Study Of Chiral Oxazoline-carbene Copper Complexes Catalyzed Asymmetric Boration Reactions

Besides the ligands incorporating central chirality, the ligands used in asymmetric catalysis can also include axial chirality or planar chirality or combination of them. Since the first report of isolation of stable carbenes, 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 [2,2]paracyclophane has attracted people’s attention because of its own unique advantages, such as:(1) The convenience of introducing chiral factors.(2) A good chemical stability:the skeleton is less prone to racemize and has a high degree of stability to most acids, bases, oxidants and reducing agents.(3) The high rigidity because of the molecule tension. 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 chiral oxazoline heterocyclic carbene metal complexes based on [2.2] paracyclophane may be better than a single chiral ligand if combinated NHC and [2.2] paracyclophane. Our group have synthesized heterocyclic carbene metal complexes successfully and applied to a series of asymmetric reactions, such as:asymmetric boron addition of α,β-unsaturated keton, asymmetric addition boronic acid to naphthalene formaldehyde.The corresponding anions affect catalytic activity of carbene metal complexes, so we synthesized a series of chiral oxazoline-imidazolium chloride salts based on the analog trifiuoromethane suifonat salts. This dissertation discussed the synthesis of oxazolinyl [2.2]paracyclophanyl-imidazo [1,5-a] pyridinium salts and their application in aymmetric (3-borylation of α,β-unsaturated esters. The experimental section includes several parts as following:1、Synthesis of [2.2]paracyclophane and pseudo-ortho-dibromo [2.2]pracyclophaneUnder the alkaline environment of NaOH aq in DMSO, the chloride ion of paramethylbenzyl-ammonium chloride was substituted by hydroxide ion and then Hoffman elimination and dimolecular radical polymerization were happened to form [2.2]paracyclophane.4,16-dibromo[2.2]paracyclophane was obtained by bromination of [2.2]paracyclophane with iron as catalyst by controlling the amount of bromine.4,16-dibromo[2.2]paracyclophane was converted to4,12-dibromo[2.2]paracyclophane when incubated in dodecane at216℃for20h.2、Synthesis and resolution of4-amino-12-(4-tert-butyloxazoline-2-yl)[2.2] paracyclophan4-Bromo[2.2]paracyclophane-12-yl lithium prepared from4,12-dibromo[2.2] paracyclophane and BuLi reacted with CO2, acidified with HC1to afford4-bromo-12-carboxyl[2.2]paracyclophane, which reacted with (L)-tert amino alcohol, then reacted with thionyl chloride and ring closed under alkaline conditions to give diastereoisomers of4-bromo-12-(4-tert-butyl oxazoline-2-yl)[2.2]pracyclophane.4-Benzophenone imino-12-(4-tert-butyl oxazoline-2-yl)[2.2]pracyclcphane was obtained by Pd-catalyzed amination, and diastereoisomers could be separated by recrystalization with ethanol. Further treated by acid solution to give optical pure4-amino-12-(4-tert-butyl oxazoline-2-yl)[2.2]pracyclophane.3、Synthesis of enantiopure diastereoisomers of3-{12-(4-tert-butyl oxazolin-2-yl)[2.2]pracyclophane-4-yl} imidazo [1,5-a]pyridinium triflateEnantiopure4-amino-2-(4-tert-butyl oxazoline2-yl)[2.2]paracyclophane reacted with2-formyl pyridine to afford imine, treated with AgOTf and chloromethyl pivalate to give3-{12-(4-tert-butyl oxazolin-2-yl)[2.2]pracyclophane-4-yl} imidazo [1,5-a] pyridinium triflate. The final product was obtained by anion exchanging of the above triflate salt through an anion-exchange resin.4、The study on asymmetric boron addition of a,(3-unsaturated esterAsymmetric boron additions of α,β-unsaturated compounds were gathered the attention of chemists. Studies on boration of a,β-unsaturated ketone are better than that of a,β-unsaturated ester, especially the results catalyed by carbene-Cu based on [2.2]pracyclophane derived ligands are unknow. So it means a lot catalytic boration of α,β-unsaturated ester was achived by using our new ligands.The reaction conditions were screened by using the optimal ligand, such as:solvents, temperature, etc, and a range of substrates was examined.The innovation of this dissertation is as follows:1、A series of novel NHC precursors based on planar chiral [2.2]paracyclophane combined with the central chirality have been synthesized.2、The reported method to prepare the similar compounds was improved. In the process of preparing pseudo-ortho isomers, the diastereoisomers of4-amino-12-isopropyl oxazolinyl [2.2]paracyclophane and4-amino-12-tert-butyl oxazolinyl [2.2] paracyclophane were successfully resolved.3、Asymmetric boration of a,(3-unsaturated ester catalyzed by new ligands derived from [2.2]paracyclophane was performed, all of new ligands were compaired each other, and the ee is up to96%.