O
because the reaction of 2b in CH2Cl2 proceeded smoothly and
was completed within two days. This method was also quite
effective in the construction of the larger rings. Cyclic
polyethers 1c (6-8-6-6), 1d (6-9-6-6) and 1e (6-10-6-6 system)
were synthesized from 2c–e, respectively, in good yields. The
structures of these products were unambiguously determined by
NMR and mass spectroscopy.
The present technique will serve as a versatile synthetic tool
for the synthesis of polyether marine toxins. Further synthetic
studies of ciguatoxin are presently being conducted in our
laboratory.
This work was supported in part by a Grant-in-aid for
Scientific Research from the Ministry of Education, Science,
Sports, and Culture of Japan, the Naito Foundation and the
Uehara Memorial Foundation. We also wish to thank Dr M.
Ueno and Mr T. Sato, Instrumental Analysis Center for
Chemistry, Faculty of Science, Tohoku University for the
measurement of NMR and mass spectra.
TIPSO
I
OBn
OBut
+
O
O
O
3
4
i
BnO
H
BnO
H
H
O
H
TIPSO
TIPSO
ButO2C
O
O
ButO2C
+
O
O
H
H
H
H
O
H
H
3 : 1
6
5
ii
NOE
H
BnO
H
RO
H
O
H
O
O
O
H
O
viii
O
O
Notes and References
O
H
H
H
H
H
† E-mail: hirama@ykbsc.chem.tohoku.ac.jp
H
O
‡ Compounds 3 and 4 were prepared from (2R,3S)- and (2S,3R)-
2-(benzyloxymethyl)tetrahydropyran-3-ol, respectively, by standard proce-
dures.4
NOE
12 R = Bn
13 R = H
7
ix
iii
x or xi or xii
1 M. Murata, A. M. Legrand, Y. Ishibashi, M. Fukui and T. Yasumoto,
J. Am. Chem. Soc., 1990, 112, 4380; M. Satake, A. Morohashi, H. Oguri,
T. Oishi, M. Hirama, N. Harada and T. Yasumoto, J. Am. Chem. Soc.,
1997, 119, 11325.
2 E. Alvarez, M. T. D´ıaz, L. Hanxing and J. D. Mart´ın, J. Am. Chem. Soc.,
1995, 117, 1437; S. Hosokawa and M. Isobe, Synlett, 1995, 1179;
M. Inoue, M. Sasaki and K. Tachibana, Tetrahedron Lett., 1997, 38,
1611.
3 T. Suzuki, O. Sato, M. Hirama, Y. Yamamoto, M. Murata, T. Yasumoto
and N. Harada, Tetrahedron Lett., 1991, 32, 4505; O. Sato and
M. Hirama, Synlett, 1992, 705; H. Oguri, S. Hishiyama, T. Oishi and
M. Hirama, Synlett, 1995, 1252; T. Oishi, M. Shoji, K. Maeda,
N. Kumahara and M. Hirama, Synlett, 1996, 1165; H. Oguri,
S. Hishiyama, O. Sato, T. Oishi, M. Hirama, M. Murata, T. Yasumoto
and N. Harada, Tetrahedron, 1997, 53, 3057; T. Oishi, K. Maeda and
M. Hirama, Chem. Commun., 1997, 1289; T. Oishi, M. Shoji,
N. Kumahara and M. Hirama, Chem. Lett., 1997, 845.
BnO
H
OR
O
H
O
O
l
H
O
H
O
H
O
H
H
H
O
H
H
8 R = H
9 R = Me
iv
H
O
O
H
2c l = 0
2d l = 1
2e l = 2
v or vi
NOE
BnO
H
H
R
R
O
H
O
O
vii
O
O
O
4 T. Oishi, Y. Nagumo and M. Hirama, Synlett, 1997, 980.
5 W. J. Zuercher, M. Hashimoto and R. H. Grubbs, J. Am. Chem. Soc.,
1996, 118, 6634 and references cited therein.
H
H
O
H
H
H
H
10 R = H
11 R = Me
2a R = H
2b R = Me
6 For recent applications of the metathesis reactions to the synthesis of
monocyclic and terminal cyclic ether systems, see: K. C. Nicolaou,
M. H. D. Postema and C. F. Claiborne, J. Am. Chem. Soc., 1996, 118,
1565; K. C. Nicolaou, M. H. D. Postema, E. W. Yue and A. Nadin,
J. Am. Chem. Soc., 1996, 118, 10335; J. S. Clark and J. G. Kettle,
Tetrahedron Lett., 1997, 38, 123; J. S. Clark and J. G. Kettle,
Tetrahedron Lett., 1997, 38, 127; M. Delgado and J. D. Mart´ın,
Tetrahedron Lett., 1997, 38, 6299; M. T. Crimmins and A. L. Choy,
J. Org. Chem., 1997, 62, 7548.
7 D. L. Lewis, J. K. Cha and Y. Kishi, J. Am. Chem. Soc., 1982, 104,
4976.
8 K. Tomooka, K. Matsuzawa and K. Suzuki, Tetrahedron Lett., 1987, 28,
6339.
Scheme 2 Reagents and conditions: i, LDA, HMPA, THF, 278 to 0 °C,
61%; ii, Bu4NF, THF, TsOH·H2O (cat.), toluene, 90 °C, 84%; iii,
H2CNCHMgBr, THF, 278 °C, 80%; iv, CH(OMe)3, CSA, CH2Cl2, 80; v,
Et3SiH, BF3·OEt2, MeCN, 220 °C, 71%; vi, Me3Al, BF3·OEt2, CH2Cl2,
0 °C to room temp., 72%; vii, Li, C10H8, THF; (COCl)2, Et3N, DMSO,
CH2Cl2, 278 to 240 °C; Ph3P+MeBr2 NaN(SiMe3)2, THF, 0 °C to room
temp., 72% (for 2a), 64% (for 2b); viii, H2CNCHCH2MgBr, THF, Et2O,
278 °C; Et3SiH, BF3·OEt2, MeCN, 220 °C to room temp., 90%; ix, Li,
C10H8, THF, 91%; x, (COCl)2, Et3N, DMSO, CH2Cl2, 278 to 0 °C;
Ph3P+MeBr2, NaN(SiMe3)2, THF, 0 °C to room temp., 83%; xi, Tf2O, Py,
CH2Cl2, 215 °C; LiC·CH, DMPU, THF, 278 to 0 °C; H2, Lindlar cat.
AcOEt, 47%; xii, Tf2O, Py, CH2Cl2, 215 °C; H2CNCHCH2MgBr, CuBr,
Et2O, 0 to 10 °C, 84%
9 H.-J. Liu, J. Yip and K.-S. Shia, Tetrahedron Lett., 1997, 38, 2253.
10 H. Kotsuki, I. Kadota and M. Ochi, Tetrahedron Lett., 1989, 30, 1281;
H. Kotsuki, I. Kadota and M. Ochi, Tetrahedron Lett., 1990, 31, 4609.
81 and 94% yield, respectively. These reactions required five to
seven days. However, we found a remarkable solvent effect
Received in Cambridge, UK, 2nd March 1998; 8/01678J
1042
Chem. Commun., 1998