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

Organic & Biomolecular Chemistry Pub Date: 2016-03-07 DOI: 10.1039/C6OB00303F

Abstract

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 Csp2 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.

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