recently we have reported that functionalized ring opening
metathesis polymers (we have termed these ROMPgels)
provide an effective alternative.6 We have also reported the
use of these ROMPgels in Horner-Emmons,7 acyl transfer,8
oxadiazole synthesis,9 and amine-scavenging reactions.10 We
herein report the synthesis and application of a ROMPgel
Tosmic reagent.
Scheme 1a
The Tosmic reagent 2, introduced by van Leusen, facili-
tates a wide range of transformations. These include the
synthesis of heterocycles such as oxazoles, pyrroles, imida-
zoles, and thiazoles.11 Substituted Tosmic reagents have also
found synthetic uses.12 Purification of Tosmic reaction
products have generally required chromatography, although
Ganesan and co-workers have attempted to address this
problem. They have used Ambersep 900 hydroxide resin as
an ion-exchange base13 and obtained a variety of aromatic
oxazoles in good isolated yields (54-85%) but moderate
crude purities (57-94%). They also used a Tentagel-
supported Tosmic reagent14 to prepare a variety of aromatic
oxazoles in lower yields (25-50%), and chromatography was
needed to obtain adequately pure compounds.
We envisaged that a ROMPgel Tosmic reagent should
provide pure products when used in conjunction with a strong
amine base such as tert-butyltetramethylguanidine.15 Such
a reagent should be available from the ring opening metath-
esis of isonitrile monomer 3 or the corresponding formamide
4 followed by dehydration.
a Key: (i) acrylonitrile, Triton B, 92%; (ii) 3-ClC6H4CO3H,
CH2Cl2, 95%; (iii) Pd(PPh3)2(OAc)2 (5 mol %), norbornadiene (5
equiv), piperidine (5 equiv), HCO2H (3 equiv), DMF, 65%; (iv)
NaOEt, EtOH, 100%; (v) paraformaldehyde (4 equiv), formamide
i
(8 equiv), formic acid (4 equiv), 65 °C, 3 h, 71%; (vi) Pr2NH (3
equiv), POCl3 (1.1 equiv), CH2Cl2, 90% (crude yield).
m-chloroperbenzoic acid and proceeded in excellent yield
to give 8.
Palladium-catalyzed exo-hydroarylation of norbornadiene
with 8 provided 9 in good yield.16 Careful temperature control
was required for optimum yields in this reaction due to
competitive elimination at higher temperatures. Conversion
to the sulfinate salt and its subsequent transformation to give
formamide 4 proceeded in good yield.17,18 All of these
reactions proved amenable to multigram synthesis. Dehydra-
tion of formamide 4 using POCl3 and iPr2NH gave the desired
isonitrile monomer 3. While isonitrile 3 failed to undergo
ROM polymerization presumably due to bonding to the
coordinatively unsaturated ruthenium intermediate, forma-
mide 4 was converted into the ROMP 11 in quantitative yield
using 1.5 mol % of 5 under standard conditions.
Michael addition of 4-bromothiophenol to acrylonitrile
under basic conditions gave sulfide 7 in 92% yield after
recrystallization (Scheme 1). It was found necessary to
oxidize the sulfide to the sulfone at this stage as epoxidation
was found to be a side reaction once the norbornene moiety
had been introduced. This oxidation was performed using
(6) The name originates from the swelling properties which these
polymers exhibit when solvated.
(7) Barrett, A. G. M.; Cramp, S. M.; Roberts, R. S.; Zecri, F. J. Org.
Lett. 1999, 1, 579.
(8) Barrett, A. G. M.; Cramp, S. M.; Roberts, R. S.; Zecri, F. J. Org.
Lett. 2000, 2, 261.
(9) Barrett, A. G. M.; Cramp, S. M.; Roberts, R. S.; Zecri, F. J. Comb.
Chem. High Throughput Screening 2000, 3, 131.
(10) Arnauld, T.; Barrett, A. G. M.; Cramp, S. M.; Roberts, R. S.; Zecri,
F. J. Org. Lett. 2000, 2, 2663.
(11) van Leusen, A. M.; van Leusen, D. Encylopedia of reagents in
organic synthesis; Paquette, L. A., Ed.; J.; Wiley: New York, 1995; p 4973.
(12) Sisko, J.; Kassick, A. J.; Mellinger, M.; Filan, J. J. Allen, A.; Olsen,
M. A. J. Org. Chem. 2000, 65, 1516.
(13) Kulkarni, B. A.; Ganesan, A. Tetrahedron Lett. 1999, 40, 5637.
(14) Kulkarni, B. A.; Ganesan, A. Tetrahedron Lett. 1999, 40, 5633.
(15) tert-Butyltetramethylguanidine or Barton base is commercially
available from Fluka.
Copolymerization of formamide 4 with norbornene gave
a gellike polymer which underwent a facile dehydration to
provide the target ROMP 1 in quantitative yield and 2.7
mmol/g loading. The dehydration step was carefully moni-
(16) Arcadi, A.; Marinelli, F.; Bernocchi, E.; Cacchi, S.; Ortar, G. J.
Organomet. Chem. 1989, 368, 249.
(17) Truce, W. E. Roberts, F. E. J. Org. Chem. 1963, 28, 593.
(18) van Leusen, A. M.; Boerma, G. J. M.; Helmholdt, R. B.; Siderius,
H.; Strating, J. Tetrahedron Lett. 1972, 23, 2367.
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Org. Lett., Vol. 3, No. 2, 2001