ORGANIC
LETTERS
2001
Vol. 3, No. 21
3397-3399
Free Radical Reactions on Soluble
Supports from Ring-Opening Metathesis
Eric J. Enholm* and Maria E. Gallagher
Department of Chemistry, UniVersity of Florida, GainesVille, Florida 32611
Received August 22, 2001
ABSTRACT
Free radical reactions were performed on soluble ring-opening metathesis (ROM) polymers. These polymers have high substrate loading,
short reaction times, and the benefit of a facile purification. All reactions on these supports were obtained in good yields as white crystalline-
like materials readily separated from tin byproducts.
Recent interest in soluble organic supports has demonstrated
that these polymers can be applied to a variety of standard
synthetic transformations and offer significant advantages
over popular classic hard resin supports.1 Unlike standard
solid-phase organic synthesis, huge excesses and/or concen-
trated reagents are not necessary because soluble support
offers the faster reaction kinetics of a single solution phase.
These supports, soluble in chloroform, THF, ether, hexanes,
and CH2Cl2, can also be conveniently monitored by standard
1H NMR spectroscopy without cleavage from the polymer
backbone.
phase resins cannot achieve this level of loading mainly
because the substrate is incompletely covalently attached to
the polymer. With this methodology, the substrate is
completely incorporated into each monomer and then
subsequently polymerized.
We decided to use norbornyl monomers in these studies
for three reasons.3 First, they polymerize readily by ring-
opening metathesis with Grubbs well-defined ruthenium
catalysts.4 The small amount of strain inherent with nor-
bornenes assists and accelerates the metathesis.5 Second, a
wide variety of norbornenes are commercially available or
Since most soluble supports are not readily available
commercially, we have prepared them by custom synthesis
for each particular application as “designer supports”. We
now report a soluble designer support compatible with free
radical transformations made from ring-opening metathesis
polymerizations. Prior to our work, soluble organic supports
were not applied to radical reactions.2
Each monomer unit contains one or two reaction sites
integrated into the backbone so that the designer polymer
essentially has 100-200% loading capacity. Standard solid-
(2) For recent examples of radical reactions on solid-phase resins, see:
(a) Yim, A.-M.; Vidal, Y.; Viallefont, P.; Martinez, J. Tetrahedron Lett.
1999, 40, 4535. (b) Caddick, S.; Hamza, D.; Wadman, S. N. Tetrahedron
Lett. 1999, 40, 7285. (c) Zhu, X.; Ganesan, A. J. Comb. Chem. 1999, 1,
157. (d) Sibi, M. P.; Chandramouli, S. V. Tetrahedron Lett. 1997, 8929-
8932.
(3) For examples of ROMP supports in synthesis, see: (a) Ball, C. P.;
Barrett, A. G. M.; Poitout, L. F.; Smith, M. L.; Thorn, Z. E. Chem. Commun.
1998, 2453-2454. (b) Barrett, A. G. M.; Cramp, S. M.; Roberts, R. S.;
Zecri, F. J. Org. Lett. 1999, 1, 579-582. (c) Barrett, A. G. M.; Cramp, S.
M.; Roberts, R. S.; Zecri, F. J. Org. Lett. 2000, 2, 261-264. (d) Arnauld,
T, Barrett, A. G. M.; Cramp, S. M.; Roberts, R. S.; Zecri, F. J. Org. Lett.
2000, 2, 2663-2666.
(4) (a) Maughon, B. R.; Grubbs, R. H. Macromolecules 1997, 30, 3459-
3469. (b) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 2000,
1, 953-956. Chang, S.; Jones, L.; Wang, C. M.; Henling, L. M.; Grubbs,
R. H. Organometallics 1998, 17, 3460-3465.
(5) Makovetsky, K. L.; Finkelshtein, E. S.; Ostrovskaya, I. Y.; Portnykh,
E. B.; Gorbacheva, L. I.; Goldberg, A. L.; Ushakov, N. V.; Yampolsky, Y.
P. J. Mol. Catal. 1992, 76, 107-121.
(1) (a) Wentworth, P.; Janda, K. D. Chem. Commun. 1999, 1917-1924.
(b) Toy, P. H.; Janda, K. D. Tetrahedron Lett. 1999, 40, 6329-6332. (c)
Gravert, D. J.; Janda, K. D. Curr. Opin. Chem. Biol. 1997, 1, 107-113.
(d) Enholm, E. J.; Gallagher, M. E.; Lombardi, J. S.; Moran, K. M.; Schulte,
J. P. Org. Lett. 1999, 1, 689-691. (e) Enholm, E. J.; Schulte, J. P. Org.
Lett. 1999, 1, 1277-1279.
10.1021/ol016632n CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/15/2001