Visible-light-catalyzed Radical Cross-Coupling:Synthesis Of 6-benzyl-6-hydroxyindolo[2,1-b] Quinazolin12(6H)-ones And Homoallylamines

With the rapid development of modern industries and the increasing scarcity of fossil fuels,green and sustainable visible-light catalysis has become a popular research field.Both C-C bonds and C-N bonds are widely existing in organic molecules,so it is of great research significance to construct C-C bonds and C-N bonds efficiently in organic synthesis.Visible-light-catalyzed radical cross-coupling reaction with the features of excellent efficiency and mild reaction conditions,has become one of the most effective strategies for constructing chemical bonds in organic chemistry.Tryptanthrins and their derivatives are natural alkaloid with good pharmacological activities and homoallylamines are key intermediates for the synthesis of many bioactive molecules.Efficient synthesis of these compounds has attracted wide attention in organic synthesis.However,the traditional synthesis methods are accompanied by disadvantages such as the use of stoichiometric metal reagents,high temperature conditions or limited substrate scope.Therefore,it is necessary to develop greener methods to effectively synthesize tryptanthrin derivatives and homoallylamines.In this thesis,the one-pot synthesis of tryptanthrin derivatives and homoallylamines by radical cross-coupling strategy under visible-light catalysis was mainly described.In the first chapter of this thesis,the basic principles of visible-light catalysis and the radical cross-coupling reaction were mainly summarized.And then the research background and development status of tryptanthrins derivatives and homoallylamines were briefly reviewed.In addition,the mechanism and application of halogen atom transfer(XAT)were concisely introduced.Finally,the research basis and significance were discussed.In the second chapter of this thesis,the one-pot synthesis of 6-benzyl-6-hydroxyindolo[2,1-b]quinazoline-12(6H)-ones from isatin/isatin anhydride and benzyl potassium trifluoroborate by visible-light catalysis was mainly introduced.In this study,we optimized the reaction conditions such as photocatalyst,solvent,additive and reactant loading ratio,and synthesized 6-benzyl-6-hydroxyindolo[2,1-b]quinazoline-12(6H)-one with a yield of 76%,which was confirmed by X-ray single crystal diffraction.Under the optimum conditions,the substrate range was investigated by two methods(Method A:two-component reaction of isatin and benzyl potassium trifluoroborate;Method B: threecomponent reaction of isatin,isatin anhydride and benzyl potassium trifluoroborate).And31 new 6-benzyl-6-hydroxyindolo[2,1-b]quinazoline-12(6H)-ones were successfully synthesized and characterized.Finally,based on the control experiments,UV-visible absorption experiments,cyclic voltammetry experiments,radical trapping experiments,we put forward a possible reaction mechanism.This study provides an innovative approach to constructing the tryptanthrin skeleton and benzylating at the C-6 position in a one-pot synthesis and enriches the diversity of indole derivatives.In the third chapter of this thesis,the synthesis of homoallylamines with imine and allyl bromide as raw materials and N,N-diisopropylethylamine as sacrificial reducing agent by combining visible-light catalysis with halogen atom transfer(XAT)was mainly introduced.In this work,after optimizing the reaction conditions of photocatalyst,solvent,additive and reactant loading ratio,N-benzyl-1,1-diphenylbut-3-en-1-amine was obtained with a yield of 99%.Subsequently,we carried out a gram-scale experiment and successfully obtained the target compound with a yield of 98%.By investigating the range of substrates,it was found that this reaction was suitable for a variety of imines prepared from aromatic ketones/aldehydes and aromatic amines/aliphatic amines,including aldehyde imines with high activity to synthesize α-trisubstituted homoallylamines,and ketoimines with lower activity and greater steric hindrance to synthesize α-tetrasubstituted homoallylamines.We successfully synthesized 39 homoallylamines and characterized their structures.In addition,functional groups such as ester,cyano,amides,thioamides exhibited good functional group tolerance in the reaction.Finally,based on control experiment,UV-visible absorption experiment,cyclic voltammetry experiment,fluorescence quenching experiment and radical trapping experiment,we put forward a plausible reaction mechanism for this system.This method is green,mild and efficient,which highlights its application potential and provides a green and concise solution for the synthesis of homoallylamines.