Article
DOI: 10.1002/bkcs.12173
BULLETIN OF THE
S. W. Cho et al.
KOREAN CHEMICAL SOCIETY
Electronic Effects on the Depropargylation Process in the
Reaction-based Fluorescent Detection of Palladium Species:
Benzocoumarin-based Ratiometric Sensing Systems
*
Seo Won Cho, Ye Jin Reo, Sourav Sarkar, and Kyo Han Ahn
Department of Chemistry, POSTECH, Pohang 37673, Republic of Korea. *E-mail: ahn@postech.ac.kr
Received October 26, 2020, Accepted November 29, 2020, Published online December 29, 2020
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 sys-
tem 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.
Keywords: Fluorescence, Palladium, Depropargylation, Ratiometric, Electronic effect
Introduction
propargyl ether can detect common Pd species, such as
PdCl2, PdCl2(CH3CN)2, Pd(OAc)2, (NH4)2PdCl2, and
Na2PdCl4, with high selectivity from other various metal spe-
cies. The depropargylation process seems to proceed through
two routes depending on the Pd species: in the case of
Pd(0) species, it proceeds through the allenyl palladium inter-
mediate; in the case of Pd(II) or Pd(IV) species, it proceeds
through the hydration route (Scheme 1).9 In both cases, the
end product is the depropargylated aryl alcohol (ArOH).
Therefore, it is possible to develop various fluorescent detec-
tion systems for Pd species at different oxidation states,
starting from fluorescent ArOH. Indeed, since this work, var-
ious aryl propargyl ether-type fluorescent detection systems
have been developed by other groups.10
Recently, we have developed push-pull type
benzocoumarin compounds as novel fluorophores. As
π-extended coumarin analogues, the linear-shape
benzocoumarins have promising photophysical properties
for bioimaging applications. Additionally, they are photo-
and chemo-stable, and show rather environment-insensitive
emission behavior in spite of the dipolar nature.11–16 In our
continuous efforts to explore fluorescent probes,17 we have
reinvestigated the palladium sensing system based on a
benzocoumarin dye, which responds to Pd(0)/Pd(II) species
with ratiometric fluorescence changes. Compared to the
fluorescein-based sensing system that provides turn-on fluo-
rescence response,8 this ratiometric sensing system may
find usefulness in the quantitative analysis of Pd species in
synthetic samples. In this work, to develop an efficient rati-
ometric sensing system based on the depropargylation
Palladium (Pd) species are widely used as important cata-
lysts in organic synthesis and fuel cells. For example, the
modern carbon–carbon cross-coupling reactions are fre-
quently conducted with Pd catalysts in academia as well as
in industry. The detection of residual Pd species in pharma-
ceutical products is crucial for their quality control.1,2 Con-
ventionally, inductively coupled plasma mass spectrometer
(ICP-MS) has been widely used for analysis of the residual
Pd species.3,4 ICP-MS needs complex sample preparation
steps, well experienced personnel, and high cost, demand-
ing an alternative and efficient analysis method. The fluo-
rescence detection method thus has received much attention
in recent years since the pioneering works by Koide and
coworkers who developed a fluorescein allyl ether as the
first reaction-based fluorescent sensing system for Pd spe-
cies.5 The fluorescein allyl ether undergoes the well-known
Pd(0)-catalyzed Tsuji–Trost oxidative insertion that causes
deallylation and release the fluorescent fluorescein derivative
(Scheme 1). As this sensing scheme detects catalytically
active Pd(0) species, additives such as tris(2-furyl)phosphine
and sodium borohydride are required to sense Pd(II/IV) spe-
cies.6 The sensing system can be also used to detect Pd(II) or
Pt(IV) directly through
a catalytic aromatic Claisen
rearrangement but at 50 ꢀC in dimethyl sulfoxide (DMSO)–
pH 10 buffer (1:4).7 Our group subsequently devised a dif-
ferent sensing scheme, the depropargylation route
(Scheme 1), which required no additives to detect Pd species
regardless of their oxidation states.8 This fluorescein
Bull. Korean Chem. Soc. 2021, Vol. 42, 135–139
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