【作者】 谢凯；

【导师】 谭泽；

【作者基本信息】 湖南大学 ， 有机化学， 2012， 博士

【摘要】 钯催化的卤代烃与芳基金属交叉偶联反应是合成联芳烃的有效方法。由于多数情况下要预先制备化学计量的有机金属试剂，因此有必要发展更加高效、绿色的偶联反应。Goossen开创了钯催化的芳香羧酸与卤化烃的脱羧偶联反应，从而为金属钯催化开辟一个新的研究方向，这一课题成为最近十年金属有机化学研究的热点。芳香羧酸在偶联反应中具有既可作为亲电试剂，又可作为亲核试剂的特殊性质，这样可以参与的反应非常多，应用前景广泛。使用芳香羧酸作为偶联反应底物，制备简单，来源丰富。本文发展一系列钯催化的芳香羧酸为底物构建碳碳键的有机合成新反应，且反应原子经济性较高，对环境污染较小。本论文的具体内容包括以下几个方面：1、综述了近年来钯催化芳香羧酸的脱羧偶联反应，钯或铜催化的联苯类化合物的合成反应，钯催化的烯基芳烃的芳构化反应、铟催化的C-C键的形成反应等研究进展。2、研究了钯催化的苯并噻唑、苯并噁唑以及五氟苯类化合物与取代苯甲酸的脱羧偶联反应。采用的反应体系是20mol%氯化钯作催化剂，40mol%三苯基膦作配体，3.0当量碳酸银作碱和氧化剂，DMSO作溶剂，反应温度130oC。利用该反应条件，合成了一系列的噻唑、噁唑的衍生物和多氟取代联苯类化合物，并对反应提出了两种可能性的机理。通过后续处理可回收一部分的银盐，使得该反应原子经济性较高，对环境友好，适应于绿色化学。3、研究了钯催化的芳香羧酸的自身偶联和交叉偶联反应，合成了一系列的对称与不对称的联苯型化合物。与传统的重氮化反应及Ullmann反应相比，具有条件简单、底物来源丰富的优点，可应用于众多天然产物、手性配体、液晶材料的合成。4、实现了钯催化的芳香羧酸与苯硼酸的脱羧偶联反应。反应体系有低毒性、原料易于保存的特点，但存在着有较大量的副产物干扰产物分离的缺点。5、研究了钯催化的烯基酰胺的氧化脱氢反应，芳构化生成乙酰苯胺类化合物。该反应同样使用Pd-Ag-酸-DMSO的催化体系，其中催化量的羧酸作为助剂，较大幅度提高了反应的产率。该反应方法条件温和，产率高，在合成天然芳香化合物以及生物碱中可起到一定的作用。6、研究了铟盐催化的芳基烯烃分子内环化反应，合成了四氢化萘和苯并二氢吡喃类化合物，并提出了可能机理。四氢化萘和苯并二氢吡喃广泛存在于天然产物中，具有一定的生理活性和药用价值。相比于钌盐和银盐共催化的分子内环化反应，使用三氟甲基磺酸铟作催化剂，产率较高，区域选择性也较高，且铟的价格比钌更便宜，适合较大规模生产。7、应用强碱和菲啰啉配体，在较高温度下实现了卤代芳烃分子内的自由基关环反应。加入无水Fe(OAc)2催化剂也可以得到相应产物。该反应方法可应用于含有氧原子或氮原子的稠环化合物的合成。以上有机合成新方法的研究，拓展了芳香羧酸在偶联方面的应用范围，可应用于天然产物、医药化合物、生物碱、手性配体及联苯型液晶材料等合成，适应于现代有机化学发展的趋势。更多还原

【Abstract】 Pd-catalyzed cross-coupling between aryl halides and aryl metals has becomeone of the most powerful methods for the syntheses of biaryls. However, onefundamental drawback with these coupling reactions is that they require the use of astoichiometric amount of an expensive organometallic reagent that often has to beprepared either beforehand or in situ. Recently, benzoic acids have emerged as viablecoupling partners, largely through the efforts of Goossen and others.What is interesting is that benzoic acids can be used not only as the source ofthe aryl electrophile but also as the aryl metal equivalent after undergoing in situdecarboxylation to generate the aryl-Pd species. As a result, we have decided to developPd-catalyzed couplings that use benzoic acids as substates.In this thesis a series of reactions catalzyled either by Pd or In were studied andthe results are described.In chapter1, a general review on Pd-catalyze decarboxylation coupling, Pd-orCu-catalyzed biphenyl synthesis and In-catalyze carbon-carbon bond-formingreaction was given.In chapter2, we have shown that, using Pd as the catalyst and Ag2CO3as thebase and the oxidant, substituted benzoic acids can be used to arylate thiazoles,benzoxazole and polyfluorobenzenes after in situ decarboxylation. We opted to usethe combination of PdCl2/2PPh3/Ag2CO3as our standard conditions. The reactionoccurs with high chemo-and regioselectivity, representing an excellent alternative tothose Pd-, Ni-, or Cu-catalyzed coupling with aryl halides and sulfonates.In chapter3, we have demonstrated that not only symmetrical but alsounsymmetrical biaryls can be efficiently synthesized through the Pd-catalyzeddecarboxylative homo-or heterocoupling of substituted benzoic acids. Compared tothe traditional route of first converting the acids into amines, followed bydiazotization to form aryl halides, which are then subjected to Ullmann couplingconditions to produce the desired biaryls,this method is much more straightforwardand simple to run, provided that the needed benzoic acid is commercially availableor can be readily synthesized.In chapter4, an efficient Pd-catalyzed decarboxylative coupling reaction forpreparing biaryl from benzoic acid and phenyl boronic acid has been developed. In chapter5, a novel way of converting cyclohexenamides into anilides wasdeveloped with Pd-catalysis using Ag2CO3as the oxidant. The high yield of thereaction was found to be critically dependent on the addition of a catalytic amount ofacid as additive.In chapter6, we have developed a method for the synthesis of tetralin andchromane derivatives via an intramolecular hydroarylation of ω-aryl-1-alkenes viaIn-catalysis. Tetralins and chromanes are important structural motifs and they arepresent in a wide variety of natural products and pharmaceuticals. The use ofcheaper indium salts instead of the expensive noble metal Ru could be advantageouswhen the reaction is run on a large scale. Though narrower in substrate scope, theindium catalyzed reaction could potentially be useful in selected cases andcomplementary to the Ru-catalyzed version.In chapter7, we found that the intramolecular cyclization of aryl halides couldbe mediated by base with the aid of a catalytic amount of1,10-phenanthrolinederivative to from dibenzofurans, carbozole and other heterocyclic compoundsthrough a free radical mechanism. Anhydrous Fe(OAc)2as catalyst can also be used.Through the above works, the scope of Pd-catalyze decarboxylation coupling ofarycarboxylic acids has been greatly expanded, and these transformations can findapplications in the synthesis of natured products, drugs, alkaloids, ligands andbiphenyl liquid crystals, etc.更多还原