Ruthenium-Catalyzed Synthesis of Pyridones and Isoquinolones

Significance

Reported here is the synthesis of 3(2H)-isoquinolones 2 via the ruthenium-catalyzed cycloisomerization of o-alkynylphenyl nitrones 1. The reaction is tolerant of both EDGs and EWGs on the aromatic ring, as well as either a methyl or benzyl group on the nitrone moiety. The scope of this cycloisomerization was extended to the synthesis of α-pyridones from non-aromatic 3-en-5-ynyl nitrones in high yield. A plausible mechanism for this reaction is proposed which involves formation of a vinylidene-ruthenium intermediate followed by 8π-electrocyclization, N-O bond cleavage and a final 6π-electrocyclization to generate the product. Deuterium-labeling studies were carried out which support this mechanism.