The Synthesis Of Oxindoles,Isoindolinones And Isobenzofuranones Promoted By Tin Powder

Heterocycle skeletons are undoubtedly the most important structural scaffolds in a large number of pharmaceuticals,agrochemicals and natural products.Among various heterocycles,3-spiro-2-oxindoles,isoindolinones,pyrazoloisoindol-8-ones and isobenzofuranones are common architectures in medicinal chemistry due to their wide ranging biological activities.Therefore,it is of great significance to develop an efficient and facile approach for the construction of these heterocyclic compounds.On the other hand,organotin compounds such as allyltributylstannane usually display good stability toward heat,hydrolysis and oxidation,the tolerance to functional groups,and high selectivity in organic reactions.Hence,they have been widely applied in organic synthesis.However,most allyltributylstannanes are toxic,and not atom economic and environmentally benign.In subsequent studies,it was found that allylstannanes could be formed in situ from tin powder and allyl bromide in organic reactions,and then reacted with substrates directly.This method not only kept the advantages of organotin reagents,but also avoided the use of toxic allylstannanes.Herein,we will be exploring the synthesis of oxindoles,isoindolinones and isobenzofuranones from reactions promoted by tin powder.This thesis is mainly composed of the following four charpters:The chapter one: The research progress of synthesis of aza-and oxa-heterocycles from reactions promoted by allyl organometallic reagents and metalsIn this chapter,we mainly classified reactions according to the application of different allyl organometallic reagents and metals in the synthesis of aza-and oxa-heterocycles,and described the research progress of synthesis of aza-and oxa-heterocycles from reactions promoted by metals and involved in allyl organometallic reagents respectively in recent years.The chapter two:Tin powder promoted synthesis of trifluoroethylaminecontaining 3,3-disubstituted-2-oxindoles and 3-spiro-2-oxindolesIn this chapter,we have developed a new protocol for the synthesis of trifluoroethylamine-containing 3,3-disubstituted-2-oxindoles and 3-spiro-2-oxindoles from reactions of isatins,trifluoroethylamine hydrochloride and allyl bromides or 2-(bromomethyl)acrylic ester promoted by tin powder.This protocol used simple and commercially available trifluoroethylamine hydrochloride as a trifluoroethylamine building block and gave various of trifluoroethylamine-containing 3-substituted-2-oxindole derivatives with potentially biologically active,and avoided the use of toxic stannanes.This work further extends the application of tin powder-promoted reactions in organic synthesis.The chapter three:Tin powder promoted synthesis of isoindolinones and pyrazoloisoindol-8-onesIn this chapter,we established a convenient and four-component one-pot cascade cyclization for the synthesis of isoindolinones from reactions of 2-formylbenzoic acids,hydrazides and allyl bromides promoted by tin powder.Further manipulation of 3-allylisoindolin-1-ones by iodocyclization process afforded the tricyclic pyrazolo[5,1-a]isoindol-8-one derivatives,which could be converted into more complicacted tetracyclic azirino[1',2':2,3]pyrazolo[5,1-a]isoindol-4-ones.The method further extended the application of tin powder-promoted reactions in preparation of heterocyclic compounds,espically in synthesis of highly functional group dense heterocyclic compounds.The chapter four:Tin powder promoted synthesis of isobenzofuran-1(3H)-onesIn this chapter,an efficient three-component one-pot cascade cyclization was developed to synthesize isobenzofuranones by using 2-formylbenzoic acids,allyl bromides or ?-bromocarbonyl compounds and tin powder without other additives or catalysts.The process constructed one C-C and one C-O bond through one-pot tandem promoted by tin powder,which provides asimple and efficient method for the snythesis of isobenzofuranone derivatives.