Competitive intramolecular C-C vs. C-O bond coupling reactions toward C6 ring-fused 2-pyridone synthesis

• Published in: Organic & biomolecular chemistry Vol. 14; no. 14; pp. 3564 - 3573
• Main Authors: Lepitre, T, Pintiala, C, Muru, K, Comesse, S, Rebbaa, A, Lawson, A M, Daïch, A
• Format: Journal Article
• Language: English
• Published: England 14.04.2016
• Subjects: Carbon - chemistry; Magnetic Resonance Spectroscopy; Oxygen - chemistry; Pyridones - chemistry; Spectrometry, Mass, Electrospray Ionization
• 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 C6-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 C6-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.