Pd-catalyzed [2+2+1] Cyclization Reaction

Five-membered rings are significant structures in organic compounds,which widely exist in natural products,pharmaceuticals and functional materials.Developing new strategies to construct five-membered rings quickly and efficiently has been a hot research topic in the field of organic synthesis.Cyclization reactions can build multiple chemical bonds simultaneously in a single step,providing a variety of powerful strategies to construct structurally complex and diversely functionalized carbocycles and heterocycles.Representative methodologies for the formation of five-membered rings include[3+2],[4+1]and[2+2+1]cyclization reactions,and numerous five-membered carbocyclic and heterocyclic compounds have been successfully synthesized based on these strategies,among which,[2+2+1]cyclization strategy has attracted considerable attention due to its better controllability and flexibility.In this context,the crucial role of[2+2+1]cyclization strategy in the construction of five-membered carbocyclic and heterocyclic compounds has been discussed in this dissertation,and we aim to explore novel and efficient[2+2+1]cyclization reactions to construct synthetically valuable five-membered carbocyclic and heterocyclic compounds.The dissertation consists of three chapters as follows:In the first chapter,the importance of five-membered carbocyclic and heterocyclic compounds is briefly introduced,the representative methodologies for the formation of five-membered rings are introduced and the[2+2+1]cyclization strategy is highlighted.Then the recent advances of[2+2+1]cyclization reaction,which according organized by the different types of C1,N1 synthons and other hetero one-atom fragments,such as oxygen,sulfur and silicon were discussed detailedly.Based on the previous works,the research idea during my doctoral period is put forward.In the second chapter,a simple and efficient Pd(0)-catalyzed dearomatizing[2+2+1]spiroannulation is described.The key feature of this method is the use of readily available1,2-dihaloarenes,alkynes and 2-naphthols for the rapid assembly of spirocarbocyclic molecules,and a high chemo-and regioselectivity was obtained.It also should be mentioned that 2-naphthols as C1 synthons in this reaction.In the third chapter,a novel Pd(0)-catalyzed[2+2+1]annulation of alkyne-tethered aryl iodides with tertiary hydroxylamines,which as bifunctional single-nitrogen sources,has been developed.Through alkyne-directed palladacycle formation and consecutive diamination,a wide range of 3,4-fused tricyclic indoles were obtained in a single-step transformation.New finding of unconventional selectivity by cutting off the larger groups of tert-butyl-or benzyl-substituted tertiary amines(via an S_N1 pathway),guiding us to find a suitable amino source to exclusively construct a removable alkyl group beared tricyclic indoles.