2842
G. Chelucci et al. / Tetrahedron Letters 49 (2008) 2839–2843
10. The diacetylene compound 8, useful starting point for Bergman
cyclization, has been prepared by Russell and Kim in yields ranging
from 19% to 47%, depending on the starting pyridine derivatives.8
11. Mio, M. J.; Kopel, L. C.; Braun, J. B.; Gadzikwa, T. L.; Hull, K. L.;
Brisbois, R. G.; Markworth, C. J.; Grieco, P. A. Org. Lett. 2002, 4,
3199.
on the bromo-carbon bond in the alkene moiety (Suzuki–
Miyaura), notwithstanding the high electrophilicity of the
bromo-carbon bond in the 2-position of the pyridine ring.
Both protocols allow to obtain the key intermediate 10
from the same starting material 5 in similar overall yields
(50–60%), but the first one requires less steps (2 vs 3) and
moreover appears to be cheaper. Although the presented
procedures have been developed to obtain 11, the simplest
exponent of alkenes of type 2, they can be likely extended
to more complex cis-1,2-dipyridylethene derivatives. In this
case, the choice of the method is however dictated by either
the availability of the starting points, namely the iodo- or
formylpyridine derivative, or the symmetry of the target
compound. In general, availability of starting material
being equal, the Sonogashira protocol appears to be prefer-
able if the dipyridylalkyne to be synthesized is symmetri-
cally substituted, whereas the Suzuki–Miyaura protocol
comes out if the target is a dipyridylalkyne substituted on
only one heterocycle ring. Therefore, the methods are
complementary and can be chosen according to the desired
dipyridylalkyne. Further studies on this subject are
currently in progress.
12. 2-Bromo-3-(2-(2-bromopyridin-3-yl)ethynyl)pyridine (10): A 25 mL
round-bottom flask with teflon-coated magnetic stir bar was fitted
with a rubber septum and flame-dried under vacuum. The flask was
purged with dry argon, and charged with PdCl2(PPh3)2 (16.8 mg,
6 mol %), CuI (15.2 mg, 10 mol %) and 2-bromo-3-iodopyridine
(0.228 g, 0.80 mmol). Septum was parafilmed after solids were added.
While stirring, dry benzene (4.0 mL, starting material is 0.20 M in dry
benzene) sparged with dry argon was added by syringe. Argon-
sparged DBU (718 lL, 6 equiv) was then added by syringe, followed
by a purge of the reaction flask with argon. Ice-chilled trimethylsily-
lethynylene (57 lL, 0.50 equiv) was then added by syringe, followed
immediately by distilled water (5.8 lL, 40 mol %). The reaction flask
was covered with aluminum foil and left stirring at a high speed for
7 h, at the end of which the reaction mixture was partitioned in ethyl
ether and distilled water (50 mL each). The organic layer was washed
with saturated aqueous NaCl (1 Â 75 mL), dried over MgSO4,
gravity-filtered and the solvent was removed in vacuo. The crude
product was purified by flash chromatography (petroleum ether/
ethyl acetate = 8:2 to 1:1) to give 10: mp 195–197 °C; 1H NMR
(300 MHz, CDCl3): d 8.40 (m, 2H), 7.92–7.84 (m, 2H), 7.36–7.28 (m,
2H). 13C NMR (75.4 MHz, CDCl3): d 149.3, 144.4, 141.2, 122.8,
122.2, 92.3.
13. For some review, see: (a) Miyuaura, N.; Suzuki, A. Chem. Rev. 1995,
95, 2457; (b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147; (c)
Kotha, S.; Lahitri, K.; Kashinath, D. Tetrahedron 2002, 58, 9633; (d)
Suzuki, A.; Brown, H. C. In Organic Syntheses via Boranes; Aldrich
Chemical Company: Milwauke, 2003; Vol. 3.
14. Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault, S.
Tetrahedron 2002, 58, 3323.
15. Compound 5 is a commercial product (Aldrich), otherwise it can be
prepared according to a well described procedure: Melnyk, P.;
Gasche, J.; Thal, C. Synth. Commun. 1993, 2723.
16. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769.
17. The cross-coupling of 16 with 1-(2-bromoethynyl)benzene has been
reported, whereas there are no data for the coupling of 1-(2-
bromoethynyl)arenes with boronic acids or esters: Ishiruka, M. T.;
Kamada, T. M.; Ohta; Terashima, M. Heterocycles 1884, 22, 2475.
18. Shen, W. Synlett 2000, 737.
19. (Z)-2-Bromo-3-(1-bromo-2-(2-bromopyridin-3-yl)vinyl)pyridine (16):
A mixture of 2-bromo-3-(2,2-dibromovinyl)pyridine (0.342 g, 1.0
mmol), 2-bromo-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyri-
dine (0.298 g, 1.05 mmol) and Cs2CO3 (0.706 g, 2.0 mmol) in 1,
4-dioxane (5.0 mL) and H2O (2.0 mL) was degassed by bubbling
nitrogen for few minutes. Then, Pd2(dba)3 (23 mg, 0.025 mmol) and
tris(2-furyl)phosphine (TFP) (35 mg, 0.15 mmol) were added and the
resulting mixture was heated at 65 °C under nitrogen for the proper
time (Table 1). After cooling the mixture was diluted with ethyl
acetate (50 mL) and washed with brine (2 Â 15 mL). The organic
phase was dried over anhydrous Na2SO4, the solvent was evaporated
and the residue was purified by flash chromatography (petroleum
ether/ethyl acetate = 7:3) to give 16: 0.377 g (90%); mp 125–127 °C;
1H NMR (300 MHz, CDCl3): d 8.41 (dd, 1H, J = 4.8, 1.8 Hz), 8.38
(dd, 1H, J = 4.8, 1.8 Hz), 8.14 (dd, 1H, J = 7.8, 1.8 Hz), 7.79 (dd, 1H,
J = 7.8, 1.8 Hz), 7.43–7.35 (m, 2H), 7.05 (s, 1H). 13C NMR
(75.4 MHz, CDCl3): d 150.2, 149.6, 143.1, 141.8, 138.9, 138.7, 138.6,
133.2, 132.3, 122.8, 122.7, 122.4.
Acknowledgments
Financial support from MIUR (PRIN 2005035123,
Regio- and enantioselective reactions mediated by transi-
tion metal catalysts for innovative processes in fine chemi-
cals synthesis) and from the University of Sassari is
gratefully acknowledged by G.C.
References and notes
1. (a) Durand, J.; Milani, B. Coord. Chem. Rev. 2006, 250, 542; (b)
Fujita, M.; Toming, M.; Hori, A.; Therrien, B. Acc. Chem. Res. 2005,
38, 369; (c) Schoffers, E. Eur. J. Org. Chem. 2003, 1145; (d) Chelucci,
G.; Thummel, R. P. Chem. Rev. 2002, 102, 3129; (e) Armaroli, N.
Chem. Soc. Rev. 2001, 30, 113; (f) Kaes, C.; Katz, A.; Hosseini, M. W.
Chem. Rev. 2000, 100, 3553.
2. Chelucci, G.; Addis, D.; Baldino, S. Tetrahedron Lett. 2007, 48, 3359.
3. Gosney, I.; Lloyd, S. In Comprehensive Organic Functional Group
Tranformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.;
Pergamon Press: New York, 1995; Vol. 1, p 719.
4. (a) Siegel, S. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 8, p 417; (b)
Hudlicky, M. Reduction in Organic Chemistry; John Wiley & Sons:
New York, 1984; (c) Rylander, P. N. Hydrogenation Methods;
Academic Press: Orlando, 1985.
5. Metal-catalyzed Cross-Coupling Reactions; Diedrich, F., Stang, P. J.,
Eds.; Wiley-VCH: Weinheim, 1998.
6. Acetylene Chemistry; Diederich, F., Stang, P. J., Tykwinski, R. R.,
Eds.; Wiley-VCH: Weinheim, 2005.
7. Negishi, E.; Anastasia, L. Chem. Rev. 2003, 103, 1979.
8. (a) Sakamoto, T.; Shiraiwa, M.; Kondo, Y.; Yamada, H. Synthesis
1983, 312; (b) Dix, I.; Doll, C.; Hopf, H.; Jones, P. G. Eur. J. Org.
Chem. 2002, 2547. The reaction of 2,3-dichloropyridine and trimeth-
ylacetylene under Sogonashira conditions [Pd(PPh3)4, CuI, i-Pr2NH,
170 °C, 13 h] afforded in low yield only the monoacetylene adduct
derived from insertion in the 2 position of the pyridine ring: (c) Sik,
C.; Russel, K. C. J. Org. Chem. 1988, 63, 8229.
´ ´
20. Ratovelomanana, V.; Rollin, Y.; Gebehemnne, C.; Gosmini, C.;
´
Perochon, J. Tetrahedron Lett. 1994, 35, 4777.
21. For a review, see: Eymery, F.; Iorga, B.; Savignac, P. Synthesis 2000,
185.
22. All new compounds showed satisfactory spectroscopic and analytical
data. 2-Bromo-3-ethynylpyridine (9): mp 98–99 °C; 1H NMR
9. Duan, X.-F.; Li, X.-H.; Li, F. Y.; Huang, C.-H. Synthesis 2004, 2614.