The diorgano dichalcogenides addition to benzyne under mild conditions

Article abstract of DOI:10.1016/j.tetlet.2007.09.111

The reaction between diorgano dichalcogenides and o-(trimethylsilyl)phenyl triflate in the presence of CsF at room temperature produced o-bis(organochalcogenide)benzenes in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2007.09.111

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Tetrahedron Letters 48 (2007) 8125–8127
The diorgano dichalcogenides addition to benzyne under
mild conditions
Fabiano T. Toledo, Henrique Marques, Joao V. Comasseto and Cristiano Raminelli*
˜
Instituto de Quı´mica, Universidade de Sa˜o Paulo, Av. Prof. Lineu Prestes, 748, 05508-000, Sa˜o Paulo, SP, Brazil
Received 20 July 2007; revised 12 September 2007; accepted 18 September 2007
Available online 21 September 2007
Abstract—The reaction between diorgano dichalcogenides and o-(trimethylsilyl)phenyl triflate in the presence of CsF at room tem-
perature produced o-bis(organochalcogenide)benzenes in moderate to good yields.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Benzyne is an important reactive intermediate in organic
chemistry, which has found application in mechanistic
studies, total synthesis, and synthesis of functional
materials.1 Accordingly, benzyne has been generated
by using several organic precursors.1 However, we stand
out o-(trimethylsilyl)phenyl triflate as a commercially
available and bench stable reagent to generate benzyne
under very mild reaction conditions.2 In line with this,
silylaryl triflates have emerged as outstanding reagents
for generating arynes which have recently found use in
a number of insertion reactions into r bonds.3
chalcogenide)benzenes,4,5 the published procedures are
not general, and fail or give very low yields, when diphe-
nyl dichalcogenides or eletron-poor diaryl dichalcoge-
nides are employed.4,5
In the attempt to establish a more general procedure
involving mild conditions for the insertion of benzyne
into diorgano dichalcogenides, we decided to explore
the reaction between dichalcogenides and o-(trimethyl-
silyl)phenyl triflate in the presence of a fluoride ion
source.2,3
Although arynes generated under harsh conditions have
reacted with diaryl dichalcogenides to give o-bis(aryl-
Initially, allowing diphenyl diselenide (1a) to react with
1.5 equiv of o-(trimethylsilyl)phenyl triflate (2) and
Table 1. Optimization of the synthesis of o-bis(phenylselenide)benzene (3a) (Eq. 1)a
Se
Se
TMS
Base
+
Se
ð1Þ
Solvent, Temperature
24 h
OTf
2
1a
2
3a
Entry
2 (equiv)
Base (equiv)
Solvent
Temp (ꢁC)
% isolated yield
1
2
3
4
5
6
7
1.5
1.5
2
CsF (3)
CsF (3)
CsF (3)
CsF (4)
MeCN
MeCN
MeCN
MeCN
THF
rt
80
rt
42
47b
53
76
16c
8
2
rt
1.5
1.5
2
n-Bu4NF (1.8)
KF/[18]crown-6 (1.5/1.5)
rt
0–rt
rt
THF
MeCN
0
a Reaction conditions: 0.3 mmol of diphenyl diselenide (1a), the indicated amount of benzyne precursor 2, the indicated amount of base, and 3 mL of
solvent were stirred at the temperature shown for 24 h.
b This reaction was stirred for 12 h.
c This reaction was stirred for 3 h.
*
Corresponding author. Tel.: +55 11 3091 2176; fax: +55 11 3091 1180; e-mail: cristiano@usp.br
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.111

8126
F. T. Toledo et al. / Tetrahedron Letters 48 (2007) 8125–8127
3 equiv of CsF in acetonitrile at room temperature, we
obtained o-bis(phenylselenide)benzene (3a) in a 42%
yield (Table 1, entry 1).
gave o-bis(phenylselenide)benzene (3a) in a 76% yield
(Table 1, entry 4).6 In order to explore the effect of the
fluoride source on the reaction, 1.8 equiv of tetrabutyl-
ammonium fluoride (TBAF) was added to a mixture
of diphenyl diselenide (1a) and 1.5 equiv of o-(trimethyl-
silyl)phenyl triflate (2) in THF at room temperature.
After 3 h, compound 3a was obtained in a 16% isolated
yield (entry 5). In line with this, diphenyl diselenide (1a)
was treated with 1.5 equiv of o-(trimethylsilyl)phenyl tri-
flate (2), 1.5 equiv of KF and 1.5 equiv of [18]crown-6 in
THF initially at 0 ꢁC with slow increase to room temper-
ature, producing the o-bis(phenylselenide)benzene (3a)
in an 8% isolated yield (entry 6). As can be seen in Table
In an attempt to improve the yield, subsequent work fo-
cused on the optimization of these reaction conditions
(Table 1). When the transformation was performed at
80 ꢁC, compound 3a was obtained in a slightly better
yield of 47% (entry 2). By using 2 equiv of the benzyne
precursor 2 at room temperature, we isolated 3a in a
53% yield (entry 3). Treatment of diphenyl diselenide
(1a) with 2 equiv of o-(trimethylsilyl)phenyl triflate (2)
and 4 equiv of CsF in acetonitrile at room temperature
Table 2. Synthesis of o-bis(organochalcogenide)benzenes (3) by the reaction of diorgano dichalcogenides (1) and o-(trimethylsilyl)phenyl triflate (2)
in the presence of CsFa
Entry
Diorgano dichalcogenide
Benzyne precursor
Product
Se
% isolated yield
76
TMS
Se
1
OTf
2
Se
1a
2
3a
Se
Cl
Cl
Cl
F
Se
2
3
4
5
6
7
8
2
2
2
2
2
2
2
35
Se
2
1b
3b
Se
F
F
Se
35
Se
2
1c
3c
Se
S
S
Se
43
S
2
Se
1d
3d
S
S
29b
2
S
1e
3e
Se
CH3
CH3
CH3
Se
74c
2
Se
1f
3f
Se
Se
Traces
Traces
2
Se
1g
3g
Se
Se
Se
2
1h
3h
a Reaction conditions: 0.3 mmol of diorgano dichalcogenide (1), 0.6 mmol of o-(trimethylsilyl)phenyl triflate 2, 1.2 mmol of CsF, and 3 mL of MeCN
were stirred at room temperature for 24 h.
b This reaction was stirred for 48 h.
c This reaction was carried out at 50 ꢁC.

F. T. Toledo et al. / Tetrahedron Letters 48 (2007) 8125–8127
8127
1, entry 7, product 3a was not obtained and the starting
Supplementary data
materials 1a and 2 were recovered when the reaction was
carried out in the absence of CsF. This experiment
clearly shows that the success of the reaction depends
on the presence of a fluoride ion source.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.09.111.
Employing the optimal conditions shown in Table 1,
entry 4, we examined the scope of this process using
some diorgano dichalcogenides (Table 2). The reaction
using the electron-poor diaryl dichalcogenide 1b with
the benzyne precursor 2, gave o-bis(p-chlorophenylsele-
nide)benzene (3b) in a 35% isolated yield (entry 2).
The same yield was obtained for 3c, when the reaction
was carried out using the diaryl diselenide 1c, bearing
fluoro groups (entry 3). When dithienyl diselenide (1d)
was allowed to react with 2, the product was isolated
in a 43% yield (entry 4). Allowing diphenyl disulfide
(1e) to react with 2 equiv of the benzyne precursor 2
and 4 equiv of CsF in acetonitrile at room temperature
for 24 h, we obtained o-bis(phenylsulfide)benzene (3e)
in a 27% isolated yield. Increasing the reaction time to
48 h, product 3e was formed in a similar yield of 29%
(entry 5). For our surprise, when the electron-rich diaryl
dichalcogenide 1f was subjected to the reaction with
o-(trimethylsilyl)phenyl triflate (2), o-bis(p-tolylsele-
nide)benzene (3f) was obtained in a very low yield of
15%. In the attempt to increase this yield, the same
reaction was performed at 50 ꢁC, and compound 3f
was isolated in a good yield of 74% (Table 2, entry 6).
When dibenzyl diselenide (1g) was allowed to react with
the benzyne precursor 2 in the presence of CsF in aceto-
nitrile at room temperature for 24 h, traces of the prod-
uct 3g were obtained along with some by-products. The
starting materials were completely consumed, and no at-
tempts were made to identify the by-products. On the
other hand, when dibutyl diselenide (1h) was submitted
to the same reaction conditions, it was almost com-
pletely recovered after 24 h.
References and notes
1. (a) Hoffmann, R. W. Dehydrobenzene and Cycloalkynes;
Academic Press: New York, 1967; (b) Gilchrist, T. L. In
The Chemistry of Functional Groups; Patai, S., Rappoport,
Z., Eds.; Wiley: Chichester, 1983; Supplement C, Chapter
11; (c) Hart, H. In The Chemistry of Triple-Bonded
Functional Groups; Patai, S., Ed.; Wiley: Chichester, 1994;
Supplement C2, Chapter 18; (d) Kitamura, T.; Yamane,
M.; Inoue, K.; Todaka, M.; Fukatsu, N.; Meng, Z.;
Fujiwara, Y. J. Am. Chem. Soc. 1999, 121, 11674–
11679.
2. Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett.
1983, 1211–1214.
´
´
3. (a) Pena, D.; Perez, D.; Guitian, E. Angew. Chem., Int. Ed.
2006, 45, 3579–3581; (b) Liu, Z.; Larock, R. C. J. Am.
Chem. Soc. 2005, 127, 13112–13113; (c) Tambar, U. K.;
Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 5340–5341; (d)
Yoshida, H.; Watanabe, M.; Morishita, T.; Ohshita, J.;
Kunai, A. Chem. Commun. 2007, 1505–1507; (e) Yoshida,
H.; Mimura, Y.; Ohshida, J.; Kunai, A. Chem. Commun.
2007, 2405–2407.
4. (a) Bonilha, J. B. S.; Petragnani, N.; Toscano, V. G. Chem.
Ber. 1978, 111, 2510–2516; (b) Petragnani, N.; Toscano,
V. G. Chem. Ber. 1970, 103, 1652–1653; (c) Gulliver, D. J.;
Hope, E. G.; Levason, W.; Murray, S. G.; Potter, D. M.;
Marshall, G. L. J. Chem. Soc., Perkin Trans. 2 1984, 429–
434; (d) Lambert, C.; Christiaens, L. Tetrahedron Lett.
1984, 25, 833–834.
5. Nakayama, J.; Tajiri, T.; Hoshino, M. Bull. Chem. Soc.
Jpn. 1986, 59, 2907–2908.
6. Experimental procedure for the synthesis of o-bis(organ-
ochalcogenide)benzenes (3): To a vial (20 mL) were added
the appropriate diorgano dichalcogenide 1a–h (0.3 mmol),
o-(trimethylsilyl)phenyl triflate (2) (178.8 mg, 0.6 mmol),
acetonitrile (3 mL) and CsF (182.4 mg, 1.2 mmol). The vial
was sealed using a cap and the mixture was stirred for 24 h
at room temperature unless otherwise indicated. After-
wards, brine (30 mL) was added to the mixture, which was
extracted with ethyl acetate (3 · 30 mL). The organic phase
was dried over MgSO4. After filtration, the solvent was
evaporated under reduced pressure. The residue was
purified by preparative thin layer chromatography using
silica gel and hexane as eluent, affording the desired
products 3a–f. o-Bis(p-chlorophenylselenide)benzene (3b):
The structures of compounds 3a–f were assigned accord-
ing to its LRMS, IR, 1H, and 13C NMR spectra. All new
compounds (3b–d) provided elemental analyses that
agree with the proposed structures.
In summary, a simple and more general procedure
involving mild conditions for the insertion of benzyne
into diorgano dichalcogenides has been developed, and
o-bis(organochalcogenide)benzenes were prepared in
moderate to good yields.
1
yield 48.0 mg (35%); light yellow solid; mp 97–100 ꢁC; H
NMR (300 MHz, CDCl3) d (ppm) 7.44–7.40 (m, 4H), 7.30–
7.24 (m, 4H), 7.21–7.17 (m, 2H), 7.13–7.09 (m, 2H); 13C
NMR (75 MHz, CDCl3) d (ppm) 135.6, 135.1, 134.2, 133.2,
129.7, 128.7, 128.3; IR (KBr, cmꢀ1) 3070, 3046, 1559, 1469,
1438, 1088, 1009, 817, 745; LRMS (m/z, %): 422 (29), 232
(78), 152 (72), 40 (100); Anal. Calcd for C18H12Cl2Se2: C,
47.30; H, 2.65. Found: C, 47.32; H, 2.81.
Acknowledgments
We gratefully acknowledge FAPESP and CNPq for
financial support.