Radical-Mediated Synthesis of Imidazopyridinones

Significance

A rare regioselective cyclization via a radical attack on a pyridine nitrogen to give 2,3-dihydroimidazo[1,2-a]pyridine-5(1H)-one is reported. Interestingly, azaindoline is obtained as the only product when R¹ = Ac while when R¹ = Boc or CO₂Me, imidazopyridinones are formed as single or major products. The proposed mechanism involves two competitive C- or N-ring-closure reactions. When R¹ = Boc, the steric repulsion and unfavorable dipole-dipole interaction between the lone pairs of pyridine nitrogen and the carbamate oxygen are suggested to force the side chain into an alternate rotamer conformation placing the radical into a favorable position for C-N bond formation. Lauroyl peroxide effects oxidation to the cationic species and the resulting lauric acid is involved in the hydrolysis step to the product. The scope of this reaction was not adequately explored.