Glycerol as a promoting medium for cross-coupling reactions of diaryl diselenides with vinyl bromides

Article abstract of DOI:10.1016/j.tetlet.2010.10.107

We described herein the use of glycerol as a novel solvent in the cross-coupling reaction of diaryl diselenides with vinyl bromides catalyzed by CuI. This cross-coupling reaction was performed with diaryl diselenides and (Z)- or (E)-vinyl bromides bearing electron-withdrawing and electron-donating groups, affording the corresponding vinyl selenides in good to excellent yields. The mixture glycerol/catalyst can be directly reused for further cross-coupling reactions.

Full text of DOI:10.1016/j.tetlet.2010.10.107

Tetrahedron Letters 51 (2010) 6772–6775
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Glycerol as a promoting medium for cross-coupling reactions of diaryl
diselenides with vinyl bromides
⇑
Loren C. Gonçalves, Gabriela F. Fiss, Gelson Perin, Diego Alves, Raquel G. Jacob, Eder J. Lenardão
Instituto de Química e Geociências, LASOL, Universidade Federal de Pelotas—UFPel, PO Box 354, 96010-900 Pelotas, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
We described herein the use of glycerol as a novel solvent in the cross-coupling reaction of diaryl disel-
enides with vinyl bromides catalyzed by CuI. This cross-coupling reaction was performed with diaryl
diselenides and (Z)- or (E)-vinyl bromides bearing electron-withdrawing and electron-donating groups,
affording the corresponding vinyl selenides in good to excellent yields. The mixture glycerol/catalyst
can be directly reused for further cross-coupling reactions.
Received 29 September 2010
Revised 20 October 2010
Accepted 21 October 2010
Available online 28 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Vinyl selenides
Glycerol
Cross-coupling
The versatility and utility of organochalcogen compounds in
organic synthesis are well documented through the publication
of a number of reviews1 and books.2 Organochalcogen compounds
are attractive synthetic targets because of their selective reac-
tions,1 their use in asymmetric catalysis,3 natural products synthe-
sis4, and also due to their interesting biological activities.5 Due to
their usefulness in organic reactions, vinyl selenides and tellurides
are certainly the most applied compounds in organochalcogen
chemistry. A large number of synthetic methods have been re-
ported to prepare these compounds and they follow two main cat-
egories: (a) use of the organochalcogen as an electrophile and (b)
use of nucleophilic organochalcogen species.1,2 Alternatively, in re-
cent years, copper-catalyzed protocols have become a versatile tool
for the synthesis of vinyl selenides or tellurides.6 Unfortunately,
the majority of synthetic approaches to obtain vinyl chalcogenides
have some disadvantages, such as, harsh reaction conditions,
expensive reagents, and the use of toxic organic solvents.
In this context, the choice of the solvent is a crucial step in a
chemical reaction. The development of green solvents from renew-
able resources has gained much interest recently because of the
extensive uses of solvents in almost all of the chemical industries
and the predicted disappearance of fossil oil.7 The wanted charac-
teristics for a green solvent include no flammability, high availabil-
ity, obtainability from renewable sources, and biodegradability.8
With the increase in biodiesel production world-wide, the market
saturation of glycerol, a co-product of biodiesel production, is
inevitable.9 The use of glycerol as a sustainable solvent for green
chemistry was recently related by Gu and Jèrôme.10 These include
Pd-catalyzed Heck and Suzuki cross-couplings, base- and acid- pro-
moted condensations, catalytic hydrogenation, and asymmetrical
reduction.10
The peculiar physical and chemical properties of glycerol, such
as polarity, low toxicity, biodegradability, high boiling point, and
ready availability from renewable feedstocks,11 prompted us to
extend its use as a green solvent in organic synthesis. In this sense
and due to our interest on green protocols correlated to the organ-
ochalcogen chemistry,12 we describe herein the use of glycerol as a
green solvent in the copper-catalyzed coupling reaction of diaryl
diselenides with vinyl bromides (Scheme 1).
To identify the optimum reaction conditions, we first investi-
gated the reaction of (E)-b-bromostyrene 1a (0.6 mmol) with diph-
enyldiselenide 2a (0.3 mmol) in glycerol under nitrogen
atmosphere at 110 °C using different copper salts. From the variety
of copper salts examined [CuI, CuCl, CuCN, CuO, CuCl2 and Cu
(OAc)2], CuI gave the best result and using 5 mol % of this catalyst,
the desired product 3a was obtained in 43% yield. Fortunately, the
addition of zinc dust (0.6 mmol) as an additive to the reaction mix-
ture could afford the corresponding product 3a in 95% yield after
4 h. In other experiments, the catalyst loading was varied from 1
to 10 mol % and 5 mol % of CuI gave better results. When, in the
Br
SeAr
CuI (5%), Zn
glycerol
R
R
R
R
or
ArSeSeAr
or
+
110 oC, N2
Br
SeAr
⇑
Corresponding author. Tel. /fax: +55 5332757533.
E-mail address: lenardao@ufpel.edu.br (E.J. Lenardão).
Scheme 1. Synthesis of vinyl selenides using glycerol.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.107

L. C. Gonçalves et al. / Tetrahedron Letters 51 (2010) 6772–6775
6773
separate control experiment, the catalyst was fully absent in the
reaction mixture, zinc alone could not promote this reaction and
no product 3a was detected. Thus, it was evident that in this reac-
tion, the use of both the copper catalyst (CuI) and zinc gave the
best result.
In an optimized reaction, (E)-b-bromostyrene 1a (0.6 mmol),
diphenyl diselenide 2a, CuI (5 mol %), and zinc dust (0.6 mmol)
were dissolved in glycerol (1.5 mL) and reacted under nitrogen
at 110 °C during 4 h, yielding 3a in 95% yield (Table 1, entry
1).13
In order to demonstrate the efficiency of this protocol, we ex-
plored the generality of our methodology reacting other vinyl bro-
mides 1b–i with diphenyl diselenide 2a (Table 1). A closer
inspection of the results showed in Table 1 revealed that the reac-
tion worked well with a sort of substituted vinyl bromides, afford-
ing excellent yields of the desired products. In a general way, the
(E)-vinyl bromides 1a–f afforded the respective (E)-vinyl selenides
3a–f with good selectivity, maintaining the (E):(Z) ratio of the
starting halides (Table 1, entries 1–6). In contrast, the selectivity
for the (Z)-vinyl selenides 3g–i, slightly decreased when compared
with the starting (Z)-vinyl bromides 1g–i (Table 1, entries 7–9). In
an attempt to broaden the scope of our methodology, the possibil-
ity of performing the reaction with other diselenides was also
investigated (Table 2). (E)-b-Bromostyrene 1a (E:Z ratio = 93:7)
was coupled efficiently with a variety of aryl diselenides (2b–g).
For all the examples tested, the respective (E)-vinyl selenides 3j–
o were selectively obtained in very good yields using the optimized
conditions (Table 2, entries 1–6). (E)-b-(Naphthyl)seleno styrene
3o was obtained exclusively in 86% yield after stirring a mixture
of 1a and di(2-naphthyl) diselenide 2g at 110 °C for 5 h (Table 2,
entry 6).
Studies regarding the preparation and reactivity of zinc seleno-
late species generated ‘on water’,14 in ionic liquid,15 and in the
presence of other solvents16 were recently described. Due to the
polarity of glycerol (three-OH groups), we believe that a nucleo-
philic species like PhSeZnSePh could be involved, similar to that
described by Santi et al. for the reaction in the presence of water.14a
Our glycerol-based method was also successfully applied in the
Table 1
Coupling products using vinyl bromides 1a–i and diphenyl diselenide 2a
SePh
Br
CuI (5%), Zn
R
R
+
PhSeSePh
glycerol
110 oC, N2
1a-i
2a
3a-i
Entry
1
Vinyl bromide ratio (E:Z)
Time (h)
4
Product
Yield (%)a,b
Ratio (E:Z)
Br
SePh
95
90:10
1a (93:7)
3a
Br
SePh
2
3
4
5
4
4
4
6
90
93
85
90
100:0
92:8
MeO
MeO
1b (100:0)
3b
Br
SePh
1c (87:13)
3c
Br
SePh
90:10
91:9
Cl
Cl
1d (97:3)
3d
Br
SePh
OMe
OMe
1e (99:1)
3e
MeO
MeO
Br
SePh
6
24
75
99:1
OMe
OMe
1f (99:1)
3f
Br
SePh
7
8
4
4
86
75
8:92
1g (2:98)
3g
Br
SePh
15:85
Cl
Cl
1h (4:96)
3h
OMe
OMe
9
3
88
19:81
Br
SePh
1i (2:98)
3i
a
Reactions performed in the presence of vinyl bromide 1a–i (0.6 mmol), diphenyl diselenide (0.3 mmol), Zn dust (0.6 mmol), and 5 mol % of CuI in glycerol (1.5 mL).
Yields are given for isolated products.
b

6774
L. C. Gonçalves et al. / Tetrahedron Letters 51 (2010) 6772–6775
Table 2
Coupling products using (E)-b-bromostyrene 1a and diaryl dichalcogenides 2b–h
CuI (5%), Zn
glycerol
110 C, N2
Br
YAr
+
ArYYAr
Ph
Ph
o
1a
2b-h
3j-p
Entry
1
Diaryl dichalcogenide
Time (h)
24
Product
Yield (%)a,b
Ratio (E:Z)
Se
Ph
MeO
Se
2
68
90:10
OMe
2b
3j
Se
Ph
Ph
Se
2
2
3
4
5
90
86
90:10
88:12
2c
3k
Se
Cl
Se
2
Cl
2d
3l
Se
Ph
Ph
Se
4
5
6
96
85
92:8
93:7
2
2e
3m
Se
F3C
CF3
Se
10
2
3n
Se
2f
Ph
Ph
Se
6
7
5
86
85
100:0
100:0
2
3o
Te
2g
Te
2
20
2h
3p
a
Reactions performed in the presence of (E)-b-bromostyrene 1a (0.6 mmol; E:Z ratio = 93:7), diaryl dichalcogenide (0.3 mmol), Zn dust (0.6 mmol), and 5 mol % of CuI in
glycerol (1.5 mL).
b
Yields are given for isolated products.
synthesis of (E)-styryl telluride 3p, which was obtained exclusively
in 85% yield after stirring a mixture of 1a and diphenyl ditelluride
2h for 20 h (Table 2, entry 7).
A reuse study of the catalyst/glycerol mixture was carried out
for the reaction showed in Figure 1. After the consumption of start-
ing materials, the reaction mixture was diluted with hexanes and
the product was isolated. After complete removal of residual hex-
anes, the remaining CuI/Zn/glycerol mixture was directly reused
for further reactions. It was observed that a good level of efficiency
was maintained even after being reused four times (Fig. 1). The
product 3a was obtained in 95%, 93%, 92%, 86%, and 72% yields
after successive cycles.
In summary, glycerol/CuI/Zn has proved to be an efficient and
recyclable catalytic system for the copper-catalyzed cross-coupling
reactions of vinyl bromides with diaryl diselenides. The reactions
proceed easily using this green protocol and the desired products
were obtained in good to excellent yields. The glycerol/CuI/Zn can
be easily recovered and utilized for further cross-coupling reactions.
SePh
Br
CuI (5%), Zn
glycerol
110 oC, N2
+
PhSeSePh
Acknowledgments
1a
2a
3a
We are grateful to FAPERGS (FAPERGS/PRONEX 10/0005-1),
CAPES, FINEP and CNPq for the financial support.
95
93
92
86
100
80
72
Supplementary data
Yield
3a (%)
60
40
20
0
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.10.107.
References and notes
1
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Figure 1. Reuse of CuI/Zn/glycerol.

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6775
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under nitrogen atmosphere, containing CuI (0.03 mmol; 5 mol %) and Zn dust
(0.6 mmol) was added glycerol (1.5 mL). The reaction mixture was stirred for
30 min at 110 °C and cooled to room temperature. After that, diaryl
dichalcogenide (0.3 mmol) and vinyl bromide (0.6 mmol) were added and
the reaction mixture was allowed to stir at 110 °C for the time indicated in the
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concentrated under vacuum. The residue was purified by flash
chromatography on silica gel using ethyl acetate/hexanes as the eluent.
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(2C), 127.2, 116.0, 114.2 (2C), 55.4. MS m/z (%) 290 (M+, 13), 210 (100), 195
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