Cu(OTf)2-mediated cross-coupling of nitriles and N-heterocycles with arylboronic acids to generate nitrilium and pyridinium products
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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(sp2) precursors and can be applied to drug synthesis and late‐stage N‐arylation, and the limitations in the methodology are mechanistically evidenced.
Bell , N , Xu , C , Fyfe , J , Vantourout , J C , Brals , J , Chabbra , S , Bode , B E , Cordes , D B , Slawin , A M Z , McGuire , T M & Watson , A J B 2021 , ' Cu(OTf) 2 -mediated cross-coupling of nitriles and N-heterocycles with arylboronic acids to generate nitrilium and pyridinium products ' , Angewandte Chemie International Edition , vol. 60 , no. 14 , pp. 7935-7940 . https://doi.org/10.1002/anie.202016811
Angewandte Chemie International Edition
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DescriptionFunding: Leverhulme Trust (Grant Number(s): RPG-2015-308), Leverhulme Trust (Grant Number(s): RPG-2018-362), Engineering and Physical Sciences Research Council (Grant Number(s): EP/R025754/1).
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