Construction And Asymmetric Alkylation Of C₂-symmetric Biphenyl And Biphenanthrene Phase Transfer Catalysts

Phase transfer catalysts are widely used in academia and industry due to their mild reaction conditions and environmental friendliness.And chiral phase transfer catalysts are increasingly important in the preparation of chiral pharmaceutical compounds,core structures of natural products,and chiral functional molecules.In order to develop and prepare the core structure of the C₂-symmetric chiral biphenyl quaternary ammonium salt catalyst,that is,the optically pure C₂-symmetric chiral biphenyl skeleton,in this paper,taking esterification reaction with the commercial(R)-?-methoxy benzene acetic acid as resolution agent,the chiral 2,2'-biphenylphenols was achieved.After recrystallization,its ee value was identified by high-performance liquid analyzer More than99%.The optically pure C₂-symmetric chiral 2,2'-biphenol compound obtained by chiral resolution was introduced into the aryl group through the Suzuki reaction,and the hydroxyl group was protected by methyl iodide,and the methyl benzyl group was brominated,and the amination was used to form a salt reaction,and the boron tribromide was used to deprotect hydroxymethyl groups and so on,successfully synthesized eight optically pure C₂-symmetric biphenyl quaternary ammonium salt catalysts.At the same time,the catalytic effects of those obtained catalysts on the asymmetric alkylation of glycine derivatives were investigated.The results showed that the yield of the alkylated product catalyzed by the optically pure biphenyl skeleton quaternary ammonium salt catalyst is as high as 97%,and the enantioselectivity is as high as 96%,which provided a good catalytic synthesis method for the manual preparation of chiral?-amino acids.Research on the structure activity relationships of the catalysts found that the C2 and C2'positions with methoxy groups were conducive to improve the enantioselectivity of the catalytic reaction,such as catalysts(S)-14,(S)-16,(R)-24,(R)-26.The C3 and C3'positions with tert-butyl group reduced the reaction selectivity,such as catalysts(S)-13,(S)-15,(R)-23,(R)-25.The C5 position and C5'position with 3,4,5-trifluorophenyl and 3,5-bis(trifluoromethyl)phenyl all showed better catalytic activity and higher Enantioselectivity,such as the catalysts such as catalysts(S)-(13-14)and(R)-(23-26).In addition,the novel chiral quaternary ammonium salt catalysts based on phenanthrene were successfully designed and synthesized in this thesis.Taking the asymmetric reaction of9-hydroxyphenanthrene under the catalysis of chiral ligand,the chiral biphenanthrene skeleton was constructed.After recrystallization,its ee value was determined to be greater than 99%by high-performance liquid analyzer.The obtained optically pure C₂-symmetric chiral phenanthrene skeleton was protected by hydroxyl group with trifluoromethanesulfonic anhydride,methylated by the format reagent methylmagnesium iodide,benzyl carbon was used to bromination reaction,amination to salt reaction and so on,respectively prepared the chiral biphenanthrene type of phase-transfer catalysts(S)-42 and(S)-45.The obtained phenanthrene quaternary ammonium salt catalysts with optically pure bare skeleton chiral cavity was initially used in the catalytic study of the asymmetric alkylation reaction of glycine derivatives.The yield of the obtained alkylation product was as high as 95%and the selectivity was 23%.The research on new chiral quaternary ammonium salt phase-transfer catalysts are expected to open up new catalytic reaction conditions,which will help to provide efficient preparation methods for chiral pharmaceutical compounds and chiral functional molecules.