Synthesis Of Oxazoline Substituted Planar Chiral Carbene Precursors And Their Application In Asymmetric Catalysis

Besides the ligands incorporating central chirality, the ligands used in asymmetric catalysis also can include axial chirality or planar chirality or combination of them. Since the end of last century, more and more literatures about planar chiral substituted [2.2]paracyclophane used as ligands in asymmetric catalysis were reported. The planar chirality plays more important role in homogeneous organometallic catalytic chemistry. Since the first report of isolation of stable carbenes in 1991, because of their good electron-donating and readily modification of the structure, N-heterocarbenes(NHCs) concentrated the interest of a lot of chemists in the area of homogeneous catalysis and organocatalysis. The most famous application is the Grubbs catalysts in the olefin metathesis. The first successful application of chiral NHCs in asymmetric catalysis was reported at the beginning of 21st century, since then, the literatures of design and synthesis and application of chiral NHCs were reported explosively.We will obtain a series of novel chiral NHCs when introducing the planar chirality of substituted [2.2]paracyclophane in the design and synthesis of NHCs. The synthesis and application of NHCs based on the backbone of [2.2]paracyclophane were meaningful in asymmetric catalysis. This dissertation discussed the synthesis of oxazolinyl-[2.2]paracyclophanyl- imidazo[1,5-a]pyridinium salts and their application in aymmetricβ-borylation of chalcone and its analogues. The experimental section include several parts as following:Ⅰ. Synthesis of [2.2]paracyclophane, monobromo[2.2]paracyclophane and pseudo-ortho-dibromo[2.2]paracyclophane.Under the alkaline environment of NaOH aq in DMSO, the chloridion of paramethylbenzyl- ammonium chloride was substituted by hydroxide ion and then Hoffman elimination and dimolecular radical polymerization were happened to form [2.2]paracyclophane. 4-bromo[2.2]paracyclophane and 4,16-dibromo[2,2]paracyclophane were obtained by bromination of [2,2]parayclophane with iron as catalyst by controlling the amount of bromine. 4,16-dibromo[2,2]paracyclophane was converted to 4,12-dibromo[2,2]paracyclophane when incubated in dodecane at 216℃for 20hⅡ. Synthesis and resolution of 4-bromo-13-phenyloxazolinyl[2.2]paracyclophane Use 4-bromo[2.2]paracyclophane as the material to prepare Grignard reagent and reacted with CO2, acidified with HCl to afford 4-carboxy[2.2]paracyclophane, which reacted with (R)-phenylglycinol and under Bryce's condition to generate 4-phenyloxazolinyl[2.2]paracyclophane. It was bromination under the standard condition to afford diastereoisomers of 4-bromo-13-phenyl[2.2]paracyclophane, which can be separated when subjected to chromatography of silica gel.Ⅲ. Synthesis of enantilpure diastereoisomers of (4,13)-oxazolinyl-[2.2]paracyclopphanyl-imidazo[1,5a]pyridinium salts.The enantiopure 4-bromo-13-phenyloxazolinyl[2.2]pracyclophane was lithiation with n-BuLi and bobbled with CO2 to afford 4-carboxy-13-phenyloxazolinyl[2.2]pracyclophane, which under improved Curtis rearrangement to afford 4-amino-13-phenyl[2.2]paracyclophane. It reacted with picolinaldehyde in reflux toluene resulted in the formation of imine, which was readily to prepare the target imidazole under the method reported by Glorius by using AgOTf and chloromethyl pivalate.Ⅳ. Synthesis of 4-bromo-12-phenyloxazolinyl[2.2]paracyclophaneUse (4,12)-dibromoparacyclophane as the starting material, proceeding lithiation, reacted with CO2 and acidified to afford 4-bromo-12-carboxy[2.2]paracyclophane. Then it reacted with R-phenylglycinol to afford the corresponding amide, which was readily to prepare 4-bromo-12-phenyloxazolinyl[2.2]paracyclophane with SOCl2 and NaOH aq.Ⅴ. Synthesis of enantiopure 4-amino-12-phenyloxazolinyl[2.2]paracyclophane 4-bromo-12-phenyloxazolinyl[2.2]paracyclophane was aminated catalyzed by Pd(dppf)Cl2 to afford the 4-benzophenone imine-12- phenyloxazolinyl[2,2] paracyclophane. The diastereoisomers can be separated at this step. The isomers of enantiopure 4-amino-12-phenyloxazolinyl[2.2]paracyclophane were obtained after acid hydrolysis.VI. Synthesis of enantilpure diastereoisomers of (4,12)-oxazolinyl- [2.2] paracyclopphanyl-imidazo[1,5a]pyridinium salts.Use the enantiopure 4-amino-12-phenyloxazolinyl[2.2]paracyclophane as the starting material to prepare (4,12)-oxazolinyl- [2.2] paracyclopphanyl-imidazo[1,5a]pyridinium salts under the same method of preparing pseudo-geminal isomers.VII. Applied the NHC precursors in the asymmetric catalysis.After evaluation and selection, we chose Cu(Ⅰ)-complexes catalyzed P-borylaton of enone as the target reaction. We evaluated the effects of different ligands and modified the structure of the NHC precursor. This reaction was very important method to constructed C-N, C-O, C-C bonds and the catalyzed asymmetricβ-borylaton of enone was rarely reported. These were why we choose this reaction.The innovation of this dissertation is as follows:1. Synthesis of a series of novel NHC precursors based on backbone of [2.2]paracyclophane and combined the central chirality with planar chirality. We also improved the reported method to prepare similar compounds. In the process of preparing pseudo-ortho isomers, we successfully resolved the isomers of 4-amino-12-phenyloxazolinyl[2.2]paracyclophane.2. We used the novel method proposed by Seung Uk Son recently and prepared the Cu(Ⅰ)-NHC complexes in situ, which were readily to catalyzed theβ-borylaton of enone without separation.