Iron/copper promoted oxidative homo-coupling reaction of terminal alkynes using air as the oxidant

Article abstract of DOI:10.1016/j.tet.2010.04.017

An inexpensive catalytic system, which used a readily available Fe(acac)₃ and trace quantity of Cu(acac)₂ as the co-catalyst and air as the oxidant for the homo-coupling of terminal alkynes, has been developed. The catalytic system could also apply to the cross-coupling reaction of two different terminal alkynes.

Full text of DOI:10.1016/j.tet.2010.04.017

Tetrahedron 66 (2010) 4029e4031
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Iron/copper promoted oxidative homo-coupling reaction of terminal alkynes
using air as the oxidant
*
Xu Meng, Chuanbin Li, Baochun Han, Tiansheng Wang, Baohua Chen
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Tianshui Road, Lanzhou 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An inexpensive catalytic system, which used a readily available Fe(acac)3 and trace quantity of Cu
(acac)2 as the co-catalyst and air as the oxidant for the homo-coupling of terminal alkynes, has been
developed. The catalytic system could also apply to the cross-coupling reaction of two different ter-
minal alkynes.
Received 24 February 2010
Received in revised form 2 April 2010
Accepted 6 April 2010
Available online 9 April 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Diynes are very useful compounds building blocks in organic
synthesis and a recurring functional group in linearly -conjugated
For initial optimization of the reaction conditions, phenyl-
acetylene was chosen as a model substrate. This preliminary survey,
carried out in DMF at 50 ꢀC under air, allowed us to evaluate and
optimize the most efficient catalytic system (Table 1). The initial
results showed that only using catalytic amounts of Fe, FeCl2, FeCl3
or Fe(acac)3 were not able to promote the reaction (entries 1e4).
The other blank experiments in the absence of an iron additive but
in the presence of a trace amount of copper catalyst revealed no
conversion of phenylacetylene to diyne efficiently (entries 5e7).
Recently, It was noticed that Buchwald and Bolm found that
trace quantity of copper impurities would influence several types of
Fe/ligand-catalyzed cross-coupling reactions obviously.11e There-
fore, when using 10 mol % Fe and trace quantity of Cu salts (0.1 mol
%) as a co-catalyst, the yields of the desired product enhanced
slightly (entries 8e10). According to alter the kind of Fe sources, it
was surprisingly found that the homo-coupling of phenylacetylene
was successful with good yields in the presence of catalytic
amounts of Fe and trace amounts of Cu salts (entries 10 and 11).
Note that O2 played a significant role in the Fe/Cu co-catalyzed
homo-coupling reaction (entry 11). When carrying out the experi-
ment under O2 rather than N2, the high yield of diyne was obtained. It
was noted that an almost same yield of diyne could be obtained when
using free air instead of O2, because O2 of air plays a role of oxidan.12
Other copper sources with different oxidation state (I, II) were
examined but the outcomes were not so satisfactory (entries
12e15). Then the influence of altering the base on the homo-cou-
pling reaction was examined. This confirmed that the homo-cou-
pling reactions were not able to occur without a base (entry 16). It
was found that K2CO3 and Cs2CO3 were both more efficient than
other bases (entries 11, 16e20). It is reasonable to employ the later
as the base in the reaction, because Cs2CO3 is much more expensive
p
acetylenic oligomers and polymers,1 nature products,2 bioactive
compounds,2a,3 molecular recognition processes,4 and nonlinear
optical materials.5 One of the main methods to create this type of
bond is Glaser oxidative homo-coupling reaction of terminal alky-
nes.6,7a Among CeC bond-forming processes, palladium catalysis
has played a key role because of its mild, efficient, and selective
properties.7 This well-known method, however, suffers from sev-
eral drawbacks such as the use of expensive palladium reagents,
phosphorus or amine ligands, and the lack of environmental
friendliness. So there is a need for new methods that involve cheap
and environmentally friendly catalytic systems to create 1,3-diynes.
In the past years, several groups have developed homo-coupling
reactions of terminal alkynes using Pd-free catalytic systems.8 Jia
and co-workers described the homo-coupling reaction of terminal
alkynes in the presence of CuI/I2.9 Although the result was en-
couraging, a major drawback was the required presence of stoi-
chiometric amounts of CuI and I2. Recently, our group reported the
homo-coupling reaction of terminal alkynes in the presence of
CuCl2 under solvent-free condition, but the drawback was required
to use amine reagent necessarily.10 It is generally acknowledged
that iron complexes, which are cheap and environmentally friendly
comparatively, associated with other metals, have not catalyzed
this type of reactions.11 Herein, we report an efficient and eco-
nomically competitive Fe/Cu (trace quantity of copper) co-catalytic
system for homo-coupling reaction of terminal alkynes.
* Corresponding author. Fax: þ86 931 8912582; e-mail address: chbh@lzu.edu.cn
(B. Chen).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.017

4030
X. Meng et al. / Tetrahedron 66 (2010) 4029e4031
Table 1
Table 2
Preliminary survey of the iron/copper catalytic system for the homo-coupling
reaction of phenylacetylene
Iron/copper co-catalyzed homo-coupling reaction of terminal alkynesa
Fe(acac)3 (0.1 eq)
Cu(acac)2 (0.001 eq)
2
R
R
R
K2CO3 (2 eq)
DMF, 50oC, air
Entry [Fe] cat (0.1 equiv) [Cu] cat (0.001 equiv) Base
Yielda (%)
Entry
R¼
Ph
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
Fe
FeCl2
FeCl3
Fe(acac)3
d
d
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
EtN3
0
0
0
0
0
15
25
27
d
1
2
3
4
5
6
7
8
8
8
8
8
8
8
8
8
8
12
12
12
12
12
12
12
94
86
88
91
87
66
67
62
90
86
89
91
49
57
87
64
d
4-CH3C6H4
4-CH3OC6H4
4-n-C5H11OC6H4
3-NH2C6H4
4-FC6H4
b
d
Cu
Cu2O
d
d
Cu(acac)2
CuI
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu2O
FeCl3
FeCl2
FeCl3
4-ClC6H4
2-ClC6H4
9
40
75
10
11
12
13
14
15
16
17
18
19
20
21
22
9
a
-Naphthyl
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
Fe(acac)3
94 (95,c traced)
10
11
12
13
14
15
16
n-C4H9
66
89
83
n-C5H11
2-OH-propyl
ClCH2
BrCH2
3-Thienyl
Ferrocenyl
CuI
CuCl2
Cu(OAc)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
90
34 (0e)
Pyridine 89
KOBut
81
Cs2CO3 96
NaOH
K2CO3
K2CO3
a
Reaction conditions: alkyne (1.0 mmol), Fe(acac)3 (0.1 mmol), Cu(acac)2
(0.001 mmol), K2CO3 (2.0 mmol), DMF (1 mL), 50 ꢀC, under air.
72
b
55f (63,g 95,h 75i)
89j (37k)
Isolated yield.
a
Isolated yield.
b
c
d
e
f
Acac¼acetylacetone.
Table 3
Under O2.
Iron/copper co-catalyzed cross-coupling reaction of two different terminal alkynesa
Under N2.
Without base.
R1
R1
R2
R1
R2
R2
Fe(acac)3 (0.1 eq)
Use of 0.001 equiv Fe(acac)3 and 0.001 equiv Cu(acac)2.
Use of 0.01 equiv Fe(acac)3 and 0.001 equiv Cu(acac)2.
Use of 0.2 equiv Fe(acac)3 and 0.001 equiv Cu(acac)2.
Use of 1 equiv Fe(acac)3 and 0.001 equiv Cu(acac)2.
90 ꢀC for 8 h.
4
3
5
g
h
i
Cu(acac)2 (0.001 eq)
K2CO3 (2 eq)
R1
R2
+
DMF, 50oC, air
j
k
Room temperature for 24 h.
Entry
R1¼
R2¼
Time (h)
Yieldb for 3 (4/5) (%)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
4-MeO-Ph
4-n-C5H11O-Ph
OHCH2
2-OH-propyl
3-Thienyl
3-Me-Ph
12
12
12
12
12
12
24
24
68 (87/8)
74 (85/5)
45 (70/10)
55 (65/8)
53 (72/8)
70 (81/7)
Trace (84/80)
Trace (88/75)
than K2CO3. Among various solvents examined, DMF turned out to
be the best, whereas use of nonpolar (such as CH2Cl2 and THF) or
nonprotic (such as acetone and benzene) resulted in more disap-
pointing conversion. The reaction temperature and the load of
catalyst were tested, the results showed using 10 mol % Fe
(acac)3þ0.1 mol % Cu(acac)2 as the co-catalyst at 50 ꢀC was the best
condition (entries 21 and 22).
4-MeO-Ph
4-MeO-Ph
n-C4H9
n-C5H11
2-OH-propyl
n-C4H9
a
Reaction condition: R1CCH (5.0 mmol), R2CCH (1.0 mmol), Fe(acac)3 (0.1 mmol),
Under the optimized condition, a wide range of terminal alkynes
were successfully homo-coupled to afford the corresponding diynes
(Table 2). AsshowninTable 2, thecatalyticsystemefficientlycatalyzed
homo-coupling reaction of terminal alkynes including aromatic and
aliphatic acetylenes. The coupling reaction of terminal alkynes with
electron-donatinggroupsprovidedproductsinbetteryieldsthanwith
electron-withdrawing groups (entries 1e9). Although taking longer
reaction time, the homo-coupling reactions of various aliphatic acet-
ylenes provided products in good yields(entries 10e14). Interestingly,
expanding the procedure to heterocyclic acetylenes such as 3-thie-
nylacetylene (entry 15) and ferrocenylacetylene (entry 16), the de-
sired products were isolated in 87% and 64% yields, respectively.
In order to expend the application of this methodology, the Fe/
Cu catalytic system was applied to the cross-coupling reaction of
two different terminal alkynes.10,12c Initially, using equal amount of
two different alkynes led to a lot of homo-coupling products of two
alkynes rather than the cross-coupling product. When the exces-
sive another alkyne (5.0 equiv) was used, the cross-coupling
product was obtained. As shown in Table 3, under the optimized
condition, several good yields of unsymmetric 1,3-diynes were
obtained from the coupling two different aromatic terminal al-
kynes, while the corresponding homo-coupling products were
Cu(acac)2 (0.001 mmol), K2CO3 (2.0 mmol), DMF (1 mL), 50 ꢀC, under air.
b
Isolated yield.
obtained unavoidably (Table 3, entries 1e6). Only using a trace
amount of copper catalyst, trace yields of cross-coupling products
were got. When using two different aliphatic terminal alkynes as
the substrates, the outcomes were disappointing.
Noteworthy is that using phenyl iodide and phenylacetylene as
the substrates under Fe/Cu catalytic system under N2 rather than
air, a largely cross-coupling product and trace homo-coupling
product were obtained at this time (Fig. 1). Combining the experi-
mental data above (Table 1, entry 11), it was found that O2 influ-
enced the reaction strongly and the iron catalyst could suppress the
Fe(acac)3 (0.1 eq)
Ph
Ph
Cu(acac)2 (0.001 eq)
trace
88%
Ph
+ Ph
I
K2CO3 (2 eq)
Ph
Ph
DMF, 50oC, N2
Figure 1. The Sonogashira-type reaction under N2.

X. Meng et al. / Tetrahedron 66 (2010) 4029e4031
4031
homo-coupling by-product in the Sonogashira-type reaction under
N2 and also could enhance the homo-coupling product in the
homo-coupling reaction of terminal alkynes under air.11c
According to our results and a number of related litera-
tures,7,12,13 a possible mechanism for Fe/Cu co-catalyzed homo-
coupling reaction of terminal acetylenes was proposed. With
the aid of a base, the reaction of terminal acetylene with Cu
(acac)2 could afford intermediate copper acetylide readily.6,7a
The next reductive elimination would release the homo-cou-
pling product and generate Cu(I). Then Fe(III) could oxidize Cu
(I) to generate Cu(II) and Fe(II). Iron catalyst might play a role
of oxidant at this aspect. Finally, reduced Fe(II) was oxidized by
terminal oxidant O2 to regenerate the Fe(III) leading to a new
catalytic cycle.
d
¼7.53e7.51(d, J¼7.4 Hz, 4H), 7.38e7.33(m, 6H). 13C NMR (75 MHz,
CDCl3):
d
¼132.4, 129.1, 128.4, 121.7, 81.5, 74.2.
Acknowledgements
The authors are grateful to the project sponsored by the Scientific
Research Foundation for the State Education Ministry (No. 107108).
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.04.017.
References and notes
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In conclusion, we have discovered an efficient, environmentally
friendly and economical method for transforming same terminal
acetylenes into 1,3-diynes and two different terminal alkynes into
unsymmetric diynes in moderated to good yields and found that
a trace amount of copper salt could influence the homo-coupling
reactions obviously. The present procedure is mild, general, and
tolerate of a variety of functional groups.
4. Experimental
4.1. General
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All reactions were carried out under air. Solvents were dried and
degassed by the standard methods and all alkynes are readily
available. Fe and Cu salts were purchased from commercial sup-
pliers and the purities >99.99%. Flash column chromatography was
performed using silica gel (300e400 mesh). Analytical thin-layer
chromatography was performed using glass plates pre-coated with
200e400 mesh silica gel impregnated with a fluorescent indicator
(254 nm). NMR spectra were recorded in CDCl3 on a Varian Inova-
300 or 400 MHz NMR spectrometer with TMS as an internal ref-
erence. Products were characterized by comparison of 1H NMR and
13C NMR data with those in the literature.
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70, 703; (c) Li, J.-H.; Liang, Y.; Xie, Y.-X. J. Org. Chem. 2005, 70, 4393; (d) Lei, A.;
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4.2. Typical experimental procedure for the Fe/Cu co-
catalyzed homo-coupling reaction (Table 2, entry 1)
To a stirred solution of phenylacetylene (4 mmol) in DMF (4 mL),
Fe(acac)3 (purity>99.99%) (0.4 mmol), Cu(acac)2 (0.004 mmol), and
K2CO3 (8 mmol) were added successively. The mixture was heated
to 50 ꢀC in air and stirred for indicated time. After cooling to room
temperature, the mixture was diluted with ethyl acetate and fil-
tered. The filtrate was removed under reduced pressure to get the
crude product, which was further purified by silica gel chroma-
tography (petroleum/ethyl acetate as eluent) to yield 1,4-diphe-
nylbuta-1,3-diyne; white solid. 1H NMR (300 MHz, CDCl3):
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