T. J. Brocksom et al. / Tetrahedron Letters 45 (2004) 9289–9291
9291
We suggest18 that compounds 19 and 20 may be formed
initially from 11 and 12 by an RCM reaction, and then
through a sequence of hydrolysis and dehydration reac-
tions catalyzed by silica gel produce 17 and 18. The pos-
sible intermediates 21 could also be involved in the
formation of 17 and 18. Our interest in the RCM reac-
tion of 11 and 12 to 19 and 20 is due to their structural
similarity with dimeric ether guaianolides that have been
recently isolated19 and show strong antidiabetic activity.
3. Hanson, J. R. Nat. Prod. Rep. 1996, 13, 529–535.
4. Marshall, J. A. Synthesis 1972, 517–525; Heathcock, C. H.
et al. In The Total Synthesis of Natural Products; ApSi-
mon, J., Ed.; John Wiley: New York, 1983; Vol. 5, pp 1–
541.
5. Trost, B. M.; Higuchi, R. I. J. Am. Chem. Soc. 1996, 118,
10094–10105.
6. Blay, G.; Bargues, V.; Cardona, L.; Collado, A. M.;
Garcia, B.; Mun˜oz, M. C.; Pedro, J. R. J. Org. Chem.
2000, 65, 2138–2144.
´
7. Coquerel, Y.; Greene, A. E.; Depres, J. P. Org. Lett. 2003,
5, 4453–4455.
8. Mehta, G.; Umarye, J. D. Org. Lett. 2002, 4, 1063–
1065.
9. Mehta, G.; Umarye, J. D.; Gagliardini, V. Tetrahedron
Lett. 2002, 43, 6975–6978.
10. Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413–
4450.
11. Hoveyda, A. H.; Gillingham, D. G.; Veldhuizen, J. J. V.;
Kataoka, O.; Garber, S. B.; Kingsbury, J. S.; Harrity, J. P.
A. Org. Biomol. Chem. 2004, 2, 8–23.
12. Faria, M. L.; Magalha˜es, R. A.; Silva, F. C.; Matias, L. G.
O.; Ceschi, M. A.; Brocksom, U.; Brocksom, T. J.
Tetrahedron: Asymmetry 2000, 11, 4093–4103.
13. Schpector, J. Z.; Caracelli, I.; Carvalho, C. C.; Faria, M.
L.; Silva, F. C.; Matias, L. G. O.; Brocksom, T. J. J.
Brazil. Chem. Soc. 2001, 12, 154–158.
In summary, we have developed a new synthetic route
for the perhydroazulene ring system using a ring-closing
metathesis reaction as a key step. Guaiane and nor-guai-
ane derivatives 16, 17, and 18 were synthesized in enan-
tiomerically pure forms from commercially available
(R)-(À)-carvone, together with spiro compound 10.
These guaiane derivatives are versatile advanced inter-
mediates for further functionalization, and open a path-
way for the synthesis of natural guaianes and related
compounds.
Acknowledgements
`
The authors wish to thank the Fundac¸a˜o de Amparo a
Pesquisa do Estado de Sa˜o Paulo (FAPESP), the
14. Winkler, J. D.; Kim, S. Chem. Soc. Rev. 1997, 26, 387–
399.
´
Conselho Nacional de Desenvolvimento Cientıfico e Tec-
nologico (CNPq) and the Coordenadoria de Aperfeic¸oa-
15. All new compounds were fully characterized by IR, NMR,
mass spectroscopy, and microanalytical analyses.
16. The crude products 13 and 14 can be used directly in the
next step; the lowering of yield on silica gel purification is
due to the instability of the bis-allyl tertiary alcohol
region.
´
mento de Pessoal do Ensino Superior (CAPES) for
financial support. The (R)-(À)-carvone used as starting
material was generously donated by S. A. Dragoco
and S. A. Firmenich.
17. Poulsen, C. S.; Madsen, R. Synthesis 2003, 1–18, see p 4;
Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl.
1997, 36, 2036–2056, see p 2043.
References and notes
18. The formation of possible intermediates 19 and 20 has not
been demonstrated experimentally.
19. Hou, C. C.; Lin, S. J.; Cheng, J. T.; Hsu, J. L. J. Nat.
Prod. 2003, 66, 625–629.
1. Fraga, B. M. Nat. Prod. Rep. 2003, 20, 392–413.
2. (a) Hanson, J. R. Nat. Prod. Rep. 2004, 21, 312–320; (b)
Appendino, G.; Tron, G. C.; Jarevang, T.; Sterner, O.
Org. Lett. 2001, 3, 1609–1612.