8656
N. E. Leadbeater, B. J. Tominack / Tetrahedron Letters 44 (2003) 8653–8656
acetylene as substrates. We obtained a 79% yield of
product after 18 h. Our methodology is certainly easier,
faster and requires less catalyst. Although the substrate
scope of aryl bromides is not as wide as that of Bohm
and Herrmann11 or Najera and co-workers,16 compari-
son shows that for aryl iodide substrates our method is
certainly faster and easier.
9. Pal, M.; Parasuraman, K.; Gupta, S.; Yeleswarapu, K. R.
Synlett 2002, 1976.
10. Alami, M.; Ferri, F.; Linstrumelle, G. Tetrahedron Lett.
1993, 34, 6403.
11. Bo¨hm, W. P. W.; Herrmann, W. A. Eur. J. Org. Chem.
2000, 3679.
12. Heidenreich, R. G.; Ko¨hler, K.; Krauter, J. G. E.;
Pietsch, J. Synlett 2002, 1118.
In conclusion, we have developed a methodology for
easy and rapid copper-free Sonogashira couplings. The
methodology has the advantage of short reaction times,
ease of reaction and the use of a readily available
palladium complex. The quantity of amine used is
much less than previously reported for copper-free pro-
tocols. Attempts to develop the methodology further
and increase its scope are currently underway in our
laboratory.
13. Nguefack, J.-F.; Bolitt, V.; Sinou, D. Tetrahedron Lett.
1996, 37, 5527.
14. Uozumi, Y.; Kobayashi, Y. Heterocycles 2003, 59, 71.
15. Fukuyama, T.; Shinmen, M.; Nishitani, S.; Sato, M.;
Ryu, I. Org. Lett. 2002, 4, 1691.
16. Alonso, D. A.; Na´jera, C.; Pacheco, M. C. Tetrahedron
Lett. 2002, 43, 9365.
17. Nova´k, Z.; Szabo´, A.; Re´pa´si, J.; Kotschy, A. J. Org.
Chem. 2003, 68, 3327.
18. Procedure for coupling aryl iodides to alkynes: In a 10 mL
glass tube was placed aryl iodide (1.0 mmol), alkyne (1.0
mmol), piperidine (0.3 mL, 3 mmol), PdCl2(PPh3)2 (14
mg, 0.02 mmol) and a magnetic stir bar. The vessel was
sealed with a septum and placed in an oil bath pre-heated
to 70°C and held there for 10 min. After this time, the
reaction vessel was opened and the contents poured into
a separating funnel and the tube washed with water and
then with ether, these washings being added to the sepa-
rating funnel. Further water and diethyl ether (20 mL of
each) were added and the organic material extracted and
then washed with acid (15% v/v HCl) until the washings
were neutral. The organic layer was again washed with
water (40 mL) before being dried over MgSO4 and the
ether removed under vacuum leaving the crude product.
Products were characterized by comparison of 1H and
13C NMR spectra with those of authentic samples or in
the literature and yields determined by NMR with refer-
ence to a known quantity of an internal standard.
19. Procedure for coupling aryl bromides to alkynes: In a 10
mL glass tube was placed aryl bromide (1.0 mmol),
Acknowledgements
The Royal Society is thanked for a University Research
Fellowship (NEL).
References
1. Review: Rossi, R.; Carpita, A.; Bellina, F. Org. Prep.
Proc. Ind. 1995, 129.
2. Sonogashira, K. J. Organomet. Chem. 2002, 653, 46.
3. (a) Paterson, I.; Davies, R. D.; Marquez, R. Angew.
Chem., Int. Ed. 2001, 40, 603; (b) Toyota, M.; Komori,
C.; Ihara, M. J. Org. Chem. 2000, 65, 7110; (c)
Yoshimura, F.; Kawata, S.; Hirama, M. Tetrahedron
Lett. 1999, 40, 8281; (d) Miller, M. W.; Johnson, C. R. J.
Org. Chem. 1997, 62, 1582; (e) Sakai, A.; Aoyama, T.;
Shioiri, T. Tetrahedron Lett. 1999, 40, 4211; (f) Graham,
A. E.; McKerrecher, D.; Davies, D. H.; Taylor, R. J. K.
Tetrahedron Lett. 1996, 37, 7445.
4. (a) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed.
Engl. 1991, 30, 1387; (b) Grissom, J. W.; Gunawardena,
G. U.; Klingberg, D.; Huang, D. Tetrahedron 1996, 52,
6453.
5. (a) Wu, R.; Schumm, J. S.; Pearson, D. L.; Tour, J. M. J.
Org. Chem. 1996, 61, 6906; (b) Bunz, U. H. F. Chem.
Rev. 2000, 100, 1605.
alkyne (1.0 mmol), piperidine (0.3 mL,
3 mmol),
PdCl2(PPh3)2 (28 mg, 0.04 mmol) and a magnetic stir bar.
The reaction was run and worked up in an identical
manner as for the aryl iodides.
20. Elangovan, A.; Wang, Y. H.; Ho, T.-I. Org. Lett. 2003, 5,
1841.
21. Procedure for the 10 mmol scale coupling of 4-iodoanisole
to phenylacetylene: In a 150 mL capacity Schlenk tube
was placed aryl iodide (10 mmol), phenylacetylene (1.1
mL, 10 mmol), piperidine (3 mL, 30 mmol), PdCl2(PPh3)2
(140 mg, 0.2 mmol) and a magnetic stir bar. The vessel
was sealed with a septum and placed into an oil bath
pre-heated to 70°C and held there for 10 min. The
reaction was worked up in an identical manner as for the
reactions on a 1 mmol scale.
6. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 4467.
7. (a) Rossi, R.; Carpita, A.; Bigelli, C. Tetrahedron Lett.
1985, 26, 523–526; (b) Liu, Q.; Burton, D. J. Tetrahedron
Lett. 1997, 38, 4371.
8. Nishihara, Y.; Ikegashira, K.; Hirabayashi, K.; Ando,
J.-I.; Mori, A.; Hiyama, T. J. Org. Chem. 2000, 65, 1780.