Synthesis of pyrazolo[5,1-a] isoquinolines through copper-catalyzed regioselective bicyclization of N-propargylic sulfonylhydrazones

An expeditious strategy for the synthesis of pyrazolo[5,1-a]isoquinolines has been developed. The tricyclic scaffolds are formed through a four-step cascade sequence, including copper(II)-catalyzed regioselective bicyclization, nucleophilic addition of H2O, aerobic oxidation, and aromatization through eliminating a molecule of TsH. The synthetic utility of this method is demonstrated through the synthesis of a potential CDC25B inhibitor.