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

Abstract

The Ni-catalyzed reaction of ortho -fluoro-substituted aromatic amides with alkynes results in C–F/N–H annulation to give 1(2 H )-isoquinolinones. A key to the success of the reaction is the use of KO t Bu or even weak base, such as Cs 2 CO 3 . 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(2 H )-isoquinolinone derivatives.

Topics & Concepts