The following protocol describes the selective cross-coupling of an amine with an aryl halide using a Pd-based catalyst to provide the corresponding N-arylated amine. This general procedure for C-N bond formation includes a detailed description of an appropriate reaction setup, two methods for assaying the crude reaction mixtures (thin layer chromatography (TLC) and gas chromatography (GC)) and procedures for the isolation, purification and characterization of the anticipated product. Reagents and catalyst precursors can be manipulated in the air; however, the cross-coupling reactions must be performed under an inert atmosphere. Two Pd-catalyzed C-N bond-forming reactions are included in the text as representative examples of these procedures. Although the reactions can proceed in <5 min, the protocols, including workup, generally take 6-30 h to complete.
“Pd-catalyzed amination reactions of aryl halides using bulky biarylmonophosphine ligands”, Nature Protocols, 2007, 2(11), 2881-2887.