Syntheses Of N-Heterocycles Via C–H Activation And Alkyne Annulation

Nitrogen-containing heterocycles(N-heterocycles)such as isoquinolines and indoles widely exist in natural products,and they are privileged structure in the drug discovery and fabrication of functional materials.Therefore,it is of great value for the development of buliding these heterocyclic skeletons.The atom and step economy,as well as substrate scope are limited in heterocycle syntheses via carbon–halogen bond cleavage,while synthetic systems via direct transformation of C–H bonds are highly in demand.In this dissertation,several methods with high efficiency,selectivity and step economy have been established for syntheses of N-heterocycles via C–H activation and alkyne annlution,following by some preliminary exploration of mechanism and application.The concept of auto-directing group was proposed in this study and illustrated by design and development of oximes and hydrazones,which were auto-intalled and auto-cleavable in the reaction system,enabling higher step-economy for C–H activation and annlution.Based on oxime auto-directing groups,a one-pot synthesis of multisubstitued isoquinolines was developed via three-componet cascade reaction of aryl ketones/nitriles,hydroxylamine,and alkynes.This system can also be extended to alkenyl and heterocyclic substrates to afford pyridines and diverse heterocycle-fused pyridines.A multi-functional hydrazone auto-directing group with N–N bond as internal oxidant has been designed and employed for the synthesis of indoles from aryl hydrazines and alkynes.The hydrazone group formed from isobutyraldehyde was found to be the best directing group for the reaction.The above two reaction systems have mild conditions,broad scopes,and high selectivity for aryl–alkyl asymmetric alkynes,which can be used for synthesis of bioactive molecules such as a 5-hydroxytryptamine antagonist.Several versatile methods for construction of polycyclic N-heterocycles were further developed in this study.The tricyclic skeleton of natural product cassiarins and its sulfur-ananoluge were constructed by extending the oxime auto-directing group strategy to chroman-4-ones and thiochroman-4-ones.Two types of ketone–alkyne bifunctional molecules were designed and enpolyed as substrates for syntheses of diverse natural product-like polycyclic pyridines and fused ?-carbolines.A new type of N-doped polycyclic conjuaged system was constructed by expansion of heterocyclic skeleton and extention of ?-system of 2-aryl phenanthroimidazoles via C–H activation and alkyne annulation.In the crystal of these polycyclic conjuaged molecules,1D structure formed by ?–? stacking can be observed.A thiophene–imidazole fused conjuaged molecule was designed and synthesized,which can be used as a florescent probe for Fe3+.In this dissertation,general synthetic methods were established for isoquinolines,1-aminoisoquinolines,heterocycle-fused pyridines and indoles by using oxime or hydazone as an auto-directing group.Also,strategies were developed for modular construction of natural product-like polycyclic N-heterocycles and N-doped polycyclic conjuaged systems.Theses studies enriched reaction strategies and applications of C–H activation and alkyne chemistry.