Asymmetric Synthesis And Application Of Biaryl–Quinolines

Biaryl-quinolines exist widely in natural products,because of its special structure,which are often used in the research and development of drugs,as catalysts,new ligands and so on.So far,the main methods to synthesize these compounds include:kinetic resolutiondynamic kinetic resolution,coupling reaction,cyclization reaction,etc.However,most of these methods are catalyzed by the use of expensive transition metals.It is of great significance to develop an economical and environment-friendly organocatalysis for the construction of biaryl-quinolines.This thesis mainly includes three chapters:The first chapter reviewed the recent progress in synthesis of biaryl-quinoline compounds.The main methods to synthesize these compounds include:kinetic resolution,dynamic kinetic resolution,coupling reaction,cyclization reaction,etc.The second chapter introduces the construction of biaryl-quinolines catalyzed by chiral phosphoric acids.This process is operationally simple,efficientand and under mild conditions.When naphthol compounds were used as substrates and chiral phosphoric acid 4i as catalyst,a series of biaryl-quinolines with 72%-96%yield were obtained by reaction at 45 ? for 60 h.Using naphthalamines as substrates,chiral phosphoric acid 4k as catalyst,5(?)molecular sieve as additive,a series of biaryl-quinolines with 15%-83%ee were obtained by reaction at 40 ? for 96 h.The third chapter introduces some common phosphine ligands,such as monophosphorus ligand H-MOP,Diphosphine ligand BINAP,etc.Based on the Povarov reaction and the central-to-axial chirality conversion,we constructed biaryl-quinolines and used this product as a precursor synthesized a novel monophosphorus ligand.Although the method has undergone six chemical transformations,the enantioselectivity of each transformation was not lost.Then the ligand was used in asymmetric allylation reaction,and the target product was obtained with 90%yield and 50%ee by optimizing the conditions.