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.