Chlorostyrenes in Iron-Catalyzed Biaryl Coupling Reactions
Chlorostyrenes in Iron-Catalyzed Biaryl Coupling Reactions
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DOI：
10.1002/anie.201106110
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Jacobi von Wangelin, Axel
中科院分区：
文献类型：
--
作者：
Guelak, Samet;Jacobi von Wangelin, Axel
钯和镍催化的交叉偶联反应是组装联芳基化合物的最广泛的方法之一，这些化合物构成了精细化工、材料、药物和天然产物的重要结构基元。芳基硼酸和芳基卤化物之间的Suzuki-Miyaura反应是在特别温和的条件下进行的，具有很高的官能团耐受性。[1，2]钯的世界市场价格不断上涨，[3]镍化合物的毒性，[4]以及芳基硼酸的费力合成[5]促使人们寻找强有力的替代品，特别是在工业过程中。过去的几年见证了铁催化方案的发展，这些方案具有很高的操作实用性和合成效率：前催化剂是廉价且无毒的铁盐；不需要复杂的、对空气敏感的配体；温和的反应条件允许各种官能团。[6]到目前为止，铁催化的芳基格氏物种和芳基(假)卤化物合成联芳基被证明是相当不选择性的。[7]此外，只有一种方案被报道有效地利用了廉价但迟缓的芳基氯化物，从而大大抑制了竞争同质偶联。这种方法需要一种特殊的氟化铁和卡宾配体的预催化剂组合，在前一步生成催化活性物种，并提高反应温度。[8]在我们针对铁催化的联芳基合成的研究项目中，我们开始对活化取代基的作用感兴趣。电负性杂原子基团通常会增强其反应活性。然而，碳氢化合物作为活性取代基很少受到关注。[10]基于低氧化态中烯烃与铁的丰富配位化学，我们推测了一种新的烯烃取代芳基氯化物的活化模式。[11]我们假设催化剂上顺序的烯烃配位和亲触性迁移可以影响氯苯乙烯的C+Cl键活化。在此，我们报道了一种利用这一前所未有的活化机制进行铁催化合成联芳基的有效方法。在三(乙酰丙酮)铁[Fe(Acac)3]作预催化剂的条件下，芳基格氏物种与氯苯乙烯的反应在温和而实用的条件下进行。乙烯基团上的竞争反应(如聚合、碳金属化和取代)不会发生(方案1)。
Palladium-and nickel-catalyzed cross-coupling reactions are among the most versatile methods for the assembly of biaryl compounds, which constitute important structural motifs of fine chemicals, materials, pharmaceuticals, and natural products. Suzuki–Miyaura reactions between arylboronic acids and aryl halides are carried out under especially mild conditions and exhibit high functional-group tolerance.[1, 2] The constantly increasing world market price of palladium,[3] the toxicity of nickel compounds,[4] and the laborious synthesis of arylboronic acids [5] are prompting the search for powerful alternatives, especially for industrial processes. The past years have witnessed the development of iron-catalyzed protocols, which boast high operational practicality and synthetic efficiency: the precatalysts are cheap and nontoxic iron salts; complex, air-sensitive ligands are not required; the mild reaction conditions tolerate various functional groups.[6] To date, iron-catalyzed biaryl syntheses from aryl Grignard species and aryl (pseudo) halides proved rather unselective.[7] Furthermore, only one protocol that largely suppressed the competing homocoupling has been reported for the effective utilization of cheap but sluggish aryl chlorides. This method requires a special precatalyst combination of iron (II) fluoride and a carbene ligand, the generation of the catalytically active species in a prior step, and elevated reaction temperatures.[8] During our research program directed at iron-catalyzed biaryl syntheses, we became interested in the role of activating substituents. Electronegative heteroatom-based groups at the electrophile generally enhance its reactivity.[9] Hydrocarbons, however, have received only little attention as activating substituents.[10] Based upon the rich coordination chemistry of olefins with iron in low oxidation states, we postulated a novel mode of activation for olefin-substituted aryl chlorides.[11] We assumed that sequential olefin coordination at the catalyst and haptotropic migration could effect CÀCl bond activation of chlorostyrenes. Herein, we report an efficient iron-catalyzed biaryl synthesis by exploiting this unprecedented activation mechanism. The reaction of aryl Grignard species with chlorostyrenes proceeds under mild and practical reaction conditions in the presence of iron (III) tris (acetylacetonate)[Fe (acac) 3] as precatalyst. Competitive reactions at the vinyl group (eg, polymerization, carbometalation, and substitution) do not occur (Scheme 1).[12]