4950
M. F. Semmelhack et al. / Tetrahedron Letters 43 (2002) 4947–4950
This communication outlines an efficient route to the
preparation of an [8.3.0] bicyclic enediyne in quantity
and should allow a full exploration of the structure–
reactivity parameters in cycloaromatization for this sys-
tem. Our preliminary analysis indicates that subtle
changes in hybridization within the [8.3.0] framework
lead to changes in reactivity which correlate well with
DDHf values obtained from semiempirical calculations.
12. (a) Nishikawa, T.; Shibuya, S.; Hosokawa, S.; Isobe, M.
Synlett 1994, 485. The authors report a direct transfor-
mation from a silylacetylene. For a conversion to the
halo-alkyne from an acetylene, see: (b) Guanti, G.; Riva,
R. Chem. Commun. 2000, 1171.
13. (a) Takai, K.; Kuroda, T.; Nakatsukasa, S.; Oshima, K.;
Nozaki, H. Tetrahedron Lett. 1985, 26, 5585; (b) Jin, H.;
Uenishi, J.; Christ, W. J.; Kishi, Y. J. Am. Chem. Soc.
1986, 108, 5644; (c) Takai, K.; Tageshima, M.; Kuroda,
T.; Oshima, K.; Utimoto, K.; Nozaki, H. J. Am. Chem.
Soc. 1986, 108, 6048.
Acknowledgements
14. Saravanan, P.; Chandrasekhar, M.; Vijaya Anand, R.;
Singh, V. K. Tetrahdron Lett. 1998, 39, 3091.
15. Regioisomeric ratios were determined by a comparison of
the integrated area of the vinyl proton resonances (4.45
ppm for 22a and 4.47 ppm for 22b) of the silyl enol ether.
16. The value DSE is the difference in strain energy (MM2)
between the arene product and the enediyne. A smaller
difference suggests a faster reaction: (a) Carter, P. A.;
Magnus, P. J. Am. Chem. Soc. 1988, 110, 1626; (b)
Magnus, P.; Huffman, J. C. J. Am. Chem. Soc. 1988, 110,
6921.
Financial support from the National Institutes of
Health in the form of a research grant (CA 54819) is
gratefully acknowledged.
References
1. Thorson, J. S.; Sievers, E. L.; Ahlert, J.; Shepard, E.;
Whitwam, R. E.; Onwueme, K. C. R. Curr. Pharm. Des.
2000, 6, 1841.
17. Saegusa, T.; Hirao, T.; Ito, Y. J. Org. Chem. 1978, 43,
1011.
18. (a) Kende, A. S.; Roth, B.; Sanfilippo, P. J. J. Am. Chem.
Soc. 1982, 104, 1784; (b) Kende, A. S.; Roth, B.; Sanfi-
lippo, P. J.; Blacklock, T. L. J. Am. Chem. Soc. 1982,
104, 5808.
2. DeVoss, J. J.; Hangeland, J. J.; Townsend, C. A. J. Am.
Chem. Soc. 1990, 112, 4554.
3. Semmelhack, M. F.; Gu, Y.; Ho, D. M. Tetrahedron Lett.
1997, 38, 5583.
19. In a typical experiment, keto-enediyne 21 was dissolved
in THF and added dropwise to freshly prepared LiH-
MDS at −78°C to generate the kinetic enolate. The
trimethylsilyl enol ether 22 was obtained upon quenching
with TMSCl. The crude silyl enol ether was isolated by
removal of the solvents under reduced pressure at 0°C
and then dissolved in a minimal amount of anhydrous
DMF. The mixture was added to a stoichiometric
amount of Pd(TFA)2 in DMF at 0°C. In a parallel
reaction, the enolate (generated with LiHMDS at −78°C
in THF) was added directly via cannula to Pd(TFA)2 in
DMF at −30°C. In both instances, a complex mixture of
products was produced from which the desired a,b-unsat-
urated compound 26 could not be isolated.
4. Nicolaou, K. C.; Zuccarello, G.; Ogawa, Y.; Schweiger,
E. J.; Kumazawa, T. J. Am. Chem. Soc. 1988, 110, 4866.
5. (a) Banfi, L.; Guanti, G. Tetrahedron Lett. 2000, 41,
6523; (b) Banfi, L.; Guanti, G.; Basso, A. Eur. J. Org.
Chem. 2000, 939.
6. Gu, Y.; Ph.D. Dissertation, Princeton University, 1997.
7. Calculated at the AM1 level using MacSpartan.
8. Rosenquist, A.; Kvarnstrom, I.; Svensson, S. C. T.; Clas-
son, B.; Samuelsson, B. Acta Chem. Scand. 1992, 46,
1127.
9. Oshima, T.; Kagechika, K.; Adachi, M.; Sodeoka, M.;
Shibasaki, M. J. Am. Chem. Soc. 1996, 118, 7108.
10. Manchand, P. S.; Schwartz, A.; Wolff, S.; Belica, P. S.;
Madan, P.; Patel, P.; Saposnik, S. J. Heterocycles 1993,
35, 1351. The procedure reports generation of the lithium
acetylide. Commercial lithium acetylide ethylene diamine
complex (ALDRICH®, CAS c 6867,30-7) was used in
our case. The use of lithium acetylide ethylene diamine
complex to effect SN2 displacement of a primary bromide
is reported: Bestmann, H. J.; Brosche, T.; Koschatzky, K.
H.; Michaelis, K.; Platz, H.; Roth, K.; Suß, J.;
Vostrowsky, O.; Knauf, W. Tetrahedron Lett. 1982, 23,
4007.
20. Evans, P. A.; Longmire, J. M.; Modi, D. P. Tetrahedron
Lett. 1995, 36, 3985.
21. Reich, H. J.; Renga, J. M.; Reich, I. L. J. Am. Chem.
Soc. 1975, 97, 5434.
22. Protonation of the resulting a-phenyl selenyl enolate was
expected to occur from the a face based on steric block-
ing of the b face by the tert-butyl dimethyl siloxy substi-
tuted methine carbon.
23. (a) Reich, H. J. Acc. Chem. Res. 1979, 12, 22; (b) Clive,
D. L. J. Tetrahedron 1978, 34, 1049.
11. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetra-
hedron Lett. 1975, 16, 4467; (b) Takahashi, S.;
Kuroyama, Y.; Sonogashira, K.; Hagihara, N. Synthesis
1980, 627.
24. (a) Sharpless, K. B.; Lauer, R. F.; Teranisin, A. Y. J.
Am. Chem. Soc. 1973, 95, 6137; (b) Abul-Hajj, Y. J.
Chem. Soc., Chem. Commun. 1985, 21, 1479.