Synthesis of pyrazolo[5,1-a]isoquinolines via a silver(i)-catalyzed reaction of (1-arylethylidene)hydrazides with N′-(2-alkynylbenzylidene)hydrazides

Abstract

A silver(I)-catalyzed reaction of (1-arylethylidene)hydrazides with N′-(2-alkynylbenzylidene)hydrazides is reported, which provides an efficient approach for the synthesis of pyrazolo[5,1-a]isoquinolines. During the reaction process, azo-alkene and isoquinolinium-2-yl amide acted as the key intermediates, which then underwent [3 + 2] cycloaddition and intramolecular rearrangement leading to the corresponding pyrazolo[5,1-a]isoquinolines. Azo-alkene would be formed in situ from (1-arylethylidene)hydrazide in the presence of I₂ and TBHP, and isoquinolinium-2-yl amide would be generated in situ via a silver(I)-promoted 6-endo cyclization of N′-(2-alkynylbenzylidene)hydrazide. This transformation proceeds smoothly under mild conditions and tolerates a broad range of functional groups.