Palladium(II)-Catalyzed Substituted Pyridine Synthesis from α,β-Unsaturated Oxime Ethers via a C-H Alkenylation/Aza-6π-Electrocyclization Approach.

An efficient synthetic method for multisubstituted pyridines from β-aryl-substituted α,β-unsaturated oxime ethers and alkenes via Pd-catalyzed C-H activation has been developed. Systematic optimization of catalyst ligands revealed that sterically hindered pyridines increased the reactivity. Mechanistic studies suggested that the products are formed by Pd-catalyzed β-alkenylation of α,β-unsaturated oxime followed by aza-6π-electrocyclization. Various oximes and alkenes could be utilized to afford multisubstituted pyridines with complete regioselectivity. The usefulness of this methodology was showcased by the synthesis of 4-aryl-substituted pyridine derivatives, which are difficult to access with previously reported Rh-catalyzed approaches with alkenes.