I. Kadota et al. / Tetrahedron Letters 42 (2001) 3645–3647
3647
O
O
a
b
c
7
O
OH
O
OTES
OTES
19
18
O
O
OH
O
O
OH
e
d
f
O
O
O
OR
OTES
OTES
OTES
21: R = H
20
22: R = Pv
OMs
g
OPv
O
H
OPv
H
O
16
23
Scheme 4. (a) TESCl, 2,6-lutidine, CH2Cl2, 0°C to rt, 100%; (b) 9-BBN, THF, rt; H2O2, NaOH, rt, 86%; (c) (i) Dess–Martin
d
periodinane, NaHCO3, CH2Cl2, rt, 84%; (ii) Ipc2B-allyl, ether, −78°C; H2O2, NaOH, rt, 95%; (d) O3, MeOH, −78°C; Me2S, −78
to 0°C; NaBH4, 0°C to rt, 71%; (e) PvCl, pyridine, CH2Cl2, 0°C to rt, 56%; (f) MsCl, Et3N, CH2Cl2, 0°C to rt, 100%; (g) TBAF,
THF, rt, 84%.
Acknowledgements
4.4%
2.23
Hb
3.40
Ha
This work was financially supported by the Grant-in-
Aid for Scientific Research from the Ministry of Educa-
tion, Science and Culture of Japan.
OPv
O
O
Me
Hc
4.13
0.91
Me
H
O
References
4.6%
1. (a) Nagai, H.; Torigoe, K.; Satake, M.; Murata, M.;
Tasumoto, T.; Hirota, H. J. Am. Chem. Soc. 1992, 114,
1102–1103; (b) Nagai, H.; Murata, M.; Torigoe, K.;
Satake, M.; Tasumoto, T. J. Org. Chem. 1992, 57, 5448–
5453.
2. Morohashi, A.; Satake, M.; Nagai, H.; Oshima, Y.;
Yasumoto, T. Tetrahedron 2000, 56, 8995–9001.
3. Chakraborty, T. K.; Suresh, V. R. Tetrahedron Lett. 1998,
39, 7775–7778.
Figure 1. NOE experiments on 16.
above trials indicated that the TBS ether having two
methyl groups on neighboring carbons was quite stable
under the usual deprotection conditions.
Scheme 4 shows our final synthetic approach using a
TES ether as the protective group instead of TBS. The
alcohol 7 was converted to the cyclization precursor 23
in good yield by similar procedures to those described
in Schemes 2 and 3. Treatment of 23 with TBAF at
room temperature promoted the cleavage of the TES
ether smoothly and the subsequent intramolecular SN2
reaction to give the tetrahydrofuran 16 as the sole
product in 84% yield.
4. Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem.
Soc. 1982, 104, 1737–1738.
5. Conversion to the corresponding Weinreb amide failed.
Decomposition of the substrate 5 took place under these
conditions.
MeNHOMe·HCl
AlMe3
O
N
5
O
OMe
CH2Cl2, -10 ˚C
O
6. (a) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986,
108, 293–294; (b) Brown, H. C.; Bhat, K. S. J. Am. Chem.
Soc. 1986, 108, 5919–5923.
7. Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56,
401–404.
8. Feng, F.; Murai, A. Synlett 1995, 863–865.
9. No reaction took place with TBAF in the presence of
acetic acid. The use of HF·pyridine or SiF4 caused decom-
position of the starting material.
1
The stereochemistry of 16 was confirmed by H NMR
analysis and NOE experiments as shown in Fig. 1. The
observed NOE (4.4%) between Ha (3.40 ppm) and Hb
(2.23 ppm) indicates the cis relationship of these pro-
tons. Irradiation of the methyl protons (0.91 ppm) gave
a significant enhancement (4.6%) of the resonance of
the Hc proton (4.13 ppm). No NOE was observed
between the Ha and Hc protons.
.
.