Rodrigalvarez J,
Nappi M,
Azuma H,
Flodén NJ,
Burns ME,
Gaunt MJ.
* University of Cambridge, UK
Catalytic C(sp
3)–H Bond Activation in Tertiary Alkylamines.
Nat. Chem. 2020;
12: 76-81
Key words
palladium catalysis - regioselectivity - C–H activation - γ-aryl tertiary amines
Significance
Gaunt and co-workers report a novel ligand-enabled palladium(II)-catalyzed γ-C(sp3)–H arylation. Selective functionalization of tertiary alkyl amines is observed utilizing
arylboronic acids under mild conditions. The reaction is enantioselective, with enantiotopic
methyl group differentiation, allowing efficient and selective access to γ-aryl tertiary
amine scaffolds.
Comment
The authors propose that the reaction proceeds by amine complexation to the palladium(II)
ligand complex, followed by a concerted ligand-assisted metalation–deprotonation process
to access the palladacycle. This intermediate then undergoes transmetalation with
the boronic acid, which then undergoes a reductive elimination to afford the product.
