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 (KOBu)-Bu-t or even weak base, such as Cs2CO3. The reaction proceeds in the absence of a ligand and under mild reaction conditions (40-60 degrees 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.