Studies On The Synthesis Of Isoquinoline Derivatives Based On O-alkynyl Aldehydes

The isoquinoline and dihydroisoquinoline units are found as the core nucleus in a wide variety of natural products and pharmaceutical agents with good biologically activity.They are important substructures in a broad range of natural products as well as synthetic intermediates in total synthesis of natural alkaloids.This dissertation mainly focused on the domino reactions for the generation of isoquinoline derivatives.Firstly,a small library of benzoxazine-fused isoquinolines has been synthesized under microwave irradiation(MW)via CuI catalyzed domino reactions of o-alkynyl aldehydes and amines having embedded nucleophiles.This strategy offers a operationally simple,environmentally acceptable route to synthesize benzoxazine-fused isoquinolines in moderate to good yields.Secondly,we investigated two reactions for the preparation of isoquinoline derivatives.On the one hand: an operationally simple approach for the tandem synthesis of isoquinolines by the reaction of o-alkynylaldehydes with ammonium bicarbonate via Ag-catalyzed 6-endo-dig ring closure is described.The reaction conditions and the scope of the reaction are examined,and a variety of substituted isoquinolines are obtained in moderate to excellent yields.On the other hand : an unprecedented silver nitrate mediated novel transformation of aromatic hydrazones into various isoquinolines has been developed.This method involves a silver nitrate promoted cyclization of aromatic hydrazones followed by N–N bond cleavage,and has wide substrate scope under mild conditions.Finally,a novel and efficient route for the generation of pyrazolo isoquinolines via1,3-dipolar cycloaddition reaction of 1,3-dipolar and ethyl acetoacetate is described.Meanwhile,the selective synthesis of either pyrazolo[5,1-a]isoquinoline-1-carboxylate or2-(pyrazolo[5,1-a]isoquinolin-2-yl)acetate derivatives from the same reactants has been achieved by simply varying base and reaction conditions.