Isolation of PdCl2 using PDMS Thimbles
low tolerance levels in pharmaceutical products limit its
applications. For instance, the dietary intake of Pd is ap-
proximately <1.5 to 15 µg day-1, which translates into typical
loadings of less than 10 ppm for active pharmaceutical
ingredients that varies based on the amount of drug that is
consumed.5 This requirement imposes extensive cleaning re-
quirements of products to reach these levels and limits the
potential uses of Pd.6
Most methods to site-isolate Pd catalysts so they may be
recycled and not contaminate the product involve transformation
of a homogeneous Pd catalyst into a heterogeneous catalyst,
incarceration of Pd into polystyrene beads, encapsulation in sol
gels, or modification of its structure by attachment to a
polymer.7,8 The key limitation to site-isolating Pd catalysts is
that they may be in the homogeneous and colloidal states in
the same reaction mixture. For instance, Pd can leach from a
heterogeneous surface to form a homogeneous catalyst or fully
dissociate from a polymer to form colloidal Pd. Recently,
Rothenberg demonstrated that Pd nanoparticles are not the true
catalytic species; rather, homogeneous Pd that leached from
these particles was the active catalyst.9 In related work by Weck,
the Pd catalyst in Mizoroki-Heck coupling reactions was
formed from decomposition of the original Pd species to a
catalytically active, soluble Pd(0) catalyst.8 The fluxional nature
of the ligands around Pd and its ability to be present in the
colloidal and monomer forms in the same reaction vessel makes
FIGURE 1. Pd catalysts remained encapsulated by PDMS thimbles
because of their low solubility in PDMS, but organic molecules had
high flux through the walls.
site-isolation of these catalysts a challenge and necessitates a
different approach that focuses less on the catalyst and more
on its environment.
Here, we report a new method for the site-isolation of
homogeneous Pd catalysts that does not require modification
of their ligand structures and is not adversely affected by the
homogeneous/colloid fluxional nature of the catalyst. The focus
of this work is not on changing the catalyst; rather, the focus is
on its environment and how that environment can be used to
site-isolate the catalyst. Commercially available Pd catalysts
were used and site-isolated by encapsulation within hollow
macroscopic thimbles composed of polydimethylsiloxane
(PDMS).10 These thimbles had widths of 2 cm, heights of 5
cm, and walls that were 100-200 µm thick; dozens of these
thimbles could be fabricated in a day. The catalysts used in
this study were based on “ligandless” PdCl2 that are highly polar
and soluble only in protic solvents. The catalysts were added
to the interiors of the thimbles and did not flux to the exterior,
but organic molecules had high flux to the exterior. The reason
for the difference in flux was the hydrophobic nature of PDMS;
PdCl2 was simply not soluble in this polymer due to its highly
polar structure, but organic molecules were soluble in it (Figure
1). This simple difference in solubility required Pd catalysts to
remain encapsulated while organic molecules were free to flux
through the walls of the thimble. In this paper, we will describe
a method for site-isolation that allowed the Pd catalyst to be
recycled at levels up to >99.998%, products to be isolated that
possess low levels of Pd (less than 2.1 ppm), and otherwise
impossible sequential reactions to be developed.
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Results and Discussion
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Several examples of the Wacker-Tsuji oxidation of olefins
and homocoupling of arylboronic acids were completed on the
interior of PDMS thimbles (Table 1). Standard conditions were
used with a variety of different solvents to demonstrate that
the thimbles were compatible with each of them. Each reaction
went to quantitative conversions with lower yields found for
the Wacker-Tsuji oxidations than the coupling reactions. These
low yields are common for this reaction as a result of byproduct
formation and represent limitations of the reaction rather than
problems with the thimbles.4 This method did not place any
limitations on the catalysts or reagents. For instance, the
homocoupling reactions required the addition of p-toluenesulfo-
nyl chloride, and the addition of this reagent was readily
accommodated by this method. No concern for the reactive state
(homogeneous versus colloidal) of the Pd catalyst was necessary
because the reaction was run under standard conditions.
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J. Org. Chem. Vol. 74, No. 13, 2009 4835