mechanistic studies4c-f on the reductive elimination of
palladium(II) arylthiolate complexes with chelating phos-
phines, in 1996, Zheng and co-workers reported the first
general palladium-based protocol for the synthesis of aryl
sulfides from aryl triflates.4h More recently, in 2001, Scho¨pfer
and Schlapbach reported a general palladium-catalyzed
method for the synthesis of aryl sulfides from aryl iodides,
in toluene, using DPEPhos as the ligand.4i In this report, we
present a palladium-free general method for the formation
of aryl-sulfur bonds from aryl iodides using catalytic
amounts of copper iodide and neocuproine (2,9-dimethyl-
1,10-phenanthroline).5
Table 1. Reactions of Aryl Iodides with Thiophenol
Traditional copper-mediated reactions suffer from draw-
backs such as high reaction temperatures, the use of copper
salts in greater than stoichiometric amounts, sensitivity to
functional groups on the aryl halide, and irreproducibility.2a
Yet, they remain as the reactions of choice in large- and
industrial-scale syntheses.8d,e In the past five years, there has
been a resurgence in interest in developing mild synthetic
methods based on copper-based catalysts as an alternative
to palladium(0) catalysts for the formation of aryl-carbon
and aryl-heteroatom bonds. In this regard, our group,6
Buchwald’s group,7 and others8 have reported copper-based
methods for the formation of aryl-carbon, aryl-nitrogen,
and aryl-oxygen bonds. In addition to being simple and
mild, these protocols also accommodate substrates that do
not undergo coupling by palladium catalysis.9 Moreover, in
comparison to palladium, copper-based catalysts are quite
attractive from an economic standpoint. We now extend the
utility of copper-based catalysts for the formation of aryl-
sulfur bonds through the cross-coupling reaction between aryl
iodides and thiols.
We first chose to study the efficacy of copper(I)-based
catalysts in the cross-coupling reaction between iodobenzene
and thiophenol, in toluene, using Cu(phenanthroline)(PPh3)-
Br and Cu(neocuproine)(PPh3)Br complexes. We had previ-
ously shown the utility of these complexes in the formation
of aryl-acetylene, aryl-nitrogen, and aryl-oxygen bonds.6b,c
Our initial choice of base was Cs2CO3. We based this choice
on observations by Buchwald, Snieckus, and our group that
Cs2CO3 was essential in copper-based protocols for the
formation of aryl-oxygen bonds. In 24 h, although we
observed the formation of diphenyl sulfide by GC analyses,
the overall conversion was less than 50%. When we replaced
Cs2CO3 with NaOt-Bu, we observed complete consumption
of the starting materials when Cu(neocuproine)(PPh3)Br was
the catalyst. However, if Cu(phenanthroline)(PPh3)Br was
used as the catalyst, GC traces showed the presence of
starting materials in trace amounts in the same time period.
Trace amounts of starting materials were also observed if
KOt-Bu was used as the base. Diphenyl sulfide was formed
only in trace amounts if bromobenzene was used indicating
that the reaction was selective to iodides.
As a part of our control experiments, we replaced Cu-
(neocuproine)(PPh3)Br with 10 mol % CuI, CuI/neocuproine,
or CuCl/neocuproine as the catalyst. We found that CuI/
neocuproine was as effective as Cu(neocuproine)(PPh3)Br.
However, only a trace amount of diphenyl sulfide was
observed if CuI alone was used as the catalyst. This indicated
that neocuproine was essential for acceleration of the
reaction. Also, GC traces indicated the presence of starting
(5) Kiplin Guy and co-workers have reported a palladium-free method
for the coupling of mercaptans with aryl boronic acids using Cu(OAc)2.
See ref 1f.
(6) (a) Gujadhur, R.; Venkataraman, D. Synth. Commun. 2001, 31, 2865-
2879. (b) Gujadhur, R.; Venkataraman, D.; Kintigh, J. T. Tetrahedron Lett.
2001, 42, 4791-4793. (c) Gujadhur, R. K.; Bates, C. G.; Venkataraman,
D. Org. Lett. 2001, 3, 4315-4317.
(7) (a) Marcoux, J. F.; Doye, S.; Buchwald, S. L. J. Am. Chem. Soc.
1997, 119, 10539-10540. (b) Kiyomori, A.; Marcoux, J. F.; Buchwald, S.
L. Tetrahedron Lett. 1999, 40, 2657-2660. (c) Klapars, A.; Antilla, J. C.;
Huang, X. H.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7727-7729.
(d) Wolter, M.; Klapars, A.; Buchwald, S. L. Org. Lett. 2001, 3, 3803-
3805. (e) Kwong, F. Y.; Klapars, A.; Buchwald, S. L. Org. Lett. 2002, 4,
581-584. (f) Wolter, M.; Nordmann, G.; Job, G. E.; Buchwald, S. L. Org.
Lett. 2002, 4, 973-976. (g) Hennessy, E. J.; Buchwald, S. L. Org. Lett.
2002, 4, 269-272.
(8) (a) Zhang, S.; Zhang, D.; Liebeskind, L. S. J. Org. Chem. 1997, 62,
2312-2313. (b) Ma, D.; Zhang, Y.; Yao, J.; Wu, S.; Tao, F. J. Am. Chem.
Soc. 1998, 120, 12459-12467. (c) Kalinin, A. V.; Bower, J. F.; Riebel, P.;
Snieckus, V. J. Org. Chem. 1999, 64, 2986-2987. (d) Goodbrand, H. B.;
Hu, N.-X. J. Org. Chem. 1999, 64, 670-674. (e) Fagan, P. J.; Hauptman,
E.; Shapiro, R.; Casalnuovo, A. J. Am. Chem. Soc. 2000, 122, 5043-5051.
(9) See refs 6b and 7c,f,g for examples.
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Org. Lett., Vol. 4, No. 16, 2002