One-pot synthesis of unsymmetrical diaryl thioethers by palladium-catalyzed coupling of two aryl bromides and a thiol surrogate

Article abstract of DOI:10.1002/chem.200902313

Extraordinarily simple, convenient, and efficient: A general and operationally simple one-pot synthesis of unsymmetrical diaryl sulfides by coupling two different bromoarenes and triisopropylsilanethiol (TIPS-SH) is reported. This protocol overcomes the narrow availability of arene thiols and their instability to oxidation. These reactions catalyzed by palladium complexes generated from the alkylbisphosphine CyPF-tBu occur in good to excellent yields with wide scope and high tolerance of functional groups.

Full text of DOI:10.1002/chem.200902313

COMMUNICATION
DOI: 10.1002/chem.200902313
One-Pot Synthesis of Unsymmetrical Diaryl Thioethers by Palladium-
Catalyzed Coupling of Two Aryl Bromides and a Thiol Surrogate
Manuel A. Fernꢀndez-Rodrꢁguez and John F. Hartwig*[a]
Aromatic thioethers are valuable synthetic intermediates
frequently found in biologically and pharmaceutically active
molecules or in polymeric materials. In particular, diaryl-
and aryl-heteroaryl thioethers are essential components of
numerous drugs with potential application in the treatment
of inflammation, cancer, human immunodeficiency virus
(HIV), asthma, Alzheimerꢀs and Parkinsonꢀs diseases.[1–6]
Furthermore, diaryl thioethers are precursors to the corre-
sponding sulfoxides and sulfones that also exhibit important
biological activities and are contained in antifungal and anti-
cancer agents as well as in potential drug candidates for Alz-
heimer’s disease or HIV.[7–11] Classical methods for the syn-
thesis of such thioethers encompass thermal reaction of
arenes with sulfur,[12,13] base-mediated reactions of activated
chloroarenes with thiophenols,[14] and condensation of orga-
nolithium or Grignard reagents with chlorophenyl sulfide.[15]
However, these reactions often require harsh reaction condi-
tions, occur with low regioselectivity, and form disulfide and
thiantrene side products.[12,13]
ments, but both processes require drastic thermal conditions.
In addition, many aromatic thiols are unstable to oxidation,
and these thiols can decay upon storage. Thus, a process to
generate diaryl thioethers from an H2S equivalent and two
different aryl halides would be a marked improvement over
current methods. Palladium-catalyzed reactions of hydrogen
sulfide surrogates, such as isooctyl-3-mercaptopropio-
nate[18,28] and triisopropylsilanethiol (TIPS-SH) or its corre-
sponding alkali metal thiolates are known,[29–31] but these re-
actions have not been developed into a simple sequence to
form unsymmetrical diaryl thioethers.
The most active and functional-group-tolerant catalyst
system for the coupling of haloarenes with thiols is based on
the complex containing the alkylbisphosphine ligand in
Scheme 1 (1, CyPF-tBu).[32–35] Detailed mechanistic studies
To address these limitations, cross-coupling reactions cata-
lyzed by transition metals, including reactions catalyzed by
complexes of palladium,[16–19] nickel,[20] copper,[21–23] iron,[24]
and cobalt,[25] have been developed to form aromatic
carbon–sulfur bonds. Although these metal-catalyzed cou-
pling reactions often occur in high yield under milder condi-
tions than the uncatalyzed methods, few aromatic thiols are
commercially available. Such arenethiols are accessible from
phenols by Newman–Kwart[26] and Schçnberg[27] rearrange-
Scheme 1. Palladium-catalyzed synthesis of p-tolyl phenyl sulfide from
phenyl triisopropylsilyl sulfide and p-bromotoluene.
on these coupling reactions have also been published recent-
ly.[36] Reactions with this catalyst occur with turnover num-
bers and substrate scope that far surpass those of previous
catalysts containing other ligands. Herein, we report reac-
tions of aryl halides with TIPS-SH catalyzed by the palladi-
um complex generated from the alkylbisphosphine 1,[37] and
the use of this process to prepare unsymmetrical diaryl sul-
fides in a one-pot fashion from two different aryl bromides
or in a tandem fashion with one aryl bromide and one aryl
chloride. This synthesis of diaryl thioethers thus occurs with
readily available reagents and avoids the need to independ-
ently prepare and isolate an intermediate arene thiol.
[a] Dr. M. A. Fernꢁndez-Rodrꢂguez, Prof. Dr. J. F. Hartwig
Department of Chemistry
University of Illinois at Urbana-Champaign
600 South Mathews Avenue, Urbana, IL 61801 (USA)
and
Department of Chemistry
Yale University
PO Box 208107 New Haven, CT 06520-8107 (USA)
Fax : (+1)217-244-8024
E-mail: jhartwig@uiuc.edu
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902313.
Chem. Eur. J. 2010, 16, 2355 – 2359
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2355

To prepare diaryl thiothers in a simple fashion, we envi-
sioned a one-pot protocol involving the reaction of aryl hal-
ides with TIPS-SH, followed by coupling of this silylated thi-
oether. We previously reported[34] the synthesis of p-tolyl
phenyl sulfide 2a from reaction of phenyl triisopropylsilyl
sulfide with p-bromotoluene in the presence of CsF and the
palladium catalyst (Scheme 1). These preliminary data sug-
gested that a one-pot method to form diaryl thioethers
should be possible through the silyl thioether.
performed at the lower temperature of 908C in the presence
of 0.1 mol% catalyst (Table 1, entry 4). These reactions oc-
curred with aryl chlorides, as well as aryl bromides, although
longer reaction times (12 h) were required when using just
0.1 mol% catalyst (Table 1, entry 5). Reactions of bromo-
naphthalene also occurred with 0.05 mol% catalyst (Table 1,
entry 12).
After establishing these reaction conditions, we explored
the scope of this process with aryl bromides that often react
in coupling processes in lower yields or require large
amounts of catalyst. TIPS-SH successfully coupled with a
variety of such aryl bromides in good to excellent yields
within short reaction times (2–4 h) with relatively low cata-
lyst loadings. For example, the coupling of bromoarenes that
are electron-rich or sterically demanding or both (Table 1,
entries 7 and 8), as well as the coupling of thienyl bromide
(Table 1, entry 9) and aryl bromides containing a cyano or
hydroxyalkyl group (Table 1, entries 10 and 11) all occurred
with just 0.25 mol% catalyst. These reactions occur with
turnover numbers that are one or two orders of magnitude
higher than those previously reported for related couplings
of TIPS-SH with other catalysts.[29–31]
To enact this proposed synthesis, it was necessary to
develop a general coupling of aryl bromides with TIPS-
37, 38]
SH.[31,
Studies of the coupling reactions of TIPS-SH
with the model aryl bromide 4-bromotoluene under reaction
conditions initially developed for the reaction of phenyl trii-
sopropylsilyl sulfide[34] showed that the protected thiophenol
forms in excellent yield (Table 1, entry 1) in the presence of
just 500 ppm of catalyst and LiHMDS as base in toluene at
1108C. In contrast to related couplings with the same cata-
lyst,[32] reactions of TIPS-SH with NaOtBu as base or in
DME (1,2-dimethoxyethane) as solvent occurred in slightly
lower yields (Table 1, entries 2 and 3). Reactions were also
To test the viability of using the developed methodology
to prepare pure, unprotected aromatic thiols, we investigat-
ed conditions for removal of the silyl group. Pure naphtha-
lene-1-thiol was obtained by deprotection with TBAF in situ
after the coupling process (Table 1, entry 13). However, the
analogous sequence with p-bromotoluene exclusively
formed, under all conditions tested, di-p-tolyl disulfide from
oxidation of the aromatic thiol. Furthermore, partial cleav-
age of the silicon–sulfur bond to give thiol and disulfide im-
purities occurred during the purification of some of the silyl
thioethers. Thus, a decrease in the yield from that deter-
mined by GC/MS and NMR spectroscopy of the crude reac-
tion was observed in some cases after isolation (Table 1, en-
tries 9–11).[39]
Table 1. Coupling of aryl halides with TIPS-SH catalyzed by PdACTHNUTRGNEUNG(OAc)2
and CyPF-tBu ligand.[a]
Entry ArX
Cat. [mol%] Product
Yield [%]
1
0.05
0.05
0.05
0.1
98
88
90
91
2[b]
3[c]
4[d]
5[e]
0.1
96
91
6
0.05
These observations imply that an efficient methodology to
synthesize diaryl sulfides from two aryl halides using TIPS-
SH as hydrogen sulfide surrogate should avoid both the iso-
lation and deprotection of silyl aryl sulfides. Considering
that catalysts containing CyPF-tBu as ligand are able to
couple aromatic silyl sulfides in the presence of CsF
(Scheme 1), we investigated the potential for developing a
one-pot procedure that would circumvent the isolation of
protected thiols and, therefore, prevent competing undesired
deprotection of the silyl thioether and subsequent oxidation
of the resulting thiol.
7
8
0.25
0.25
96
99
9
0.25
0.25
76
87
10
11
12
0.25
0.05
74
97
We selected the combination of bromobenzene, bromoto-
luene, and TIPS-SH as a model system and tested several
reaction conditions with 0.5 mol% PdACTHNUTRGENUG(N OAc)2 and ligand 1.
13
0.05
95[f]
The initial reaction between TIPS-SH and bromobenzene
occurred in less than 1 h in toluene at 908C with LiHMDS
(1.1 equiv) as base. Addition of p-bromotoluene and four
equivalents of CsF to the resulting reaction mixture, fol-
lowed by heating at 1108C for an additional 5 h, formed p-
tolyl phenyl sulfide 2a in 97% yield (Table 2). Reactions
conducted in DME at different temperatures produced 5–
[a] Reactions were conducted with a 1:1 ratio of metal to ligand, 1 mmol
of both ArX and thiol, and 1.1 equiv of LiHMDS at 1108C in toluene
(1.5 mL) requiring 2–4 h to complete. [b] Reaction performed with
NaOtBu as base. [c] Reaction conducted in DME. [d] Reaction per-
formed at 908C. [e] Reaction required 12 h to complete. [f] TBAF
(2 equiv) was added to the crude mixture and stirred 30 min at RT.
2356
www.chemeurj.org
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 2355 – 2359

Unsymmetrical Diaryl Thioethers
COMMUNICATION
Table 2. One-pot synthesis of unsymmetrical diaryl sulfides from two
electron-deficient bromoarene was added in the second step.
However, none of these side products were detected when
the more electron-deficient bromoarene was added in the
first step. Reactions of hindered ortho-substituted aryl bro-
mides also occurred to furnish the corresponding sulfides
2 f–h efficiently. The synthesis of very sterically hindered
sulfides 2g and 2h with 2.0–3.0 mol% is particularly note-
worthy.
aryl bromides and HSTIPS catalyzed by Pd
ACHTUNGRTEN(NUNG OAc)2 and CyPF-tBu ligan-
d.[a]
Products (Yield [%])
We also evaluated the tolerance of the one-pot process to
the presence of functional groups. In this regard, we have
previously reported the extraordinary functional-group tol-
erance of palladium catalyst derived from ligand 1. There-
fore, we focused our studies on bromoarenes that would
challenge the functional group tolerance of this new
method.[32,33] Reactions with aryl bromides that contain an
aldehyde or an enolizable ketone produced the diaryl sul-
fides 2i–j in good yields. A diaryl sulfide that bears both
free alcohol and free amine 2k was also formed in good
yield with just 1.0 mol% catalyst. Additionally, reactions to
generate aryl heteroaryl and di-heteroaryl sulfides 2l–m also
occurred in high yields.
Having obtained excellent results on the one-pot synthesis
of unsymmetrical diaryl sulfides by successive coupling of
two aryl bromides, we decided to explore the feasibility of
performing the coupling in a tandem, rather than one-pot
sequential, fashion.[40] In this tandem process, both aryl hal-
ides would be added together with the catalyst at the begin-
ning of the reaction. We have previously established that
catalysts derived from CyPF-tBu are fully selective for thio-
etherification of aryl bromides over aryl chlorides with both
aliphatic and aromatic thiols.[32] We have also shown in the
present report that the coupling reactions of TIPS-SH with
p-bromotoluene and p-chlorotoluene are different (Table 1,
entries 1 and 5). With these data in mind, we envisioned an
ideal, three-component tandem reaction in which TIPS-SH
selectively couples with an aryl bromide to form a silylated
thiol that subsequently reacts with the aryl chloride in the
presence of the fluoride additive. In this process, the fluo-
ride would activate or fully cleave the silyl aryl thioether to
generate the thiolate for coupling, but would not cleave the
silyl thiol because the thiol is present in the anionic thiolate
form.
Once again we selected the formation of p-tolyl phenyl
sulfide 2a as a prototype transformation, and several reac-
tion conditions were examined. We found that the desired
tandem reaction occurs to afford the unsymmetrical diaryl
sulfide 2a in 80% yield in the presence of 1.0 mol% cata-
lyst, and under conditions similar to those determined to be
appropriate for the sequential one-pot procedure
(Scheme 2). Apparently, the fluoride additive selectively ac-
tivates the silyl aryl sulfide over the silyl thiol for the cou-
pling process, as designed.
[a] All reactions were conducted with a 1:1 ratio of metal to ligand and
1 mmol of each aryl bromide and TIPS-SH. [b] 0.25 mol% catalyst load-
ing. [c] <5% of symmetrical sulfides were detected. [d] 2.0 mol% cata-
lyst loading. [e] 3.0 mol% catalyst loading. [f] 1.0 mol% catalyst loading.
10% of undesired symmetrical diaryl sulfides as side prod-
ucts[33] or required higher catalyst loadings to reach full con-
versions. Reactions conducted with 0.25 mol% for a total
time of 9 h occurred in yields that were comparable to those
from reactions with 0.5 mol% palladium over 4–6 h.
The identity of the base was crucial for obtaining high
yields of the mixed thioether. Both LiHMDS and CsF were
needed in the amounts showed in Table 2. Reactions con-
ducted with a larger excess of LiHMDS, fewer equivalents
of CsF, or the addition of CsF during the first step of the
process all occurred in lower yield. Moreover, reactions con-
ducted with alkali metal carbonates were slow and led to
low yields after the second step, presumably due to signifi-
cant catalyst decomposition during the second coupling. Re-
actions conducted with KF instead of CsF did not lead to ef-
ficient cleavage of the silyl thioether, as determined by GC/
MS, and formed the diaryl thioether in <5% yield.
Reactions of a series of representative aryl bromides were
conducted to evaluate the scope of the one-pot procedure,
and the results are summarized in Table 2. Under the opti-
mized conditions, unsymmetrical diaryl sulfides 2a–e bear-
ing neutral, electron-rich or electron-deficient substituents
were synthesized in nearly quantitative yields in short over-
all reaction times (5–6 h). Undesired symmetrical byprod-
ucts were formed (<5%) in the preparation of 2d when the
In summary, we have shown that palladium complexes de-
rived from the bisphosphine CyPF-tBu ligand can be used to
prepare protected arenethiols by coupling aryl halides with
triisopropylsilanethiol (TIPS-SH) and that this reaction can
be further developed into a one-pot sequential or tandem
Chem. Eur. J. 2010, 16, 2355 – 2359
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2357

J. F. Hartwig and M. A. Fernꢁndez-Rodrꢂguez
rical sulfides, which could not be separated from the unsymmetrical sul-
fide, in this case, by column chromatography.
Acknowledgements
Scheme 2. Tandem reaction between p-bromotoluene, TIPSSH, and
chlorobenzene catalyzed by Pd(OAc)2 and CyPF-tBu.
AHCTUNGTRENNUNG
We thank the NIH-NIGMS (GM-55382) for support of this work. M.F.-
R. thanks the Ministerio de Educaciꢄn y Ciencia (Spain) for a MEC/Ful-
bright fellowship.
synthesis of unsymmetrical diaryl thioethers. The reactions
of aryl bromides with TIPS-SH occur with broad scope and
with turnover numbers 1 or 2 orders of magnitude higher
than those of related couplings of TIPS-SH by previously re-
ported catalysts. In addition, this catalyst allows the synthe-
sis of unsymmetrical diaryl sulfides by coupling two aryl
bromides and TIPS-SH in a one-pot fashion. This protocol
overcomes the limited availability and stability of arene-
thiols. These reactions occur in good to excellent yield with
0.25 to 3.0 mol% catalyst. The process exhibits a substrate
scope that includes hindered aryl bromides, heteroaryl bro-
mides, as well as bromides containing an aldehyde or an
enolizable ketone. Finally, we have demonstrated the viabili-
ty of a tandem process using two different halides in the
same vessel.
Keywords: aryl bromides · aryl sulfides · cross-coupling ·
palladium · thiol surrogate
[1] S. Pasquini, C. Mugnaini, C. Tintori, M. Botta, A. Trejos, R. K.
Arvela, M. Larhed, M. Witvrouw, M. Michiels, F. Christ, Z. Debyser,
F. Corelli, J. Med. Chem. 2008, 51, 5125–5129.
[2] A. Gangjee, Y. Zeng, T. Talreja, J. J. McGuire, R. L. Kisliuk, S. F.
Queener, J. Med. Chem. 2007, 50, 3046–3053.
[3] M.-L. Alcaraz, S. Atkinson, P. Cornwall, A. C. Foster, D. M. Gill,
L. A. Humphries, P. S. Keegan, R. Kemp, E. Merifield, R. A. Nixon,
A. J. Noble, D. OꢀBeirne, Z. M. Patel, J. Perkins, P. Rowan, P.
Sadler, J. T. Singleton, J. Tornos, A. J. Watts, I. A. Woodland, Org.
Process Res. Dev. 2005, 9, 555–569.
[4] J. W. Clader, W. Billard, H. Binch III, L.-Y. Chen, G. Crosby, Jr.,
R. A. Duffy, J. Ford, J. A. Kozlowski, J. E. Lachowicz, S. Li, C. Liu,
S. W. McCombie, S. Vice, G. Zhou, W. J. Greenlee, Bioorg. Med.
Chem. 2004, 12, 319–326.
[5] G. Liu, J. R. Huth, E. T. Olejniczak, R. Mendoza, P. DeVries, S.
Leitza, E. B. Reilly, G. F. Okasinski, S. W. Fesik, T. W. von Geldern,
J. Med. Chem. 2001, 44, 1202–1210.
Experimental Section
[6] S. F. Nielsen, E. O. Nielsen, G. M. Olsen, T. Liljefors, D. Peters, J.
Med. Chem. 2000, 43, 2217–2226.
[7] S. Sciabola, E. Carosati, M. Baroni, R. Mannhol, J. Med. Chem.
2005, 48, 3756–3767.
[8] L. Llauger, H. He, J. Kim, J. Aguirre, N. Rosen, U. Peters, P. Davies,
G. Chiosis, J. Med. Chem. 2005, 48, 2892–2905.
[9] T. Otzen, E. G. Wempe, B. Kunz, R. Bartels, G. Lehwark-Yvetot, W.
Hꢅnsel, K.-J. Schaper, J. K. Seydel, J. Med. Chem. 2004, 47, 240–
253.
[10] Y. Wang, S. Chackalamannil, Z. Hu, J. W. Clader, W. Greenlee, W.
Billard, G. Binch III, G. Crosby, Jr., V. Ruperto, R. A. Duffy, R.
McQuade, J. E. Lachowicz, Bioorg. Med. Chem. Lett. 2000, 10,
2247–2250.
[11] Z.-Y. Sun, E. Botros, A.-D. Su, Y. Kim, E. Wang, N. Z. Baturay, C.-
H. Kwon, J. Med. Chem. 2000, 43, 4160–4168.
[12] G. Dougherty, P. D. Hammond, J. Am. Chem. Soc. 1935, 57, 117–
118.
[13] H. B. Glass, E. E. Reid, J. Am. Chem. Soc. 1929, 51, 3428–3430.
[14] J. R. Campbell, J. Org. Chem. 1964, 29, 1830–1833.
[15] N. Kharasch, S. J. Potempa, H. L. Wehrmeister, Chem. Rev. 1946, 39,
269–332.
General procedure for the coupling of aryl bromides with triisopropylsi-
lanethiol: The appropriate quantity of catalyst system (see the Support-
ing Information) was added to a 4 mL vial containing the aryl bromide
or chloride (1.00 mmol) and LiHMDS (184 mg, 1.10 mmol) in toluene
(1.5 mL). TIPS-SH (214 mL, 1.00 mmol) was then added, and the vial
sealed with a cap containing a PTFE septum. The mixture was heated at
1108C until the aryl halide was consumed, as determined by GC. Solvent
was removed under reduced pressure and the crude mixture was purified
by flash chromatography on silica gel. Protected aryl thiols were isolated
in the yields reported in Table 1.
General procedure for the one-pot synthesis of unsymmetrical diaryl sul-
fides 2 from two aryl bromides and triisopropylsilanethiol: The appropri-
ate amount of PdACHTUNGTRENNUNG(OAc)2 and CyPF-tBu ligand was added to a 4 mL vial
containing an aryl bromide (1.00 mmol) and LiHMDS (184 mg,
1.10 mmol) in toluene (1.5 mL). TIPS-SH (214 mL, 1.00 mmol) was then
added, and the vial sealed with a cap containing a PTFE septum. The
mixture was heated at 908C until the aryl bromide was consumed (1–
2 h), as determined by GC. The second aryl bromide (1.00 mmol) and
CsF (608 mg, 4.00 mmol) were then added, and the mixture heated at
1108C until the aryl bromide was consumed (4–24 h), as determined by
GC. Solvent was removed under reduced pressure and the crude mixture
was purified by flash chromatography on silica gel. The corresponding
diaryl sulfides were isolated in the yields reported in Table 2.
[16] L. Cai, J. Cuevas, Y.-Y. Peng, V. W. Pike, Tetrahedron Lett. 2006, 47,
4449–4452.
[17] C. Mispelaere-Canivet, J.-F. Spindler, S. Perrio, P. Beslin, Tetrahe-
dron 2005, 61, 5253–5259.
Tandem reaction between p-bromotoluene, TIPS-SH and chlorobencene:
Pd
(OAc)2 (2.2 mg) and CyPF-tBu (5.5 mg) were added to a 4 mL vial
[18] T. Itoh, T. Mase, Org. Lett. 2004, 6, 4587–4590.
[19] M. Murata, S. L. Buchwald, Tetrahedron 2004, 60, 7397–7403.
[20] Y. Zhang, K. C. Ngeow, J. Y. Ying, Org. Lett. 2007, 9, 3495–3498.
[21] M. T. Herrero, R. SanMartin, E. Domꢂnguez, Tetrahedron 2009, 65,
1500–1503.
[22] M. Carril, R. SanMartin, E. Domꢂnguez, I. Tellitu, Chem. Eur. J.
2007, 13, 5100–5105.
[23] For a review on cooper-catalyzed coupling, see: S. V. Ley, A. W.
Thomas, Angew. Chem. 2003, 115, 5558–5607; Angew. Chem. Int.
Ed. 2003, 42, 5400–5449.
containing 4-bromotoluene (121 mL, 1.00 mmol), chlorobenzene (102 mL,
1.00 mmol), LiHMDS (184 mg, 1.10 mmol), and CsF (608 mg, 4.00 mmol)
in toluene (1.5 mL). The vial was sealed with a cap containing a PTFE
septum, and the mixture was heated at 1008C until the chlorobenzene
was consumed, as determined by GC. Silica gel (0.5 g) was added, and
the solvents were evaporated under reduced pressure. The crude residue
was purified by column chromatography on silica gel using hexane as
eluent. p-Tolyl phenyl sulfide 2a was obtained as the major product in
80% yield (160 mg). This isolated material contained 8% of the symmet-
2358
www.chemeurj.org
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 2355 – 2359

Unsymmetrical Diaryl Thioethers
COMMUNICATION
[24] A. Correa, M. Carril, C. Bolm, Angew. Chem. 2008, 120, 2922–2925;
Angew. Chem. Int. Ed. 2008, 47, 2880–2883.
[25] Y.-C. Wong, T. T. Jayanth, C.-H. Cheng, Org. Lett. 2006, 8, 5613–
5616.
[26] For a recent review, see: G. C. Lloyd-Jones, J. D. Moseley, J. S.
Renny, Synthesis 2008, 661–689.
[35] J. F. Hartwig, Acc. Chem. Res. 2008, 41, 1534–1544.
[36] E. Alvaro, J. F. Hartwig, J. Am. Chem. Soc. 2009, 131, 7858–7868.
[37] For the introduction of triisopropylsilylthiol as a reagent for the syn-
thesis of thiols, see: a) J. C. J. de Pomar, J. A. Soderquist, Tetrahe-
dron Lett. 1998, 39, 4409; b) E. I. Miranda, M. J. Diaz, I. Rosado,
J. A. Soderquist, Tetrahedron Lett. 1994, 35, 3221.
[27] H. R. Al-Kazimi, D. S. Tarbell, D. Plant, J. Am. Chem. Soc. 1955, 77,
2479–2482.
[28] T. Itoh, T. Mase, J. Org. Chem. 2006, 71, 2203–2206.
[29] M. Kreis, S. Brꢅse, Adv. Synth. Catal. 2005, 347, 313–319.
[30] J. C. Arnould, M. Didelot, C. Cadilhac, M. J. Pasquet, Tetrahedron
Lett. 1996, 37, 4523–4524.
[38] For reactions with other thiol surrogates tested, such as NaSH and
AcSH either no conversion was observed or complex mixtures were
obtained. On the other hand, reactions with thiourea afforded sym-
metrical diarylsulfides as main products as a result of in situ depro-
tection and the subsequent reaction with a second molecule of aryl
bromide.
À
[31] A. M. Rane, E. I. Miranda, J. A. Soderquist, Tetrahedron Lett. 1994,
35, 3225–3226.
[39] The cleavage of the Si S bond during chromatography purification
of aryl triisopropylsilyl sulfides was previously observed: see refer-
[32] M. A. Fernꢁndez-Rodrꢂguez, J. F. Hartwig, J. Org. Chem. 2009, 74,
1663–1672.
ence [22,23].
[40] D. E. Fogg, E. N. dos Santos, Coord. Chem. Rev. 2004, 248, 2365–
[33] M. A. Fernꢁndez-Rodrꢂguez, Q. Shen, J. F. Hartwig, Chem. Eur. J.
2006, 12, 7782–7796.
[34] M. A. Fernꢁndez-Rodrꢂguez, Q. Shen, J. F. Hartwig, J. Am. Chem.
Soc. 2006, 128, 2180–2181.
2379.
Received: August 21, 2009
Revised: November 23, 2009
Published online: January 28, 2010
Chem. Eur. J. 2010, 16, 2355 – 2359
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2359