Microwave-promoted TBAF-catalyzed SNAr reaction of aryl fluorides and ArSTMS: An efficient synthesis of unsymmetrical diaryl thioethers

Article abstract of DOI:10.1055/s-0030-1259959

Microwave irradiation was found to promote tetrabutylammonium fluoride catalyzed nucleophilic aromatic substitution of aryl fluorides and arylthiotrimethylsilanes, affording high yields of unsymmetrical diaryl thioethers efficiently under mild, transition-metal- and base-free conditions. Microwave showed unusual improvement on the reaction in not only the conditions and reaction rate, but also in selectivity and substrate scope. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1259959

LETTER
1143
Microwave-Promoted TBAF-Catalyzed SNAr Reaction of Aryl Fluorides and
ArSTMS: An Efficient Synthesis of Unsymmetrical Diaryl Thioethers
An
Efficient Syn
h
U
ns
u
ymmetrical
D
a
iaryl Thio
n
ethers zhi Liu, Xufeng Zang, Baohua Yu, Xiaochun Yu,* Qing Xu*
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, P. R. of China
Fax +86(577)88373111; E-mail: qing-xu@wzu.edu.cn; E-mail: xiaochunyu@wzu.edu.cn
Received 29 January 2011
cat. Pd/L
Ar-X
+ E-H
(1)
(2)
(3)
Abstract: Microwave irradiation was found to promote tetrabutyl-
Ar-E
Ar-E
Buchwald–Hartwig couplings
ammonium fluoride catalyzed nucleophilic aromatic substitution of
aryl fluorides and arylthiotrimethylsilanes, affording high yields of
unsymmetrical diaryl thioethers efficiently under mild, transition-
metal- and base-free conditions. Microwave showed unusual im-
provement on the reaction in not only the conditions and reaction
rate, but also in selectivity and substrate scope.
[Cu]
Ar-X E-H
+
Ullmann condensation
base
E-H
+
X
E
SNAr reaction
EWG
EWG
Key words: microwave irradiation, tetrabutylammonium fluoride,
aryl halides, arylthiotrimethylsilane, nucleophilic aromatic substi-
tution
X = F, Cl, Br, I, etc.; E = N, O, S, etc.
Scheme 1
On the other hand, trialkylsilyl groups play important
roles as protecting groups and nucleophile activating
functionals.12 The trialkylsilyl-protected nucleophiles
(NuSiR3), one of the most useful reagents in organic syn-
thesis due to their ready availability, stability, reactivity
and high tolerance of various functionalities,12,13 have
long been recognized as effective alternatives to tradition-
al proton nucleophiles (NuH). Since proton abstraction
from NuH usually requires strong bases at elevated tem-
peratures, it is relatively more demanding and may lead to
incompatibility of the conditions with other functional
groups. In comparison, generation of nucleophiles from
NuSiR3 by various Lewis bases is generally easier and
more reactive than that from corresponding NuH. Howev-
er, compared with the broad utilities of carbon-, nitrogen-,
and oxygen-centered trialkylsilyl nucleophiles that have
aroused extensive interests in synthesis, examples of sul-
fur nucleophiles (RSSiR3) are still limited.12,13 So far their
reactions have been mainly focused on transition-metal-
catalyzed coupling with aryl halides,14 additions to carbo-
nyls,15 ring-opening reactions of aziridrines16 and ox-
iranes.17 Besides, in contrast to the corresponding oxygen
nucleophiles (ROSiR3) that have been frequently utilized
in diaryl ether synthesis,11 similar methods for diaryl thio-
ethers using RSSiR3 are still rare and the result was not
good.11a As our ongoing interests in organochalcogenide
synthesis18 and the development of new and efficient
methods for thioether synthesis,10,11 we report herein, by
taking advantage of fluoride anion in desilylation and nu-
cleophile activation reactions,12 the preliminary results of
a microwave (MW)-promoted tetrabutylammonium fluo-
ride (TBAF)-catalyzed SNAr reaction of arylthiotrimeth-
ylsilane (ArSTMS, 1) and aryl fluorides 2 that can give
functionalized unsymmetrical diaryl thioethers 3 in high
yields under mild, transition-metal- and base-free condi-
tions (Scheme 2).
Transition-metal-catalyzed carbon–heteroatom bond for-
mations have attracted tremendous interests in the past
decades1 since numerous compounds containing these
structures are of great significance in the fields of synthe-
sis, catalysis, biology, pharmacy, material science and
natural product synthesis.2 Unsymmetrical thioethers are
also valuable intermediates abounding in natural prod-
ucts, biologically and pharmaceutically active com-
pounds.3 In fact, they are not only important precursors to
corresponding sulfoxides and sulfones that also exhibit
important biological activites,4 but are also effective cata-
lysts in organocatalysis5 and good ligands in metal-cata-
lyzed reactions.6 Moreover, amine-substituted diaryl
thioethers are also pivotal intermediates for biologically
and pharmaceutically active molecule synthesis.7 Due to
their significance in such broad fields, various methods
have been developed for thioether synthesis from organo-
halides and thiols (Scheme 1) that can be majorly classi-
fied as (1) transition-metal-catalyzed Buchwald–Hartwig
coupling,1 (2) classical copper-assisted Ullmann
condensations8 and (3) nucleophilic aromatic substitution
(SNAr) reactions.9 Despite the great advancements
achieved in Ullmann condensation and metal-catalyzed
methods1,8 that include some new developments in the
area such as the decarboxylative C–S cross-coupling of
carboxylic acids and thiols,10 SNAr reactions are still at-
tractive routes9,11 since they are relatively milder in condi-
tions, more environmentally benign, and require no
expensive noble metal catalysts and capricious ligands for
catalyst activation.
SYNLETT 2011, No. 8, pp 1143–1148
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x.
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x.
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Advanced online publication: 18.04.2011
DOI: 10.1055/s-0030-1259959; Art ID: W03511ST
© Georg Thieme Verlag Stuttgart · New York

1144
C. Liu et al.
LETTER
STMS
Table 1 Optimization of Conditions for TBAF-Mediated SNAr
Reaction of PhSTMS and p-Nitrophenyl Fluoridea
R
STMS
1
S
cat. TBAF, MW
MeCN, under air
+
EWG
FG
R
F
1a
S
TBAF, MW
3
EWG
FG
+
air, MeCN, r.t.
F
NO2
3aa
2
NO2
Scheme 2
2a
The reaction of 1a (PhSTMS) and nitroaryl fluorides was
chosen as the model reaction to optimize the conditions
(Table 1). Firstly, solvent effect (CH2Cl2, CHCl3, toluene,
dioxane, THF, DMF, DMSO, MeCN, etc.) was investigat-
ed, showing that polar solvents were preferred, with ace-
tonitrile to be the best. Then, various fluoride salts such as
CsF, KF, NaF and TBAF were used for trialkylsilyl nu-
cleophile activation, showing that TBAF was the best flu-
oride salt for the reaction, giving almost quantitative yield
of the product 3aa at room temperature (entry 1). Besides,
the reaction could be conveniently carried out under air
using directly the commercial substrates and solvents
without further treatment, indicating that this reaction is
not sensitive toward air and water, and thus can greatly
simplify the operation. TBAF loadings could be reduced
so that only 1 mol% was effective enough to ensure the re-
action to completion after overnight stirring (entry 2). In
comparison, this method was found to be more efficient
than similar SNAr reactions of nitroaryl fluorides with thi-
ols,10 as the latter usually require more than stoichiometric
amount of strong bases or fluoride salts, or heating at ele-
vated temperature. In addition, it appeared that the sulfur
nucleophile generated in this way was also more reactive
than the oxygen nucleophiles from similar ROSiR311 for it
required less catalyst and could be conducted under mild-
er conditions at a lower temperature. Furthermore, micro-
wave irradiation, a good way of facilitating various
organic reactions,19 was then adopted and we were de-
lighted to observe that MW was capable of promoting the
reaction effectively. Thus, under the optimized condi-
tions, the reaction could furnish quantitative yield of the
product in only five hours (entry 3).20
Entry TBAF (equiv) Conditions
Time (h)
Yield (%)b
1
2
3
1.2
–
24
24
5
97
96
97
0.01
0.01
–
MWc
a Reaction conditions: 2a (1 mmol), 1a (1.2 mmol, 1.2 equiv), and
TBAF in MeCN (2 mL) were stirred at r.t. (ca. 25 °C) under air.
b Isolated yield based on 2a.
c MW irradiation power was 600 W.
be attributed to the steric hindrance from the crowded sub-
stituents on the benzene ring which may prevent a second
bulky trimethylsilyl-protected phenylthio nucleophile
from approaching closer.13,21
Table 2 MW-Promoted TBAF-Catalyzed SNAr Reaction of ArSTMS
and Aryl Fluoridesa
STMS
R
S
1
TBAF (0.5–1 mol%), MW
air, MeCN, r.t., 5 h
EWG
+
F
R
EWG
3
2
Entry ArF
Product
Yield (%)b
F
NO2 PhS
NO2
1
97
2a
3aa
The optimized conditions were then applied to a variety of
substrates 1 and 2 to extend its scope (Table 2). In case of
nitroaryl fluorides (entries 1–15), most of the substrates
gave the desired nitroaryl thioethers in high yields, which
are important precursors for the useful aminoaryl
thioethers7 that can be easily obtained from the reduction
of the nitro group. Electron-rich and electron-deficient
thiosilanes were similar in reactivity (entries 1–3 and 9–
11). For 2,4-difluoronitrobenzene (2e), the reaction gave
selectively the desired double-sulfenylated product 3ae
efficiently when 2.4 equivalents of 1 were used (entry 7).
Whereas, a structurally similar 1,5-difluoro-2,4-dini-
trobenzene (2f) that should be more reactive than 2e, gave
only monosubstituted product 3af under the same condi-
tions, as was confirmed by spectroscopic analysis (entry
8). The reason for this difference is not clear yet, but may
p-TolS
3ba
NO2
2
3
2a
95
92
p-ClC6H4S
NO2
2a
3ca
O2N
O2N
4
5
93
90
F
SPh
2b
O2N
3ab
O2N
NH2
NH2
SPh
F
2c
3ac
Synlett 2011, No. 8, 1143–1148 © Thieme Stuttgart · New York

LETTER
An Efficient Synthesis of Unsymmetrical Diaryl Thioethers
1145
Table 2 MW-Promoted TBAF-Catalyzed SNAr Reaction of ArSTMS
Table 2 MW-Promoted TBAF-Catalyzed SNAr Reaction of ArSTMS
and Aryl Fluoridesa (continued)
and Aryl Fluoridesa (continued)
STMS
STMS
R
R
S
S
1
2
TBAF (0.5–1 mol%), MW
air, MeCN, r.t., 5 h
1
TBAF (0.5–1 mol%), MW
air, MeCN, r.t., 5 h
EWG
EWG
+
+
F
F
R
R
EWG
EWG
3
3
2
Entry ArF
Product
Yield (%)b
Entry ArF
Product
Yield (%)b
F
F
O2N
O2N
O
O
6
96
94
95
98
17e
94
47
F
SPh
HO
F
HO
3ad
O2N
SPh
Ph
Ph
2d
O2N
2m
3am
PhS
O
F
F
7c
O
F
F
PhS
3ae
O2N
SPh
NO2
18f
2e
O2N
Ph
F
Ph
NO2
8c
3an
O
2n
O
F
SPh
F
F
19f
70
52
F
SPh
2f
3af
Ph
Ph
F
SPh
NO2
2o
3ao
PhS
O
9
F
NO2
O
20f
2g
3ag
3bg
Sp-Tol
NO2
Ph
Ph
3ap
O
10
2g
93
2p
O
21f
75
92
F
SPh
SC6H4p-Cl
NO2
2q
3aq
11
12
13
2g
96
95
98
22f
F
CHO PhS
CHO
3cg
O2N
CF3
3ar
O2N
CF3
2r
a Unless otherwise noted, 2 (1 mmol), 1 (1.2 mmol, 1.2 equiv), and
TBAF (1 mol%) in MeCN (2 mL) were stirred under air under micro-
wave irradiation at r.t. (ca. 25 °C) for 5 h. 1a: R = H; 1b: R = Me; 1c:
R = Cl.
PhS
F
2h
3ah
O2N
CHO O2N
CHO
b Isolated yield based on 2.
c Amount of 1 added: 2.4 equiv.
F
PhS
d Amount of TBAF used was 1.2 equiv.
2i
3ai
e Reaction temperature was 50 °C.
O2N
O2N
f Reaction conditions: 20 mol% TBAF at 70 °C.
O
O
14
97
95
F
PhS
As shown in the table, the present method tolerates several
reactive functionalities such as amino (entry 5), hydroxyl
(entry 6), and carbonyl groups (entries 13, 15 and 22). Un-
der other conditions, these functionalities may replace the
fluoride moiety22 or react with the sulfur nucleophile.14
Also worth noting was the reaction of 5-fluoro-2-ni-
trobenzaldehyde (2k), that in contrast to those of the sim-
ilar substrates 2i,j (entries 13 and 14), gave fluorine-
retained but nitro-replaced product 3ak (entry 15). It was
possibly because, as another good leaving group,23 the ni-
tro moiety was more reactive than the fluoro group due to
the presence of the electron-withdrawing formyl group at
2j
3aj
NO2
SPh
15d
F
CHO
F
CHO
2k
F3C
3ak
F3C
O
O
16
98
F
PhS
Ph
Ph
2l
3al
Synlett 2011, No. 8, 1143–1148 © Thieme Stuttgart · New York

1146
C. Liu et al.
LETTER
Table 3 MW-Promoted TBAF-Mediated SNAr Reaction of PhSTMS
its ortho position but meta to the fluoro. Since the fluoride
anion could be regenerated for catalysis, stoichiometric
amount of TBAF was required for a complete conversion
of 2k.
and Aryl Halidesa
STMS
In addition to nitroaryl fluorides, the reactions of other
aryl fluorides can also be catalyzed by TBAF under simi-
lar MW irradiation conditions (entries 16–22). As shown
in the table, the reaction of 2l was as efficient as the ni-
troaryl fluorides under the standard conditions, giving
high product yield (entry 16). In contrast, other aryl fluo-
rides were less reactive. For example, with 1 mol% of
TBAF, the reaction of 2m had to be stirred at 50 °C (entry
17). While with reactions of 2n–r, 20 mol% of TBAF and
heating at a higher temperature (70 °C) were required (en-
tries 18–22). For acyl-substituted difluorobenzenes 2m,n
(entries 17 and 18), unlike the nitro-substituted 2e, the re-
spective reactions gave selectively monosubstituted prod-
ucts 3am,an even when 2.4 equivalents of 1a were added.
In addition, MW irradiation was found especially useful
for these substrates, because, under usual conditions with-
out MW irradiation, stoichiometric amount of TBAF was
required due to unsuccessful catalysis by lone TBAF. Al-
though p-fluorobenzaldehyde (2r) reacted efficiently to
give high product yield under MW conditions under air
(entry 22), the reaction under normal conditions (heating
under air without MW) did not give the desired product.
Without MW, it was necessary to run the reaction under
nitrogen to obtain the target thioether 3ar. These results
revealed the advantage of the MW protocol and its inter-
esting improvement on reaction efficiency, selectivity and
substrate scope.
1a
S
TBAF (1.2 equiv), MW
air, MeCN, r.t., 5 h
+
EWG
X
3
EWG
4
X = Cl, Br, I
Entry
1
ArX
Product
Yield (%)b
95
O2N
4a
I
3aa
3aa
3aa
O2N
4b
Br
Cl
2
3
93
96
O2N
4c
Cl
SPh
NO2
4
5
96
91
NO2
4d
Cl
3ag
PhS
Cl
CHO
Cl
CHO
4e
3as
Similar to above nitroaryl fluorides, it was also observed
that other aryl halides 4 (X = Cl, Br, I) could also react ef-
a Reaction conditions: 4 (1 mmol), 1 (1.2 mmol, 1.2 equiv), and TBAF
(1.2 mmol, 1.2 equiv) in MeCN (2 mL) were stirred under microwave
ficiently with PhSTMS to give the corresponding diaryl irradiation at r.t. under air.
b Isolated yield based on 4.
thioethers in high yields (Table 3). However, stoichiomet-
ric amount of TBAF was required in these cases. MW ir-
radiation was also found to greatly enhance the reaction
In summary, we have developed a useful and efficient
rates as normal reactions usually required overnight stir-
ring at room temperature. Herein, MW’s promotion effect
on the reaction could also be exemplified by the reaction
of 3,4-dichlorobenzaldehyde (4e) bearing a reactive
formyl group (entry 5). Thus, low yield of the desired
product (20%) could be greatly enhanced by MW irradia-
tion to 91%.
method for the preparation of unsymmetrical diaryl thio-
ethers via a MW-promoted TBAF-catalyzed SNAr reac-
tion of aryl fluorides and ArSTMS. This transition-metal-
and base-free method is simple and convenient in opera-
tion, mild in conditions, and tolerant to several reactive
functional groups. Microwave irradiation also showed in-
teresting improvement on the reaction in reaction efficien-
Based on literature knowledge13,21 and our findings, the cy, selectivity and substrate scope. Due to the increasingly
above reactions most probably proceeded via a typical effective synthesis of the fluoroorganic compounds,21 this
SNAr mechanism. Thus, the fluoride anion derived from new method may be of broad utility and interest,25 as well
TBAF may first attack ArSTMS to generate an active as useful for particular applications in biologically and
arylthio nucleophile, which then adds to the aryl fluorides pharmaceutically active compound synthesis. Further ex-
to give a dearomatized anionic intermediate stabilized by tension and applications of this method are under way in
ortho- or para-EWGs. The fluoride anion – that can fur- our laboratory.
ther act as the catalyst – leaves and aromatization of the
intermediate anion finally gives the product diaryl thio-
ether. This mechanism is consistent with the reaction it-
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
self by using TBAF and aryl fluorides as the advantageous
catalyst and substrate.24
Synlett 2011, No. 8, 1143–1148 © Thieme Stuttgart · New York

LETTER
An Efficient Synthesis of Unsymmetrical Diaryl Thioethers
1147
N.; Toumi, M. Chem. Rev. 2008, 108, 3054. (g) Sawyer,
J. S. Tetrahedron 2000, 56, 5045. (h) Frlan, R.; Kikelj, D.
Synthesis 2006, 2271.
Acknowledgment
We are grateful to the National Natural Science Foundation of Chi-
na (Project No. 20902070), the Natural Science Foundation (No.
Y4100579) and the Qianjiang Talents Program (No. QJD0902004)
of Zhejiang Province for financial support.
(9) (a) Bunnett, J. F.; Zahler, R. E. Chem. Rev. 1951, 49, 273.
(b) Sawyer, J. S. Tetrahedron 2000, 56, 5045. (c) Sawyer,
J. S.; Schmittling, E. A.; Palkowitz, J. A.; Smith, W. J. III
J. Org. Chem. 1998, 63, 6338. (d) Duan, Z.; Ranjit, S.; Liu,
X. Org. Lett. 2010, 12, 2430. (e) Cevera, M.; Marquet, J.;
Martin, X. Tetrahedron 1996, 52, 2557. (f) Delfín, D. A.;
Morgan, R. E.; Zhu, X.; Werbovetz, K. A. Bioorg. Med.
Chem. 2009, 17, 820.
References and Notes
(1) (a) Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534.
(b) Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed.
2008, 47, 6338. (c) Kondo, T.; Mitsudo, T.-A. Chem. Rev.
2000, 100, 3205. (d) Evano, G.; Blanchard, N.; Toumi, M.
Chem. Rev. 2008, 108, 3054. (e) Prim, D.; Campagne, J.;
Joseph, D.; Andrioletti, B. Tetrahedron 2002, 58, 2041.
(f) Van de Jeught, S.; Stevens, C. V. Chem. Rev. 2009, 109,
2672. (g) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem.
Rev. 2004, 248, 2337. (h) Xu, Q.; Han, L.-B. J. Organomet.
Chem. 2011, 696, 130.
(2) (a) Negwar, M. In Organic-Chemical Drugs and Their
Synonyms (An International Survey), 7th ed.; Akademie:
Berlin, 1994. (b) Evano, G.; Blanchard, N.; Toumi, M.
Chem. Rev. 2008, 108, 3054. (c) Corbet, J.-P.; Mignani, G.
Chem. Rev. 2006, 106, 2651. (d) Blaser, H.-U.; Indolese,
A.; Naud, F.; Nettekoven, U.; Schnyder, A. Adv. Synth.
Catal. 2004, 346, 1583.
(3) (a) Liu, L.; Stelmach, J. E.; Natarajan, S. R.; Chen, M.-H.;
Singh, S. B.; Schwartz, C. D.; Fitzgerald, C. E.; O’Keefe, S.
J.; Zaller, D. M.; Schmatz, D. M.; Doherty, J. B. Bioorg.
Med. Chem. Lett. 2003, 13, 3979. (b) Kaldor, S. W.; Kalish,
V. J.; Davies, J. F. I. I.; Shetty, B. V.; Fritz, J. E.; Appelt, K.;
Burgess, J. A.; Campanale, K. M.; Chirgadze, N. Y.;
Clawson, D. K.; Dressman, B. A.; Hatch, S. D.; Khalil, D.
A.; Kosa, M. B.; Lubbehusen, P. P.; Muesing, M. A.; Patick,
A. K.; Reich, S. H.; Su, K. S.; Tatlock, J. H. J. Med. Chem.
1997, 40, 3979. (c) Liu, G.; Huth, J. R.; Olejniczak, E. T.;
Mendoza, R.; DeVries, P.; Leitza, S.; Reilly, E. B.;
Okasinski, G. F.; Fesik, S. W.; von Geldern, T. W. J. Med.
Chem. 2001, 44, 1202.
(4) (a) Sciabola, S.; Carosati, E.; Baroni, M.; Mannhol, R.
J. Med. Chem. 2005, 48, 3756. (b) Llauger, L.; He, H.; Kim,
J.; Aguirre, J.; Rosen, N.; Peters, U.; Davies, P.; Chiosis, G.
J. Med. Chem. 2005, 48, 2892. (c) Otzen, T.; Wempe, E. G.;
Kunz, B.; Bartels, R.; Lehwark-Yvetot, G.; Hänsel, W.;
Schaper, K.-J.; Seydel, J. K. J. Med. Chem. 2004, 47, 240.
(d) Sun, Z.-Y.; Botros, E.; Su, A.-D.; Kim, Y.; Wang, E.;
Baturay, N. Z.; Kwon, C.-H. J. Med. Chem. 2000, 43, 4160.
(5) McGarrigle, E. M.; Myers, E. L.; Illa, O.; Shaw, M. A.;
Riches, S. L.; Aggarwal, V. K. Chem. Rev. 2007, 107, 5481.
(6) (a) Mellah, M.; Voituriez, A.; Schulz, E. Chem. Rev. 2007,
107, 5133. (b) Murray, S. G.; Hartley, F. R. Chem. Rev.
1981, 81, 365.
(10) (a) Duan, Z.; Ranjit, S.; Zhang, P.; Liu, X. Chem. Eur. J.
2009, 15, 3666. (b) Ranjit, S.; Duan, Z.; Zhang, P.; Liu, X.
Org. Lett. 2010, 12, 4134.
(11) (a) Lee, J.; Fuchter, M. J.; Williamson, R. M.; Leeke, G. A.;
Bush, E. J.; McConvey, I. F.; Saubern, S.; Ryanc, J. H.;
Holmes, A. B. Chem. Commun. 2008, 4780. (b) Saunders,
D. G. Synthesis 1988, 377. (c) Urgaonkar, S.; Verkade, J. G.
Org. Lett. 2005, 7, 3319. (d) Oriyama, T.; Noda, K.; Yatabe,
K. Synlett 1997, 701. (e) Ueno, M.; Hori, C.; Suzawa, K.;
Ebisawa, M.; Kondo, Y. Eur. J. Org. Chem. 2005, 1965.
(f) Samarakoon, T. B.; Hur, M. Y.; Kurtz, R. D.; Hanson,
P. R. Org. Lett. 2010, 12, 2182.
(12) (a) Brook, M. A. Silicon in Organic, Organometallic, and
Polymer Chemistry; John Wiley & Sons: New York, 2000.
(b) Colvin, E. Silicon in Organic Synthesis; Butterworth:
London, 1981. (c) Weber, W. P. Silicon Reagents for
Organic Synthesis; Springer-Verlag: Berlin, 1983.
(d) Green, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; Wiley: New York, 1999.
(13) (a) Gawronski, J.; Wascinska, N.; Gajewy, J. Chem. Rev.
2008, 108, 5227; and references cited therein. (b) Furin, G.
G.; Vyazankina, O. A.; Gostevsky, B. A.; Vyazankin, N. S.
Tetrahedron 1988, 44, 2675; and references cited therein.
(14) Fernandez-Rodriguez, M. A.; Hartwig, J. F. Chem. Eur. J.
2010, 16, 2355.
(15) Evans, D. A.; Truesdale, L. K.; Grimm, K. G.; Nesbitt, S. L.
J. Am. Chem. Soc. 1977, 99, 5009.
(16) Sala, G. D.; Lattanzi, A. Org. Lett. 2009, 11, 3330.
(17) (a) Capperucci, A.; Tiberi, C.; Pollicino, S.; Innocenti, A. D.
Tetrahedron Lett. 2009, 50, 2808. (b) Degl’Innocenti, A.;
Capperucci, A.; Cerreti, A.; Pollicino, S.; Scapecchi, S.;
Malesci, I.; Castagnoli, G. Synlett 2005, 3063. (c) Tanabe,
Y.; Mori, K.; Yoshida, Y. J. Chem. Soc., Perkin Trans. 1
1997, 671.
(18) (a) Xu, Q.; Huang, X.; Yuan, J. J. Org. Chem. 2005, 70,
6948. (b) Huang, X.; Liang, C. G.; Xu, Q.; He, Q. W. J. Org.
Chem. 2001, 66, 74.
(19) (a) Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563.
(b) Yu, X.; Huang, X. Synlett 2002, 1895. (c) Xu, Q.; Han,
L.-B. Org. Lett. 2006, 8, 2099. (d) Ren, A.; Yang, X.; Hong,
J.; Yu, X. Synlett 2008, 2376.
(20) (a) Typical Procedure for Microwave-Promoted TBAF-
Catalyzed SNAr Reaction of ArSTMS and Aryl
Fluorides: The mixture of phenylthiotrimethylsilane (1a;
0.218 g, 1.2 mmol, 1.2 equiv), p-nitrophenyl fluoride (2a;
0.141 g, 1.0 mmol), and TBAF (2.61 mg, 1 mol%) in MeCN
(2 mL) was placed in a microwave oven flask under air and
then stirred at r.t. (ca. 25 °C) under microwave irradiation
(600 w) for 5 h and the reaction was monitored by TLC and/
or GC–MS. The solvent was then evaporated under reduced
pressure and the residue was purified by flash column
chromatography on silica gel to give 97% yield of 3aa. An
XH-100A microwave synthesis/extraction instrument, made
by Beijing Xiang Hu Science and Technology Development
Co. Ltd., was employed in above microwave irradiation
reactions.
(7) (a) Marcincal-Letebvre, A.; Gesquiere, C.; Lemer, C.;
Dupuis, B. J. Med. Chem. 1981, 24, 889. (b) Liu, G.; Link,
J. T.; Pei, Z.; Reilly, E. B.; Leitza, S.; Nguyen, B.; Marsh,
K. C.; Okasinski, G. F.; von Geldem, T. W.; Ormes, M.;
Fowler, K.; Gallatin, M. J. Med. Chem. 2000, 43, 4025.
(c) Gangjee, A.; Zeng, Y.; Talreja, T.; McGuire, J. J.;
Kisliuk, R. L.; Queener, S. F. J. Med. Chem. 2007, 50, 3046.
(d) Jarkas, N.; McConathy, J.; Voll, R. J.; Goodman, M. M.
J. Med. Chem. 2005, 48, 4254.
(8) (a) Ullmann, F. Chem. Ber. 1904, 37, 853. (b) Moroz, A.
A.; Shvartsberg, M. S. Russ. Chem. Rev. 1974, 43, 679.
(c) Lindley, J. Tetrahedron 1984, 40, 1433. (d) Thomas,
A. W.; Ley, S. V. Angew. Chem. Int. Ed. 2003, 42, 5400.
(e) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, C.; Lemaire,
M. Chem. Rev. 2002, 102, 1359. (f) Evano, G.; Blanchard,
Synlett 2011, No. 8, 1143–1148 © Thieme Stuttgart · New York

1148
C. Liu et al.
LETTER
(4-Nitrophenyl)phenylthioether (3aa): 1H NMR (300
MHz, CDCl3): d = 8.05 (d, J = 7.0 Hz, 2 H), 7.53–7.56 (m, 2
H), 7.45–7.48 (m, 3 H), 7.17 (d, J = 7.0 Hz, 2 H). 13C NMR
(75 MHz, CDCl3): d = 148.5, 145.4, 134.7, 130.4, 130.0,
129.7, 126.7, 124.0. (b) This compound is known, see: Lee,
J. Y.; Lee, P. H. J. Org. Chem. 2008, 73, 7413.
(23) Beck, J. R. Tetrahedron 1978, 34, 2057.
(24) It was observed other TBAX salts (X = Cl, Br, I) did not
show any catalytic activity at all in the present reactions.
(25) After submission of this work, we noticed that Thiel and co-
workers reported a similar fluoride ion catalyzed amination
of substituted fluoroarenes using trimethylsilylimidazole as
the nitrogen source: Dehe, D.; Munstein, I.; Reis, A.; Thiel,
W. R. J. Org. Chem. 2011, 76, 1151.
(21) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119; and
references cited therein.
(22) (a) Kim, Y. M.; Yu, S. J. Am. Chem. Soc. 2003, 125, 1696.
(b) Wendt, M. D.; Kunzer, A. R. Tetrahedron Lett. 2010, 51,
3041. (c) Li, F.; Wang, Q.; Ding, Z.; Tao, F. Org. Lett. 2003,
5, 2169.
Synlett 2011, No. 8, 1143–1148 © Thieme Stuttgart · New York

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