 1). If successful, this procedure would be especially convenient and straightforward for the preparation of ynamides.Drawing from recent experiences in the field of coppercatalyzed cross coupling reactions,[19, 20] we wondered whether such a reaction could be performed using catalytic amounts of copper (I) salts. Two important precedents provided a basis for our investigation of this transformation: the synthesis of