CuI/iodine-mediated homocoupling reaction of terminal alkynes to 1,3-diynes

Article abstract of DOI:10.1016/j.tetlet.2008.07.138

A facile and efficient pathway for CuI/iodine-mediated homocoupling reaction of terminal alkynes to symmetrical 1,4-disubstituted 1,3-diynes in good to excellent yields was reported.

Full text of DOI:10.1016/j.tetlet.2008.07.138

Tetrahedron Letters 49 (2008) 5918–5919
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Tetrahedron Letters
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CuI/iodine-mediated homocoupling reaction of terminal alkynes to 1,3-diynes
*
Dafeng Li, Kun Yin, Jian Li, Xueshun Jia
Department of Chemistry, Shanghai University, Shanghai 200444, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile and efficient pathway for CuI/iodine-mediated homocoupling reaction of terminal alkynes to
symmetrical 1,4-disubstituted 1,3-diynes in good to excellent yields was reported.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 26 May 2008
Revised 23 July 2008
Accepted 25 July 2008
Available online 29 July 2008
Keywords:
CuI/iodine
Homocoupling
Terminal alkyne
1,3-Diyne
Homocoupling reaction of terminal alkynes to give 1,3-diynes is
highly important for a number of applications, particularly in the
2
Ph
Ph
Ph
DMF
construction of linearly
p-conjugated acetylenic oligomers and
polymers,1 natural products,2 supramolecular materials,3 and
molecular recognition processes.4 Traditional methods for the syn-
thesis of 1,3-diynes include Glaser oxidative dimerization of ter-
minal alkynes,5 various improved Glaser oxidative homocoupling
reactions of terminal alkynes,6–8 and Sonogashira coupling.9 Cata-
lytic systems mediated by palladium, Pd(0) or Pd(II), are arguably
the most mild, efficient, and selective for homocoupling reactions
of terminal alkynes.10–17 However, palladium reagents are expen-
sive, and they often required air-sensitive and expensive phos-
phine ligands as well as amine reagents. Here, we report our
finding of CuI/iodine mediated homocoupling reaction of terminal
alkynes in detail.
Scheme 1.
in DMF (1 mL) at 80 °C for 3 h (Table 1, entry 6). We have also per-
formed a number of control experiments: (1) in the absence of CuI,
no homocoupling product of phenylacetylene was observed, with
only (iodoethynyl)benzene was obtained in 35% yield (Table 1, en-
try 8); (2) in the presence of CuI (5–70 mol %), the reaction pro-
ceeded slowly in relatively low yields (Table 1, entries 2–5); (3)
in the absence of iodine or at room temperature, the poor yields
were obtained (Table 1, entries 7, 9); (4) a 96% yield was observed
when Na2CO3 was replaced by NaOAc (Table 1, entry 10); (5) when
Na2CO3 was replaced by Et3N, the reaction conducted slowly, and a
low yield was observed (Table 1, entry 11).
Under above optimized condition, we have examined the sub-
strate scope of this reaction. Our experiments indicate that a vari-
ety of terminal alkynes including aliphatic and aromatic acetylenes
successfully underwent the homocoupling to produce the corre-
sponding 1,3-diynes in good to excellent yields (Scheme 2, Table
2). Also, the reaction was sluggish in the case of the aliphatic al-
kyne, propargyl alcohol, giving a relatively low yield after a longer
reaction time (Table 2, entries 8–11). Especially, the homocoupling
of 1-ethynyl-4-fluoro- benzene needed prolonged reaction time
(10 h, Table 2, entry 7). This is likely due to the presence a fluoro
atom which decreases the reactivity of 1-ethynyl-4-fluorobenzene.
Scheme 3 illustrates the proposed mechanism for the sp–sp
homocoupling reaction of terminal alkynes. The alkynylcopper
intermediate A is formed from the reaction of a terminal alkyne
and CuI in the presence of Na2CO3, and then it undergoes smooth
Recently, our research interest focused on Baylis-Hillman chem-
istry.18 Our initial study was to attempt the addition reaction of
phenylacetylene to Baylis-Hillman adducts. However, no product
was observed in the presence of Na2CO3 in DMF under various
temperature. Subsequently, we tried to further activate phenyl-
acetylene with CuI and iodine. Interestingly, after addition of CuI
(10 mol %) and iodine (10 mol %) to the above reaction system,
the homocoupling product of phenylacetylene was detected. This
encouraging result led us to explore the homocoupling reaction
of phenylacetylene. After some optimization (Scheme 1, Table 1),
the best result for homocoupling of phenylacetylene leading to
1,4-diphenyl-1,3-butadiyne in 99% yield was afforded using phen-
ylacetylene (1 mmol), CuI (1 mmol), I2 (1 mmol), Na2CO3 (2 mmol)
* Corresponding author. Tel.: +86 21 66132408; fax: +86 21 66132797.
E-mail address: xsjia@mail.shu.edu.cn (X. Jia).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.138

D. Li et al. / Tetrahedron Letters 49 (2008) 5918–5919
5919
Table 1
Screening reaction parameters for the homocoupling of phenylacetylene
Entry
CuI (equiv)
Iodine (equiv)
Base (2 equiv)
Time (h)
Temp. (°C)
Yielda (%)
b
1
2
3
4
5
6
7
8
9
0.05
0.05
0.1
0.5
0.7
1.0
1.0
0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
NaOAc
Et3N
24
24
24
12
8
rt
—
80
80
80
80
80
rt
80
80
80
80
85
87
92
95
99
32
3
24
24
24
3
c
—
1.0
1.0
1.0
18
96
72
10
11
1.0
1.0
20
a
Isolated yield.
A trace amount of (iodoethynyl)benzene was formed.
(Iodoethynyl)benzene was afforded in 35% yield.
b
c
Acknowledgements
CuI, I2
R
R
R
Na2CO3, DMF
The authors thank the National Natural Science Foundation of
China (No. 20572068) and Innovation Fund of Shanghai University
for financial support.
Scheme 2.
References and notes
Table 2
CuI/iodine-mediated homocoupling reaction of terminal alkynes
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Entry
R
Time (h)
Isolated yield (%)
1
2
3
4
5
6
7
8
9
C6H5
3
3
3
3
3
3
10
5
5
5
5
99
94
96
95
92
93
92
86
87
89
70
4-MeC6H4
4-EtC6H4
4-n-PrC6H4
4-n-C5H11C6H4
4-MeOC6H4
4-FC6H4
n-C4H9
n-C5H11
n-C6H13
HOCH2
10
11
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Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York, 2002; Vol. 1, p
989.
I2
R
Cu
R
R
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12. Lei, A.; Srivastava, M.; Zhang, X. J. Org. Chem. 2002, 67, 1969.
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A
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CuI, Na2CO3
R
CuI
R
Na2CO3
Scheme 3.
19. To a stirred solution of alkyne (1 mmol) in DMF (1 mL), CuI (1 mmol), Na2CO3
(2 mmol), and iodine (1 mmol) were added successively. The resulting mixture
was then allowed to react at 80 °C in air. Progress of this reaction was monitored
by TLC. After completion of the reaction, 5 mL of ethyl acetate was added. The
mixture was filtered through a pad of diatomite under reduced pressure, and the
filtration residue was washed with ethyl acetate. The filtrate was then washed
with saturated Na2S2O3, saturated brine, and dried over anhydrous Na2SO4. The
solvent was removed under reduced pressure. The residue was then was
purified by TLC using petroleum ether as eluent to afford the corresponding 1,3-
diynes. All of the products are known and were characterized by comparison of
their spectral data with those of authentic samples.
oxidative dimerization with iodine to the sp–sp homocoupling
product.
In conclusion, we have successfully developed a facile and effi-
cient pathway for CuI/iodine-mediated homocoupling reaction of
terminal alkynes.19 The great attractiveness of the current method
lies in simple procedure (without exclusion of air or moisture), the
use of a solid base (Na2CO3) instead of amines and good to excel-
lent yields. Furthermore, the application of this methodology for
the cross-coupling of terminal alkynes is ongoing and will be
reported in due course.
Selected data of 1,4-bis(4-ethylphenyl)-1,3-butadiyne: IR (KBr): 3041, 2963, 2132,
1599, 1457, 1370, 828 cmÀ1 1H NMR (500 MHz, CDCl3): d 7.44 (d, J = 8.0 Hz, 4H),
.
7.16 (d, J = 8.0 Hz, 4H), 2.65 (q, J = 7.5 Hz, 4H), 1.23 (t, J = 7.5 Hz, 6H). MS: m/z =
258 (M+, 100%).