Nickel-Catalyzed Tandem Knoevenagel Condensation and Intramolecular Direct Arylation: Synthesis of Pyrazolo[5,1-a]-isoquinoline Derivatives

Abstract

A simple and efficient method for the synthesis of pyrazolo[5,1-a]isoquinoline derivatives has been developed using the nickel-catalyzed reaction of 1-aryl-2-(1H-pyrazol-1-yl)ethan-1-ones and 2-bromo aldehydes. The overall transformation involves tandem Knoevenagel condensation and intramolecular direct arylation via activation of the C5−H bond of the pyrazole ring. A series of 27 drug-like aroyl−substituted pyrazolo[5,1-a]isoquinolines has been synthesized in moderate to good yields.