Syntheses Of N-Heterocycles Via Alkynes And Nitriles Annulation

Nitrogen-containing heterocycles have been attracted great concern,which can be used as building blocks in many pharmaceutical intermediates and potentially biologically active molecules.Among nitrogen-heterocycles,the structures of indoles,quinolines and isoquinolines widely exist in natural products,biologically active molecule and drugs.It is very important to develope the efficient synthetic methods to construct nitrogen-heterocyclic skeleton selectively or to introduce suitable substituents into the heterocycle backbone for modifying the properties of nitrogen-heterocycle to meet their specific function.Therefore,the design and establishment of highly selective methods for nitrogen-heterocycle synthesis is one of the important and interesting research topics in catalytic synthesis chemistry,pharmaceutical chemistry and organic material chemistry.Alkynes and nitriles are unsaturated compounds containing carbon-carbon triple bond or carbon-nitrogen triple bond,which have high reactivity for transformation.The triple bonds can coordinate to transition metal and the formed carbon-metal bond can be converted into carbon-carbon bond and carbon-hetero bonds.The transformation of alkynes or nitriles into heterocycles usually shows atom-efficiency and step economy,which provides a powerful tool for building diversity heterocycle skeleton.This dissertation focuses on the application of alkynes or/and nitriles as synthons to develop new catalytic systems in the synthesis of nitrogen-heterocycles.Firstly,a one-pot synthetic method for the formation of multi-substituted2-aminoquinolines from the cyclization of 1-aryl tetrazoles with internal alkynes via rhodium?III?-catalyzed double C–H activation,and copper?II?-mediated denitrogenation was developed.Secondly,an efficient protocol for the synthesis of fused polycyclic indoles of[1,2-a]indol-10-imines via a Cu?OTf?₂-catalyzed intramolecular cyclization of N-?2-cyanophenyl?indoles with the use of diaryliodonium salts as an aryl reagent was also developed.Thirdly,a novel synthetic method for the synthesis of 1-aminoisoquinolines and heterocycle-fused pyridines by Rh?III?-catalyzed activation of C–H bond of N'-hydroxybenzimidamide formed in situ via the reaction of nitriles with hydroxylamine hydrochloride,and its annulation with internal alkynes.The present procedure can be applied in the synthesis of fluoro-substituted or heterocycle-fused 1-aminoisoquinolines,which are not easily accessible by traditional synthetic methods.