title: Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides.
abstract: (Hetero)Aryl amines, an important class of organic molecules in medicinal chemistry, are most commonly synthesized from anilines, which are in turn synthesized by hydrogenation of nitroarenes. Amine synthesis directly from nitroarenes is attractive due to improved step economy and functional group compatibility. Despite these potential advantages, there is yet no general method for the synthesis of (hetero)aryl amines by carbon-nitrogen cross-coupling of nitroarenes. Here we report the reductive coupling of nitroarenes with alkyl halides to yield (hetero)aryl amines. A simple iron catalyst enables the coupling with numerous primary, secondary and tertiary alkyl halides. Broad scope and high functional group tolerance are demonstrated. Mechanistic study suggests that nitrosoarenes and alkyl radicals are involved as intermediates. This new C-N coupling method provides general and step-economical access to aryl amines.
authors: Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISIC-LSCI, BCH 3305, 1015 Lausanne, Switzerland.
authors: Chi Wai
authors: CW
authors: Cheung
authors: Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISIC-LSCI, BCH 3305, 1015 Lausanne, Switzerland.
authors: Xile
authors: 0000-0001-8335-1196
authors: X
authors: Hu
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000191:economics; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D006865:Hydrogenation; D007501:Iron / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry; D010084:Oxidation-Reduction
chemical_list: D000588:Amines; D002244:Carbon; D007501:Iron; D009584:Nitrogen