Palladium-Catalyzed Fast Decaging of Propargyloxycarbonyl (Proc)-Caged Guanidines

Abstract

The Pd-catalyzed decaging reaction enables spatiotemporal control of amine-containing biomolecules, but analogous methods for guanidino-containing substrates remain underdeveloped. Here, we report a new Pd-catalyzed decaging chemistry for guanidines, with a propargyloxycarbonyl (Proc) moiety as the caging group in the absence of a phosphine ligand. Compared to our previous allyloxycarbonyl (Alloc)-based approach and the classical amine decaging chemistry, this system achieves remarkably accelerated decaging kinetics and high efficiency for both aromatic and aliphatic guanidines. Mechanistic studies reveal that the adjacent nitrogen atoms of the guanidino group accelerate the decaging process, probably in a “self-liganded” manner. Further application of this strategy is highlighted by the Pd-triggered release of Proc-caged guanidinyl fluorophores within minutes in living cells.