A Tris(benzyltriazolemethyl)amine-based Cage as CuAAC Ligand tolerant to exogeneous bulky nucleophiles

The archetypal tris(benzyltriazolemethyl)amine (TBTA) ligand was equipped with a bowl-shaped cap in the cage Hm-TBTA. Hm-TBTA accelerates CuAAC reactions without suffering from product inhibition. Furthermore, this shielded ligand efficiently protects the copper center from deactivation by the CuI–chelator glutathione, opening the way to novel approaches for efficient CuAAC reactions in complex media.