Nickel-Catalyzed C–F/N–H Annulation of Aromatic Amides with Alkynes: Activation of C–F Bonds under Mild Reaction Conditions

The Ni-catalyzed reaction of ortho-fluoro-substituted aromatic amides with alkynes results in C–F/N–H annulation to give 1­(2H)-isoquinolinones. A key to the success of the reaction is the use of KOtBu or even weak base, such as Cs2CO3. The reaction proceeds in the absence of a ligand and under mild reaction conditions (40–60 °C). DFT calculations suggest that the pathway for this Ni-catalyzed C–F/N–H annulation involves N−H deprotonation, oxidative addition of a C–F bond, migratory insertion of an alkyne, and reductive elimination to form 1­(2H)-isoquinolinone derivatives.