Synthetic Strategies To Biaryl And Triptophan Analogues Based On[3,3]-rearrangement Cascade Reactions

Biaryl compounds and tryptophan derivatives are two important privileged skeletons,which are widely applied in the fields of pharmaceuticals,catalysts and functional materials.They are also important intermediates or synthetic precursors for the synthesis of other complex functional molecules.Therefore,it is of great scientific significance to develop new synthetic methods for the preparation of biaryls and tryptophan analogues.In addition,because of the unique structure of N-O bond with relatively low bond energy,arylhydroxylamine compounds are highly valuable reaction substrates since they are easy to react with electrophiles and undergo the N-O bond cleavage and the subsequent rearrangement reactions.In this thesis,based on the reaction of aryhydroxylamine substrates,we conducted the copper salt-promoted Chan-Lam C-O coupling reaction with arylboronic acid and the gold/zinc cooperative catalyzed O-alkenylation with amino acid skeleton-based alkynes.The efficient preparation of NOBIN-type biaryl compounds and tryptophan derivatives was achieved through the cascade in situ construction of highly reactive intermediates and the subsequent[3,3]-sigmatropic rearrangement and rearomatization process.This thesis contains the following three sections:In the first section,the application,research significance and known synthetic methods of biaryl compounds are briefly presented,including the transition metal catalyzed direct coupling strategy,radical coupling or single electron transfer strategy,Br?nsted acid-catalyzed synthetic routes to BINAM,BINOL and NOBIN analogues,synthesis of axial chiral biaryl compounds with indole skeleton catalyzed by Br?nsted acid,construction of biaryl compounds by[3,3]-rearrangement reaction and(dynamic)kinetic resolution of biaryl compounds.The development trends and existing problems in this field are also analyzed.In the second section,the Chan-Lam C-O coupling reaction between arylhydroxylamine substrates and inexpensive and readily available arylboronic acids under the catalysis of copper triflate,was developed.The highly reactive N,O-diarylhydroxylamine intermediates were constructed in situ,and this intermediates underwent the subsequent[3,3]-sigmatropic rearrangement and rearomatization process to afford structurally diverse NOBIN-type biaryl compounds.This method,utilizes arylboronic acids as arylation reagent,which has the characteristics of high atomic economy,excellent regioselectivity,simple operation,diversified product structure and good compatibility of functional groups.In the third section,the important applications of tryptophan derivatives and the main synthetic methods are summarized.Then,chiral phase-transfer-catalysis was employed as the key step to successfully design and prepare the alkyne substrates containing amino acid skeleton.In the end,the tandem O-alkenylation of arylhydroxylamines and the subsequent[3,3]-rearrangement were successfully achieved under the cooperative catalysis of gold and zinc,and a series of tryptophan derivatives with diverse structures and various substituents were efficiently synthesized.This method is different from the conventional modification of indole skeleton in existing reports,but it is a novel strategy for the efficient construction of tryptophan skeleton from non-indole acyclic substrates.Related studies enrich and develop the content of tryptophan synthesis strategies.