9606
J . Org. Chem. 1998, 63, 9606-9607
Communications
P a lla d iu m -Ca ta lyzed Syn th esis of Ar yl
Su lfid es fr om Ar yl Tr ifla tes
Sch em e 1
Nan Zheng,* J . Christopher McWilliams, Fred J . Fleitz,
J oseph D. Armstrong III, and R. P. Volante
was not clear. Other chelating ligands, such as DPPF and
PHANEPHOS,7 were significantly less effective for the
coupling (entries 6 and 7). An improved yield for the coupling
reaction was observed when Pd(dba)2 was replaced by
Pd(OAc)2, presumably due to inhibition of the oxidative
addition to phenyl triflate by the dba ligand8 (entry 14). The
yield for the coupling reaction was further improved when
employing Tol-BINAP as ligand and Pd(OAc)2 as precatalyst
(entry 18). These results indicated that the specific struc-
tures of BINAP and Tol-BINAP might be the key to the
success of this catalyst system.9
We have also surveyed a variety of bases and additives
for this coupling reaction. The use of bases weaker than
NaOt-Bu, such as K2CO3, NaHCO3, and TEA, afforded lower
yields of the coupled product (entries 10-12). CuI has been
used as cocatalyst with Pd2(dba)3 to promote the coupling
of 2-naphthyl triflate and N-acetyl-L-cysteine.2e We found
that the use of 10 mol % of CuI improved the yield for the
coupling when employing Pd(dba)2 and BINAP with TEA
as base (entry 13). Added LiCl is often necessary for the
successful coupling of aryl triflates and organostannanes
(Stille coupling),10 although this effect is poorly understood
and strongly depends on the solvent and the ligand of the
palladium.11 Buchwald and Hartwig found that added
halides either had no effect on the amination of aryl triflates
or were detrimental to the coupling.4a,b In the case of our
studies for the coupling of aryl triflates and thiols, addition
of LiCl or LiBr improved the yield of the reaction when using
Pd(OAc)2 as precatalyst and BINAP as ligand (entries 15
and 16). Suprisingly, the presence of CuI completely shut
down the catalyst activity under the condition of Pd(OAc)2
and BINAP (entry 17).
Despite the success of the catalyst system consisting of
Pd(OAc)2 and BINAP with LiCl (entry 15, Table 1), we
decided to choose the combination of Pd(OAc)2 and Tol-
BINAP (entry 18, Table 1) as the optimal catalyst system
for the coupling of aryl triflates and sodium alkanethiolates
mainly due to its simplicity and convenience. A wide range
of aryl triflates was examined. As can be seen in Table 2,
this chemistry appears to be general for alkyl aryl sulfides.
Good to excellent yields of coupled products were obtained
with electronically neutral or deficient aryl triflates such as
phenyl triflate, 4-tert-butylphenyl triflate, 2-methylphenyl
triflate, 4-cyanophenyl triflate, 4-benzoylphenyl triflate and
2-naphthyl triflate (entries 1, 3-8). In contrast, 4-nitrophen-
yl triflate gave a significantly lower yield (entry 9). The
coupling reaction was very sluggish with electron-rich aryl
triflates such as 4-methoxyphenyl triflate (entry 5). This
Department of Process Research, Merck Research Laboratories,
P.O. Box 2000, Mail Drop R80Y-360,
Rahway, New J ersey 07065
Received J uly 27, 1998
Aryl sulfides are useful chemical intermediates in organic
synthesis.1 A number of synthetic methods have been
developed to prepare them from aryl halides.2 Since the
number of commercially available phenols is greater than
that of aryl halides, a mild and efficient conversion of
phenols into aryl sulfides would have significant synthetic
value. However, the palladium-catalyzed formation of aryl
sulfides from phenols has been elusive.2e,3 Buchwald4a and
Hartwig4b have had recent success in the palladium-
catalyzed amination of aryl triflates based on chelating bis-
(phosphine) ligands, such as BINAP, Tol-BINAP, and DPPF,
and we felt that this type of coupling reaction could be
extended to the conversion of aryl triflates to aryl sulfides.
Herein we report that a combination of Pd(OAc)2 and Tol-
BINAP is an effective catalyst for the coupling of aryl
triflates with sodium alkanethiolates to give alkyl aryl
sulfides.
Our initial studies were conducted with phenyl triflate
and 1-butanethiol (Scheme 1) in toluene.5 The effectiveness
of different palladium catalyst systems for the coupling
reaction of phenyl triflate with this thiol to give n-butyl
phenyl sulfide is detailed in Table 1. As expected, in the
absence of Pd catalyst and ligands no n-butyl phenyl sulfide
was detected by HPLC (entry 1). Other attempts to promote
the coupling that were also unsuccessful included the use
of Pd(dba)2 or Pd(OAc)2 without additional ligands or
employment of a combination of Pd(dba)2 and monodentate
phosphine ligands such as P(o-tol)3 and P(2-furyl)3 (entries
2-5). In contrast, a combination of Pd(dba)2 and BINAP gave
n-butyl phenyl sulfide in 69% yield (entry 8). Suprisingly,
preformed Pd(dba)BINAP6 resulted in a much lower yield
of the coupled product (23%) (entry 9), although its origin
(1) For general reviews on sulfides see: Comprehensive Organic Chem-
istry; J ones, D. N., Ed; Pergamon Press: Oxford, 1979; Vol. 3, pp 33-103.
(2) (a) Kosugi, M.; Shimizu, T.; Migita, T. Chem. Lett. 1978, 13-14. (b)
Migita, T.; Shimizu, T.; Asami, Y.; Shiobara, J .; Kato, Y.; Kosugi, M. Bull.
Chem. Soc. J pn. 1980, 53, 1385-1389. (c) Kosugi, M.; Ogata, T.; Terada,
M.; Sano, H.; Migita, T. Bull. Chem. Soc. J pn. 1985, 58, 3657-3658. (d)
Martinez, A. G.; Barcina, J . O.; Cerezo, A. F.; Subramanian, L. R. Synlett
1994, 561-562. (e) Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett.
1995, 36, 4133-4136. (f) Beller, M.; Riermeier, T. H.; Reisinger, C.
Herrmann, W. A. Tetrahedron Lett. 1997, 38, 2073-2074. (g) Baranano,
D.: Hartwig, J . F. J . Am. Chem. Soc. 1995, 117, 2937-2938. (h) Louie, J .;
Hartwig, J . F. J . Am. Chem. Soc. 1995, 117, 11598-11599. (i) Foa, M.; Santi,
R.; Garavaglia, F. J . Organomet. Chem. 1981, 206, C29-C32.
(7) Pye, P. J .; Rossen, K.; Reamer, R. A.; Tsou, N. N.; Volante, R. P.;
Reider, P. J . J . Am. Chem. Soc. 1997, 119, 6207-6208.
(8) Amatore, C.; J utand, A.; Khalil, F.; M′Barki, M. A.; Mottier, L.
Organometallics 1993, 12, 3168-3178.
(3) Arnould, J . C.; Didelot, M.; Cadilhac, C.; Pasquet, M. J . Tetrahedron
Lett. 1996, 37, 4523-4524.
(4) (a) Wolfe, J . P.; Buchwald, S. L. J . Org. Chem. 1997, 62, 1264-1267
and references therein. (b) Louie, J .; Driver, M. S.; Hamann, B. C.; Hartwig,
J . F. J . Org. Chem. 1997, 62, 1268-1273 and references therein.
(5) In control experiments without Pd catalyst and ligands, phenyl triflate
decomposed faster in THF, DMF, and p-dioxane than in toluene under the
condition of preformed sodium butanethiolate. The major byproduct was
phenol. Thus, toluene was chosen as the solvent in our studies.
(6) Amatore, C.; Broeker, G.; J utand, A.; Khalil, F. J . Am. Chem. Soc.
1997, 119, 5176-5185 and references therein.
(9) The mechanism for this reaction presumably follows
a similar
pathway to the one proposed by Buchwald4a for the palladium-catalyzed
amination of aryl triflates, although no intermediates in the catalytic cycle
have yet been identified or isolated.
(10) Echavarren, A. M.; Stille, J . K.J . Am. Chem. Soc. 1987, 109, 5478-
5486.
(11) J utand, A.; Mosleh, A. Organometallics 1995, 14, 1810-1817 and
references therein.
10.1021/jo9814703 CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/05/1998