Pd(0) Catalysts on Microelectrode Arrays
A R T I C L E S
Scheme 1
Figure 2. A “confined” Heck reaction on a 1K array.
Scheme 2
Figure 3. Fluorescence image of Heck reaction: -2.4 V, time on 0.5 s,
time off 0.1 s, allyl methyl carbonate confined. Lower right: methyl acrylate
substrate for 6 min, a blank with no fluorescence for comparison. Upper
right: 1-pyrenemethyl acrylate, reaction running for 3 min. Lower left:
1-pyrenemethyl acrylate, reaction running for 6 min. Upper left: 1-pyren-
emethyl acrylate, reaction running for 12 min.
locations on the array by utilizing a new set of microelectrodes
for generating the desired chemical reagent (Scheme 1). This
is best understood with an example.
of this strategy can be seen in Figure 2. The figure shows a 1K
array (1024 microelectrodes/cm2) with a dot in a box pattern of
microelectrodes used as cathodes (-2.4 V relative to a Pt
counter electrode for 300 cycles of 0.5 s on and 0.1 s off) to
accomplish the reaction illustrated in Scheme 1. Following this
reaction, a different pattern could be placed on the same array
by simply repeating the reaction while using a new set of
electrodes for the reduction of Pd(II).
Interestingly, the Heck reactions worked beautifully with
either the aryl iodide or the acrylate derivative on the surface
of the array. The “inverse” Heck reaction (acrylate on the
surface) worked in spite of the arylpalladium intermediate for
the reaction being generated in solution where it would be free
to migrate.12 Apparently, the Heck reaction on the surface is
fast enough to prevent the migration.
Although the reactions worked well and confinement was easy
to obtain, there was an underlying problem with reactions
requiring longer reaction times. As the reaction time was
increased, the intensity of fluorescence from the selected
microelectrodes decreased (Figure 3). In this image, an array is
shown with four experiments having been run on its surface.
The first is shown in the lower right portion of the array. It
utilized methyl acrylate instead of the pyrene-derived substrate
for the Heck reaction and served as a control showing no
fluorescence. The second experiment is shown in the upper right.
This experiment was identical to the one illustrated in Figure
2. The reduction was run for 300 cycles. In the third experiment,
shown in the lower left, the reduction was run for 600 cycles.
In the fourth, shown in the upper left, the reduction was run for
1200 cycles. Clearly, the intensity of the fluorescence decreased
with increasing reaction time.
Due to the tremendous synthetic versatility of Pd(0) catalysts,
we have been working to develop them as tools for synthesis
on the arrays.11 Particularly attractive is the potential that Heck
and Suzuki-type reactions hold as strategies for coupling new
molecules to the surface of an array. For example, consider the
chemistry highlighted in Scheme 2.11a In this experiment, the
surface of the array was coated with agarose. The agarose is
used as a porous reaction layer to attach molecules to the surface
of the array. The layer needs to be porous so that reagents can
reach the electrodes below. 4-Iodobenzoic acid was then placed
on the agarose next to every microelectrode in the array using
a base-catalyzed esterification reaction.7,9-11 Pd(OAc)2 and allyl
methyl carbonate were placed in the solution above the array
(a DMF/MeCN/water mixture containing triphenylphosphine as
a ligand for the Pd and tetra-n-butylammonium bromide as an
electrolyte) along with a pyrene-labeled acrylated derivative for
the Heck reaction. Selected microelectrodes in the array were
then used as cathodes to reduce Pd(OAc)2 and form a Pd(0)
catalyst for effecting the Heck reaction. The allyl methyl
carbonate “confining agent” was placed in solution to scavenge
the Pd(0) catalyst being generated by reacting with it to form a
π-allyl-Pd(II) species. In so doing, the allyl methyl carbonate
prevented the Pd(0) catalyst from migrating to microelectrodes
on the array that were not used to form the catalyst. The success
(6) For Pd(II) reactions, see: (a) Tesfu, E.; Roth, K.; Maurer, K.; Moeller,
K. D. Org. Lett. 2006, 8, 709. (b) Tesfu, E.; Maurer, K.; Ragsdale,
S. R.; Moeller, K. D. J. Am. Chem. Soc. 2004, 126, 6212. (c) Tesfu,
E.; Maurer, K.; McShae, A.; Moeller, K. D. J. Am. Chem. Soc. 2006,
128, 70.
At the time, we wondered if the methoxide generated from
reaction of the confining agent with the Pd(0) catalyst was
cleaving either the ester linkage between the molecule on the
surface of the array and the agarose polymer or the acrylate
ester.
These initial findings left us with three questions: Were the
conditions developed for initiating Pd(0)-catalyzed reactions
general? Did all Pd(0)-catalyzed reactions have the problem
(7) For examples of the site-selective generation of base, see ref 4b and
the work of Maurer et al. [ Maurer, K.; McShea, A.; Strathmann, M.;
Dill, K. J. Comb. Chem. 2005, 7, 637].
(8) For the site-selective generation of acid, see: Kesselring, D.; Maurer,
K.; Moeller, K. D. Org. Lett. 2008, 10, 2501.
(9) For the use of CAN in a site-selective fashion, see: Kesselring, D.;
Maurer, K.; Moeller, K. D. J. Am. Chem. Soc. 2008, 130, 11290.
(10) For the site-selective use of Sc(III), see: Bi, B.; Maurer, K.; Moeller,
K. D. Angew. Chem., Int. Ed. 2009, 48, 5872.
(11) For preliminary accounts of this work, see: (a) Tian, J.; Maurer, K.;
Tesfu, E.; Moeller, K. D. J. Am. Chem. Soc. 2005, 127, 1392. (b) Hu,
L.; Maurer, K.; Moeller, K. D. Org. Lett. 2009, 11, 1273.
(12) Tang, F.; Chen, C.; Moeller, K. D. Synthesis 2007, 3411.
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J. AM. CHEM. SOC. VOL. 132, NO. 46, 2010 16611