C O M M U N I C A T I O N S
(6) Prepared by sequential epoxidation and acidic periodate cleavage of
t-BuPh2Si-protected geraniol.
(7) (a) Still, W. C.; Mitra, A. J. Am. Chem. Soc. 1978, 100, 1927-1928. (b)
Still, W. C.; McDonald, J. H., III; Collum, D. B.; Mitra, A. Tetrahedron
Lett. 1979, 593-594.
that the absolute stereoarrangement of 1 is opposite to that of the
plant-derived natural product â-caryophyllene (20).
Many of the steps used in the synthesis of antheliolide A
described above have implications beyond the present work, as well
as being of crucial importance to the success of this project. These
include (1) formation of the mixed acetal 7, (2) the diastereose-
lective bicyclization to form 8 in which stereocenters are correctly
established at each carbon of the four-membered ring, (3) the chain
extension 8 f 11, (4) the efficient closure of the nine-membered
ring of 12, (5) the mild oxidative cleavage sequence 14 f 17, and
(6) the successful and quick formation of the last three rings of 1
from aldehyde 17 via 18. It seems logical that the one-step
conversion of 18 to 1 occurs via the intermediate 21 by [2 +
4]-cycloaddition which is made even more facile by steric accelera-
tion. The same pathway may be involved in the biosynthesis of 1.
The approach described above for the synthesis of 1 is completely
different from that employed in these laboratories earlier for the
construction of the structural relative â-caryophyllene.27
(8) Napolitano, E.; Fiaschi, R.; Mastrorilli, E. Synthesis 1986, 122-125.
(9) For background on methodology, see (a) Corey, E. J.; Rao, K. S.
Tetrahedron Lett. 1991, 36, 4623-4626. (b) Corey, E. J.; Kang, M.-C.;
Desai, M. C.; Ghosh, A. K.; Houpis, I. N. J. Am. Chem. Soc. 1988, 110,
649-650. (c) Corey, E. J.; Gavai, A. V. Tetrahedron Lett. 1988, 29, 3201-
3204. (d) Corey, E. J.; Desai, M. C.; Engler, T. A. J. Am. Chem. Soc.
1985, 107, 4339-4340. (e) Snider, B. B.; Hui, R. A. H. F.; Kulkarni, Y.
S. J. Am. Chem. Soc. 1985, 107, 2194-2196.
(10) Suzuki, M.; Kimura, Y.; Terashima, S. Chem. Lett. 1984, 1543-1546.
(11) This separation was accomplished in one pass using a 2 cm diameter OD-H
column available from Chiral Technologies, Inc.
(12) (a) Hiroi, K.; Kato, F. Tetrahedron 2001, 57, 1543-1550. (b) Hiroi, K.;
Kato, F.; Nakasato, H. Chem. Lett. 1998, 27, 553-554.
(13) Hu, T.; Corey, E. J. Org. Lett. 2002, 4, 2441-2443.
(14) See Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1345-
1353 and also ref 13.
(15) (a) Maurer, B.; Hauser, A. HelV. Chim. Acta 1983, 66, 2223-2235. (b)
Kaiser, R.; Lamparsky, D. HelV. Chim. Acta 1976, 59, 1803-1808.
(16) This assignment is also consistent with a three-dimensional analysis of
the structures 13 and 19 for an n f π* transition as the basis for optical
rotation.
(17) (a) Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. J. Am. Chem. Soc. 1978,
100, 3611-3613. (b) Pine, S. H.; Shen, G. S.; Hoang, H. Synthesis 1991,
165-167. (c) Pine, S. H.; Kim, G.; Lee, V. Org. Synth. 1993, Vol. VIII,
512-516.
(18) (a) Corey, E. J.; Shibasaki, M.; Knolle, J.; Sugahara, T. Tetrahedron Lett.
1977, 785-788. (b) Hong, B.-C.; Kim, S.; Kim, T.-S.; Corey, E. J.
Tetrahedron Lett. 2006, 47, 2711-2715.
(19) Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P. Synthesis 1994,
639-666.
(20) (a) Davis, F. A.; Vishwakarma, L. C.; Billmers, J. G.; Finn, J. J. Org.
Chem. 1984, 49, 3241-3243. (b) It is essential that any unreacted PhCH-
(O)NSO2Ph be reduced by quenching of the reaction mixture with Me2S
before product isolation in order to prevent further oxidation of the
R-hydroxy lactone.
(21) (a) Ogura, H.; Takahashi, H.; Itoh, T. J. Org. Chem. 1972, 37, 72-75.
(b) 1-Lithiopropyne was generated by reaction of 1-bromo-1-propene with
n-Buli in THF at -78 °C for 2 h.
Although the xenicane family of marine natural products is
sizable and growing steadily,28 only a few studies have appeared
on approaches to their synthesis.29 Structurally intricate and rigid
polycylic natural products such as 1 are likely to possess interesting
biological activity. The availability of synthetic 1 should facilitate
the study of this possibility.
(22) Zhong, Y.-L.; Shing, T. K. M. J. Org. Chem. 1997, 62, 2622-2624.
(23) A sample of naturally occurring antheliolide A (ca. 200 µg) was obtained
from Prof. Yoel Kashman, Tel Aviv University, who generously provided
his remaining stock of natural 1 for this research.
(24) Details are provided in the Supporting Information.
(25) (a) Miyaoka, H.; Nakano, M.; Iguchi, K.; Yamada, Y. Heterocycles 2003,
61, 189-196. (b) Miyaoka, H.; Mitome, H.; Nakano, M.; Yamada, Y.
Tetrahedron 2000, 56, 7737-7740. (c) Miyaoka, H.; Nakano, M.; Iguchi,
K.; Yamada, Y. Tetrahedron 1999, 55, 12977-12982.
Acknowledgment. We thank Drs. Tao Hu and Wei-Dong Z.
Li for their contributions in the exploratory phase of this work and
also Prof. Y. Kashman and Dr. Thomas B. Lewis, of Chiral
Technologies, Inc., for their kind assistance.
(26) For two apparent exceptions, see Norte, M.; Gonza´lez, A. G.; Arroyo, P.;
Za´rraga, M.; Perez, C.; Rodriguez, M. L.; Ruiz-Perez, C.; Dorta, L.
Tetrahedron 1990, 46, 6125-6132.
(27) (a) Corey, E. J.; Mitra, R. B.; Uda, H. J. Am. Chem. Soc. 1963, 85, 362-
363. (b) Corey, E. J.; Mitra, R. B.; Uda, H. J. Am. Chem. Soc. 1964, 86,
485-492. (c) Corey, E. J.; Bass, J. D.; Le Mahieu, R. E.; Mitra, R. B. J.
Am. Chem. Soc. 1964, 86, 5570-5583. (d) Liu, D.; Hong, S.; Corey, E.
J. J. Am. Chem. Soc. 2006, 128, 8160-8161.
Supporting Information Available: Experimental procedures and
characterization data for all reactions and products. This material is
(28) (a) Shen, Y.-C.; Lin, Y.-C.; Ahmed, A. F.; Kuo, Y.-H. Tetrahedron Lett.
2005, 46, 4793-4796. (b) El-Gamal, A. A. H.; Chiang, C.-Y.; Huang,
S.-H.; Wang, S.-K.; Duh, C.-Y. J. Nat. Prod. 2005, 68, 1336-1340. (c)
El-Gamal, A. A. H.; Wang, S.-K.; Duh, C.-Y. Tetrahedron Lett. 2005,
46, 6095-6096. (d) El-Gamal, A. A. H.; Wang, S.-K.; Duh, C.-Y.
Tetrahedron Lett. 2005, 46, 4499-4500. (e) El-Gamal, A. A. H.; Wang,
S.-K.; Duh, C.-Y. Org. Lett. 2005, 7, 2023-2025. (f) Anta, C.; Gonza´lez,
N.; Santafe´, G.; Rodr´ıguez, J.; Jime´nez, C. J. Nat. Prod. 2002, 65, 766-
768.
(29) (a) Renneberg, D.; Pfander, H.; Leumann, C. J. J. Org. Chem. 2000, 65,
9069-9079. (b) Liu, G.; Smith, T. C.; Pfander, H. Tetrahedron Lett. 1995,
36, 4979-4982. (b) Pollex, A.; Hiersemann, M. Org. Lett. 2005, 7,
5705-5708.
References
(1) (a) Green, D.; Carmely, S.; Benayahu, Y.; Kashman, Y. Tetrahedron Lett.
1988, 29, 1605-1608. (b) Smith, A. B., III; Carroll, P. J.; Kashman, Y.;
Green, D. Tetrahedron Lett. 1989, 26, 3363-3364.
(2) The absolute configuration of antheliolide A has remained undetermined.
(3) Antheliolide A is related structurally to the xenicane family of marine
natural products: Hooper, G. J.; Davies-Coleman, M. T.; Schleyer, M. J.
Nat. Prod. 1997, 60, 889-893.
(4) The vinylic bromide 2 was prepared in 91% yield by reaction of
prenylmagnesium bromide with 2-bromoallyl bromide in the presence of
10 mol % of CuCN in THF at -78 °C for 2 h.
(5) Corey, E. J.; Beames, D. J. J. Am. Chem. Soc. 1972, 94, 7210-7211.
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