An efficient copper-catalyzed homocoupling of terminal alkynes to give symmetrical 1,4-disubstituted 1,3-diynes

Article abstract of DOI:10.1002/adsc.201100035

A facile and efficient pathway for the copper iodide and ligand N,N,N',N'-tetramethylethane-1,2-diamine promoted homocoupling reaction of terminal alkynes under ambient temperature and air as an oxidant was reported. The alkynes, including aromatic alkynes and aliphatic alkynes, could afford the symmetrical 1,4-disubstituted 1,3-diynes in good to excellent yields. Copyright

Full text of DOI:10.1002/adsc.201100035

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DOI: 10.1002/adsc.201100035
An Efficient Copper-Catalyzed Homocoupling of Terminal
Alkynes to Give Symmetrical 1,4-Disubstituted 1,3-Diynes
Songlin Zhang,a,* Xiaoyan Liu,a and Tongqiang Wanga
a
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials
Science, Dushu Lake Campus, Soochow University, Suzhou, 215123, Peopleꢀs Republic of China
Fax : (+86)-512-6588-0352; e-mail: zhangsl@suda.edu.cn
Received: January 15, 2011; Revised: March 28, 2011; Published online: May 23, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100035.
Abstract: A facile and efficient pathway for the
copper iodide and ligand N,N,N’,N’-tetramethyl-
ethane-1,2-diamine promoted homocoupling reac-
tion of terminal alkynes under ambient temperature
and air as an oxidant was reported. The alkynes, in-
cluding aromatic alkynes and aliphatic alkynes,
could afford the symmetrical 1,4-disubstituted 1,3-
diynes in good to excellent yields.
aliphatic diynes.[8c,10] For these reasons, the develop-
ment of an effective procedure for the homocoupling
of alkynes would be significant. Hence we report an
environmentally friendly, economic and efficient
system that allows the homocoupling reactions of ter-
minal alkynes based on catalytic amounts of CuI
under an atmosphere of air at ambient temperature.
And it provides good to excellence yields with ali-
phatic alkynes as substrates for the homocoupling re-
actions.
Keywords: ambient temperature process; catalysis;
copper; 1,3-diynes; N,N,N’,N’-tetramethylethane-
1,2-diamine
In our initial study, the reaction of phenylacetylene
(1a) was chosen as a model for the homocoupling re-
Table 1. Optimization of the reaction conditions.[a]
Conjugate 1,3-diyne derivatives are very important
materials in the fields of biology and materials sci-
ence. They have been employed for a number of ap-
plications, particularly in the construction of linearly
p-conjugated acetylenic oligomers and polymers,[1]
supramolecular materials[2] and substituted heterocy-
clic compounds.[3] Following the pioneering work by
Glaser in 1869,[4] much attention has been paid to the
development of efficient procedures for the synthesis
of 1,3-diyne derivatives. Traditionally, the homocou-
pling reaction of a terminal alkyne promoted by palla-
dium or copper salts is a powerful tool for the forma-
tion of conjugate 1,3-diynes. The palladium-catalyzed
homocoupling reaction of terminal alkynes represents
one of the most attractive routes to synthesize sym-
metrical diynes due to its mildness and efficiency.[5]
However, palladium reagents are expensive and often
require air-sensitive and expensive phosphine ligands.
The copper-mediated homecoupling reactions is an al-
ternative and promising strategy,[6–10] however, it usu-
Entry Cu source
Ligand
Base
Solvent Yield
[%][b]
1
Cu
N
6
88
2
3
CuI
Cu
TMEDA K2CO3 THF
TMEDA K2CO3 THF
DMEDA K2CO3 THF
trace
67
trace
trace
42
4
5
6
7
8
9
10
11
12
13
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
NMP
K2CO3 THF
DABCO K2CO3 THF
TMEDA Cs2CO3 THF
TMEDA Na2CO3 THF
TMEDA Et3N
TMEDA Et3N
TMEDA Et3N
TMEDA Et3N
TMEDA Et3N
85
THF
89
CH3CN 78
DMSO 56
acetone 91
acetone 91[c]
[a]
The reaction was performed with phenylacetylene
(1.0 mmol), Cu source (5 mol%), ligand (20 mol%) and
base (3.0 mmol) in solvent (5 mL) at ambient tempera-
ture for 20 h.
Isolated yield.
TMEDA (10 mol%).
ally need stoichiometric amount of copper salts,[4,7]
,
excess of oxidants,[8] rigid inorganic base and high
temperature[9] or affords low to moderate yields for
[b]
[c]
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Songlin Zhang et al.
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Table 2. CuI/TMEDA homocoupling reaction of terminal alkynes.[a]
Entry
Substrate
Product
Yield [%][b]
1
2
3
4
91
95
97
98
5
6
80
92
7
8
78
83
9
91
86
10
11
12
87
91
89
13
[a]
The reaction was performed with phenylacetylene (1.0 mmol), CuI (5 mol%), TMEDA (10 mol%) and Et3N (3.0 mmol)
in acetone (5 mL) at ambient temperature for 20 h.
Isolated yield.
[b]
action. As shown in Table 1, a series of experiments TMEDA (N,N,N’,N’-tetramethylethane-1,2-diamine)
was carried out to evaluate the ability of various Cu furnished the product in 88% yield (Table 1, entry 2).
sources, ligands, bases and solvents for the reaction Although K2CO3 Na2CO3 and Et3N all gave the
,
process. On investigating the Cu sources, we obtained product in good yields (Table 1, entries 2, 8 and 9),
a good yield (Table 1 entry 2) when CuI was used and we use the Et3N as the base instead of a rigid inorgan-
both CuACHTUNGTRENNUNG(OAc)2·H2O and copper power gave the prod- ic base such as K2CO3 and Na2CO3. Then the different
uct in low yields (Table 1, entries 1 and 3). Hence CuI solvents were investigated for this reaction. Acetone
was used in experiments to investigate the effect of was the best one with the highest yield compared
the ligand in the homocoupling reaction. Both NMP with THF, DMSO and acetonitrile under ambient
(N-methylpyrrolidin-2-one) and DABCO (1,4- temperature conditions (Table 1, entries 9–12). Final-
diazabicycloACHTUNGTRENNUNG[2.2.2]octane) were not effective for the ly, on reducing the amount of TMEDA from 20 to
homocoupling (Table 1, entries 5 and 6), a 67% yield 10 mol%, the reaction proceeds and still affords
of 2a was obtained when DMEDA (N,N’-dimethyl- yields of 91% of 2a (Table 1, entry 13). Balancing all
ethane-1,2-diamine) was used (Table 1, entry 4) and these results, it was concluded that the optimal condi-
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Adv. Synth. Catal. 2011, 353, 1463 – 1466

An Efficient Copper-Catalyzed Homocoupling of Terminal Alkynes
Table 4. CuI/TMEDA cross-coupling reaction of iodoethy-
nylbenzene and terminal alkynes.[a]
tions for the homocoupling reaction involved the use
of CuI (5 mol%), TMEDA (10 mol%), Et3N as the
base and air as an oxidant at ambient temperature.
Using the optimized conditions, we set out to study
the effect of substituents on the homecoupling reac-
tions of terminal alkynes (Table 2). Both the electron-
rich (Table 2, entries 2 and 3) and electron-deficient
(Table 2, entry 4) ethynylbenzene derivatives provid-
ed the corresponding aromatic 1,4-disubstituted-1,3-
diyne derivatives in excellent yields. Then we exam-
ined the application of the present protocol to the ho-
mocoupling of various alkylacetylenes. It is known
that aliphatic terminal alkynes are less reactive in un-
dergoing Glaser dimerization, probably due to the
weaker acidity of the acetylenic proton.[8,9] Under the
above reaction conditions, 1-hexyne (Table 2, entry 5),
1-decyne (Table 2, entry 6) and ethynylcyclopropane
(Table 2, entry 7) were converted into the correspond-
ing 1,4-dialkyl-1,3-diynes in good to excellent yields.
Entry
R1 =
R2 =
Yield [%][b] for 6 (7/8)
1
2
3
Ph
Ph
Ph
4-MeO-C6H4
HOCH2
2-pyridyl
46 (35/21)
34 (29/24)
50 (19/36)
[a]
1
ꢀ
The reaction was performed with R C CI (1.1 mmol),
2
ꢀ
R C CH
(1.0 mmol),
CuI
(5 mol%),
TMEDA
(10 mol%) and Et3N (3.0 mmol) in acetone (5 mL) at
ambient temperature for 20 h.
[b]
Isolated yield.
Alkynes based on propargylic alcohols (Table 2, en- when using iodoethynylbenzene and terminal alkynes
tries 8 and 9) also gave the corresponding diynes in as the substrates, middle yields of cross-coupling
high yields. And alkynes bearing other oxy functional- products were observed when with catalytic amounts
ities, such as ester (Table 2, entry 10) or ether of CuI under an atmosphere of air at ambient temper-
(Table 2, entry 11), were converted into the corre- ature (Table 4).
sponding conjugated diynes in good yield. Finally, we
In summary, we have demonstrated an efficient
found that the reactions of heteroatom-containing al- CuI/TMEDA-catalyzed homocoupling reaction of ter-
kynes (Table 2, entries 12 and 13) also proceeded effi- minal alkynes to produce conjugated 1,3-diynes in
ciently.
good to excellent yields. The reaction proved to be
In order to expand the application of this method- tolerant to a variety of functional groups in air and at
ology, our catalytic system was applied to the cross- ambient temperture with catalytic amounts of CuI.
coupling reaction of two different terminal alkynes.[12] And as for aliphatic diynes, it also furnished high
Because this catalytic system proved to be tolerant to yields. These features make this technique environ-
a variety of alkynes including aromatic alkynes, ali- mentally friendly, economic and very attractive to
phatic alkynes and heteroatom-containing alkynes apply on an industrial scale.
(Table 2), low yields of cross-coupling products and
medium yields of homocoupling products were ob-
tained when using two different aliphatic terminal al- Experimental Section
kynes as the substratesACTHNUTRGNE(NUG Table 3). Noteworthy is that
Typical Procedure (2a)
Table 3. CuI/TMEDA cross-coupling reaction of two differ-
Phenylacetylene (102 mg, 1.0 mmol), TMEDA (11.6 mg,
10 mol%), CuI (9.5 mg, 5 mol%) and Et3N (303 mg,
3 mmol) were added to acetone (5 mL) at ambient tempera-
ture. The reaction mixture was stirred at room temperature
for 20 h. The progress of the reaction was monitored by
TLC. After completion of the reaction, the solvent was re-
moved under reduced pressure and the crude product ob-
tained was purified by column chromatography over silica
gel to afford 1,4-diphenylbuta-1,3-diyne(2a) as a white solid.
ent terminal alkynes.[a]
Entry
R1 =
R2 =
Yield [%][b] for 3 (4/5)
1
2
3
Ph
Ph
Ph
4-MeO-C6H4
HOCH2
2-pyridyl
39 (60/39)
26 (50/45)
34 (63/58)
Acknowledgements
The work was partially supported by the National Natural
Science Foundation of China (No. 21072143).
[a]
1
ꢀ
The reaction was performed with R C CH (1.0 mmol),
2
ꢀ
R C CH
(1.0 mmol),
CuI
(5 mol%),
TMEDA
(10 mol%) and Et3N (3.0 mmol) in acetone (5 mL) at
ambient temperature for 20 h.
[b]
Isolated yield.
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