Asymmetric Synthesis of Polycyclic Heterocyclic Compounds via Friedel–Crafts Reaction/Cyclization Reaction Catalyzed by Nickel Catalyst

The first highly enantioselective asymmetric Friedel-Crafts reaction/cyclization reaction of 5-aminopyrazoles with 3-alkenyloxindoles to afford polycyclic heterocyclic compounds bearing an all-carbon quaternary stereocenter catalyzed by a complex of Ni^II with the C₂-symmetric bipyridine-N,N'-dioxide ligand L₁₂ has been developed. The relevant products with a wide range of substrates and good functional tolerance were obtained in 89-98% yield with 56-99% ee in the presence of 10 mol % Ni(OTf)₂ and 11 mol % L₁₂ in DCM at 25 °C. Moreover, an experiment on scaling up the process along with the transformations of the cycloadducts further emphasized the practical application of the synthesis.