Synthesis Of Substituted 1-aminoisoquinolines And Axially Chiral Biaryl Compounds

Substituted 1-aminoisoquinolines and axially chiral biaryl compounds widely exist in many natural products and biologically active molecules,such as Papaverine,Sanguinarine,Mastigophorene and Steganacin.In addition,1,1’-bi-2-naphthol(BINOL),2-amino-2’-hydroxy-1,1’-binaphthyl(NOBIN)and 1,1’-bi-2-naphthylamine(BINAM),as representative biaryl compounds,have been widely used in the field of asymmetric catalysis.Therefore,the efficient construction of substituted 1-aminoisoquinolines and axially chiral biaryl compounds has always been a hot research topic in organic synthesis and medicinal chemistry.Our group has developed a series of research methodologies in the synthesis of nitrogen-containing aromatic compounds.Following the previous research direction,this dissertation realizes the direct or indirect synthesis of substituted 1-aminoisoquinolines.We have attempted the catalytic asymmetric synthesis of NOBIN analogs and axially chiral hexaarylbenzene(HAB).This dissertation mainly includes the following two parts:The first part outlines the research progress of substituted 1-aminoisoquinolines,summarizes the synthesis strategies of 1-aminoisoquinolines according to the types of reactions.It seems that the existing strategies mainly focus on the synthesis of Nsubstituted 1-aminoisoquinolines while less involving the synthesis of N-unsubstituted1-aminoisoquinolines(Chapter 1).Therefore,we have developed a copper-catalyzed[4+2] cyclization of 2-cyanobenzaldehyde and 2-isocyanoacetate to synthesize Nunsubstituted 1-aminoisoquinolines.The reaction is simple and efficient with good material applicability(Chapter 2).On the other hand,following our group’s research interests in the synthesis and application of N,N-disubstituted aminomalononitriles,ortho-substituted benzonitriles were synthesized by aryne insertion reaction.Substituted 1-aminoisoquinolines were indirectly synthesized through one-step cyclization reaction(Chapter 3).The second part summarizes the research on axially chiral biaryl compounds,in particular,the asymmetric synthesis methods of axially chiral biaryl compounds in recent years(Chapter 4).The catalytic asymmetric synthesis of NOBIN analogs catalyzed by chiral phosphoric acid was carried out,and the target product was obtained in high yield and high enantioselectivity.The low diastereoselectivity of the product was solved through product derivatization.A possible [5,5]-rearrangement reaction mechanism was proposed based on experimental verification and theoretical analysis(Chapter 5).Finally,the asymmetric synthesis of axial chiral HAB was studied and explored,and the possibility of reaction chirality control was preliminarily verified.The further research on chirality control research is still in progress in our group(Chapter6).