H. O6aa et al. / Tetrahedron Letters 42 (2001) 5749–5752
5751
O
OR
Me
H
O
O
a, b, c
+
14
TBSO
OEt
O
O
TBSO
15
16 R=H
d
e
18 R= TBS
f
OR1
OTBS
OH
Me
CO2Et
CO2Et
h
TBSO
OR2
TBSO
g
TBSO
OH
Me
O
Me
17 R1=H R2=H
R1= TBS R2= H
19 R1= TBS R2= Ac
O
O
5
3
4
Scheme 3. (a) NaIO4, MeOH/H2O; (b) Et3N, MeOH, H2O; (c) Ph3PꢀCHCOOEt, CH3CN, 72% (three steps); (d) LiAlH4, THF,
−78 to 0°C, 77%; (e) TBSOTf, lutidine, CH2Cl2, −30°C, 98%; (f) DIBAL-H, CH2Cl2/n-hexane −78 to −30°C, 90%; (g)
Ac2O/pyridine, 96%; (h) NaCH(COOEt)2, 10 mol% [(dba)3Pd2]·CHCl3, 20 mol% dppb, THF, 66%.
a small amount (5%) of the diolefinic derivative 17. The
formation of 3 may be ascribed to an intramolecular
3%-hydroxyl-assisted hydride delivery.16 On the other
hand, reduction of disilylated derivative 18, obtained by
silylation of 16 using TBSOTf, with DIBAL-H afforded
4 in a yield of 90%. The potential usefulness of 4 was
illustrated in performing an intermolecular reaction
with a carbon nucleophile and palladium catalysis.17
For example, reaction of the acetate 19, with the
sodium salt of diethyl malonate in the presence of the
complex [(dba)3Pd2]·CHCl3 and the ligand dppb gave,
after purification, homogeneous 5 in a yield of 66%.
Mateos, J. L.; Noriega, L.; Guzman, A.; Mijarez, A.;
Tovar, L.; Shefter, E. J. Org. Chem. 1982, 47, 1310.
2. (a) Kanojia, R. M.; Chin, E.; Smith, C.; Chen, R.;
Rowand, D.; Levine, S. D.; Wachter, M. P.; Adams, R.
E.; Hahn, D. W. J. Med. Chem. 1985, 28, 769; (b) Hahn,
D. W.; Ericson, E. W.; Lai, M. T.; Probst, A. Contracep-
tion 1981, 23, 133.
3. For a review on seven-membered oxacycles, see: Hoberg,
J. O. Tetrahedron 1998, 54, 12631.
4. (a) Cookson, R. C.; Liverton, N. J. J. Chem. Soc., Perkin.
Trans. 1 1985, 1589; (b) Chen, R.; Rowand, D. A. J. Am.
Chem. Soc. 1980, 102, 6609; (c) Nicolaou, K. C.; Clare-
mon, D. A.; Barnette, W. E. J. Am. Chem. Soc. 1980,
102, 6611; (d) Kocienski, P.; Love, C.; Whitby, R.;
Roberts, D. A. Tetrahedron Lett. 1988, 29, 2867; (e)
Kocienski, P. J.; Love, C. J.; Whitby, R. J.; Costello, G.;
Roberts, D. A. Tetrahedron 1989, 45, 3839; (f) Kane, V.
V.; Doyle, D. L. Tetrahedron Lett. 1981, 22, 3027; (g)
Kane, V. V.; Doyle, D. L. Tetrahedron Lett. 1981, 22,
3031.
In conclusion, the simple and straightforward chiron
approach presented here gives access to interesting
analogs of zoapatanol. A full report on the scope of
this approach as well as the potential antifertility activ-
ity of this type of analogs will be reported in due
course.
5. Trost, B. M.; Greenspan, P. D.; Geissler, H.; Kim, J. H.;
Greeves, N. Angew. Chem., Int. Ed. Engl. 1994, 33, 2182.
6. Ovaa, H.; Leeuwenburgh, M. A.; Overkleeft, H. S.; Van
der Marel, G. A.; Van Boom, J. H. Tetrahedron Lett.
1998, 39, 3025.
7. Shing, T. K. M. et al. (see: Tetrahedron: Asymmetry 1996,
7, 1323) used 6 in a study towards oxepanes via a
cycloaddition approach.
8. All new compounds were obtained in an analytically pure
form and fully characterized by spectroscopic techniques
(1H and 13C NMR) and (high-resolution) analysis of their
molecular ion masses.
Acknowledgements
The authors would like to thank Jasper Plaisier for
performing X-ray crystallographic measurements. This
work was supported by the Netherlands Foundation
for Chemical Research (SON) with financial aid from
the Netherlands Organization for Scientific Research
(NWO).
References
9. Dykstra, H. B.; Lewis, F. J.; Boord, C. E. J. Am. Chem.
Soc. 1930, 52, 3396.
1. (a) Levine, S. D.; Adams, R. E.; Chen, R.; Cotter, M. L.;
Hirsch, A. F.; Kane, V. V.; Kanojia, R. M.; Shaw, C.;
Wachter, M. P.; Chin, E.; Huettemann, R.; Ostrowski,
P.; Mateos, J. L.; Noriega, L.; Guzma´n, A.; Mijarez, A.;
Tovar, L. J. Am. Chem. Soc. 1979, 101, 3404; (b)
Kanojia, R. M.; Wachter, M. P.; Levine, S. D.; Adams,
R. E.; Chen, R.; Chin, E.; Cotter, M. L.; Hirsch, A. F.;
Huettemann, R.; Kane, V. V.; Ostrowski, P.; Shaw, C. J.;
10. For a recent review on RCM, see: Fu
3 rstner, A. Angew.
Chem., Int. Ed. 2000, 39, 3013.
11. Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1996, 118, 100.
12. Huwe, M.; Velder, J.; Blechert, S. Angew. Chem., Int. Ed.
Engl. 1996, 35, 2376.
13. Scholl, M.; Ding, S. D.; Lee, C. W.; Grubbs, R. H. Org.
Lett. 1999, 1, 953.