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

Autor: Bell NL; EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK., Xu C; EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK., Fyfe JWB; EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK., Vantourout JC; GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK., Brals J; EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK., Chabbra S; EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK., Bode BE; EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK., Cordes DB; EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK., Slawin AMZ; EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK., McGuire TM; AstraZeneca, Darwin Building, Unit 310, Cambridge Science Park, Milton Road, Cambridge, CB4 0WG, UK., Watson AJB; EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Mar 29; Vol. 60 (14), pp. 7935-7940. Date of Electronic Publication: 2021 Feb 26.
DOI: 10.1002/anie.202016811
Abstrakt: 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.
(© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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