Metalloradical approach to 2H-chromenes

Area of Science:

• Organic Chemistry
• Catalysis
• Radical Chemistry

Background:

• Cobalt complexes, particularly porphyrins, are effective catalysts in various organic transformations.
• Radical addition reactions offer versatile pathways for carbon-carbon bond formation.
• 2H-chromenes are important heterocyclic compounds with diverse biological activities.

Purpose of the Study:

• To develop a novel cobalt-catalyzed method for synthesizing 2H-chromenes.
• To investigate the mechanism of cobalt-carbene radical generation and subsequent reactions.
• To explore the scope and limitations of the developed synthetic strategy.

Main Methods:

• Metalloradical activation of salicyl N-tosylhydrazones using cobalt(II)-porphyrin complexes.
• Radical addition of generated cobalt(III)-carbene radicals to terminal alkynes.
• Electron paramagnetic resonance (EPR) spectroscopy and radical trapping with TEMPO to confirm radical intermediates.
• Density Functional Theory (DFT) calculations to elucidate the reaction mechanism.

Main Results:

• Efficient synthesis of 2H-chromenes via cobalt-catalyzed radical addition and hydrogen atom transfer (HAT).
• Formation of salicyl-vinyl radical intermediates followed by intramolecular HAT.
• Identification of an o-quinone methide intermediate and its subsequent ring-closing reaction.
• Good isolated yields and tolerance for various substituents on the substrates.

Conclusions:

• A novel and efficient cobalt-catalyzed pathway for 2H-chromene synthesis has been established.
• The mechanism involves metalloradical activation, radical addition, and an unexpected o-quinone methide intermediate.
• The methodology provides a valuable tool for accessing substituted 2H-chromenes.