Visible Light-Mediated Syntheses of γ-CF₃ Pyridines via 1,2-Radical Migration

Area of Science:

• Organic Chemistry
• Fluorine Chemistry
• Photocatalysis

Background:

• Trifluoromethyl pyridines are important structural motifs in pharmaceuticals and agrochemicals.
• Efficient synthetic methods for introducing the CF3 group, particularly at the gamma position, are highly sought after.
• Radical-mediated reactions offer unique pathways for C-C and C-heteroatom bond formation.

Purpose of the Study:

• To develop an efficient visible light-mediated method for synthesizing gamma-trifluoromethyl pyridines.
• To explore a novel 1,2-radical migration strategy for this transformation.
• To investigate the mechanism involving trifluoromethyl radical addition, acyloxy migration, and trapping.

Main Methods:

• Visible light photocatalysis was employed to initiate the radical reaction.
• The synthesis involved the reaction of allyl carboxylates with N-aminopyridinium salts.
• A key step was the 1,2-acyloxy migration facilitated by radical intermediates.

Main Results:

• An efficient synthesis of gamma-CF3 pyridines was achieved.
• The reaction proceeds via a proposed mechanism involving trifluoromethyl radical addition to allyl carboxylates.
• Subsequent 1,2-acyloxy migration and trapping with N-aminopyridinium salts led to the desired products.

Conclusions:

• The presented visible light-mediated 1,2-radical migration strategy is an effective method for gamma-CF3 pyridine synthesis.
• This approach provides a valuable new tool for accessing fluorinated pyridine derivatives.
• The study highlights the utility of photocatalysis in radical-mediated synthetic transformations.