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Cu(OTf) 2 ‐Mediated Cross‐Coupling of Nitriles and N‐Heterocycles with Arylboronic Acids to Generate Nitrilium and Pyridinium Products **
Author(s) -
Bell Nicola L.,
Xu Chao,
Fyfe James W. B.,
Vantourout Julien C.,
Brals Jeremy,
Chabbra Sonia,
Bode Bela E.,
Cordes David B.,
Slawin Alexandra M. Z.,
McGuire Thomas M.,
Watson Allan J. B.
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202016811
Subject(s) - transmetalation , pyridinium , chemistry , reductive elimination , aryl , cationic polymerization , ligand (biochemistry) , oxidative addition , reactive intermediate , combinatorial chemistry , covalent bond , medicinal chemistry , coupling reaction , stereochemistry , polymer chemistry , catalysis , organic chemistry , biochemistry , alkyl , receptor
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.