Asymmetric Friedel-Crafts Alkylation Of Indole Enabled By Visible-Light Photoredox And Chiral Phosphate Catalysts

In recent years,visible light-induced organic reactions has received widespread attention from chemists,and these reactions generally involve free radicals intermediates.However,the high reactivity of free radicals makes the control of stereoselectivity in visible light-induced asymmetric reactions to be quite difficult.Chiral organocatalysis is a hot fields in modem organic synthetic chemistry,and has been a widely used protocol for the creation of asymmetric reactions.The integration of chiral organocatalysis and photoredox catalysis has been demonstrated to provide abandunt opportunities to deleveop various unprecedented asymmetric reactions.Indole derivatives have been widely used as key intermediates or bulding blocks in the synthesis of natural products and bioactive molecules,such as arrhythmia ajmaline,anticancer drug,vinblastine and therapeutic convulsion drug,strychnine.As a useful methods to access chiral indole derivatives,asymmetric Friedel-Crafts alkylation has attracted the great interest of chemists.A wide variety of effective catalyst systems have been developed to achieve these reactions.In this thesis,we will focus on an asymmetric Friedel-Crafts reaction between indole and redox active esters by using photoredox and chiral phosphate combined catalysis.This reaction can tolerate a wide range of indoles and divergent a-amino acid-derived redox active esters,providing a robust method to access chiral indole derivatives.In addition,mechanistic studies reveal that this reaction might proceed in a tandem process,consisting of photoredox catalytic formation of N-acetylimines from a-amino acid-derived redox active esters and subsequent chiral phosphate catalyzed asymmetric Friedel-Crafts reaction of indoles.