A general approach to creating soluble catalytic polymers heterogenized in microcapsules

Article abstract of DOI:10.1021/ol071360v

A general method for preparing site-isolated polymeric catalysts is presented. Linear chloromethyl and azide polymers have been sequestered within polyurea microcapsules and small molecule catalysts soaked through the shell walls to functionalize the soluble polymers. Reaction onto each type of support is quantitative and MacMillan, DMAP, and TEMPO test catalysts are shown to have faster reaction rates than the analogous resin-supported catalysts.

Full text of DOI:10.1021/ol071360v

ORGANIC
LETTERS
2
007
Vol. 9, No. 17
449-3451
A General Approach to Creating Soluble
Catalytic Polymers Heterogenized in
Microcapsules
3
Brian P. Mason, Andrew R. Bogdan, Anandarup Goswami, and
D. Tyler McQuade*
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell
UniVersity, Ithaca, New York 14853
dtm25@cornell.edu
Received June 25, 2007
ABSTRACT
A general method for preparing site-isolated polymeric catalysts is presented. Linear chloromethyl and azide polymers have been sequestered
within polyurea microcapsules and small molecule catalysts soaked through the shell walls to functionalize the soluble polymers. Reaction
onto each type of support is quantitative and MacMillan, DMAP, and TEMPO test catalysts are shown to have faster reaction rates than the
analogous resin-supported catalysts.
We recently reported the preparation of encapsulated catalytic
linear polymers. When the capsules were swollen in the
chloromethyl- and azide-functionalized linear polymers can
be directly functionalized with small molecule catalysts
(Scheme 1). From these premade supports, we prepared three
encapsulated catalysts: a MacMillan-type catalyst for Diels-
Alder reactions, a 4-(N,N-dimethylamino)pyridine (DMAP)
acylation catalyst, and a 2,2,6,6-tetramethylpiperidinyloxy
(TEMPO) oxidation catalyst. Rates for the catalysts were
compared to those of analogous resin-supported catalysts.
We first investigated capsules directly analogous to
1
reaction solvent, polymeric catalysts bound within remained
2
active and in a solution-like environment. We demonstrated
that reaction rates were directly dependent on capsule wall
thickness, and that the encapsulated catalyst showed greater
activity than the same catalyst on cross-linked polystyrene
support. This approach may not be widely adopted, however,
because a linear polymer-bound catalyst must first be
synthesized and then encapsulated within a polymeric shell.
This requires that the catalyst be robust enough to survive
the encapsulation conditions. Also, differences in the mo-
lecular weight and functionality of the polymer-bound
catalyst change the nature of the polyurea shell.
3,4
Merrifield resin. Poly(chloromethylstyrene-co-styrene) was
5,6
generated by using well-known methods and microencap-
1,7
sulated in polyurea shells. To determine if an active catalyst
could be made from these microcapsules, an imidazolidinone
Herein, we report general approaches to overcome these
barriers by demonstrating that polyurea capsules containing
(3) Merrifield, R. B. J. Am. Chem. Soc. 1963, 85, 2149-2154.
(
4) Benaglia, M.; Puglisi, A.; Cozzi, F. Chem. ReV. 2003, 103, 3401-
3
429. Cozzi, F. AdV. Synth. Catal. 2006, 348, 1367-1390.
5) Chen, S. Q.; Janda, K. D. J. Am. Chem. Soc. 1997, 119, 8724-
8725.
(
(
1) Price, K. E.; Mason, B. P.; Bogdan, A. R.; Broadwater, S. J.; Stein-
bacher, J. L.; McQuade, D. T. J. Am. Chem. Soc. 2006, 128, 10376-10377.
2) Price, K. E.; Broadwater, S. J.; Bogdan, A. R.; Keresztes, I.;
Steinbacher, J. L.; McQuade, D. T. Macromolecules 2006, 39, 7681-7685.
(6) Malagu, K.; Guerin, P.; Guillemin, J. C. Synlett 2002, 316-318.
(7) Scher, H. B. Encapsulation Process and Capsules Produced Thereby.
U.S. Patent 4285720, Aug 25, 1981.
(
1
0.1021/ol071360v CCC: $37.00
© 2007 American Chemical Society
Published on Web 07/24/2007

Scheme 1. Functionalization of Preformed Microcapsules
Scheme 3. Synthesis of Encapsulated Azide Polyacrylate
preformed microcapsule, they require a pendant group for
attachment, like the phenolic group on 1. The handle had to
be easily deprotonated by a reasonably weak base, since a
strong base would be quenched by the polyurea shell of the
microcapsules. Also, the chloromethyl capsules could not
support a nucleophilic catalyst like DMAP, which cross-links
the polymer, negating any rate enhancement from linear
polymer solubility. To overcome these limitations, we turned
to the copper-catalyzed Huisgen “click” reaction between
an azide and a terminal acetylene as a method of function-
1
0,11
alization.
8
9
catalyst featuring a phenol group (1) was deprotonated and
Because the polymer backbone can play a large role in
the rate of catalysis, we decided to make more than one type
of soluble polymer support for encapsulation and compare
them. To narrow our focus, we looked at a polyacrylate-
based system (Scheme 3) versus a polystyrene-based system
reacted onto the encapsulated polymer (Scheme 2), as well
Scheme 2. Imidazolidinone Functionalization and Catalysis
(Scheme 4). These polymers were functionalized with azide,
Scheme 4. Synthesis of Encapsulated Azide Polystyrene
as onto the commercially available Merrifield resin. Loading
was determined by chlorine elemental analysis before and
after catalyst functionalization. Reaction rates for the Diels-
Alder reaction of 1,3-cyclohexadiene with acrolein increased
for the microencapsulated catalyst compared to those for the
catalyst on Merrifield resin (Table 1).
to be reacted with acetylene-containing small molecule
catalysts.
To determine if an active catalyst could be “clicked” into
microcapsules, a DMAP analogue with an acetylene (2)12
was synthesized and reacted into the azide-functionalized
capsules with a copper(I) catalyst (Scheme 5). The resulting
DMAP capsules showed complete loss of the azide by ATR-
IR. While DMAP has been shown to ligate to copper, it was
found that a simple wash with 1 M HCl, followed by
neutralization removed any residual copper present to below
detectable limits by elemental analysis.
Table 1. Relative Rates of the Diels-Alder Reaction (4 mol %
of Catalyst)
10
a
catalyst
krel
yield, %
imidizolidinone on PS-DVB
imidizolidinone in µCapsule
µCapsule (background)
1.0
1.7
0.4
52
52
18
a
After 24 h.
To test the capsules, we compared them against the pre-
“
clicked” azide capsules using the method of initial rates
for the acylation of 1-phenylethanol. The encapsulated
While the above test case showed that a small molecule
catalyst could be functionalized onto a linear polymer in a
(10) Demko, Z. P.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41,
2
113-2116.
(
8) Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2000, 122, 4243-4244.
9) Puglisi, A.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Celentano, G. Eur.
J. Org. Chem. 2004, 567-573.
(11) Wang, Q.; Chittaboina, S.; Barnhill, H. N. Lett. Org. Chem. 2005,
2, 293-301.
(
(12) Bogdan, A. R.; Mason, B. P.; Sylvester, K. T.; McQuade, D. T.
Angew. Chem., Int. Ed. 2007, 46, 1698-1701.
3450
Org. Lett., Vol. 9, No. 17, 2007

Scheme 5. DMAP Functionalization and Catalysis
Scheme 6. TEMPO Functionalization and Catalysis
PA-based TEMPO microcapsules was again sluggish com-
pared to that of the analogous TEMPO-modified Merrifield
resin, the PS-based capsules catalyzed the reaction 2.5 times
faster than the resin (Table 3). The catalyst gave an isolated
DMAP triazole on polyacrylate (PA) was 60 times more
active than that of unfunctionalized capsules (Table 2).
Table 2. Relative Acylation Rates of 1-Phenylethanol (0.75
mol % of Catalyst)
Table 3. Relative Oxidation Rates of 1-Phenylethanol (0.33
mol % of Catalyst)
a
catalyst
krel
conversion, %
a
catalyst
krel
conversion, %
DMAP on PS-DVB
1.0
0.48
2.1
3.9
0.008
99
56
99
99
6.0
DMAP triazole in µCapsule (PA)
DMAP triazole in µCapsule (PS)
DMAP analogue (2)
TEMPO triazole on PS-DVB
1.0
0.24
2.5
>99
61
>99
5.0
TEMPO triazole in µCapsule (PA)
TEMPO triazole in µCapsule (PS)
azide µCapsule (background)
azide µCapsule (background)
0.06
aAfter 20 h.
a After 24 h.
yield of 96% and even under fast stirring did not show signs
of capsule breakage, allowing the capsules to be recycled
three times.
However, these rates were only about half the rate of
commercially available DMAP on PS resin, and we had
previously observed high activity for DMAP on a polystyrene-
based encapsulated polymer.1
We have developed a new system for preparing site-
isolated polymeric catalysts that are more active than resin-
supported catalysts. We have also shown that the type of
functionalized polymer used as the catalyst backbone in these
microcapsules is critical for reasonable reaction rates. Rather
than having to develop encapsulation conditions for each new
polymer-supported catalyst, any appropriately functionalized
small molecule or catalyst can be readily attached to an
already encapsulated soluble polymer and quickly assayed.
In the case of the second, polystyrene-based catalyst
(Scheme 4), the azides also survived the encapsulation
conditions, as indicated by ATR-IR, and were reacted to
completion with 2 with copper catalyst. Notably, the micro-
capsules showed a greater rate of reaction than commercially
available DMAP on Merrifield resin (Table 2). These
capsules gave an isolated yield of 89% after chromatography,
could be isolated by filtration, and were recycled three times.
To see if this method could be generalized we next
functionalized the azide-functionalized capsules with a
Acknowledgment. We thank ARO (MAP-MURI), ARO
(Grant No. W911NF-06-1-0315), NSF (SENSORS), the
1
3
TEMPO analogue containing a pendant acetylene (3) via
the Huisgen reaction14 (Scheme 6). Although the rate of
oxidation of sec-phenethyl alcohol to acetophenone for the
Dreyfus and Beckman Foundations, 3M, Rohm and Haas,
and NYSTAR.
Supporting Information Available: Experimental meth-
ods, elemental analysis data, ATR-IR and NMR spectra, and
rate data. This material is available free of charge via the
Internet at http://pubs.acs.org.
(
13) Sterling, J.; Sklarz, B.; Herzig, Y.; Lerner, D.; Falb, E.; Ovadia, H.
Preparation of propargyl or indanyl 2,2,6,6-tetramethylpiperidine nitroxides
and their use for the treatment of neurologic diseases and disorders. U.S.
Patent Appl. 2006025446, Feb 2, 2006.
(
14) Gheorghe, A.; Matsuno, A.; Reiser, O. AdV. Synth. Catal. 2006,
3
48, 1016-1020.
OL071360V
Org. Lett., Vol. 9, No. 17, 2007
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