Synthesis Of Planar Chiral Imidazo [1,5-a]Pyridinium Salts 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 in1991, 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 of21st century, since then, the literatures of design, synthesis and application of chiral NHCs were reported explosively.We have obtained a series of novel chiral NHCs when introducing the planar chiral 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 aymmetric β-borylation of chalcone and its analogues. The experimental section includes several parts as following:1、Synthesis of [2.2]paracyclophane and the enantiopure4-bromo-13-amino [2.2]pracyclophaneUnder the alkaline environment of NaOH aq in DMSO, the chlorid 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. Then after nitration, bromination and reduction, racemic4-bromo-13-amino [2.2]paracyclophane was obtained. Resolution of the above racemic mixtures with L-camphor sulfonic acid gave the enantiopure4-bromo-13-amino [2.2]paracyclophane2、Synthesis of (4SP,5RP,13Rp)-4-amino-5-diphenylphosphoryl-13-bromo[2.2] pracyclophane(4Sp,13Rp)-4-amino-13-bromo [2.2]pracyclophane as raw material reacted with acetic anhydride to generate acetamide, which transformed to4-acetoxy-13-bromo[2.2]pracyclophane by diazotization, and followed by hydrolysis in methanol and potassium hydroxide to afford4-hydroxy-13-bromo[2.2] pracyclophane. Then4-hydroxy-13-bromo [2.2]pracyclophane reacted with diphenyl phosphoryl chloride to provide diphenyl phosphate. Using LDA as base, Fires rearrangement happened to give4-hydroxy-5-diphenylphosphoryl-13-bromo [2.2] pracyclophane. Then reacted with N, N-ditrifluoromethanesulfonyl aniline to generate trifluoromethanesulfonate, followed by Pd-catalyzed amination, but the desired product was not gotten.3、Synthesis of (4SP,5Rp)-4-amino-5-diphenyl phosphoryl [2.2]pracyclophaneSimilar as above,(4SP,5Rp)-4-amino-5-diphenyl phosphoryl [2.2]pracyclophane was not obtained from5-diphenyl phosphoryl [2.2]pracyclophane-4-trifluoromethanesulfonate by Pd-catalyzed amination.4、Synthesis and resolution of4-amino-12-(4-isopropyl oxazoline-2-yl)[2.2] paracyclophaneUse4,12-dibromo [2.2]paracyclophane as the material to prepare Grignard reagent and reacted with CO2, acidified with HC1to afford4-bromo-12-carboxy[2.2]paracyclophane, which reacted with (L)-Valine alcohol, then reacted with thionyl chloride and ring closed under alkaline conditions to give diastereoisomers of4-bromo-12-(4-isopropyl oxazoline-2-yl)[2.2]pracyclophane.4-Benzophenone imino-12-(4-isopropyl oxazoline-2-yl)[2.2]pracyclophane 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-isopropyl oxazoline-2-yl)[2.2]pracyclophane.5、Synthesis of enantiopure diastereoisomers of3-{12-(4-isopropyloxazolin-2-yl)[2.2]pracyclophane-4-yl} imidazo [l,5-a]pyridinium triflate Enantiopure4-amino-2-(4-isoproyloxazoline2-yl)[2.2]paracyclophane reacted with2-formyl pyridine to afford imine, treated with AgOTf and chloromethyl pivalate to give the desired3-{12-(4-isopropyloxazolin-2-yl)[2.2]pracyclophane-4-yl} imidazo [1,5-a] pyridinium triflate.6-. Synthesis and resolution of4-amino-12-(4-tert-butyloxazoline-2-yl)[2.2] paracyclophanUse4-bromo[2.2]paracyclophane as the material to prepare Grignard reagent and reacted with CO2, acidified with HC1to afford4-bromo-12-carboxy[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]pracyclophane 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.7、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 give the desired3-{12-(4-tert-butyl oxazolin-2-yl)[2.2]pracyclophane-4-yl} imidazo [1,5-a] pyridinium triflate.8、Application of the NHC precursors in the asymmetric catalysis.After evaluation and selection, we chosed carbene-Cu(I) catalyzed β-borylaton of enone with Bpin2as 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, however the Cu-catalyzed asymmetric β-borylaton of enone with Bpin2was rarely reported.The innovation of this dissertation is as follows: 1、A series of novel phosphine ligands derived from [2.2]paracyclophane have been synthesized, and they provided a sound basis for further research.2、A series of novel NHC precursors based on planar chiral [2.2]paracyclophane combined with the central chirality have been synthesized. We also improved the reported method to prepare the similar compounds. In the process of preparing pseudo-ortho isomers, we successfully resolved the diastereoisomers of4-amino-12-isopropyl oxazolinyl [2.2]paracyclophane and4-amino-12-tert-butyl oxazolinyl [2.2] paracyclophane.