6094
N. R. Jogdand et al. / Tetrahedron Letters 50 (2009) 6092–6094
Table 2
protocol by Chen and Chen was not shown to couple aryl bromides
with thiols.18 All the other bromides, whether electron-rich (Table
2, entries 13 and 14) or electron-poor (Table 2, entry 12), worked
well under these conditions. In these cases good conversions were
observed, although slightly longer reaction time was required com-
pared with that required for aryl iodides. Like aryl iodides, aryl bro-
mides with an electron-withdrawing group (Table 2, entry 12)
showed better reactivity compared with those bearing electron-
donating groups (Table 2, entries 13 and 14). The products ob-
tained by this method have been well characterized by physical
and spectroscopic data.
In conclusion, we have developed an operationally simple, effi-
cient, and general methodology for the copper-catalyzed thioethe-
rification reaction of aryl halides with thiols using commercially
available, inexpensive tripod ligand, tris-(2-aminoethyl)amine.
These conditions tolerate a wide degree of functionality on both
the partners as shown by the numerous examples synthesized
and broaden the scope of C–S bond forming reactions. Efforts to ex-
pand the utility of the protocol to other types of carbon–hetero-
atom bond-forming reactions in combination with mechanistic
studies are in progress.
Coupling of thiol with aryl halide using CuI-tris-(2-aminoethyl)amine catalyst system
Entry
1
Thiol
Aryl halide
Time (h)
Yielda (%)
SH
SH
SH
SH
SH
SH
SH
I
20
88
I
I
2
3
18
18
19
20
18
17
18
18
20
20
21
23
23
24
22
84
84
82
83
86
90
87
89
78
86
85
82
80
65
84
I
4
OCH3
OCH3
I
I
5
Acknowledgment
6
The authors are thankful to the Head, Department of Chemistry,
Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431
004, MS, India, for providing the laboratory facility.
O
I
7
References and notes
NO2
1. (a) Wang, Y.; Chackalamannil, S.; Hu, Z.; Clader, J. W.; Greenlee, W.; Billard, W.;
Binch, H.; Crosby, G.; Ruperto, V.; Duffy, R. A.; McQuade, R.; Lachowicz, J. E.
Bioorg. Med. Chem. Lett. 2000, 10, 2247; (b) Neilsen, S. F.; Neilsen, E. O.; Olsen, G.
M.; Liljefors, T.; Peters, D. J. Med. Chem. 2000, 43, 2217.
2. De Martino, G.; Edler, M. C.; La Regina, G.; Cosuccia, A.; Barberah, M. C.; Barrow,
D.; Nicholson, R. I.; Chiosis, G.; Brancale, A.; Hamel, E.; Artico, M.; Silvestri, R. J.
Med. Chem. 2006, 49, 947.
3. (a) Jones, D. N.. In Comprehensive Organic Chemistry; Barton, D. H., Ollis, D. W.,
Eds.; Pergamon: New York, 1979; Vol. 3, (b) Rayner, C. M. Contemp. Org. Synth.
1996, 3, 499; (c) Tiecco, M. Synthesis-Stuttgart 1998, 749; (d) Herradura, P. S.;
Pendola, K. A.; Guy, R. K. Org. Lett. 2000, 2, 2019. and references cited therein;
(e) Procter, D. J. J. Chem. Soc. Perkin Trans. 1 2001, 335.
4. (a) Lindley, J. Tetrahedron 1984, 40, 1433; (b) Kondo, T.; Mitsudo, T. A. Chem.
Rev. 2000, 100, 3205.
5. (a) Migita, T.; Shimizu, T.; Asami, Y.; Shiobara, J.; Kato, Y.; Kosugi, M. Bull. Chem.
Soc. Jpn. 1980, 53, 1385; (b) Kosugi, M.; Ogata, T.; Terada, M.; Sano, H.; Migita, T.
Bull. Chem. Soc. Jpn. 1985, 58, 3657.
6. Zheng, N.; McWilliams, J. C.; Fleitz, F. J.; Armstrong, J. D.; Volante, R. P. J. Org.
Chem. 1998, 63, 9606.
7. Schopfer, U.; Schlapbach, A. Tetrahedron 2001, 57, 3069.
8. Fernandez-Rodriguez, M. A.;Shen, Q.;Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 2180.
9. Verma, A. K.; Singh, J.; Chaudhary, R. Tetrahedron Lett. 2007, 48, 7199.
10. Bates, C. G.; Gujadhar, R. K.; Venkataraman, D. Org. Lett. 2002, 4, 2803.
11. Lv, X.; Bao, W. J. Org. Chem. 2007, 72, 3863.
12. Bagley, M. C.; Dix, M. C.; Fussil, V. Tetrahedron Lett. 2009, 50, 3661.
13. Prasad, D. J. C.; Naidu, A. B.; Sekar, G. Tetrahedron Lett. 2009, 50, 1411.
14. Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2002, 4, 3517.
15. Jogdand, N. R.; Shingate, B. B.; Shingare, M. S. Tetrahedron Lett. 2009, 50, 4019.
16. (a) Kunz, K.; Schloz, U.; Ganzer, D. Synlett 2003, 2428; (b) Ley, S. V.; Thomas, A.
W. Angew. Chem., Int. Ed. 2003, 42, 5400; (c) Beletskaya, I. P.; Cheprakov, A. V.
Chem. Rev. 2004, 248, 2337; (d) Bates, C. G.; Saejueng, P.; Doherty, M. Q.;
Venkataramana, D. Org. Lett. 2004, 6, 5005.
17. Representative procedure:Coupling of 4-iodo-acetopheneone and thiophenol
(Table 2, entry 6): Into a 25 ml capacity one neck round-bottomed flask was
charged dioxane (3 ml) followed by ligand L (0.1 mmol), CuI (0.1 mmol), 1-(4-
iodophenyl)ethanone (1 mmol), thiophenol (1.02 mmol), and Cs2CO3
(2.04 mmol). The reaction mixture was stirred with a magnetic stir bar and
heated to 110 °C in an oil bath for 18 h. The completion of the reaction was
monitored by TLC. After the complete consumption of 1-(4-iodophenyl)ethanone,
the reaction mixture was cooled to room temperature and water (20 ml) was
added. Thecrude mixturewasextractedwithethylacetateandpurifiedbycolumn
chromatography on silica gel to afford 4-phenylsulfanylacetophenone (0.087 g,
86%) as white solid. 1H NMR (CDCl3, 400 MHz, d ppm): 7.80 (2H, d), 7.48–7.50 (2H,
m), 7.38–7.40 (3H, m), 7.19 (2H, d), 2.53 (3H, s). 13C NMR (50 MHz, CDCl3, d ppm):
26.3, 127.4, 128.6, 128.8, 129.5, 132.0, 133.6, 134.4, 144.7,197.0.Thespectroscopic
data are in full agreement with those described in the literature.10,11,18
18. Chen, Y.-J.; Chen, H.-H. Org. Lett. 2006, 8, 5609.
SH
I
I
I
8
SH
9
H3CO
Cl
SH
10
11
12
13
14
15
16
SH
SH
SH
SH
Br
Br
O
Br
Br
OCH3
SH
Br
Br
Cl
SH
a
Isolated yields after column chromatography.