Palladium-catalyzed coupling of 3-halo-substituted coumarins, chromenes, and quinolones with various nitrogen-containing nucleophiles

An efficient and general palladium-catalyzed coupling reaction between 3-bromocoumarins, 3-bromoquinolin-2(1H)-ones, and 3-iodo-2H-chromenes with a variety of nitrogen-containing nucleophiles (azole, amide, lactam, sulfonamide, aniline, amine, and urea) is described. The reaction proceeded rapidly and cleanly in dioxane providing the coupling products in good to excellent yields. The chemoselectivity of this reaction was also studied with polyhalocoumarins. Under optimized conditions, these underwent a site-selective amination at the C-3-Br bond, regardless of the nature of the nitrogen-containing nucleophile used. The coupling of 3-bromocoumarins, 3-iodochromenes, and 3-bromoquinolones with nitrogen-containing nucleophiles was effectively catalyzed by Pd(OAc) ₂/Xantphos. The process was efficient and selective with a broad range of nucleophiles including alkylamines, anilines, amides, lactams, sulfonamides, urea, and azole derivatives to give the 3-N-substituted heterocycles in good yields.