Transition Metal-Catalyzed Synthesis Of N-Fused Heterocycles

N-Heterocycles are ubiquitous in a variety of natural products and biologicallyactive molecules, and they play important roles in the pharmaceutical and agrochemicalindustries. The development of transition metal-catalyzed cross-coupling reactions forthe formation of heterocycles continues to be an active area of research. Recently, thedirect functionalization of C-H bonds has made great progress. Their application on theconstruction of N-heterocycles has been reported. In this dissertation, new transitionmetal-catalyzed methods have been developed for synthesis of N-fused heterocycles,and some important results were obtained.A simple and efficient copper-catalyzed one-pot tandem method has beendeveloped for synthesis of benzimidazo[1,2-b]isoquinolin-11-one derivatives. Theprotocol used cheap CuCl as the catalyst, readily available substituted2-halo-N-（2-halophenyl）benzamides and alkyl2-cyanoacetates or malononitrile as thestarting materials. The couplings of substituted2-halo-N-（2-halophenyl）benzamideswith alkyl2-cyanoacetates or malononitrile were performed well under mild conditionswithout addition of any ligand or additive, and the correspondingbenzimidazo[1,2-b]isoquinolin-11-ones were obtained in good to excellent yields. Thepresent method shows economical, practical and starting material readily availableadvantages over the previous methods, so it will provide a new strategy for constructionof diverse and useful N-fused heterocyclic compounds for organic chemistry andmedicinal chemistry.A convenient and efficient copper-catalyzed cascade method has been developedfor synthesis of benzimidazoisoquinoline derivatives. The protocol used inexpensiveCuI as the catalyst, readily available substituted2-（2-halophenyl）benzoimidazoles andalkyl cyanoacetates as the starting materials, and the corresponding alkyl6-aminobenzimidazo[2,1-a]isoquinoline-5-carboxylates were obtained in good toexcellent yields. The novel method provides diverse and useful N-fused heterocycles forcombinatorial chemistry and medicinal chemistry.A convenient and efficient palladium-catalyzed synthesis of aromatic ketones andisoindolobenzimidazoles has been developed via selective aromatic C-H bond acylation. The protocol used Pd（OAc）₂as the catalyst, readily available carboxylic acids as theacylating reagents,（CF₃CO）₂O as the activated agent of the acids, and thecorresponding aromatic ketones and isoindolobenzimidazoles were obtained in good toexcellent yields. The novel and practical method provides a new and useful strategy forsynthesis of aromatic ketones and isoindolobenzimidazoles.An efficient copper-catalyzed aerobic oxidative intramolecular alkene C-Hamination leading to N-heterocycles has been developed. The protocol used cheap andreadily available Cu（O₂CCF₃）₂as the catalyst, substituted3-benzylidene-2-pyridin-2-ylmethyl-2,3-dihydro-isoindol-1-ones as the startingmaterials, economical and environment friendly air as the oxidant, and thecorresponding N-heterocycles were obtained in good to excellent yields. This methodshould provide a new and useful strategy for constructing N-fused heterocycles.