4180
C. E. D. Nazario et al. / Tetrahedron Letters 52 (2011) 4177–4181
C6H5
References and notes
C6H5
SnBu3
C6H5
I
C6H5
1. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 36, 3769.
14l
2. (a) Dabdoub, M. J.; Dabdoub, V. B.; Baroni, A. C. M. J. Am. Chem. Soc. 2001, 123,
9694; (b) Kadota, I.; Ueno, H.; Ohnob, A.; Yamamoto, Y. Tetrahedron Lett. 2003,
44, 8645; (c) Lipshutz, B. H.; Keil, R.; Barton, J. C. Tetrahedron Lett. 1992, 33,
5861.
LiCl/CuI/Pd(PPh3)4
DMSO
16
61%
C6H5
º
º
25 C-60 C
C6H5
3. Dabdoub, M. J.; Baroni, A. C. M. J. Org. Chem. 2000, 65, 54.
4. Tsuji, J. Palladium Reagents and Catalysts: New Perspectives for The 21st Century;
John Wiley: Chichester, UK, 2004.
Scheme 7.
5. Uenishi, J.; Iwamoto, T.; Ohmi, M. Tetrahedron Lett. 2007, 48, 1237.
6. Hwang, G. T.; Son, H. S.; Ku, J. K.; Kim, B. H. J. Am. Chem. Soc. 2003, 125, 11241.
7. Shen, W.; Wang, L. J. Org. Chem. 1999, 64, 8873.
8. Grissom, J. W.; Gunwardena, G. U.; Klingberg, D.; Huang, D. Tetrahedron 1996,
52, 6453.
9. Iverson, S. L.; Uetrecht, J. P. Chem. Res. Toxicol. 2001, 14, 175.
10. (a) Tsukamoto, S.; Takahashi, M.; Matsunaga, S.; Fusetani, N.; Van Soest, R. W.
M. J. Nat. Prod. 2000, 63, 682; (b) Goundry, W. R. F.; Lee, V.; Baldwin, J. E.
Tetrahedron Lett. 2002, 43, 2745.
The Sonogashira cross-coupling reaction using TBAOH as base
occurred faster than with the other bases studied. Usually the reac-
tion was completed within 10 min, as evaluated by thin-layer
chromatography. A possible explanation is that TBAOH is a stron-
ger base than the other amines used, and could also be acting as
a phase transfer catalyst (PTC).23–25
11. Daly, J. W. J. Med. Chem. 2003, 46, 445.
With these results, we envision a possibility of applying (Z)-
tributylstannyl enynes in the synthesis of enediynes. Conjugated
enediyne systems, represented by 1,1-diethynylethenes (3-ethy-
nyl-1-buten-3-ynes, gem-DEE)16 type 16 (Scheme 7), emerged re-
cently as a promising starting material for the synthesis of
compounds with wide applications in non-linear optics (NLO),26
macrocyclic ligands,27 and polycyclic aromatic hydrocarbons
(PAHs).28 Few methods to prepare conjugated gem-enediynes have
been reported, and most use Sonogashira metal palladium cata-
lyzed cross-coupling reactions of 1,1-dibromo-1-alkenes with 1-al-
kynes.6,29 Normally, in these processes bromoenynes are detected
as byproducts and significant amounts of the starting material
are recovered29b,c leading to low yield.30 In contrast, the Sonogash-
ira reactions of telluroketene acetals and 1-alkynes afforded the
gem-enediynes in good yields.13 However, vinyl organotelluride
compounds have shown high toxicity and teratogenic effects.31 Re-
cently, Kabalka et al.14 described an efficient method to synthesize
conjugated gem-enedyines in high yield using palladium-catalyzed
cross-coupling reactions of the readily accessible 1,1-dibromo-1-
alkenes and stable potassium alkynyltrifluoroborates. However,
these cross-coupling catalyzed metal reactions using 1,1-dibromo
alkenes or telluroketene acetals as starting material are syntheti-
cally limited, always leading to the conjugated symmetrical gem-
enedyines containing the same two alkynyl groups attached at
the sp2 carbon.13,14
12. Toyooka, N.; Dejum, Z.; Nemoto, H.; Garraffo, H. M.; Spande, T. F.; Daly, J. W.
Tetrahedron Lett. 2006, 47, 577.
13. Zeni, G.; Perin, G.; Cella, R.; Jacob, R. G.; Braga, A. L.; Silveira, C. C.; Stefani, H. A.
Synlett 2002, 6, 975.
14. Kabalka, G. W.; Dong, G.; Venkataiah, B. Tetrahedron Lett. 2005, 46, 763.
15. Xi, G.; Liu, Y.; Yan, X.; Chen, C. J. Organomet. Chem. 2007, 4612.
16. Nielsen, M. B.; Diederich, F. Chem. Rev. 2005, 105, 1837. and references cited
therein.
17. Mori, A.; Shimada, T.; Kondo, T.; Sekiguchi, A. Synlett 2001, 649.
18. Chinchilla, R.; Carmen, N. Chem. Rev. 2007, 107, 874. and references cited
therein.
19. Ji, N.; O’Dowd, H.; Rosen, B. M.; Myers, A. G. J. Am. Chem. Soc. 2006, 128, 14825.
20. Cai, M.; Zhao, H.; Ye, H.; Xia, J.; Song, C. J. Chem. Res., Synopses 2003, 6, 344.
21. Mori, A.; Kondo, T.; Kato, T.; Nishihara, Y. Chem. Lett. 2001, 286.
22. Mori, A.; Kawashima, J.; Shimada, T.; Suguro, M.; Hirabayashi, K.; Nishihara, Y.
Org. Lett. 2000, 2, 2935.
23. Lucchese, A.; Marzorati, L. Quim. Nova 2000, 23, 641.
24. Makosza, M. Pure Appl. Chem. 2000, 72, 1399.
25. Zhang, Y.; Stanciulescu, M.; Ikura, M. Appl. Catal., A 2009, 366, 176.
26. Moonen, N. N. P.; Boudon, C.; Giselbrecht, J.-P.; Seiler, P.; Gross, M.; Diederich,
F. Angew. Chem., Int. Ed. 2002, 41, 3044.
27. Campbell, K.; McDonald, R.; Ferguson, M. J.; Tykwinski, R. R. Organometallics
2003, 22, 1353.
28. Donovan, P. M.; Scott, L. T. J. Am. Chem. Soc. 2004, 5, 213.
29. (a) Rankin, T.; Tykwinski, R. R. Org. Lett. 2003, 5, 213; (b) Uenishi, J.; Matsui, K.;
Ohmiya, H. J. Org. Chem. 2002, 653, 141; (c) Shen, W.; Thomas, S. A. Org. Lett.
2000, 2, 2857.
30. (a) Kaafarani, B. R.; Neckers, D. C. Tetrahedron Lett. 2001, 42, 4099; (b)
Kaafarani, B. R.; Pinkerton, A. A.; Neckers, D. C. Tetrahedron Lett. 2001, 42, 8137.
31. Nogueira, C. W.; Zeni, G.; Rocha, J. B. T. Chem. Rev. 2004, 104, 6255. and
references cited therein.
32. Han, X.; Stoltz, M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121, 7600.
33. Typical procedure for the Sonogashira cross-coupling reaction with TBAOH. To a
solution of 9a (0.467 g; 1.0 mmol), Pd(PPh3)4 (0.058 g; 0.05 mmol,), and CuI
(0.019 g; 0.1 mmol), 1-alkyne 13 (0.192 g; 2.0 mmol), in THF (2.0 mL) at 25 °C,
under a nitrogen atmosphere was added dropwise (according to Table 3), a
solution of tetrabutylammonium hydroxide (TBAOH) (2.0 mmol, 40% aqueous
solution) diluted with methanol (3.0 mL). The reaction was stirred at 25 °C for
10 min, extracted with ethyl acetate (3 ꢁ 15.0 mL), and washed with brine
(4 ꢁ 10.0 mL). Next, the organic layer was dried over MgSO4 and the solvent
evaporated under vacuum. The crude product was purified by flash silica-gel
chromatography using hexane as mobile phase to give pure 14a as light yellow
oil. Yield: 89%. IR (neat, cmꢀ1) 2959; 2856; 2233; 1564; 1463; 1H NMR
(300 MHz, d in CDCl3): 0.90 (t, 15H, J = 7.1 Hz); 1.00 (t, 6H, J = 8.1 Hz); 1.29–
1.58 (m, 24H); 2.03 (q, 2H, J = 7.1 Hz); 2.32 (t, 2H, J = 6.9 Hz); 6.62 (t, 1H,
J = 7.1 Hz); 13C NMR (75 MHz, d in CDCl3): 10.86; 13.69; 13.99; 19.80; 22.31;
22.52; 27.38; 29.03; 29.07; 31.25; 31.90; 35.24; 84.51; 91.35; 124.01; 151.38.
34. (Z)-1-Hexyl-2-tributylstannyl-4-phenyl-1-buten-3-yne 14f as light yellow oil.
Yield: 86%. IR (neat, cmꢀ1): 2920, 2854, 2179, 1582, 1464; 1H NMR (300 MHz, d
in CDCl3): 0.90 (t, 12H, J = 6.8 Hz); 1.08 (t, 6H, J = 8 Hz); 1.39–1.56 (m, 20H);
2.12 (q, 2H, J = 7.1 Hz); 6.62 (t, 1H, J = 7.7 Hz); 7.23–7.26 (m, 2H); 7.28–
7.40 ppm (m, 3H). 13C NMR (75 MHz, d in CDCl3): 11.02; 13.69; 22.61; 27.37;
28.96; 29.63; 31.79; 35.87; 90.67; 93.89; 123.28; 124.68; 127.21; 128.15;
131.25; 153.27. HRMS 445.1926 (MꢀC4H9)+; 445.1917 (C24H37Sn 2 ppm).
35. (5Z)-2-Methyl-6-phenyl-5-(tributylstannyl)hex-5-en-3-yn-2-ol 14k as light
yellow oil. Yield: 75%. IR (neat, cmꢀ1): 3350, 2854, 2179, 1582, 1464; 1H
NMR (300 MHz, d in CDCl3): 0.84 (t, 9H, J = 6.5 Hz); 0.90 (t, 6H, J = 6.5 Hz); 1.24
(sex, 6H, J = 6.5 Hz); 1.4 (qui, 6H); 1.59 (s, 6H); 1.94 (s, 1H), 7.20–7.22 (m, 2H),
7.26–7.33 (m, 3H), 7.76 (s, 1H). 13C NMR (75 MHz, d in CDCl3): 11.68; 13.64;
27.32; 28.84; 31.69; 65.87; 87.10; 98.28; 127.3; 127.4; 127.8; 128.2; 139.9;
150.8. HRMS: 419.1392 (MꢀC4H9)+; 419.1396 (C21H31OSn 1.1 ppm).
36. (Z)-1-(3-Cloro-propyl)-4-butyl-2-tributylstannyl-1-buten-3-yne 14i as light
yellow oil. Yield: 86%. IR (neat, cmꢀ1): 2929, 2194; 1587; 1463. 1H NMR
(300 MHz, d in CDCl3): 0.88–0.93 (m, 12H); 1.04 (t, 6H, J = 7.1 Hz); 1.34 (sex,
8H, J = 7.1 Hz); 1.52 (qui, 8H, J = 6.9 Hz); 1.86 (qui, 2H, J = 7.1 Hz); 2.20 (quart,
We describe herein an application of the Corey-Stille cross-cou-
pling reaction32 for the synthesis of these compounds, represented
by the conjugated gem-enedyines 16.
We examined the reaction of (Z)-1,4-diphenyl-2-tributylstan-
nyl-1-buten-3-yne 14l (1.0 equiv) and 1-iodo-2-(phenyl) ethyne
(1.5 equiv) in a homogeneous catalytic system containing CuCl
(5.0 equiv), LiCl (6.0 equiv) in DMSO (8.0 mL) which furnished
the conjugated gem-enedyines 16 in good yield (Scheme 7).38,39
In conclusion, Sonogashira cross-coupling reactions between
(E)-1,1-iodo vinyl stannanes 9 and terminal acetylenes 13 using
Pd(PPh3)4/CuI as catalytic system and aqueous TBAOH 40% as acti-
vator proved to be efficient in the preparation of (Z)-tributylstan-
nyl enynes 14. Conjugated gem-enediynes 16 were successfully
synthesized using the Corey-Stille cross-coupling reaction of the
(Z)-tributylstannyl enyne 14l with 1-iodo-2-phenyl acetylene. A
systematic study involving Corey-Stille cross-coupling of (Z)-tribu-
tylstannyl enynes with 1-iodo-2-organyl acetylenes to synthesize
unsymmetrical gem-enediynes is in progress in our laboratory.
Acknowledgments
This work was supported by grants from FUNDECT-MS, PROPP-
UFMS and CNPq. The authors thank Dr. Janet W. Reid (JWR Associ-
ates) for assistance with English corrections and Dr. Andersson
Barison (UFPR) for the NMR facilities.