ORGANIC
LETTERS
2
000
Vol. 2, No. 9
311-1313
Stealth Star Polymers: A New
High-Loading Scaffold for Liquid-Phase
Organic Synthesis
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Neal N. Reed and Kim D. Janda*
Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for
Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037
Received March 6, 2000
ABSTRACT
Polyethylene glycol (PEG) has proven to be a versatile soluble−polymer support for organic synthesis, though the use of PEG has been
limited by its relatively low loading (0.5 mmol/g or less). We have developed a new high-loading (1 mmol/g) soluble-star polymer based on a
cyclotriphosphazene core with PEG arms that exhibit superior precipitation properties compared with those of linear PEG. Additionally, the
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heterocyclic core does not add interfering signals to the H or C NMR.
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Soluble-polymer supported organic synthesis continues to
be a rapidly growing field. While PEG has proven to be a
polymers, and for liquid crystalline behavior. The known
polyether derivatives are either oils or amorphous solids, and
none have contained polyoxyethylene chains longer than
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versatile platform for liquid-phase organic synthesis, only
recently has work been done toward developing soluble PEG
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b
heptaethylene glycol nor have these star polymers been
investigated for use as soluble-polymer supports for organic
synthesis.
To prepare our new PEG star, we required a supply of
suitably monoprotected PEG. Although monosubstituted PEG
of MW > 1000 can be prepared from PEG diol, the
purification is problematic. Tedious, labor intensive purifica-
tions or the use of hazardous reagents (e.g., tolylene-2,4-
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analogues. We report herein a new PEG star for use as a
versatile PEG alternative. Prepared in an arm-first manner
from monoprotected PEG diol and phosphonitrilic chloride
trimer, this star combines remarkable chemical stability, low
cost, and high loading while retaining the properties of PEG.
Cyclotriphosphazenes containing polyoxyethylene sub-
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stituents are easily prepared and have been investigated
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primarily as phase-transfer catalysts, as photocross-linkable
diisocyanate) preclude this approach for the preparation of
anything more than small quantities of monoprotected PEG.
However, the anionic polymerization of ethylene oxide using
a suitably monoprotected glycol initiator provides rapid
access to pure monoprotected PEG.
Monobenzyl PEG has been reported in the literature by
anionic polymerization of ethylene oxide starting from
(
1) (a) Wentworth, P.; Janda, K. D. Chem Commun. 1999, 1917-1924.
b) Gravert, D.; Janda, K. D. Chem. ReV. 1997, 97, 489-509. (c) Toy, P.
H.; Janda, K. D. Submitted for publication.
2) (a) Benaglia, M.; Annunziata, R.; Cinquini, M.; Cozzi, F.; Ressel, S.
(
(
J. Org. Chem. 1998, 63, 8628-8629. (b) Grayson, S. M.; Jayaraman, M.;
Frechet, J. M. J. Chem. Commun. 1999, 1329-1330. (c) Esswein, B.; Steidl,
N. M.; M o¨ ller, M. Macromol. Rapid Commun. 1996, 17, 143-148. (d)
Bera, T. K.; Taton, D.; Gnanou, Y. Polm. Mater. Sci. Eng. 1997, 77, 126-
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-(tert-butyldimethylsiloxy)ethanol, followed by quenching
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27. (e) Chang, J.; Oyelaran, O.; Esser, C. K.; Kath, G. S.; King, G. W.;
Uhrig, B. G.; Konteatis, Z.; Kim, R. M.; Chapman, K. T. Tetrahedron Lett.
999, 40, 4477-4480. (f) Knischka, R.; Lutz, P. J.; Sunder, A.; M u¨ lhaupt,
R.; Frey, H. Macromolecules 2000, 33, 315-320.
3) For a good, although somewhat dated review of star polymer
preparation, see: Bywater, S. AdV. Polym. Sci. 1979, 30, 89-116.
4) (a) Landry, C. J. T.; Ferrar, W. T.; Teegarden, D. M.; Coltrain, B.
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(5) Gobbi, A.; Landini, D.; Maia, A.; Delogu, G.; Podda, G. J. Org.
Chem. 1994, 59, 5059-5062.
(6) Allcock, H. R.; Cameron, C. G. Macromolecules 1994, 27, 3125-
3130.
(7) Allcock, H. R.; Kim, C. Macromolecules 1989, 22, 2596-2602.
(8) (a) Huang, J. J. Appl. Pol. Chem. 1992, 46, 1663-1671. (b) Huang,
J.; Hu, Y. J. Appl. Pol. Chem. 1993, 47, 1503-1511.
(
(
K. Macromolecules 1993, 26, 35-46. (b) Allcock, H. R.; Ravikiran, R.;
O’Conner, S. J. M. Macromolecules 1997, 30, 3184-3190.
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0.1021/ol005764y CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/06/2000