Iron-Catalyzed C-N Cross-Couplings

A promising iron-catalyzed reaction to make N-aryl pyrazoles and other aryl-substituted nitrogen compounds has been developed by Arkaitz Correa and Carsten Bolm at RWTH Aachen University, in Germany (Angew. Chem. Int. Ed. 2007, 46, 8862). The synthetic method offers a potentially less expensive and environmentally friendlier alternative to palladium- and copper-catalyzed C–N coupling reactions, the researchers say. The products of these reactions contain important structural motifs found in natural products and bioactive synthetic compounds and are essential intermediates in preparing pharmaceuticals and other chemicals. After exploring several iron salt precursors, the researchers settled on FeCl₃. Under optimized conditions, FeCl₃ paired with an ethylenediamine chelating ligand and a base in toluene solvent was used to convert aryl halides and pyrazole, indole, or other nitrogen-containing substrates into N-aryl products in moderate to high yields (one example shown). "The research has established a useful starting point for investigating future applications of iron-catalyzed N-arylation reactions," the scientists write.