A convenient synthetic route for alkynylselenides from alkynyl bromides and diaryl diselenides employing copper(I)/imidazole as novel catalyst system

Article abstract of DOI:10.1016/j.tetlet.2008.06.071

A mild, convenient, and effective strategy is developed for the synthesis of alkynyl selenides from alkynyl bromides and respective diselenides using CuI/imidazole as a novel catalyst system with Mg as additive. The procedure affords the title compounds in moderate to good yield (51-89%). The main advantages of the protocol include the use of inexpensive copper catalyst, a novel Cu(I)/imidazole combination, and good yield of the products.

Full text of DOI:10.1016/j.tetlet.2008.06.071

Tetrahedron Letters 49 (2008) 5172–5174
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A convenient synthetic route for alkynylselenides from alkynyl bromides
and diaryl diselenides employing copper(I)/imidazole as novel catalyst system
b
b,
b
c
Anuj Sharma a, , Ricardo S. Schwab , Antonio L. Braga , Thiago Barcellos , Marcio W. Paixão
*
*
a BIO5 Institute, University of Arizona, AZ, USA
b Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil
c Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
A mild, convenient, and effective strategy is developed for the synthesis of alkynyl selenides from alkynyl
bromides and respective diselenides using CuI/imidazole as a novel catalyst system with Mg as additive.
The procedure affords the title compounds in moderate to good yield (51–89%). The main advantages of
the protocol include the use of inexpensive copper catalyst, a novel Cu(I)/imidazole combination, and
good yield of the products.
Received 19 May 2008
Revised 13 June 2008
Accepted 16 June 2008
Available online 19 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
and respective diselenides using copper salt/imidazole as a novel
catalyst system. Recently, CuI has been utilized for preparation of
Organic chalcogens as structural motifs are commonly found in
a variety of molecules of biological/pharmaceutical1 and material2
interest. Among them, alkynyl chalcogenides are interesting class
of compounds having a variety of uses in organic synthesis.3 For
example, alkynylselenides have been useful precursors in hydro-
amination,4 hydrohalogenation,5 hydrosulfonation,6 hydrostannyl-
ation,7 hydrozirconation,8 and hydroboration9 reactions. They have
also been used for the preparation of selenocarboxylic esters,
which are useful acyl transfering agents.10
The commonly used method for the synthesis of alkynyl sele-
nides involves metal-assisted cross coupling with either Mg or
Cu salts.5,7,11 However, delicate reaction conditions and stoichio-
metric amount of toxic metal salts leave scope for modifications
of these protocols. In this regard, oxidative dehydrogenation of
alkynes through iodobenzene diacetate is a useful proposition,
but the scope of the protocol has to be evaluated for substituted
phenylselenides.12
The recent past has witnessed emergence of copper-catalyzed
coupling reactions as principal method of forming aromatic car-
bon–heteroatom bonds.13 Copper catalysts have been preferred
to other organometallic compounds due to obvious advantage of
their being inexpensive and providing clean reactions. We had pre-
viously reported preparation of alkynyl selenides using stoichio-
metric amount of copper(I),11b,c and realized that reducing amount
of copper to catalytic scale for preparation of alkynyl selenides
would be a significant development.
alkynyl selenides from phenylacetylene in the presence of DMSO
as oxidant.14 We decided to apply the above methodology in a
reaction between phenylacetylene bromide 1a with diphenyl disel-
enide 2a (1 equiv), CuI (10 mol %) and K2CO3 (2 equiv) in DMSO.
However, the methodology did not work in our system and within
10 min, a precipitation of 2a and no product were observed even
after 7 h of reaction.
In another reaction, 1a was reacted with 2a (1 equiv) in the
presence of CuI (10 mol %), Mg (2 equiv), in DMF at 120 °C for
24 h, unfortunately the product phenylethynyl selenide 3a was
obtained in only 25% yield, the rest being acetylene dimer and
the starting material. Recently, Beller reported a novel and efficient
Cu(I)–imidazole catalyst–ligand combination in cyanation reac-
tions.15 Inspired by their results, we decided to incorporate
copper–imidazole system in our case. Emulating the above
methodology, compounds 1a and 2a (1 equiv) were reacted with
CuI (10 mol %), imidazole (10 mol %), and Mg (2 equiv) as additive.
Much to our gratification, it brought about 83% yield of 3a in 48 h.
In order to optimize the above protocol, different Cu(I) catalysts,
ligands, additives, and solvents were screened in the above reac-
tion. For example, in one set of reactions, different copper catalysts
were tested (Table 1, entry 1–3) and CuI provided maximum yield
of the product (entry 1). The catalyst loadings were also analyzed.
It was observed that using 20 and 5 mol % of the catalyst, the
desired product was obtained with 79% and 69% of yield, respec-
tively (entries 4 and 5). However, 10 mol % CuI seemed to provide
optimum yield of 3a (entry 1).
In this context, we disclose a mild and inexpensive methodol-
ogy for the synthesis of alkynyl selenides from alkynyl bromides
Furthermore, Zn was tried in place of Mg, but was less effective
(entry 6). Moreover, reaction did not proceed in absence of either
imidazole or Cu(I) (entry 7), and only traces of 3a formed in
absence of Mg (entry 8).
* Corresponding authors. Tel.: +55 55 220 8761; fax: +55 55 220 8031 (A.L.B.).
E-mail address: albraga@smail.ufsm.br (A. L. Braga).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.06.071

A. Sharma et al. / Tetrahedron Letters 49 (2008) 5172–5174
5173
Table 1
Table 3
Effect of catalyst and additive in coupling of alkynyl bromide and diphenyl diselenidea
Effect of solvent on copper-catalyzed coupling of bromophenylacetylene and diphenyl
diselenidea
CuX
Imidazole (10 mol%)
Cu/imidazole
(10 mol%)
Ph
Br
Ph2Se2
Ph
SePh
+
Additive, DMF,
120 ºC, 48 hrs
Ph
SePh
Ph
Br
Ph2Se2
+
1a
3a
2a
Mg, solvent
120 ºC
1a
2a
1a
Entry
CuX3
Additive
Yieldb,c (%)
Entry
Solvent
Time (h)
Yieldb,c (%)
1
2
3
4
5
6
7f
8
CuI (10 mol %)
CuCl (10 mol %)
Cu(OAc) (10 mol %)
CuI (20 mol %)
CuI (5 mol %)
CuI (10 mol %)
—
Mg
Mg
Mg
Mg
Mg
Zn
83
67
51d
79
69
56e
—
1
2
3
4
5
DMF
DMSO
DCM
THF
DMF/H2O
48
48
48
48
48
83
67
59d
53d
21e
Mg
—
a
Reactions were run on a 1.1 mmol scale of 1a in solvent (5 mL) with 0.55 mmol
of 2a,10 mol % of CuI, 10 mol % of imidazole, and Mg turnings (2.2 mmol) at 120 °C
for 48 h.
CuI (10 mol %)
—
a
Reactions were run on a 1.1 mmol scale of 1a in DMF (5 mL) with 0.55 mmol of
b
Isolated yields.
2a, catalyst, 10 mol % of imidazole and additive (2.2 mmol) at 120 °C for 48 h.
c
b
Yields are based on acetylene 1a.
Unidentifiable side products observed.
Diphenyl diselenide precipitated and most of 1a remained unreacted.
Isolated yields.
Yields are based on acetylene 1a.
Dimeric product along with unidentifiable side products observed.
Unidentifiable mixture of side products observed.
d
c
e
d
e
f
Neither CuI or imidazole was used in the reaction, only starting material
remained unreacted.
Table 4
Copper-catalyzed coupling of bromoacetylene derivatives with diselenidesa
Cu/imidazole
In another set of experiments, comparisons were made among
PPh3, TMEDA, and imidazole, and 10 mol % imidazole proved to
be the most effective ligand for preparation of 3a (Table 2, entry
4). It is thus surprising that, despite being so effective, imidazole
had remained untapped as ligand in copper catalyst systems.
Similarly, a survey of solvents was conducted and DMF was
found to be the solvent of choice (Table 3, entry 1). It is worth not-
ing that DMSO and DMF–H2O combination was less effective than
DMF for the reaction. This implied a different mechanism in oper-
ation than the ones postulated in literature.14
Finally, we found that the reaction of 1a with 2a (1 equiv), in
the presence of CuI (10 mol %), imidazole (10 mol %) in DMF at
120 °C for 48 h provided optimum yield of the product.16
After having achieved optimum conditions for preparation of
alkynyl selenides, we decided to explore the scope of this reaction.
Different alkynyl bromides and diarylselenides were reacted under
the devised protocol and the results are delineated in Table 4. As
clear from the table, the reactions proceeded to provide moderate
to good yield of the products with varied substrates.
R1
Br
R2SeSeR2
SeR2
+
R1
DMF
1
3
2
120 ºC, 48 hrs
Entry
R1
R2
Product
Yieldb,c (%)
1
2
3
Ph
Ph
Ph
Ph
3a
3b
3c
83
67
79
p-ClC6H4
p-MeC6H4
4
Ph
3d
68
5
6
7
Ph
Ph
Ph
p-MeC6H4
p-CF3C6H4
p-MeOC6H4
3e
3f
3g
86
57
81
a
Reactions were run on a 1.1 mmol scale of 1 in DMF (5 mL) with 0.55 mmol of
2,10 mol % of CuI, 10 mol % of imidazole, and Mg turnings (2.2 mmol) at 120 °C for
48 h.
b
Isolated yields.
c
Yields are based on acetylene 1a.
Finally, the scope of the reaction was also extended on diphenyl
tellurides. In one reaction, compound 1a was reacted with diphen-
yl telluride (4a) using the optimized conditions. Gratifyingly, the
resulting product 5a was obtained in 65% yield (Scheme 1).
(10 mol%)
Cu/imidazole
Mg
Ph
TePh
Ph
Br
Ph2Te2
+
DMF
1a
4a
5a
120 ºC, 48 hr
Scheme 1. Copper-catalyzed coupling of bromophenylacetylene with diphenyl
ditelluride.
Table 2
Effect of ligands on copper-catalyzed coupling of bromophenylacetylene and diphenyl
diselenidea
On the basis of the Taniguchi and Onami17 and Engman and
Kumar18 results, we proposed a possible mechanistic pathway for
the synthesis of alkynyl chalcogenide as outlined in Scheme 2.
When, CuI was employed as the promoter, the reaction process
was considered as follows. Firstly, CuI was reduced to Cu(0) 1,
the oxidative addition of Cu(0) to (R2Y)2 furnished (R2Y)2Cu(II) 2.
Subsequently, the copper complex is reduced by magnesium to
CuI (10mol%)
ligand
Ph
SePh
Ph
Br
Ph2Se2
+
Mg, DMF
1a
2a
3a
120 ºC, 48 hrs
Entry
Ligand
mol %
Yieldb,c (%)
1
2
3
4
Ph3P
20
10
20
10
83
67
51d
79
(R2Y)Cu(I)
3 which is the activate species. The insertion of
TMEDA
Imidazole
Imidazole
(R2Y)Cu(I) species to alkynyl bromide produced a copper(III) species.
Finally, reductive elimination of the alkynylchalcogenylcopper(III)
intermediate 4 could undergo to form the desired alkynyl chalco-
genide and Cu(I) species leading to a new catalytic cycle.
a
Reactions were run on
a 1.1 mmol scale of 1a in dry DMF (5 mL) with
0.55 mmol of 2a, 10 mol % of CuI, ligand and Mg turnings (2.2 mmol) at 120 °C for
48 h.
In conclusion, we have successfully demonstrated a convenient
methodology for the synthesis of alkynyl chalcogenides in very
good yield with modifications over the existing methodologies.
b
Isolated yields.
Yields are based on acetylene 1a.
Rest being unreacted 1a.
c
d

5174
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Scheme 2. Plausible reaction mechanism for the copper-catalyzed synthesis of the
alkynyl chalcogenide.
This is the first report of Cu–imidazole combination as catalyst for
organochalcogen compounds. Extension of this methodology to
diversified substrates to broaden the scope of this novel catalyst
combination will be reported in due course.
Acknowledgements
The authors thank CNPq for financial support. A.S. and T.B.
thank CNPq for post-doc and masters fellowship, respectively.
A.S. thanks TWAS for travel grant.
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555; (b) Schareina, T.; Zapf, A.; Magerlein, W.; Muller, N.; Beller, M. Chem. Eur. J.
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16. General procedure for the synthesis of substituted alkynyl selenides (Table 4).
Substituted alkynyl bromide (1.1 mmol) and diphenyl diselenide (0.55 mmol)
References and notes
were added to
a 50 mL two-necked round-bottomed flask under argon
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Vol. 2; (c) Back, T. G. In Organoselenium Chemistry: A Practical Approach; Oxford
University Press: New York, 1999; (d) Liu, G.; Huth, J. R.; Olejniczak, E. T.;
Mendoza, R.; DeVries, P.; Leitza, S.; Reilly, E. B.; Okasinski, G. F.; Fesik, S. W.;
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containing CuI (209 mg, 0.11 mmol), imidazole (149 mg, 0.11 mmol), and
magnesium turnings (53 mg, 2.2. mmol) in DMF (5 mL) with continuous
stirring. The reaction mixture was heated in an oil bath at 120 °C for 48 h. After
the reaction, the resulting mixture was cooled to room temperature, added 10–
15 mL of DCM, and filtered. The filtrate was washed with brine (3 Â 5 mL),
water (3 Â 5 mL), and was dried over MgSO4. Solvent was evaporated under
reduced pressure and the crude product was purified through a pad of silica
with only hexane, providing the colorless viscous oil. The known compounds
were identified by comparison of their spectral data with those reported and
the new compounds were properly characterized by their IR, 1H NMR, and 13
NMR spectroscopic data and mass analysis.
C
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18. Kumar, S.; Engman, L. J. Org. Chem. 2006, 71, 5400.
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Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, U.K., 1986; Vol. 1, Chapter 10
(b) Hellberg, J.; Remonen, T.; Johansson, M.; Inganäs, O.; Theander, M.;