Stereoselective Synthesis of Enamides through Palladium-Catalyzed Oxidative Amidation of Conjugated Olefins with 2-Pyridones

A palladium-catalyzed oxidative amidation of conjugated olefin with 2-pyridone is described. A series of E-Enamides were synthesized in a highly stereocontrolled manner. The reaction also accommodates other cyclic and acyclic amides. Z-Enamides were predominantly prepared for primary amides probably due to the presence of an intramolecular hydrogen bond. Gram-scale synthesis of enamide and the following oxidative annulation with diphenylacetylene demonstrates the synthetic utility of this reaction.

Automated summary

A palladium-catalyzed oxidative amidation reaction between conjugated olefin and 2-pyridone is presented, enabling the synthesis of a range of E-enamides with high stereocontrol. The method also allows for the generation of cyclic and acyclic amides. The formation of predominantly Z-enamides for primary amides may be attributed to the presence of an intramolecular hydrogen bond. The synthesis of enamide on a gram-scale and subsequent oxidative annulation with diphenylacetylene highlights the synthetic utility of this reaction.