Chemistry Letters 2000
611
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the bicyclic compound 13a, corresponding to the AB-ring frag-
ment of 1, through a 4-step sequence [(i) debenzylation, (ii)
Dess-Martin oxidation,13 (iii) Wittig reaction, and (iv) RCM
with Grubbs’ catalyst]6 in a 55% total yield. Observation of
NOE (H5/H10) confirmed the desired stereochemistry at C5,
which agreed with McGarvey’s selectivity.8
Next, we examined C4-epimeric 8b, which was synthesized
from 6b originated from L-γ-gulonolactone10 in the similar man-
ner to 8a. When 8b was subjected to hydroboration with
BH3·THF followed by oxidation, 9b and 10b were produced in
13% and 79% yields, respectively.12 These 9b and 10b were
converted to bicyclic ethers 13b and 16b, respectively, according
to the above method. Existence of NOE (H5/H10) in 13b and
NOE (H4/H10) in 16b verified their stereochemistry. After all,
8b displayed the improved McGarvey’s stereoselectivity,8
though the major product 10b was not available directly in its
stereochemistry at C5 for the above 4-step route to the AB-ring
fragment of 1.
Then, an alternative route for the A-ring construction start-
ing from 10b was investigated. Protection of 10b with BzCl
followed by debenzylation gave alcohol 17b (95%), which was
converted to 19b through an oxidation-Wittig reaction process
(81%, 2 steps). After removal of cyclohexylidene acetal (91%),
diol 20b was converted to diene 21b (60%) by iodination and
elimination.14 Final RCM step proceeded smoothly to produce
bicyclic 22b (87%), whose stereochemistry was confirmed by
NOE (H5/H10).
5
6
a) H. Oguri, S. Sasaki, T. Oishi, and M. Hirama, Tetrahedron Lett.,
40, 5405 (1999). b) H. Oguri, S. Tanaka, T. Oishi, and M. Hirama,
Tetrahedron Lett., 41, 975 (2000).
For reviews on ring-closing metathesis, see: a) R. H. Grubbs and S.
Chang, Tetrahedron, 54, 4413 (1998). b) M. Schuster and S.
Blechert, Angew. Chem., Int. Ed. Engl., 36, 2036 (1997). c) R. H.
Grubbs, S. J. Miller, and G. C. Fu, Acc. Chem. Res., 28, 446 (1995).
For recent applications to 7-membered cyclic ethers, see: d) W. J.
Zuercher, M. Hashimoto, and R. H. Grubbs, J. Am. Chem. Soc., 118,
6634 (1996). e) J. S. Clark and J. G. Kettle, Tetrahedron Lett., 38,
123 (1997). f) R. J. Linderman, J. Siedlecki, S. A. O’Neill, and H.
Sun, J. Am. Chem. Soc., 119, 6919 (1997). g) M. Delgado and J. D.
Martín, Tetrahedron Lett., 38, 6299 (1997). h) M. T. Crimmins and
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M. Kooistra, H. Hiemstra, and H. E. Schoemaker, Synlett, 1998, 192.
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G. A. Van der Marel, and J. H. Van Boom, Synlett, 1999, 1945.
Position numberings in this letter are according to those of CTX1B.
a) G. J. McGarvey and J. S. Bajwa, Tetrahedron Lett., 26, 6297
(1985). See also: b) W. C. Still and J. C. Barrish, J. Am. Chem. Soc.,
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Soc., 105, 3725 (1983). d) K. N. Houk, N. G. Rondan, Y.-D. Wu, J.
T. Mets, and M. N. Paddon-Row, Tetrahedron, 40, 2257 (1984).
Oxane 5 was prepared through a 6-step process [MOMCl, i-Pr2NEt;
OsO4, NMO; NaIO4; NaBH4; BnBr, t-BuOK, TBAI; 6M HCl-THF
(1:1); 83% total yield] from (2S, 3R)-2-(2-propenyl)-3-hydroxyoxane
(98%ee) which was synthesized according to the following paper: K.
Fujiwara, K. Saka, D. Takaoka, and A. Murai, Synlett, 1999, 1037.
Thus, asymmetric synthesis of the A-ring part of 1 was
achieved by two complemental routes based on RCM as well as
diastereocontrolled hydroboration.
This study was supported by a Grant-in-Aid (K.F.: No.
11780409) from the Ministry of Education, Science, Sports and
Culture, Japan.
References and Notes
7
8
1
For reviews on ciguatoxins and related compounds, see: a) T.
Yasumoto and M. Murata, Chem. Rev., 93, 1897 (1993). b) P. J.
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Tetrahedron, 54, 1 (1998). f) T. Oka, K. Fujiwara, and A. Murai,
Tetrahedron, 54, 21 (1998).
For the syntheses of the A-ring part of 1, see: a) T. Suzuki, O. Sato,
M. Hirama, Y. Yamamoto, M. Murata, T. Yasumoto, and N. Harada,
Tetrahedron Lett., 32, 4505 (1991). b) O. Sato and M. Hirama,
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Ravelo, A. Regueiro, and J. D. Martín, Tetrahedron Lett., 33, 3389
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2
9
10 Carboxylic acids 6a and 6b were prepared by NaClO2-oxidation of
the corresponding aldehydes reported in the following papers: a) J.
Yoshida, M. Nakagawa, H. Seki, and T. Hino, J. Chem. Soc., Perkin
Trans. 1, 1992, 343. b) C. Hubschwerlen, Synthesis, 1986, 962.
11 a) F. N. Tebbe, G. W. Parshall, and G. S. Reddy, J. Am. Chem. Soc.,
100, 3611 (1978). b) F. N. Tebbe, G. W. Parshall, and G. S. Reddy,
J. Am. Chem. Soc., 101, 5074 (1979). c) S. H. Pine, R. Zahler, D. A.
Evans, and R. H. Grubbs, J. Am. Chem. Soc., 102, 3270 (1980). d) S.
H. Pine, G. Kim, and V. Lee, Org. Synth., 69, 72 (1990).
12 Treatment of 8a or 8b with thexylborane followed by oxidation could
not improve the ratio of 9 to 10. In each case, the production of 5,
which would resulted from 1,2-elimination in the corresponding
hydroboration product having a 2-alkoxyalkylborane system, was
mainly observed.
13 D. B. Dess and J. C. Martin, J. Org. Chem., 48, 4155 (1983).
14 When Samuelsson’s method (P. J. Garegg and B. Samuelsson,
Synthesis, 1979, 469) was applied to diol 20b, the reaction could not
finish and gave a mixture of the corresponding iodide and 21b.
Further treatment of the mixture with Zn was required for the com-
plete conversion to 21b.
3
4