Synfacts 2007(2): 0138-0138  
DOI: 10.1055/s-2006-955821
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart · New York

Radical-Mediated Synthesis of Imidazopyridinones

Contributor(s): Victor Snieckus, Wei Gan
M. El Qacemi, L. Ricard, S. Z. Zard*
Ecole Polytechnique, Palaiseau, France
Further Information

Publication History

Publication Date:
23 January 2007 (online)

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.