Synthesis Of Isoquinolines And Quinazolines Derivatives Via Tandem Reactions

Among the large number of strategies employed in diversity-oriented synthesis,tandem reactions that encourage the limits of synthetic efficiency have become themost attractive research frontiers and central issues in organic chemistry by using therelatively small number of synthetic reactants to create novel products with an optimalnumber of molecular diversity and complexity.These reactions are ideally suited forbuilding up the natural product-like libraries prone to display high performancebiological activities.This thesis is mainly focused on the tandem reactions for the construction ofpotentially bioactive isoquinoline and quinazoline derivatives.Firstly, we developed tandem reactions of N’-(2-alkynylbenzylidene)hydrazidewith bromoalkyne co-catalyzed by silver triflate and copper(I) iodide, which generatediverse1,2-dihydroisoquinoline derivatives. While Oxidative addition product ofbromoalkyne quickly attack α-C-H bond in situ formed isoquinolinium-2-yl amideand the next reductive elimination reaction, intramolecular5-endo cyclization,protonation and finally aromatization reactions would occur to lead to theH-pyrazolo[5,1-a]isoquinolines compounds.Secondly, we disclosed silver triflate and palladium acetate co-catalyzed tandemreactions of N’-(2-alkynylbenzylidene) hydrazide with N-allyl ynamide, which affordthe unexpected2-amino-H-pyrazolo[5,1-a]isoquinolines in good to excellent yield.The reaction proceeds smoothly under mild conditions through intramolecularcyclization,[3+2] cycloaddition,3,3-sigmatropic rearrangement, aromatization and soon.Finally, we introduced a Pd-Cu-co-catalyzed Sonogashira coupling reaction ofquinazoline-4-tosylates with terminal alkynes by using N-Heterocyclic carbenes(NHC) as ligands, which provides4-alkynylquinazolines in good yields.