Selective C—H Activation Of Indolines

Indoline skeletons extensively exist in natural products,which are found owning high biological activity.So far,indolines have been modified to diverse building blocks by pharmaceutical chemists to prepare drug molecules.Transition metal catalysed C—H bond activation provides a powerful tool to the structural modification of compounds by directly cleaving the C—H bond in the molecules and introducing new functional groups,which help realize the molecular diversification.Therefore,it is of great significance to study the selective C—H bond activation of indoline derivatives.Herein,the related work of C—H activation reactions of indolines are first reviewed,and subsequently,the new green reaction systems are developed to cover some shortages of the previous work.At the same time,the new strategy is used to realize the functionalisation of those C—H bonds difficult to activate,which efficiently achieving the diversification of indoline molecules and providing a powerful tool for the late modification of natural products or drug molecules based on the indoline skeletons.This thesis focuses on the new methodology for the selective C—H activation of indolines.Four parts are included as follow:(1)Chapter 1: Mainly introduce the reported work on selective C—H bond activation of indoline compounds in recent years,summarize the above work,and point out their shortcomings.At the same time,according to the review of the previous work,it was found that the selective C—H activation of indolines,especially for the remote one,is still a challenge.We envisage optimizing the disadvantages of the reported work and launching a new strategy to realize the remote C—H bond activation of indolines.(2)Chapter 2: Optimize the related work reported before and develop greener methods.Acetoxylation at the C7 position of the indolines provides an effective way for the synthesis of C7-hydroxyl substituted indolines,however in previous work,the noble metal rhodium is often required as the catalyst,while using the high-valent iodonium salt as an acetoxyl source.Herein,we propose to let the cheap copper(II)acetate serve as both catalyst and acetoxyl source to achieve C—H acetoxylation at the C7 position of the indoline,which greatly reduces the cost of the reaction.(3)Chapter 3: The remote C—H activation of indoline is always full of challenge.Herein,we study the selective C—H functionalisation at the C5 position of indoline.This chapter mainly introduces the strategy of free radical coupling to achieve highly selective C—H nitration at the C5 position of indoline.The method avoids the use of metal nitration reagents,and the reaction is very easily to operate,which can proceed by open stirring at room temperature.The strategy provides a new method to the C—H functionalisation of indolines at the C5 position.(4)Chapter 4: Introduce a method for preparing the isatin from indoline.Isatin always used to be produced through the oxidation of indole,however,to our best knowledge,the method of producing isatin from indoline in one step has never been reported.Since the indoline can be easily oxidized to indole,we proposed a tandem oxidation strategy to realize the conversion of indolines to isatins in one step.The reaction improves the step economy for the preparation of some isatin derivatives.