Studies On Rapid Construction Of Nitrogen-containing Heterocyclic Compounds Based On N-H/C-H Tandem Cyclizations

Indole-fused phthalazines and benzoazepines,as two types of important skeletons in active drug molecules,have been the focus of research topic among synthetic community.However,the preparation of such compounds and their analogs currently has major limitations.For instance,indole-fused phthalazine constructions are mainly limited to substrates such as phthalazine/pyridazine,α-bromoaryl ketone and alkynyl esters through multi-step process catalyzed by precious metals with lower yields as well as poor substrate applicability.Similarly,traditional syntheses of benzoazazepine compounds have the disadvantages of mult-steps and poor atomic economy.Therefore,the development of convenient synthetic protocols with well atomic economy under mild conditions is particularly attractive for such heterocyclics.Thus,the tandem synthesis strategy can simultaneously construct multiple chemical bonds,and realize the rapid construction of complex active biomolecules from simple molecular precursors,which has become an important tool for drug synthesis and development.Among them,N-H/C-H tandem cyclization strategy provides an efficient and convenient pathway to construct N-heterocyclic compounds.In this thesis,we realized the N-H/C-H cyclization with 2-alkynyl aldehyde and phenylhydrazine as the starting materials for the construction of indole-fused phthalazines derivatives under metal-free conditions(Eq.A).The process was performed under air atmosphere,and was simple to operate.Notably,this protocol behaved high atomic economy,good functional group tolerance,and was in line with the concept of green chemistry,providing new tool for the synthesis of such heterocyclic compounds.Besides,we applied N-(o-alkynylbenzene)propynamide as substrate to directly construct benzoazepine compounds through the Au(I)-catalyzed intramolecular N-H/C-H tandem cyclization process(Eq.B).The method was simple and convenient to operate with few by-products,and meets the concepts of green synthesis.