Study On The Tandem Annulation Reactions Of Sulfoxonium Ylides In The Synthesis Of Heterocycles

As the heterocyclic compound with the largest number,nitrogen heterocyclic compounds widely exist in many natural products and drug molecules that are biologically active.Nevertheless,they also can be found in fields like polymer chemistry and material chemistry.As a result,it is of great significance to research the synthetic method of nitrogen heterocyclic compounds.And meanwhile strategies for synthesizing nitrogen-containing heterocycles are also increasing.In recent years,the preparation of nitrogen-containing heterocyclic compounds based on the transition metal-catalyzed C-H bond activation has been favored by chemists because of its unique atomic economy and environmental friendliness.Among them,the metal insertion reaction using metal carbene as a precursor to achieve C-H bond functionalization has been rapidly developed.Sulfoxonium ylides is a kind of compound with high safety and easy preparation.It can be widely used as a carbene precursor in multiple tandem cyclization reactions.For example,it can efficiently construct a variety of carbocyclic and heterocyclic compounds through C-H bond activation.In this work,we summarized the cascade cyclization reactions that involves sulfur ylides in recent years and introduced the applications of different sulfur ylides as synthons in the synthesis of cyclic compounds.Next,we also reviewed the sulfoxonium ylides-participating transition metal-catalyzed C-H bond activation/cyclization reaction and introduced the construction of carbocyclic and heterocyclic compounds.This work will focus on exploring the tandem cyclization reaction based on the participation of sulfoxonium ylides,and fast and efficiently constructing 2-phenylindole,pyrrolo[1,2-a]quinoxaline,indazole N-oxides,etc from the simple and easily available substrates,.The main work of nitrogen-containing heterocyclic compounds is divided into the following aspects:1.Firstly,we developed the synthesis of 2-phenylindole derivatives using N-pyridylaniline and sulfoxonium ylides as reaction substrates through [3+2] cyclization process.In this reaction,divalent ruthenium is used as the catalyst,silver hexafluoroantimonate and zinc acetate the additives.Under the guidance of the pyridine group,we firstly realize the selective C-H bond activation at the ortho position of the aniline to achieve the acylmethylation reaction,and further intramolecular nucleophilic cyclization occurs to obtain the target product.The method has wide substrate universality,good regioselectivity and high yield,and has potential utilization value in synthesizing biological and pharmaceutical indole compounds.2.Secondly,the synthesis of pyrrolo[1,2-a] quinoxaline derivatives have been successfully developed.We use 1-(2-aminophenyl)pyrroles and sulfoxonium ylides(C1 synthon)as the initial substrate,divalent ruthenium as the catalyst,amino group as the traceless directing group,and air as the green oxidant.After the [5+1] cyclization,a series of highly selective target molecules are synthesized.3.In addition,the [4+1] tandem cyclization reaction of N-methyl-Nnitrosoaniline with sulfoxonium ylides was successfully designed and implemented.Under the catalysis of trivalent rhodium,a series of indazole N-oxide derivatives were prepared through high atomic efficiency.Nitroso not only act as the directing group but also the source of "NO" in the product.In the tandem cyclization reaction,alkylation reaction first occurred under the guidance of nitroso,and then further intramolecular cyclization occurred to synthesis the target compound.Besides,we successfully isolated the alkylated product and proved the existence of the intermediate through control experiments.4.Finally,using 7-azaindole as the directing group,the azaindole derivative was prepared by C-H bond activation.7-azaindole is an important nitrogen-containing heterocyclic ring and has high biomedical value.A lot of achievements have been reported in the construction of azaindole derivatives through the activation of C-H bonds with 7-azaindole as the directing group,for example,the C-H bond on the ortho position of the N-phenyl-7-azaindole benzene ring chlorination,amination,phosphorus amination,alkenylation,alkynylation,etc.We propose to use sulfoxonium ylides as the coupling reagent and trivalent rhodium as the catalyst to selectively perform alkylation on the aromatic ring of N-phenyl-7-azaindole.By this method,a series of ?-aryl ketone derivatives containing azaindoles were obtained.