Synthesis of Fused and Linked Bicyclic Nitrogen Heterocycles by Palladium-Catalyzed Domino Cyclization of Propargyl Bromides

The palladium(0)-catalyzed direct construction of bicyclic heterocycles is described. Treatment of propargyl bromides that have nucleophilic functional groups connected by two or three carbon atoms with catalytic [Pd(PPh3)(4)] affords bis-cyclization products in good yields. The desired bicyclic heterocycles can be obtained selectively when using substrates with appropriate nucleophilic groups. We also describe the reaction of a 2-alkynylazetidine derivative with a catalytic amount of [Pd(PPh3)(4)] under base-free conditions, which affords the same fused heterocycles as the corresponding propargyl bromides.