Organic Chemistry

Cu(OTf)2-Mediated Ionizing Cross-Coupling of N(sp) and N(sp2) with Arylboronic Acids

Abstract

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.

Content

Thumbnail image of ChemRxiv Manuscript.pdf

Supplementary material

Thumbnail image of Supplementary Information.pdf
Supplementary Information
Thumbnail image of Spectral Data.pdf
Spectral Data
Thumbnail image of Combined CIF.txt
Combined CIF