including several with some measure of strain in their
structure, most notably 210 and 3.11
forming step from 5 to 4 might hinder product formation.
Thus, the alternative, route B, was employed, using a 2-fold
Fritsch-Buttenberg-Wiechell (FBW) rearrangement to as-
semble the tetrayne framework of 4 from dibromoolefinic
precursors 6.13
Our interest in polyynes led us to consider whether simple,
cyclic alka-1,3,5,7-tetraynes could be synthesized and studied
as model systems for larger unsaturated molecules such as
the cyclo[n]carbons. With the ultimate goal of exploring
kinetic stability and spectroscopic characteristics of such
molecules as a function of ring strain, we report herein our
preliminary efforts in the study of cyclic alkyl tetraynes.
Two potential routes toward the desired tetraynes 4 were
envisioned (Figure 2). Route A would rely on the initial
Cyclic tetraynes 4 (Scheme 1) were formed from dicar-
boxylic acids 7, beginning with acyl chloride formation
Scheme 1
Figure 2. Potential synthesis of tetraynes 4. Route A would use
an oxidative homocoupling reaction, while Route B would use the
Fritsch-Buttenberg-Wiechell rearrangement.
synthesis of precursor terminal diynes 5, which could then
be subjected to an oxidative acetylenic homocoupling reac-
tion. Two issues caused concern. First, it was anticipated
that the formation and manipulation of the precursors 5 would
be challenging, given the fact that terminal diynes are often
unstable.12 Second, the ring strain encountered in the ring-
(3) (a) Diederich, F.; Gobbi, L. Top. Curr. Chem. 1999, 201, 43-79.
(b) Tobe, Y.; Wakabayashi, T. In Polyynes: Synthesis, Properties and
Applications; Cataldo, F., Ed.; CRC Press: Taylor & Francis: 2006; p 99.
(c) Tobe, Y.; Wakabayashi, T. In Acetylene Chemistry: Chemistry, Biology
and Material Science; Diederich, F., Stang, P. J., Tykwinski, R. R., Eds.;
Wiley-VCH: Weinheim, 2005; p 387. (d) Tobe, Y.; Matsumoto, H.;
Naemura, K.; Achiba, Y.; Wakabayashi, T. Angew. Chem., Int. Ed. Engl.
1996, 35, 1800-1802.
a PCl3 was used instead of SOCl2 to form the acyl chloride.
followed by a Friedel-Crafts acylation reaction14 with bis-
(trimethylsilyl)acetylene (BTMSA) in the presence of AlCl3.
The resulting diketones 8a-e were obtained in satisfactory
yields, and a subsequent Corey-Fuchs reaction15 yielded
tetrabromoolefins 9a-e, also in reasonable yields. Removal
of the two trimethylsilyl groups (K2CO3, MeOH) from 9a-e
afforded enynes that showed only limited stability in their
neat form. Thus, following workup, these products were
taken on to the macrocyclization step without further
purification.
(4) (a) Tobe, Y.; Umeda, R.; Iwasa, N.; Sonoda, M. Chem. Eur. J. 2003,
9, 5549-5559. (b) Diederich, F.; Rubin, Y.; Chapman, O. L.; Goroff, N.
S. HelV. Chim. Acta 1994, 77, 1441-1457.
(5) For an excellent review of strained dehydrobenzannulenes, see:
Hisaki, I.; Sonoda, M.; Tobe, Y. Eur. J. Org. Chem. 2006, 833-847.
(6) See, for example: Eisler, S.; McDonald, R.; Loppnow, G. R.;
Tykwinski, R. R. J. Am. Chem. Soc. 2000, 122, 6917-6928 and references
therein.
(7) To our knowledge, only two reports of cyclic alkyl triynes have
appeared; see: (a) Dale, J.; Hubert, A. J.; King, G. S. D. J. Chem. Soc.
1963, 73-86. (b) Bergel’son, L. D.; Molotkovskii, Y. G. Bull. Acad. Sci.
USSR. DiV. Chem. Sci. (Engl. Transl.) 1963, 94-98.
(8) (a) Hisaki, I.; Eda, T.; Sonoda, M.; Niino, H.; Sato, T.; Wakabayashi,
T.; Tobe, Y. J. Org. Chem. 2005, 70, 1853-1864. (b) Tobe, Y.; Ohki, I.;
Sonoda, M.; Niino, H.; Sato, T.; Wakabayashi, T. J. Am. Chem. Soc. 2003,
125, 5614-5615. (c) Bell, M. L.; Chiechi, R. C.; Johnson, C. A.; Kimball,
D. B.; Matzger, A. J.; Wan, W. B.; Weakley, T. J. R.; Haley, M. M.
Tetrahedron 2001, 57, 3507-3520. (d) Wan, W. B.; Chiechi, R. C.;
Weakley, T. J. R.; Haley, M. M. Eur. J. Org. Chem. 2001, 3485-3490.
(9) See, for example: (a) Kivala, M.; Mitzel, F.; Boudon, C.; Gissel-
brecht, J.-P.; Seiler, P.; Gross, M.; Diederich, F. Chem. Asian J. 2006, 1,
479-489. (b) Heuft, M. A.; Collins, S. K.; Fallis, A. G. Org. Lett. 2003, 5,
1911-1914. (c) Haley, M. M.; Bell, M. L.; Brand, S. C.; Kimball, D. B.;
Pak, J. J.; Wan, W. B. Tetrahedron Lett. 1997, 38, 7483-7486.
(10) Leibrock, B.; Vostrowsky, O.; Hirsch, A. Eur. J. Org. Chem. 2001,
4401-4409.
The formation of cycles 6a-e under Hay conditions16 was
more difficult than anticipated due to competition from
intermolecular cyclization and from byproducts that appeared
(13) For recent examples of polyyne formation using the FBW rear-
rangement, see: (a) Chalifoux, W. A.; Tykwinski, R. R. Chem. Rec. 2006,
6, 169-182. (b) Luu, T.; Elliott, E.; Slepkov, A. D.; Eisler, S.; McDonald,
R.; Hegmann, F. A.; Tykwinski, R. R. Org. Lett. 2005, 7, 51-54. (c) Eisler,
S.; Slepkov, A. D.; Elliott, E.; Luu, T.; McDonald, R.; Hegmann, F. A.;
Tywkinski, R. R. J. Am. Chem. Soc. 2005, 127, 2666-2676. (d) Tobe, Y.;
Umeda, R.; Iwasa, N.; Sonoda, M. Chem. Eur. J. 2003, 9, 5549-5559.
(14) Walton, D. R. M.; Waugh, F. J. Organomet. Chem. 1972, 37, 45-
56.
(11) Heuft, M. A.; Collins, S. K.; Yap, G. P. A.; Fallis, A. G. Org. Lett.
2001, 3, 2883-2886.
(12) Terminal diynes can, however, be stable; see: West, K.; Wang, C.;
Batsanov, A. S.; Bryce, M. R. J. Org. Chem. 2006, 71, 8541-8544.
(15) (a) Ramirez, F.; Desai, N. B.; McKelvie, N. J. Am. Chem. Soc. 1962,
84, 1745-1747. (b) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972,
3769-3772.
(16) Hay, A. S. J. Org. Chem. 1962, 27, 3320-3321.
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