Scope and Mechanism of Palladium-Catalyzed Amination of Five-Membered Heterocyclic Halides

Detailed studies have been conducted to determine the activity of palladium catalysts for the amination of five-membered heterocyclic halides and to determine the factors that control the scope of this reaction. Palladium-catalyzed aminations of the electron-rich furanyl, thiophenyl, and indolyl halides and of the related 2-halogenated thiazoles, benzimidazole, and benzoxazole have been shown to occur with a subset of amines. Various combinations of palladium precursors and PtBu3 were tested as catalysts for reaction of 3-bromothiophene with N-methylaniline, and the fastest reactions occurred with the Pd(I) dimer, [PdBr(PtBu3)]2. The fastest aminations of thiazoles, benzimidazoles, and benzoxazoles occurred with the combination of palladium trifluoroacetate and PtBu3 as catalyst.