ORGANIC
LETTERS
1999
Vol. 1, No. 7
1083-1086
ROMP-Spheres: A Novel High-Loading
Polymer Support Using Cross
Metathesis between Vinyl Polystyrene
and Norbornene Derivatives
,†
Anthony G. M. Barrett,* Susan M. Cramp,†,‡ and Richard S. Roberts†
Department of Chemistry, Imperial College of Science, Technology and Medicine,
London, SW7 2AY, United Kingdom and Rhone Poulenc Agriculture Limited,
Fyfield Road, Ongar, Essex, CM5 0HW, United Kingdom
Received July 29, 1999
ABSTRACT
The preparation of a polymer-supported ruthenium alkylidene metathesis catalyst is described. This immobilized catalyst has been used to
initiate a ring-opening metathesis polymerization of norbornene derivatives onto a polymer support to prepare novel high-loading resins for
use in combinatorial chemistry.
Combinatorial chemistry has received much attention of late
as a powerful tool for the discovery of new biologically
active molecules for use as pharmaceuticals and agrochemi-
cals.1 Associated with this is the explosion of work carried
out to develop solid-phase methodologies and syntheses for
the production of libraries of compounds to test in high
throughput screens.2 However, there remains the problem
that compound loadings on resin can be low, and so quite
large amounts of resin are required to obtain only a few
milligrams of compound after cleavage. In addition, for single
bead screening,3 a higher loading bead would seem advanta-
geous. High loading resins also have clear benefits in
solution-phase chemistry for polymer-supported reagents.4
Olefin metathesis has received considerable interest of
late,5 with the recent development of the well-defined
catalysts of Schrock6 and Grubbs,7 and in particular the
application to solid-phase chemistry is receiving attention.8-10
(3) Gissel, B.; Jensen, M. R.; Gregorius, K.; Elsner, H. I.; Svendsen, S.
J. Pept. Sci. 1995, 1, 217.
(4) Ley, S. V.; Schucht, O.; Thomas, A. W.; Murray, P. J. J. Chem.
Soc., Perkin Trans. 1 1999, 1251 and references therein.
(5) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413. Schuster, M.;
Blechert, S. Angew. Chem., Int. Ed. 1997, 36, 2036.
† Imperial College of Science.
‡ Rhone Poulenc Agriculture Limited.
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E. M. J. Med. Chem. 1994, 37, 1233. Terrett, N. K.; Gardner, M.; Gordon,
D. W.; Kobylecki, R. J.; Steele, J. Tetrahedron 1995, 51, 8135. Armstrong,
R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc.
Chem. Res. 1996, 29, 123. Ellman, J. A. Acc. Chem. Res. 1996, 29, 132.
Gordon, E. M.; Gallop, M. A.; Patel, D. V. Acc. Chem. Res. 1996, 29, 144.
Balkenhohl, F.; von dem Bussche-Hunnefeld, C.; Lanskey, A.; Zechel, C.
Angew. Chem., Int. Ed. 1996, 35, 2289. Curran, D. P. Angew. Chem., Int.
Ed. 1998, 37, 1175.
(2) Hermkens, P. H. H.; Ottenheijm, H. J. C.; Rees, D. C. Tetrahedron
1996, 52, 4527. Hermkens, P. H. H.; Ottenheijm, H. J. C.; Rees, D. C.
Tetrahedron 1997, 53, 5643. Boolts, S.; Hermkens, P. H. H.; Ottenheijm,
H. J. C.; Rees, D. C. Tetrahedron 1998, 54, 15385.
(6) Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; DiMare, M.; O’Regan,
M. J. Am. Chem. Soc. 1990, 112, 3875. Bazan, G. C.; Khosravi, E.; Schrock,
R. R.; Feast, W. J.; Gibson, V. C.; O’Regan, M. B.; Thomas, J. K.; Davis,
W. M. J. Am. Chem. Soc. 1990, 112, 8378. Bazan, G. C.; Oskam, J. H.;
Cho, H. N.; Park, L. Y.; Schrock, R. R. J. Am. Chem. Soc. 1991, 113,
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(7) Nguyen, S. T.; Johnson, L. K. Grubbs, R. H. J. Am. Chem. Soc. 1992,
114, 3974. Nguyen, S. T.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc.
1993, 115, 9858. Nguyen, S. T.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1995, 117, 5503. Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R.
H. Angew. Chem., Int. Ed. Engl. 1995, 34, 2039.
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Engl. 1996, 35, 1979. Peters, J. U.; Blechert, S. Synlett 1997, 348.
10.1021/ol9908878 CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/10/1999