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

Itsuki Nohira; Song Liu; Ruopeng Bai; Yu Lan; Naoto Chatani

doi:10.1021/jacs.0c08512

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

J Am Chem Soc. 2020 Oct 14;142(41):17306-17311. doi: 10.1021/jacs.0c08512. Epub 2020 Oct 1.

Authors

Itsuki Nohira¹, Song Liu², Ruopeng Bai², Yu Lan², Naoto Chatani¹

Affiliations

¹ Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan.
² School of Chemistry and Chemical Engineering and Chongqing Key Laboratory of Theoretical and Computational Chemistry, Chongqing University, Chongqing 400030, People's Republic of China.

PMID: 32981319
DOI: 10.1021/jacs.0c08512

Abstract

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 KO^tBu 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.