Investigation Of C-H Bond Functionalization Reactions Of Indoles And Their Explorations In Total Synthesis Of Akuammiline Alkaloids

Indole and its derivatives are a class of important nitrogen-containing heterocyclic compounds,which are usually found in many natural products and synthetic compounds with important biological and pharmaceutical activities.At present,many ingenious synthesis methods have been reported for the construction and functionalization of indoles,especially the development of green,mild and practical indoles functionalization strategies has become the core issue in this field.In this thesis,the regional selective C-H bond functionalization of indoles was achieved by using molecular iodine/chloramine salt and cobalt/peroxylate as catalytic oxidation systems respectively.In particular,on this basis,we rapidly constructed the continuous four-ring skeleton of akuammiline family alkaloids using iodine-catalyzed indoles C2 amidization as the key step.The paper mainly includes the following three parts.Chapter 1:An efficient and mild iodine-catalyzed synthesis of 2,3-disubstituted indole with chloramine salt as oxidant and nitrogen source was developed.This reaction is characterized by high regional selectivity,simple operation,good functional group tolerance,and wide substrate universality.On this basis,with this strategy as the key reaction,we rapidly constructed the continuous four-ring skeleton of the alkaloid of akuammiline family,laying a good foundation for further realizing the collective synthesis of the related alkaloid of this family.Chapter 2 : An efficient and mild cobalt-catalyzed synthesis of indole C2?-position acyl oxidation by 2-substituted indole as precursor,tert-butyl peroxylate as oxidant and acyloxyl source was developed.The reaction has the following characteristics :(1)cheap and easy to obtain cobalt as a catalyst;(2)the reaction is easy to operate and at ambient temperature;(3)good substrate universality and functional group tolerance.It is worth mentioning that the resulting products can be further transformed into the core skeleton of malassezindole A and B.Chapter 3:On the basis of the research in the second part,we try to develop cobalt-catalyzed C-H bond functionalization of indoles C3-position.A cobalt-catalyzed synthesis method for selective C3 acyl oxidation of indoles was developed by using readily available n-pyrimidinyl indoles as precursors and tert-butyl peroxylates as oxidants and acyloxyl sources.This reaction is characterized by high regional selectivity,good functional group tolerance and simple operation,providing an effective way to construct indoles with acyloxy at C3-position.