Palladium(II)-catalyzed oxidative cascade cyclization reactions of anilides and anilines: scope and mechanistic investigations

With Pd(OAc)(2)/pyridine as the catalyst system and molecular oxygen as a green oxidant, acrylanilides and N-allylanilines undergo oxidative cascade cyclization to form heterocyclic rings in high yields. This methodology is applicable to acrylanilides of different substitution patterns on olefinic units. Mechanistic studies revealed that cyclization of acrylanilides proceeded through an intramolecular syn-amidopalladation pathway. The reversible nature of amidopalladation serves as a "scavenging process" to prevent β-hydride elimination from occurring halfway through the catalytic cycle, thus favoring the formation of cascade cyclization products. In addition, internal coordination between an σ-alkylpalladium species and a tethered olefinic C=C double bond also appears to disfavor β-hydride elimination.