Synthesis And Application Of Bridging Chiral P-tert-Butylcalix[4]arene Tetrahydroisoquinolines

Objectives: Intrinsically chiral calix[4]arene are classified into inherently chiral calix[4]arene and bridging chiral calix[4]arene.In the past nearly three decades,the synthesis and properties of inherently chiral calix[4]arene have been extensively studied.However,the study of bridging chiral calix[4]arene is in its infancy and limited to its synthesis,and there is no any report on its properties.Asymmetric Henry reaction is an efficient way to synthesize 2-amino-1-arylethanol chiral drugs.In this thesis,referred to the structural characteristics of chiral organic catalysts in Henry reaction,bridging chiral p-tert-butylcalix[4]arene tetrahydroisoquinoline derivative was designed and synthesized,and its catalytic property in Henry reaction was further studied.Methods: Bridging chiral p-tert-butyl calix[4]arene H-3-a(or H-3-b)was used as starting material.Firstly,its conformation inversion of calix[4]arene skeleton from cone to 1,3-alternate was achieved by 1,3-crown etherification.Subsequently,its nitrogen atom was anchored on an adjacent phenyl ring after amide reduction,Polonovski oxidative demethylation,Bischler-Napieralski cyclization and further amide reduction.As a result,bridging chiral p-tert-butylcalix[4]arene tetrahydroisoquinoline derivative was successfully synthesized after conformation inversion and nitrogen anchoring.Finally,its asymmetric catalytic property in Henry reaction was studied.Results: Bridging chiral p-tert-butylcalix[4]arene tetrahydroisoquinoline derivative catalyst M-4-a(or M-4-b)was successfully synthesized and further used as chiral organocatalyst in Henry reaction.Compared to the catalytical result of Y-1-a(or Y-1-b)in cone conformation and H-5-a(or H-5-b)with freely rotating amine group,its catalytic enantioselectivity is distinctly enhanced although it is still unsatisfactory.Conclsuion: Compared to the catalytical result of bridging chiral calix[4]arenes in cone conformation and with freely rotating amine group,the catalytic enantioselectivity of bridging chiral p-tert-butylcalix[4]arene tetrahydroisoquinoline derivative is distinctly enhanced in Henry reaction,which proves that the conformation inversion of calix[4]arene skeleton and the rotational freedom reduction of catalytic amine group indeed bring beneficial effects on its catalytic stereoselectivity.