Cu(OTf)(2)‐Mediated Cross‐Coupling of Nitriles and N‐Heterocycles with Arylboronic Acids to Generate Nitrilium and Pyridinium Products

Metal‐catalyzed C–N cross‐coupling generally forms C−N bonds by reductive elimination from metal complexes bearing covalent C‐ and N‐ligands. We have identified a Cu‐mediated C–N cross‐coupling that uses a dative N‐ligand in the bond‐forming event, which, in contrast to conventional methods, generates reactive cationic products. Mechanistic studies suggest the process operates via transmetalation of an aryl organoboron to a Cu(II) complex bearing neutral N‐ligands, such as nitriles or N‐heterocycles. Subsequent generation of a putative Cu(III) complex enables the oxidative C–N coupling to take place, delivering nitrilium intermediates and pyridinium products. The reaction is general for a range of N(sp) and N(sp(2)) precursors and can be applied to drug synthesis and late‐stage N‐arylation, and the limitations in the methodology are mechanistically evidenced.