De Novo Ruthenium-Catalyzed Synthesis of 2-Pyridones

Significance

Based on a previous report (X. Li and co-workers Org. Lett. 2010, 12, 5462), a ruthenium-catalyzed oxidative synthesis of 2-pyridones 3 from acrylamides 1 and alkynes 2 involving C-H and N-H bond activation is reported. After optimization studies and comparison with the above previous methodology the need for only one equivalent of Cu(OAc)₂˙H₂O instead of a superstoichiometric amount of this oxidant combined with RuCl₂(p-cymene) was established. Under these optimized conditions, the scope was investigated showing that acrylamides 1 bearing various N-alkyl or N-aryl substituents are efficiently converted into the products 3. In contrast with the previous report, amides bearing electron-withdrawing N-substituents chemoselectively afford product 3. Moreover, β-phenyl-substituted acryl­amides, symmetrically (diaryl or dialkyl) and unsymmetrically substituted alkynes and α,β-disubstituted acrylamides are also viable substrates which failed in the study by Li and co-workers. Mechanistic studies indicate the reaction involves initial intermolecular carboruthenation of alkyne 2, and subsequent intramolecular C-N bond formation (L. Ackermann, A. V. Lygin, N. Hofmann ­Angew. Chem. Int. Ed. 2011, 50, 6379.