Synthesis Of N-heterocyclic Compounds Via Arylation

Nitrogen-containing heterocyclic compounds are ubiquitous subunits of naturalproducts, drugs, biologically active molecules. N-Heterocycles compounds haveattracted much attention because of their unique biological and pharmacologicalactivities, they were designed as the privileged scaffolds, and a number of drugs havedeveloped. Recently, there has been remarkable progress in synthesis ofN-heterocycles via various arylations. In this dissertation, we investigated synthesisof1,3-diaminoisoquinoline, tetrazolo[5,1-a]isoquinoline and indolin-2-onederivatives, and some results were obtained as follows:A novel and efficient copper-catalyzed method has been developed for synthesisof1,3-diaminoisoquinoline derivatives. The protocol used readily availablesubstituted5-(2-halophenyl)-1H-tetrazoles, alkyl2-cyanoacetates and malononitrileas the starting materials, CuI as the catalyst, Pipecolinic acid as the ligand, K2CO3asthe base, and the corresponding1,3-diaminoisoquinoline derivatives were obtained inmoderate to good yields. The domino reaction proceeded through sequentialcopper-catalyzed C-arylation, intramolecular nucleophilic addition and denitrogenation oftetrazoles. The synthesized1,3-diaminoisoquinoline derivatives with variousfunctional groups are important biological and pharmaceutical molecules. The presentmethod provides opportunity for synthesis of diverse molecules in medicinalchemistry.A practical and highly efficient copper-catalyzed method has been developed forsynthesis of tetrazolo[5,1-a]isoquinolines. The protocol used readily availablesubstituted2-5-(2-halophenyl)-1H-tetrazoles and terminal alkynes as the startingmaterials, CuI as the catalyst, NaOAc or K2CO3as the base, and DMSO as thesolvent, and no any ligand or additive was required. The reactions provided thecorresponding tetrazolo[5,1-a]isoquinolines in moderate to excellent yields. Themethod could tolerate various functional groups in the substrates. Therefore, the presentmethod will find wide application in organic chemistry and medicinal chemistry A simple and efficient copper-catalyzed method has been developed forsynthesis of oxindole derivatives. The protocol used inexpensive CuI as the catalyst,readily available N-alkyl-N-phenylalkacrylamides and diaryliodonium triflates as thestarting materials, and bis-arylations of N-alkyl-N-phenylalkacrylamides wereperformed well under mild conditions. The synthesized compounds will be helpful forscreening of diverse biological molecules.A novel, simple and efficient transition-metal-free method has been developedfor synthesis of3-(trifluoromethyl)-indolin-2-one derivatives. The protocol usedreadily available N-alkyl-N-phenylalkacrylamides as the starting materials,inexpensive and easily stored Langlois reagent (sodium trifluoromethanesulfinate) asthe trifluoromethyl sources, and PhI(OAc)2as the oxidant, and the corresponding3-(trifluoromethyl)-indolin-2-one derivatives were prepared in good to excellentyields. The procedure underwent metal-free trifluoromethylation and arylation ofalkenes. The method did not need mediation of any transition-metal which avoidedcontaminate of toxic metals to the products, so the economical and theenvironmentally friendly approach to trifluoromethylated oxindole derivatives willattract much attention.