| Having chirality is one of the characteristics of many biomolecules in nature.Chiral drug molecules are broadly used in today's pharmaceutical industry.Today,one of the main ways to obtain chrial molecules is to asymmetric catalytic organic reactions through chiral catalysts.Triazolylidene carbenes belong to the most investigated reactive species in the field of asymmetric organic chemistry including thiazolylidene or imidazolylidene carbenes.By using such catalysts with unique and nucleophilic properties,we could receive umpolung products.We could impove the totolerance of catalysts to substrates and could catalyze a new type of reaction just through introducing different groups on triazolium salts,so these triazolylidene carbenes have a large regulatory space.In recent years,researchers have focused these triazolylidene carbenes ligands on transition metal catalyzed reactions of asymmetrical catalytic reaction,which are ubiquitous.To date,organocatalysis using stable triazolylidene carbenes is researched by so many of chemists.On the other hand,some scientists used carbenes as catalysts for organocatalytic reactions which is emerging an exceptionally fruitful in synthetic organic chemistry.In general,asymmetric Stetter Reactions,Benzoin Reactions,hydrogenation acylation reaction catalyzed by triazolylidene carbenes had been extensively investigated.The general N-heterocyclic carbenes only relied on a single central chirality to control the asymmetric selectivity of the products.Recently years,researchers have attempted to combine triazolylidene carbenes with ferrocene or[2.2]paracyclophane bearing planar chirality to generate a new type of ligands with center and planar chirality.Comparing the former,the new ligands could remarkably improve the enantioselectivities and the yields.Compared with ferrocene ligands,[2.2]paracyclophane ligands could form planar chirality just by introducing one substitutional group to phenyl ring which is stable and not easy to racemize.Taking advantage of these characteristics,[2.2]paracyclophane-based ligands have been broadly applied in the field of asymmetric organic reactions.We have made great progess in synthesis such class of ligands with center and planar chirality and applied them in carbene-metal catalyzed asymmetric ?-boration,alkylation,silylation reactions to afford excellent enantioselectivity and good yield.Although our group had made some achievements in organocatalysis,some works are not deep enough.Further researches are needed to improve the asymmetric selectivity of the desired products.Accordingly,In our initial expectation,we planned to synthesize a new[2.2]paracyclophane-based chiral carbene precursor with proper substitutional groups,expected to achieve higher enantioselectivities in catalytic asymmetric conjugate boration.The main chapters of my paper were shown as follows:1.The first chapter is summary of the development of triazolylidene carbenes and[2.2]paracyclophane-based ligands and summary of our group's work on catalytic asymmetric boration of ?,?-unsaturated ketones.Triazolylidene carbenes have been widely researched in recently years.There is a constantly updating in the type of ligands and its participation in the asymmetric catalysis.It is not only limited to classical nucleophilic umpolung Stetter reaction,Benzoin reactions,as well as the type of reactions through cooperative catalysis by carbenes and Lewis acids.The most important research for us is to synthesize such class of ligands with center and planar chirality and applied them in carbene-metal catalyzed asymmetric ?-boration,alkylation,silylation reactions to afford excellent enantioselectivity and good yield.2.The second chapter is some preparatory work before the experimentIn this chapter,we introduce some commonly reagents and drugs used in the entire research work and the treatment of some special reagents.Of course,the cycle of the prepared anhydrous reagent is generally not more than a week.In this chapter there are a number of conventional preparations of intermediate compounds and the preparation of some ?,?-unsaturated ketones.3.The third chapter is the preparation of dual chiral triazolium hydrochloride with a phenolic hydroxyl group.(1).Synthesis of two optically pure 4-(2-hydroxyphenyl)-12-formohydrazino[2.2]paracyclophane hydrochlorideIn general,[2.2]paracyclophane was prepared from the quaternary ammonium salt,after Hofmanm elimination through a free radical polymerization process.The reaction product is brominated to give 4,16-dibromo[2.2]paracyclophane,followed by high temperature translocation to provide the product named 4,12-dibromo[2.2]paracyclophane.4-amino-12-bromo[2.2]paracyclophane was obtained by Pd-catalyzed amination reaction of 4,12-dibromo[2.2]paracyclophane.The product could be chirally separated to give two optically pure products:Rp-(-)-4-amino-12-bromo[2.2]paracyclophane and Sp-(+)-4-amino-12-bromo[2.2]paracyclophane.We can obtain the corresponding two optically pure dibromo products through the Sandmeyer reaction.Two optically pure N-(12-bromo[2.2]paracyclophan-4-yl)benzophenone hydrazone products were prepared by Pd-catalyzed amination of 4,12-dibromo[2.2]paracyclophane with benzophenone hydrazone.Furthermore,we could obtain the optically pure N-formyl-N-(4-bromo[2.2]paracyclophan-12-yl)benzophenone hydrazone products after a formylation reaction.In order to generate the phenolic hydroxyl,we had better to implement the Suzuki reaction.Finally,established 4-(2-hydroxyphenyl)-12-formohydrazino[2.2]paracyclophane hydrochloride could be obtained after hydrolysis in the presence of THF and hydrochloric acid.(2).Synthesis of phenolic hydroxyl substituted triazolium hydrochloride saltsFirst,the reaction of chloroacetyl chloride and chiral phenylglycinol prepared by reduction of phenylglycine afforded the desired amide.Next,the chiral imino ether was obtained through a ring-closed reaction in the presence of sodium hydride,followed by treatment with trimethyloxonium tetrafluoroborate in dry dichloromethane.Then,the reaction mixture of the chiral imino ether and optically pure 4-(2-hydroxyphenyl)-12-formohydrazino[2.2]paracyclophane hydrochloride in a solution of methanol was stirred at 50 ? for about one hour.After that,the triethyl orthoformate was added and the resulted reaction mixture was stirred at 1 1 0 ? for about 30 minutes,affording the desired phenolic hydroxyl substituted triazolium salts.4.The fourth chapter is about the studies on asymmetric boration of?,?-unsaturated ketones catalyzed by dual chiral triazolylidene carbenes containing a phenolic hydroxyl groupIn this chapter,we are working on how to improve the yield and enantioselectivity of the boration reaction by optimizing reaction conditions.After optimization of the reaction conditions,we found that adding a small amount of water can improve not only the yield but also enantioselectivity of the reaction.The highlights of the paper were shown as follows:1.A new type of dual chiral triazolium salts containing a phenolic hydroxyl group was designed and synthesized for the first time.2.The yields and enantioselectivities of the boration of chalcone derivatives were improved by using the new type of dual chiral triazolylidene carbene as catalyst,indicating that the phenolic hydroxyl group has a significant influence on the reaction.3.It was found that water plays a key role in the carbene-catalyzed asymmetric boration of chalcone derivatives. |
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