【作者】 高健；

【导师】 何良年；

【作者基本信息】 南开大学 ， 有机化学， 2012， 博士

【摘要】 随着近年来人们对环境、能源等问题的日益关注，发展更加绿色、高效、高选择性、可持续以及环境友好的有机合成方法已经成为化学领域最受关注也是最重要的研究方向和目标，绿色化学与可持续发展的理念已深入人心。因此，传统的过渡金属尤其是贵金属（如Pd, Ru, Ir, Rh, Au, Pt等）催化剂由于其稀有不易得、高成本和不可忽略的重金属毒性限制了其进一步发展和广泛应用。而作为地球上第二大储量金属的铁与上述贵金属相比具有不可比拟的优势，如储量丰富、廉价易得、相对无毒安全、氧化态易变及独特的Lewis酸性质，引起化学家越来越多的关注和研究并被应用到多种有机化学反应中。相对于其他过渡金属催化，铁催化无疑是更加环境友好并符合可持续发展的一个催化领域。基于此，本论文着眼于过渡金属铁的独特性质，发展铁催化的C-H键活化及C-C/C-N、C-O键形成反应，以拓展铁催化在有机合成中的应用。此外，二氧化碳既是最主要的温室气体，同时也是地球上分布最广、储量最丰富的碳一资源。无论从资源利用还是环境保护的角度考虑，二氧化碳的固定和化学转化的研究都具有重要意义。本论文的研究工作还包括发展新的环境友好的催化方法实现二氧化碳的资源化利用。（1）炔丙胺类化合物在含氮类化合物及药物活性分子的合成中具有广泛应用，其合成方法备受关注。近年来，醛、炔、胺三组份偶联反应（A3反应）及炔、卤代烷、胺三组份偶联反应（AHA反应）代表了可替代的、高效、原子经济性的合成炔丙胺的方法。而对于AHA反应，其催化剂多为Au、In等贵金属，我们以FeCl3作为催化剂，以1,1,3,3-四甲基胍（TMG）作为添加剂碱，发展了一种高效的铁催化的芳香炔烃、CH2Cl2、脂肪二级胺三组份一锅偶联反应合成炔丙胺的方法。研究发现，各种带有拉电子基团和给电子基团的芳香炔烃、脂肪链状及环状二级胺都能和CH2Cl2反应以37-95%的收率生成相应的炔丙胺产物。另外，通过原位红外光谱研究发现，FeCl3和有机碱TMG的协同作用能够有效活化炔烃的C-H键生成炔基-金属活性物种作为活性中间体参与反应。结合对照实验结果及其他研究证明了金属铁盐对炔烃C-H键的活化，并提出了铁催化下AHA反应的机理。该催化体系与传统的贵金属催化体系相比，其最大的优势在于使用更加绿色、可替代的过渡金属铁作为催化剂，代表了金属催化领域的发展方向。（2）过渡金属催化的芳烃、杂芳烃的苄基化反应可以高效地构筑具有生物活性的二芳基甲烷类化合物。当使用苄醇作为苄基化试剂时，水是唯一的副产物，因此该反应在很大程度上符合绿色化学和可持续发展的要求。目前，芳烃、杂芳烃苄基化反应的发展主要受限于金属催化剂（如In、Rh、Au、Fe等）成本较高，且难以实现回收循环使用。为了发展更加绿色且能实现金属回收的催化体系，我们设计合成了一种铁基功能化的离子液体C4mim-FeCl4，用于催化各种芳烃、杂芳烃的苄基化反应，能以高达98%的收率和高达100%的区域选择性合成二芳基甲烷类化合物。此外，研究发现该铁基离子液体的Lewis酸性强弱可以通过调节FeCl3的所占的比例进行调节，并且其Lewis酸性强弱对反应有很大影响。同时，该铁基离子液体催化剂能够实现回收再用，且循环使用五次后其催化活性基本保持不变。该铁基催化剂作为一种新型过渡金属功能化的离子液体，具有可调的Lewis酸性质，代表了一种可替代的环境友好的新型催化材料，具有一定的潜在工业应用价值。（3）以CO₂作为合成子原子经济性地合成具有重要应用价值的杂环类化合物如环状碳酸酯、噁唑啉酮是化学固定CO₂的有效方法之一。为了发展更加绿色、更具实际应用价值的催化剂以解决目前催化剂存在的不足，基于CO₂的活化转化原理，我们设计合成了一种氯甲基化聚苯乙烯树脂负载的铁基离子液体催化剂PS-MimFeCl4，用于催化CO₂和环氧化物的环加成反应合成环状碳酸酯。催化剂中的铁中心能够活化环氧化物并协助其开环，从而促进反应的进行。研究发现，该催化剂能够循环使用多次，且其催化活性保持不变。此外，该催化剂还能催化CO₂与氮杂环丙烷、炔丙胺反应合成噁唑啉酮类化合物。该铁基离子液体功能化的负载型催化剂，其独特优势在于Lewis酸性的铁中心的引入，对于活化底物促进反应进行有重要的作用，同时拓展了铁催化的在二氧化碳活化转化领域的应用。此外，这一新型催化剂易于合成、具有很好的催化活性及选择性、热稳定性好、且易于与产物分离，因此具有很好的工业应用前景。（4）喹唑啉-2,4（1H,3H）-二酮及其衍生物由于其广泛的生物及药物活性，一直受到人们的关注与研究。为了发展可替代且更加高效廉价的催化体系，我们研究发现有机强碱有机胍类化合物能够同时有效活化CO₂及邻氨基苯腈类底物，在无溶剂条件下，1,1,3,3-四甲基胍能够高效催化二者反应以60-95%的收率生成喹唑啉-2,4（1H,3H）-二酮类化合物。并且反应在较低的催化剂用量（2mol%）或很低的CO₂（0.5MPa）压力下仍能以82%或66%的收率得到相应的产物。这一体系代表了一种可替代的、更加绿色的化学固定与转化CO₂为有用化学品的方法。更多还原

【Abstract】 With the increasing concern of environment and energy issues, the developmentof greener, more efficient, highly selective, more sustainable and environment benignorganic synthesis is one of the most concerned and fundamental research directionsand goals in chemistry. The concept of green chemistry and sustainable developmenthas been firmly established. On the other hand, traditional transition-metal catalystsespecially based on precious metals such as palladium, rhodium, iridium, gold,platinum and ruthenium have become restricted because of their limited availability,high price as well as their unneglected toxicity. Thus it is desirable to search for moreeconomical and environmentally friendly alternatives. As the second most abundantmetal in the earth crust, iron possesses unparalleled advantages and has drawn moreand more attention compared with the aforementioned precious metals. Various ironsalts and iron complexes have been applied in the organic reactions and synthetictransformations because they are abundant, cheap and commercially accessible on alarge scale, relatively nontoxic, facile in changing the oxidation state and possessdistinct Lewis acid character. There is no doubt that iron catalysis is moreenvironmentally benign and much more sustainable compared with other metalcatalysis. This dissertation mainly focuses on the development of iron-catalyzedactivation of C-H bond and C-C/C-N, C-O bonds formation reactions to expand theapplication of iron catalysis in organic synthesis based on the distinct character ofiron and related compounds. On the other hand, the development of more efficientand sustainable process for the transformation and utilization of CO₂, which is themost abundant greenhouse gas and can be also regarded as the most abundant andrenewable C1resource, is of great significance form the viewpoint of resourceutilization and environmental protection. The development of novel and greenercatalytic systems to realize the transformation and utilization of CO₂was alsoincluded in this dissertation.（1） Propargylamines have been attracted considerable attention over the last few years due to their wide applications in the synthesis of nitrogen-containingcompounds and drug discovery. In recent years, the three-component couplingreaction of aldehydes, alkynes and amines （A3reaction） and the three-componentcoupling reaction of alkynes, haloalkanes and amines （AHA reaction） represent thealternative, efficacious and atom-efficient approaches to synthesize propargylamines.However, precious metal catalysts especially Au and In based catalyst are usuallyused in AHA reaction. Herein, we have developed an economical and practicalprotocol for facile synthesis of propargylamines through an iron（III）-catalyzedthree-component coupling reaction of aromatic terminal alkynes, CH2Cl2andaliphatic secondary amines in the presence of organic base1,1,3,3,-tetramethylguanidine （TMG）. It was found that various aromatic alkynesbearing either electron-withdrawing or electron-donating substituents, acyclic andheterocyclic secondary aliphatic amines could react with CH2Cl2affording thecorresponding propargylamines with37%-95%yields. Notably, in-situ IRspectroscopic investigation strongly suggests that FeCl3could activate the alkynylC-H bond in combination with TMG as a base with the generation of a Fe-acetylideintermediate which acts as the active nucleophilic species. Combined with otherexperimental results, the activation of C-H bond of terminal alkynes in the presenceof iron was first proved experimentaly and a possible reaction mechanism wasproposed for this iron-catalyzed AHA coupling reaction. The best advantage of thiscatalytic system studied herein is to use greener and alternative transition-metal ironas the catalyst compared with the traditional catalytic systems involing preciousmetals. And this iron-catalyzed system represents the development direction of thefield of metal catalysis.（2） Transition-metal catalyzed benzylation reactions of arenes and heteroarenescan be used for the efficient synthesis and construction of diarylmethanemotif-containing compounds which commonly possess biological activity. Whenbenzyl alcohols are used as the benzylated reagents, it would become astate-of-the-art green and sustainable process for the synthesis access diarylmethanesderivatives because water is the only side-product in this reaction. However, highcatalyst loading and difficulty for recovery of transition-metal catalysts in these processes could lead to high corrosion and increased cost to some extent. Aiming todevelop greener and recyclable catalytic system, we have established an efficientapproach to Friedel-Crafts-type benzylation of various arenes and heteroarenes usingan iron-containing IL, viz. C4mim-FeCl4as the catalyst for the synthesis ofdiarylmethane derivatives with up to98%yields and100%regioselectivity.Interestingly, the acidity of C4mim-FeCl4could be modified by varying the fraction ofFeCl3and could account for its catalytic activity in promoting the Lewisacid-catalyzed alkylation. Furthermore, the catalyst the catalyst C4mim-FeCl4couldbe reused for five times without significant loss of its catalytic activity with theretention of high regioselectivity. It is worth noting that this procedure is especiallyattractive because of its cheap, easy to handle and recyclable catalyst from the pointof view of green and sustainable chemistry. As a novel kind of transition-metalsfunctionalized ionic liquids, this iron-based catalyst possessing adjustable Lewis acidcharacter represents a novel alternative and environmentally benign catalytic materialand could have potential industrial applications.（3） The atom-efficient synthesis of five-membered heterocyclic compounds suchas cyclic carbonates and oxazolidinones using CO₂as the C1building block is one ofthe most promising strategies for the chemical transformation and utilization of CO₂.In order to develop greener and much more pratical catalyst for the transformation ofCO₂, we developed a functionalized polystyrene bearing iron-containing IL, viz.PS-MimFeCl4as an efficient and recyclable catalyst for the cycloaddition reaction ofCO₂with epoxides to synthesize cyclic carbonates in the absence of any organicsolvent or additive based on the principles of activation and transformation of CO₂,.The Lewis acidic iron center in the anion could play a crucial role in the activation ofepoxide and thus facilitate its ring-opening. Notably, the catalyst could be readilyrecovered and reused over five times without appreciable loss of catalytic activity.The present protocol has also been successfully applied to reactions ofaziridine/propargyl amines with CO₂for the synthesis of oxazolidinones. The distinctadvantage of this iron-based ionic liquid functionalized heterogeneous catalyst couldbe the introduction of the Lewis acidic iron centre which plays significant role inactivating the substrates and promoting the reaction. And this catalytic ststem also extends the application of iron catalysis in the field of CO₂activation andtransformation. This kind of the catalyst presented herein would have great potentialin industrial application thanks to its featured advantages such as easy preparation,excellent catalytic activity and selectivity, good thermal stability, and facile seperationwith the products.（4） Quinazoline-2,4（1H,3H）-diones and their derivatives have drawn muchattention and interest due to their wide range of biological and pharmacologicalactivities. In order to develop alternative, more efficient and more inexpensivecatalyst for the synthesis of quinazoline-2,4（1H,3H）-diones from CO₂, we found thatorganic guanidines which are categorized as organic superbases can activate2-aminobenzonitriles and CO₂simultaneously and TMG was proved to be an efficientcatalyst for the synthesis of quinazoline-2,4（1H,3H）-diones via a chemical fixation ofCO₂to2-aminobenzonitriles with60%-95%isolated yields under solvent-freeconditions. Notably, the reaction could work well even at2mol%of catalyst loadingor under CO₂pressure as low as0.5MPa with82%yield and66%yield, respectively.This approach would be a promising strategy for the chemical transformation of CO₂from the viewpoint of green chemistry and sustainable development.更多还原