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

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 I-2 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.