Study On The Para Asymmetric Functionalization Of N-monosubstituted Anilines

Aniline is a kind of very important and classic chemical building block,but owing to the multiple reaction sites,high regioselectivity functionalization still exists challenging.Over the past few decades,N,N,-disubstituted anilines react with electrophilic reagents has developed very fast,but asymmetric para-selective Friedel-Crafts reaction of N-monosubstituted aniline derivatives with isatin-derived ketimines has not been reported yet.This dissertation is aimed to achieve the enantioselective Friedel-Crafts reaction of N-monosubstituted aniline derivatives with isatin-derived ketimines in the presence of chiral phosphoric acids to build a series of aza-quaternary carbon 2-hydroxyindoles.The main achievements of this manuscript are:(1)This is the first example of asymmetric para-selective functionalization of anilines containing N-H bonds,which has the characteristics of high yield,high chemo-,site-,enantioselectivities and wide substrate scope,it also has important guiding significance in asymmetric para-selective C-H aminoalkylation of N-monosubstituted aniline derivatives.(2)Based on mechanism reactions,a probable asymmetric catalysis model(CPAs-OH dual-hydrogen-bond stereocontrol mode)was proposed herein.The chiral phosphoric acid interacts with the two substrates in the form of hydrogen bonds,and there is a π-π interaction that keeps the three molecules packed tightly and gives good stereocontrol over the three-dimensional configuration.(3)We also conducted subsequent research on synthesis,transformation and related applications.Enantioseletive can be well maintained.(4)A series of anticancer activities of new chiral 3-substituted 3-amino-2-oxindoles was found in this work and anticancer pharmacological researches of the aniline derivative 3-amino-2-oxindoles are ongoing.