Palladium-Catalyzed Synthesis of Five-Membered Heterocycles from 1,6-Enynes

Significance

An efficient method for the construction of five-membered aromatic (3) and nonaromatic (4) heterocycles by a palladium-catalyzed coupling-cycloisomerization of 1,6-enynes with aryl halides has been developed. The ­reaction conditions using benzenesulfonamide (1, X = NTs) and (2, R^² = 4-EtO₂C) were optimized. The scope and limitations of this methodology were investigated. The reaction of the aryl halides having electron-withdrawing groups, such as CO₂R, COMe, CHO, Cl, SO₂Me, and CN gave the five-membered heterocycles in moderate to good yields. However, systems bearing electron-donating substituents, e.g. 4-Me and 4-MeO, did not afford the corresponding five-membered heterocycles. A mechanism for the formation of both aromatic and nonaromatic products was proposed.