Ni-Catalyzed Conversion of 1,2,3-Benzo-triazin-4-ones into Isoquinolones

Significance

Reported herein is a synthesis of 4-substituted and 3,4-disubstituted isoquinoline-1-ones by Ni(0)/phosphine-catalyzed denitrogenative activation of 1,2,3-benzotriazin-4-ones followed by alkyne insertion. Both symmetrical and unsymmetrical alkynes gave excellent yields of the corresponding isoquinoline-1-ones. With unsymmetrical alkynes, the product with a larger group at C3 predominates although the regioselectivity varies from fair to good. Excellent regioselectivity was observed using the alkynes bearing R^² = Bpin and CO₂Et substituents. The bidentate phosphine DPPF ligand gave optimum yield and regioselectivity (R^³ at C4) for terminal alkyne to isoquinoline-1-one conversion. The regiochemistry was assigned using NOE experiments.