Redox Neutral Radical-Relay Cobalt Catalysis toward C-H Fluorination and Amination.

Area of Science:

• Organic Chemistry
• Catalysis
• Fluorination Chemistry

Background:

• Intramolecular C-H functionalization is crucial for complex molecule synthesis.
• Developing novel catalytic systems for selective fluorination remains a significant challenge.
• Cobalt catalysis offers a versatile platform for various organic transformations.

Purpose of the Study:

• To report a novel cobalt-catalyzed intramolecular C-H fluorination of N-fluoroamides.
• To investigate the diversion of cobalt catalysis from fluorination to amination.
• To elucidate the reaction mechanism, proposing a redox-neutral radical-relay pathway.

Main Methods:

• Cobalt-catalyzed intramolecular C-H fluorination of N-fluoroamides.
• In situ generation of cobalt fluorides as radical fluorinating agents.
• Substrate engineering to control catalytic reactivity (fluorination vs. amination).
• Mechanistic studies including UV-vis spectroscopy, cyclic voltammetry, and DFT calculations.

Main Results:

• Successful development of a redox-neutral radical-relay cobalt-catalyzed C-H fluorination.
• Demonstration of substrate-controlled switch between C-H fluorination and amination.
• Identification of in situ formed cobalt fluorides as key radical fluorinating species.
• Mechanistic evidence supporting a radical-relay pathway.

Conclusions:

• A novel cobalt-catalyzed intramolecular C-H fluorination of N-fluoroamides has been achieved.
• Catalytic reactivity can be tuned from fluorination to amination by modifying substrate conformation.
• The reaction proceeds through a redox-neutral radical-relay mechanism.