Synthesis of Multisubstituted Pyridines from Ketoximes and Alkynes

Significance

A rhodium-catalyzed coupling of α,β-unsaturated ketoximes with alkynes to afford substituted pyridines is reported. Two unsymmetrical alkynes (R⁴ = Ph, R⁵ = H, SiMe₃) were tested and their regioselective coupling was demonstrated. The substrate scope was fairly well studied. Based on known metal-catalyzed reactions, a chelation assisted CH-activation mechanism was proposed and supported by isolation of an intermediate, which was shown to be converted into the final product under refluxing toluene conditions. This appears to be the first report of this type of reaction, that is, a catalytic addition of an ­alkenyl C-H bond to alkynes followed by cyclization and elimination.