Iron-catalyzed C-C, C-O Bonds Formation Reactions

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.