Tandem Heck/Tsuji-Trost Reaction for Uncaging of Alloc-Protected Amines with Palladium Complexes in Living Cells

Abstract

The palladium-catalyzed uncaging of alloc-protected amines in living cells has been extensively studied mostly in the form of nanostructures or mesostructures. However, the scarcity of kinetic and mechanistic studies of discrete palladium complexes for deallylation reactions has hindered progress. Herein, we report the development of a series of discrete palladium complexes bearing acetanilide ligands, which exhibit a good balance between reactivity and stability in living cells. We investigated the catalytic activity and cytotoxicity of these complexes in SiHa cells and found that acetanilide[tri(2-furyl)phosphine]palladium(II) triflate showed promising results. Under physiological conditions, this palladium complex exhibited a second-order reaction rate of 30 M−1s−1, and liquid chromatography-mass spectrometry (LC-MS) studies suggested the possibility of a tandem Heck/Tsuji-Trost mechanism. Our results demonstrate the potential of using these discrete palladium complexes for bioorthogonal chemistry studies in living cells.