C O M M U N I C A T I O N S
of the nucleophilic methylation reaction. Teucladiol is thus available
in five steps from cyclopentenone and (()-11 in 28% overall yield.
silane for the introduction of the secondary hydroxyl group using
the conformational bias of the cyclooctene ring for stereocontrol.
Allylsilane ring-closing metathesis followed by electrophilic desi-
lylation is a powerful strategy for the synthesis of exo-methylidenecy-
cloalkane motifs that are found in many terpene natural products. We
have described three different ways to introduce the precursor
allylsilanes, demonstrated that this process can make six-, seven-, and
eight-membered rings, and completed short syntheses of teucladiol and
poitediol using this method as a centerpiece.
Scheme 4. Enantioselective Synthesis of (-)-Teucladiol
Acknowledgment. We thank UC Irvine for funding and Prof. B.
Rodr´ıguez and Dr. M. C. de la Torre for providing 1H NMR spectra
of teucladiol. C.D.V. thanks Amgen for a Young Investigator Award.
Supporting Information Available: Complete experimental pro-
cedures and characterization data for all new compounds. This material
References
(1) Cane, D. E. In ComprehensiVe Natural Products Chemistry. Isoprenoids,
Including Carotenoids and Steroids; Cane, D. E., Ed.; Elsevier: Oxford,
1999; Vol. 2, pp 154-200.
The synthesis of teucladiol could be rendered enantioselective
by incorporation of enantioenriched aldehyde (-)-11 into the three-
component coupling.15,21,22 Enolsilane (()-14 was generated from
9 and cyclopentenone and was subsequently transformed into its
zinc enolate for reaction with (-)-11 (1.1 equiv). The resulting
product (-)-12 was isolated in 28-36% yield23 (max. possible ca.
50%) and in 88% ee. Transformation to (-)-teucladiol followed
the sequence in Scheme 3 and proved that the absolute configuration
of teucladiol is opposite that depicted in Figure 1 and Scheme 4.
Poitediol is an unusual, rearranged sesquiterpene that was isolated
by Fenical, Clardy, and co-workers in 1978 from the red seaweed
Laurencia poitei3 and has been synthesized once by the Gadwood
group.24 Its exo-methylidenecyclooctane, which incorporates allylic
oxygenation, provided an excellent opportunity to test our strategy
for generation of the exocyclic alkene with concomitant introduction
of new functionality. Our synthesis shown in Scheme 5 borrows
substantially from Fu¨rstner and Langemann’s elegant synthesis of
the related natural product dactylol;25 our key contribution is the
strategy for introduction of the exocyclic alkene, in this case with
the simultaneous stereoselective introduction of a hydroxyl group.
The synthesis of 18 is adapted from the earlier dactylol synthesis.
Indium-mediated allylation26 of this ketone followed by in situ
silylation afforded diene 19. Grubbs second-generation catalyst
generated cyclooctene 20,27 which was epoxidized stereoselectively.
The resultant silyl epoxide was decomposed via fluoride-mediated
elimination28 with concomitant silyl ether cleavage to afford
poitediol, which provided X-ray diffraction-quality crystals.15 This
seven-step synthesis (18% overall yield) exploits the cyclic allyl-
(2) Bruno, M.; de la Torre, M. C.; Rodr´ıguez, B.; Omar, A. A. Phytochemistry
1993, 34, 245–247.
(3) Fenical, W.; Schulte, G. R.; Finer, J.; Clardy, J. J. Org. Chem. 1978, 43,
3628–3630.
(4) Collado, I. G.; Hanson, J. R.; Mac´ıas-Sa´nchez, A. J. Nat. Prod. Rep. 1998,
15, 187–204.
(5) Dong, M.; Cong, B.; Yu, S.-H.; Sauriol, F.; Huo, C.-H.; Shi, Q.-W.; Gu,
Y.-C.; Zamir, L. O.; Kiyota, H. Org. Lett. 2008, 10, 701–704.
(6) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005,
44, 4490–4527.
(7) (a) Heo, J.-N.; Micalizio, G. C.; Roush, W. R. Org. Lett. 2003, 5, 1693–
1696. (b) Adam, J.-M.; de Fays, L.; Laguerre, M.; Ghosez, L. Tetrahedron
2004, 60, 7325–7344.
(8) Hosomi, A.; Saito, M.; Sakurai, H. Tetrahedron Lett. 1980, 21, 355–358.
(9) Of course, the allylsilane can also be used for installation of functionality
by reaction with heteroatom or carbon electrophiles.
(10) Aggarwal, V. K.; Daly, A. M. Chem. Commun. 2002, 2490–2491.
(11) Narayanan, B. A.; Bunnelle, W. H. Tetrahedron Lett. 1987, 28, 6261–
6264.
(12) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, T. E.; Scholl, M.;
Choi, T.-L.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003,
125, 2546–2558.
(13) Ahmed, A. A.; Hegazy, M.-E., F.; Hassan, N. M.; Wojcinska, M.; Karchesy,
J.; Pare, P. W.; Mabry, T. J. Phytochemistry 2006, 67, 1547–1553.
(14) Trost, B. M.; Coppola, B. P. J. Am. Chem. Soc. 1982, 104, 6879–6881.
(15) Please see Supporting Information for details.
(16) Masamune, S.; Choy, W.; Petersen, J. S.; Sita, L. R. Angew. Chem., Int.
Ed. 1985, 24, 1–30.
(17) (a) Noyori, R.; Suzuki, M. Angew. Chem., Int. Ed. 1984, 23, 847–876. (b)
Chapdelaine, M. J.; Hulce, M. Org. React. 1990, 38, 225–653.
(18) Snider, B. B.; Yang, K. J. Org. Chem. 1992, 57, 3615–3626, and references
therein.
(19) For a discussion, see: Cowden, C. J.; Paterson, I. Org. React. 1997, 51,
1–200.
(20) Nakashima, K.; Fujisaki, N.; Inoue, K.; Minami, A.; Nagaya, C.; Sono,
M.; Tori, M. Bull. Chem. Soc. Jpn. 2006, 79, 1955–1962.
(21) Enantioselective conjugate addition to cyclopentenone would provide access
to enantioenriched enolate 10, but methods for asymmetric conjugate
addition of sp2-hybridized organometallics with productive use of the
resulting enolate are poorly developed, especially with cyclopentenones.
(22) (-)-11 was made by Myers pseudoephedrine amide enolate alkylation, LAB
reduction (Mosher ester analysis of the alcohol intermediate showed ca.
95% ee), and oxidation:(a) Myers, A. G.; Yang, B. H.; Chen., H.;
McKinstry, L.; Kopecky, D. J.; Gleason, J. L. J. Am. Chem. Soc. 1997,
119, 6496–6511. The recent SOMO activation procedure of MacMillan
for organocatalytic asymmetric aldehyde allylation delivered (-)-11 in fewer
operations. (b) Beeson, T. D.; Mastracchio, A.; Hong, J.; Ashton, K.;
MacMillan, D. W. C. Science 2007, 316, 582–585.
Scheme 5. Synthesis of Poitediol
(23) Other diastereomers, presumably from the mismatched combination, are
observed in the crude reaction mixture.
(24) Gadwood, R. C.; Lett, R. M.; Wissinger, J. E. J. Am. Chem. Soc. 1986,
108, 6343–6350. This instructive first synthesis proceeded in 26 steps and
ca. 1% overall yield from commercially available materials.
(25) Fu¨rstner, A.; Langemann, K. J. Org. Chem. 1996, 61, 8746–8749. For the
structure of dactylol, see the Supporting Information.
(26) Bardot, V.; Remuson, R.; Gelas-Mialhe, Y.; Gramain, J.-C. Synlett 1996,
37–38.
(27) Michaut, A.; Rodriguez, J. Angew. Chem., Int. Ed. 2006, 45, 5740–5750.
(28) Many examples of allylsilane epoxidation/silanol elimination can be found
in: Fleming, I.; Barbero, A.; Walter, D. Chem. ReV. 1997, 97, 2063–2192.
JA906241W
9
J. AM. CHEM. SOC. VOL. 131, NO. 42, 2009 15091