Competitive intramolecular C–C vs. C–O bond coupling reactions toward C 6 ring-fused 2-pyridone synthesis

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.