5628
L. C. Dias, M. A. de Sousa / Tetrahedron Letters 44 (2003) 5625–5628
with concomitant lactol formation, and a diastereose-
lective epoxidation of an allylic alcohol, followed by
epoxide opening with Me2CuCNLi2.
Tetrahedron 1996, 52, 1811; (c) Vulpetti, A.; Bernardi, A.;
Gennari, C.; Goodman, J. M.; Paterson, I. Tetrahedron
1993, 49, 685.
10. (a) Brown, H. C.; Ganesan, K.; Dhar, R. K. J. Org.
Chem. 1993, 58, 147; (b) Ganesan, K.; Brown, H. C. J.
Org. Chem. 1993, 58, 7162; (c) Paterson, I.; Norcross, R.
D.; Ward, R. A.; Romea, P.; Lister, M. A. J. Am. Chem.
Soc. 1994, 116, 11287; (d) Evans, D. A.; Ng, H. P.; Clark,
J. S.; Rieger, D. L. Tetrahedron 1992, 48, 2127.
11. The amount of Zn(BH4)2 and longer reaction times
employed for reduction seems to be critical. Best results
were obtained with the use of 5 equivalents of Zn(BH4)2
at −20°C, as well as by the use of freshly prepared
ethereal solutions of Zn(BH4)2. (a) Gensler, W. J.; John-
son, F.; Sloam, A. D. B. J. Am. Chem. Soc. 1960, 82,
6074; (b) Oishi, T.; Nakata, T. Acc. Chem. Res. 1984, 17,
338; (c) Evans, D. A.; Kim, A. S.; Metternich, R.;
Novack, V. J. J. Am. Chem. Soc. 1998, 120, 5921.
12. Alternatively, the relative stereochemistry has been ascer-
tained by conversion to the corresponding isopropylidene
acetal (Me2C(OMe)2, PPTS, 95%). 13C NMR resonances
at 19.0, 30.2, and 98.3 are characteristic of a syn ace-
tonide and the large vicinal coupling constants, JHb–
Hc=JHc–Hd=10.4 Hz are consistent with the preferred
chair conformation. (a) Rychnovsky, S. D.; Skalitzky, D.
J. Tetrahedron Lett. 1990, 31, 945; (b) Evans, D. A.;
Rieger, D. L.; Gage, J. R. Tetrahedron Lett. 1990, 31,
7099; (c) Rychnovsky, S. D.; Rogers, B. N.; Richardson,
T. I. Acc. Chem. Res. 1998, 31, 9.
Although this approach provides lactol (+)-3 and car-
boxylic acid 19 in sufficient quantity to support the
total synthesis and allow coupling studies at a later
time, further optimization, especially in order to
improve the oxidation/cyclization sequence from triol
(+)-12 to lactol (+)-3, is still required.20 Progress toward
the total synthesis continues and will be reported in due
course.
Supporting information
The following supporting information is available on
line: Spectral data for key intermediates.
Acknowledgements
We are grateful to FAEP-UNICAMP, FAPESP and
CNPq for financial support. We thank Professor Carol
H. Collins, from IQ-UNICAMP, for helpful sugges-
tions about English grammar and style. We thank also
Professor Michael Perkins, from Flinders University,
Australia, for sharing helpful information about his
efforts towards the total synthesis of dolabriferol.
13. (a) Mancuso, A. J.; Swern, D. Synthesis 1981, 165; (b)
Paterson, I.; Chen, D. Y.-K.; Acen˜a, J. L.; Franklin, A.
S. Org. Lett. 2000, 2, 1513.
14. Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
15. Takano, S.; Sekiguchi, Y.; Shimazaki, Y.; Ogasawara, K.
Heterocycles 1992, 33, 713.
16. (a) Isobe, M.; Kitamura, M.; Mio, S.; Goto, T. Tetra-
hedron Lett. 1982, 23, 221; (b) Kitamura, M.; Isobe, M.;
Ichikawa, Y.; Goto, Y. J. Org. Chem. 1984, 49, 3517; (c)
Maruyama, K.; Ueda, M.; Sasaki, S.; Iwata, Y.;
Miyazawa, M.; Miyashita, M. Tetrahedron Lett. 1998, 39,
4517.
17. (a) Nagaoka, H.; Kishi, Y. Tetrahedron 1981, 37, 3873;
(b) Lipshutz, B. H.; Kozlowski, J.; Wilhelm, R. S. J. Am.
Chem. Soc. 1982, 104, 2305.
References
1. Ciavatta, M. L.; Gavagnin, M.; Puliti, R.; Cimino, G.;
Martinez, E.; Ortea, J.; Mattia, C. A. Tetrahedron 1996,
39, 12831.
2. Manker, D. C.; Faulkner, D. J.; Stout, T. J.; Clardy, J. J.
Org. Chem. 1989, 54, 5371.
3. The numbering of 1 as well as of each intermediate
follows that suggested in Ref. 1.
4. Gage, J. R.; Evans, D. A. Org. Synth. 1990, 68, 83.
5. (a) Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem.
Soc. 1981, 103, 2127; (b) Evans, D. A.; Taber, T. R.
Tetrahedron Lett. 1980, 21, 4675.
18. Takano, S.; Akiyama, M.; Sato, S.; Ogasawara, K. Chem.
6. Levin, J. I.; Turos, E.; Weinreb, S. M. Synth. Commun.
Lett. 1983, 1593.
1982, 12, 989.
19. Bal, B. S.; Childers, W. E., Jr.; Pinnick, H. W. Tetra-
hedron 1981, 37, 2091.
7. Wilkinson, A. L.; Hanefeld, U.; Wilkinson, B.; Leadlay,
P. F.; Staunton, J. Tetrahedron Lett. 1998, 39, 9827.
8. DiBattista, J. P.; Webster, F. X. Bioorg. Med. Chem.
1996, 4, 423.
20. New compounds and the additional isolatable intermedi-
1
ates gave satisfactory H and 13C NMR, IR, HRMS, and
analytical data. Yields refer to chromatographically and
spectroscopically homogeneous materials.
9. (a) Paterson, I.; Goodman, J. M.; Isaka, M. Tetrahedron
Lett. 1989, 30, 7121; (b) Paterson, I.; Perkins, M. V.