Competitive intramolecular C-C . C-O bond coupling reactions toward C ring-fused 2-pyridone synthesis

• Published in: Organic & biomolecular chemistry 2016-03, Vol.14 (14), p.3564-3573
• Main Authors: Lepitre, T, Pintiala, C, Muru, K, Comesse, S, Rebbaa, A, Lawson, A. M, Daïch, A
• Format: Article
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c6ob00303f

An interesting competitive C-C vs . C-O bond coupling reaction on N ,3,5-trisubstituted pyridones is reported. These coupling reactions provided selective access to C- or O-ring-fused pyridones, both at the challenging C 6 -pyridone position. 1,6- C -Annulated pyridones were generally achieved in good yields with excellent chemoselectivity under Pd(0) conditions. On the other hand, full C 6 -regioselective Csp 2 aryloxylation was achieved under oxidative coupling promoted by silver salts to access 5,6- O -annulated pyridones. Based on various experiments and observations, mechanistic evidence of these competitive reactions was provided and it was proposed that C-O bond formation proceeded through radical cyclization. These processes were performed under mild reaction conditions and offer an efficient and attractive methodology to selectively access a large scope of C -arylated and O -arylated pyridones of biological interest. This work described a competitive C-C vs. C-O bond forming reaction at the challenging C 6 -position of 2-pyridones through Pd catalysis and silver radical cyclization.