Synthesis of 2-Methylquinolines via Oxidative Aza-Wacker Cyclization

Significance

Reported is a palladium-catalyzed oxidative aza-Wacker-type cyclization of aniline derivatives into substituted quinolines. The starting anilines are readily prepared by the allylation of the corresponding carbonyl compounds with allyl bromides mediated by Zn. An extensive initial study of solvents, Pd catalysts and various ligands revealed that Pd(OAc)₂ in conjunction with 1,10-phenanthroline as ligand in MeOH in the presence of air constitutes the optimum conditions. The reaction proceeds also without the ligand in relatively good yield (67% vs. 87%) whereas a phosphorus-based ligand (PPh₃) furnished only traces of product. The substrate scope was well studied and the products were obtained in good to excellent yields. The presence of air is considered necessary for the reoxidation of the Pd(0) species to Pd(II).