N-Picolinamides as ligands for Ullmann-type C[sbnd]N coupling reactions

Abstract

The use of N-phenyl-2-pyridincarboxamide-1-oxide as a ligand with Cu2O in Ullmann type CN bond formations between aryl halides and N-heteroaryls in common solvents, such as MeCN, DMF, and DMSO at 82–120°C has been successfully demonstrated. The ligand is effective when only 4% equiv is used relative to the substrate. The reaction provided the corresponding products in coupling of electron-rich, electron poor, and ortho-substituted aryl halides, including ortho aryl-chlorides, in good to very good yields. N-arylation is selectively preferred at the benzyl position when ortho-halide benzyl bromide is reacted with one equivalent of pyrazole. However, di-N-arylation is achieved in very high yields when 2.5equiv of pyrazole is used, providing a stoichiometric control over the coupling reaction.