Electronic Effects on the Depropargylation Process in the Reaction‐based Fluorescent Detection of Palladium Species: Benzocoumarin‐based Ratiometric Sensing Systems

Abstract

The palladium catalyzed cross‐coupling reactions are indispensable in organic synthesis of pharmaceutical compounds, demanding convenient tools for the analysis of residual palladium contents. Propargyl aryl ether‐type fluorescent sensing systems that detect Pd(0)/Pd(II)/Pd(IV) species through depropargylation require no additives. We investigated a ratiometric sensing system based on a benzocoumarin dye; thus, three propargyl aryl ethers bearing electronically‐different self‐immolative linkers were synthesized and their relative response rate toward Pd(0) and Pd(II) were compared. We found that the response rate became faster when the self‐immolative linker became more electron‐deficient. The best‐performing system sensed Pd(0)/Pd(II) species selectively against various other metal species, which is also capable of fluorescent imaging of Pd(0)/Pd(II) species in cells. The work provides us a clue to accelerate the catalytic depropargylation step, which, when combined with a novel fluorophore, would enable us to develop out‐performing palladium sensing systems.