One-Pot Direct Construction Of Quinolones And Quinazolines Via The Ring Expansion Of Isatins

Isatin is a famous natural product of bicyclic small molecule.Influenced by its own carbonyl group and gamma-lactam group,isatin has multiple reaction sites and shows multiple reactivities.Isatin can show both nucleophilicity and electrophilicity under different reaction conditions.At the same time,due to their advantages of simple synthesis,wide sources and low cost,isatin often used as reaction substrates in organic synthesis.The simple unit reactions with isatin as the starting substrates include addition,reduction,electrophilic substitution,etc.Such reactions mainly play a role in modifying isatin and the core skeleton remains unchanged.As an effective reaction strategy to transform isatin into other heterocyclic skeletons,the ring expansion reactions of isatin have broad application prospect in the construction of various kinds of heterocyclic skeletons with diverse potential physiological activities.Based on the ring expansion reactions of isatin,this paper hopes to further enrich and improve the diversity of aromatic heterocyclic structures directly constructed by the ring expansion reactions of isatin on the basis of the existing research achievements of our group,so as to obtain more heterocyclic structures with potential physiological activities.The main contents of this paper are as follows:In the first chapter,based on the detailed literature review,we outlined the common organic reactions from isatin including nitrogen substitution reaction,spirocyclization reaction,reduction reaction,oxidation reaction and ring expansion reactions,etc.In the second chapter,we studied an effcient transition-metal-free oxidative cyclization reaction using isatins and alkynes for the one-pot directly construct structurally diverse quinolin-4(1H)-ones.This reaction is characterized by the switchable access to substituted 3-carboxylate-quinolin-4(1 H)-ones and 1-vinyl-3-carboxylate-quinolin-4(1H)-ones by choosing different bases in the reaction.In the third chapter,our group has realized the efficient construction of a series of structurally novel Nitrogen-containing heterocyclic skeletons such as tryptanthrins,4-quinolinones,2-amino-4H-benzo[d][1,3]thiazin-4-ones,2-thioquinazolinones and benzothiazolo[2,3-b]quinazolinones based on the ring expansion reactions of isatin.On the basis of the above works,we developed a copper-catalyzed oxidation reaction to synthesize 2-acyl-4-quinazolinone derivatives using simple isatins and alkenyl azides as starting materials.This method further enriched the diversity of nitrogen heterocyclic structures constructed by isatin-based ring expansion reactions.