Investigation On N-Heterocyclization And Coupling Reaction Of Nitriles

The nitriles(RCN),as a class of important carbon-nitrogen triple bond compounds,not only exists widely in natural products with biological activities,but also can be easily obtained from several simple and efficient synthetic methods,providing some industrial organic chemicals,such as solvents and ligands.At the same time,nitriles show flexible chemical versatility in many chemical transformations by virtue of their unique cyano functional group structure.On the one hand,nitriles can undergo carbon-nitrogen triple bond cleavage under suitable conditions to recombine other new carbon-carbon or carbon-heteroatom bonds,and then transform into a series of structurally diverse organic compounds.On the other hand,due to the inherent stability and weak coordination ability of the cyano functional group,it often acts as a transition metal ligand and direacting group in some transition metal-catalyzed reactions.In recent years,the conversion of nitriles as a way to create new substances has always been the core and frontier of organic synthetic chemistry,and the corresponding research has been rapidly developed.However,due to the high bond energy of the carbon-nitrogen triple bond of nitriles,the conversion methods for common nitriles are still very limited under mild conditions.Therefore,based on the concept of green synthetic chemistry,the development of a simpler,more efficient and environmentally friendly catalytic system to achieve the precise activation and efficient conversion of common nitriles is still a research topic worthy of attention and challenging.Nitrogen-containing heterocycles are an important branch of heterocyclic compounds.Due to their physiological and pharmacological effects,N-heterocycles are common fragments in most of the commercially available drugs and medicinal chemistry research objects.They constitute an important and valuable molecular library and have made significant contributions in disease treatment and safeguarding human health.Therefore,the design and synthesis of N-heterocycles as well as the constitution of molecular library have become a bounden duty for modern organic chemistry.In this context,this thesis studies N-heterocyclization of simple nitriles and cyano-assisted coupling reaction with high efficiency,high selectivity and high atom economy.The specific content is as follows:(1)Assembly of 1H-isoindole derivatives by selective carbon–nitrogen triple bond activation:access to aggregation-induced emission fluorophores for lipid droplet imaging.A novel palladium-catalyzed strategy has been established to assemble a series of single(Z)-or(E)-1H-isoindole derivatives through selectively and sequentially activating carbon–nitrogen triple bonds in a multicomponent system of o-bromobenzonitrile,arylacetonitrile and isonitrile.The reaction provides efficient access to structurally unique fluorophores with aggregation-induced emission characteristics.Their photophysical properties and biological properties were further studied by relevant testing methods.(2)Synthesis of disubstituted pyridine derivatives from nitriles and1-methyl-1,3(ar)enynes by a sequential cyclization/aromatization strategy.In this chapter,an alkali metal salts-promoted stepwise addition reaction of nitriles and o-substituted arylalkynes and 1-methyl-1,3-enynes has been realized,and various pyridine,isoquinoline and benzothienopyridine compounds have been synthesized.The reaction mechanism was studied in detail by controlled experiments and density functional theory calculations(DFT).This method is a rare example of the reaction between nitriles and sp~3 carbon prenucleophiles.(3)Palladium-catalyzed nitrile-assisted C(sp~3)-Cl bond formation for synthesis of dichlorides.A palladium-catalyzed coupling procedure of alkenes and alkynylnitriles has been demonstrated for the synthesis of dichlorides containing acrylonitrile framework.The construction of five-membered cycle intermediate by coordination of cyano group with alkylpalladium(II)complex successfully inhibits theβ-hydride abstraction,resulting in direct and efficient construction of C(sp~3)-Cl bond.This method has the advantages of mild reaction conditions,simple operation steps,and good substrate compatibility.