Silver Triflate-Palladium Chloride Cooperative Catalysis in a Tandem Reaction for the Synthesis of H-Pyrazolo[5,1-a]isoquinolines

A tandem reaction of N'-(2-alkynylbenzylidene)hydrazone with alcohol in the presence of oxygen co-catalyzed by silver triflate and palladium chloride under mild conditions is reported, providing H-pyrazolo[5,1-a]isoquinolines in good yields. During the transformation, isoquinolinium-2-yl amide was the key intermediate via a silver(I)-catalyzed 6-endo cyclization of N'-(2-alkynylbenzylidene)hydrazone. The presence of a palladium catalyst and molecular oxygen promoted the oxidation of the alcohol to the aldehyde or ketone. Subsequent nucleophilic attack of the in situ generated enolate to isoquinolinium-2-yl amide, intramolecular condensation, and aromatization afforded the H-pyrazolo[5,1-a]isoquinolines. The easily available starting materials, good substrate generality, mild reaction conditions, and experimental ease should make this method attractive for further library construction.