CuO/CNTs-catalyzed heterogeneous process: A convenient strategy to prepare furan derivatives from electron-deficient alkynes and α-hydroxy ketones

Article abstract of DOI:10.1039/c2gc35697j

As heterogeneous catalysts and nanoparticle support materials, CNTs have attracted great interest in organic chemistry. This paper reports facile CuO/CNTs-catalyzed cyclization to form furan derivatives from electron-deficient alkynes and α-hydroxy ketones. It represents a facile synthetic route, and the eco-friendly catalyst can be easily separated by filtration and reused.

Full text of DOI:10.1039/c2gc35697j

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COMMUNICATION
CuO/CNTs-catalyzed heterogeneous process: a convenient strategy to prepare
furan derivatives from electron-deficient alkynes and α-hydroxy ketones†
Hua Cao,*a Huan-Feng Jiang,*b Xiao-Song Zhou,c Chao-Rong Qi,b Yuan-Guang Lin,a Jian-Yong Wua and
Qi-Mei Lianga
Received 8th February 2012, Accepted 2nd August 2012
DOI: 10.1039/c2gc35697j
opens new possibilities for the achievement of desirable catalytic
activity and effective separability.
As heterogeneous catalysts and nanoparticle support
materials, CNTs have attracted great interest in organic
chemistry. This paper reports facile CuO/CNTs-catalyzed
cyclization to form furan derivatives from electron-deficient
alkynes and α-hydroxy ketones. It represents a facile syn-
thetic route, and the eco-friendly catalyst can be easily sepa-
rated by filtration and reused.
Furan derivatives are one of the most important heterocyclic
compounds42 and are worth our attention, for functionalized
furans exhibit a wide range of biological activities,43–48 and
many naturally occurring compounds containing furan skeletons
as a key structural unit.49,50 Recently, our group have reported
facile one-pot nano-Cu2O-catalyzed51 and other homogeneous
catalyzed52–57 domino reactions to synthesize highly functiona-
lized polysubstituted furan derivatives. These advantages encour-
aged us to develop the heterogeneous catalytic systems
and design a new method to prepare furan molecules.58–67
Herein, we anticipated to report an environmentally friendly
CuO/CNTs-catalyzed cyclization process to synthesize furan
derivatives from electron-deficient alkynes and α-hydroxy
ketones.
Initially, substrates 1a and 2a were used as the starting
materials. The intermediate product diethyl 2-(2-oxopropoxy)-
maleate 3a was easily prepared through nucleophilic addition of
diethyl but-2-ynedioate 1a with 3-hydroxybutan-2-one 2a in the
presence of DABCO in CH2Cl2 at room temperature for ten
minutes. Then the CH2Cl2 was evaporated to dryness under
reduced pressure and a pure sample of 3a was obtained by
column chromatography. Subsequently, our study focused on
cyclization of 3a by testing various copper catalysts, substrates,
additives, solvents, and reaction times, respectively (the results
are outlined in Table 1). Several 5 mol% copper(II) and copper(I)
salts, such as CuCl2, CuBr2, Cu(OAc)2, CuO, CuI, CuBr, and
CuCl (Table 1, entries 1–7), were screened in the initial exper-
iments at 60 °C. Most gave yields of less than 10%. Only
Cu(OAc)2 and CuO could gave 24% and 25% yields respect-
ively. It was indicated that Cu(OAc)2 and CuO could catalyze
this transformation. Stimulated by these results, we attempted to
prepare CuO/CNTs to improve the yields during the reaction.
According to previous reports,65 CuO/CNTs were synthesized by
a simple hydrothermal method. The formation of the CuO/CNTs
was confirmed by TEM (Fig. 1a), XRD (Fig. 2) and XPS analy-
sis (Fig. SI-1a, ESI†).
Transition-metal-catalyzed reactions1–8 are versatile tools for the
straightforward and facile construction of new carbon–carbon
bonds from readily accessible starting materials in a single oper-
ation under mild conditions. Many significant reactions in this
area have been achieved with a variety of homogeneous metal
catalysts.9–16 However, homogeneous catalysis, in general,
suffers from the deficits in recovery of homogeneous catalysts,
the separation of products, the use of expensive ligands, such as
phosphanes or carbenes, and additives17–21 that are difficult to
prepare and handle. These problems are of particular environ-
mental and economic concern in large-scale syntheses. The het-
erogenization of homogeneous catalysts can facilitate their use
for practical processes to avoid these problems.22,23 There has
been considerable interest in the development of heterogeneous
catalytic systems that can be efficiently re-used whilst keeping
the inherent activity of the catalytic center.24–31
Carbon nanotubes (CNTs) have recently emerged as promis-
ing supports for immobilization due to their high surface area,
excellent electrical conductivity and unique structure, and also
supported catalysts can be easily separated from the reaction
medium.32–38 Copper(II) was one of the most powerful and
extensively used catalyst for synthesis of bio-active molecules,
such as drugs and agrochemicals.39–41 In this context, the devel-
opment of a promising copper/CNTs heterogeneous catalyst
aSchool of Chemistry and Chemical Engineering, Guangdong
Pharmaceutical University, Guangzhou 510006, P.R. China.
E-mail: hua.cao@mail.scut.edu.cn; Fax: (+)86(760)88207939
bSchool of Chemistry and Chemical Engineering, South China
University of Technology, Guangzhou 510640, P.R. China.
E-mail: jianghf@scut.edu.cn; Fax: (+)86(20)87112906
cSchool of Chemistry Science and Technology, and Development Center
for New Materials Engineering and Technology, Universities of
Guangdong, Zhanjiang Normal University, Zhanjiang 524048,
P.R. China
To our delight, the reaction yield of 4aa was dramatically
increased to 58% (Table 1, entry 8), when CuO/CNTs was exam-
ined in DMF at 60 °C. We were pleased to find that the reaction
time has decreased from 20 h to 6 h. This indicated that the
excellent electrical conductivity of CNTs could promote the
cyclization reaction. Some additives, such as CH3CO2H,
†Electronic supplementary information (ESI) available: Experimental
protocols and NMR Spectra for products 4aa–4eg. See DOI:
10.1039/c2gc35697j
2710 | Green Chem., 2012, 14, 2710–2714
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Table 1 Screen of reaction conditionsa
Entry Catalyst
Additive
Solvent
t (h) Yieldb (%)
1
2
3
4
5
6
7
8
CuCl2
CuBr2
Cu(OAc)2
CuO
CuI
CuBr
—
—
—
—
—
—
—
—
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
20
20
20
20
20
20
20
6
10
8
24
25
—
—
—
58
CuCl
CuO/CNTs
Fig. 2 XRD pattern of CuO/CNTs (# represents carbon nanotubes).
9
CuO/CNTs CH3CO2H DMF
6
6
6
6
6
6
6
6
6
6
6
6
6
6
89
Trace
78
Trace
Trace
70
—
87
86
50
10
11
12
13
14
15
16
17
18
19
20
21
22
CuO/CNTs F3CCO2H
CuO/CNTs PhCO2H
CuO/CNTs H2SO4
CuO/CNTs HCl
DMF
DMF
DMF
DMF
DMF
α-hydroxy ketones were examined in the presence of CuO/CNTs
to form the corresponding furan derivatives.
CuO/CNTs L-Proline
By using 1a as a fixed substrate, we first carried out the reac-
tions with various types of α-hydroxy ketones. From Scheme 1,
we found that the reaction conditions have proven to be useful
for α-hydroxy ketones 2a–2h. It was obvious that the reaction
between diethyl but-2-ynedioate (1a) and different α-hydroxy
ketones 2a–2h had a beneficial effect on the reaction products,
and in most cases the corresponding products 4aa–4ah were
obtained in moderate to good yields. It was also shown that no
matter whether R3 and R4 were aromatic or aliphatic substituted
groups, the cyclization had no effect on this transformation.
To further expand the scope of this transformation, other elec-
tron-deficient alkynes, such as dimethyl but-2-ynedioate (1b),
ethyl but-2-ynoate (1c), ethyl propiolate (1d), ethyl 3-phenylpro-
piolate (1e), 1,3-diphenylprop-2-yn-1-one (1f) and methyl oct-2-
ynoate (1g) were employed. The results showed that electron-
deficient alkynes 1b–1g were also well tolerated under the
optimum conditions and afforded the corresponding products in
good yields. These results indicated that the electron-deficient
alkynes with different substitute groups could react smoothly,
and the corresponding products were obtained in good yields.
Finally, all those cases showed that the reaction conditions were
useful for a range of electron-deficient alkynes 1b–1g and substi-
tuted α-hydroxy ketones.
—
CH3CO2H DMF
CuO/CNTs CH3CO2H CH3CN
CuO/CNTs CH3CO2H DMSO
CuO/CNTs CH3CO2H THF
CuO/CNTs CH3CO2H Toluene
CuO/CNTs CH3CO2H ClCH2CH2Cl
43
71
CuO
CH3CO2H DMF
78
Nano-CuO CH3CO2H DMF
63 (82)c
a Reaction conditions: 1a (1.0 mmol), 2a (1.1 mmol), catalyst (5% mol)
(entries 1–7); 6% mol (entries 8–20), additive (10% mol), solvent
(3.0 mL), at 60 °C for 6–20 h. b GC-yield. c The yield obtained after
reaction for 12 h.
Subsequently, we turned our attention to catalyst recycling and
reuse. After completion of the reaction, within 40–50 s, the reac-
tion mixture turned clear and the catalysts were deposited on the
button (Fig. 3), which was recovered by filtration, and then re-
used in the next reaction. The results are shown in Table 2, and
indicate that the catalytic activity was maintained even when the
catalyst was reused for 5 times (Fig. 1b and Fig. SI-2b†).
To gain further insight into the mechanism of this transform-
ation, we envisioned the possibility of trapping the intermediates
of the reaction. Firstly, intermediate A has been isolated success-
fully, then the control experiments were carried out and are
shown in Scheme 2. Finally, the results indicate that the CuO/
CNTs and H+ is essential for these reactions, however, intermedi-
ate B and C had hardly been detected.
Fig. 1 TEM images of catalyst: (a) before reaction; (b) after reaction.
F3CCO2H, PhCO2H, H2SO4, HCl and L-proline (Table 1, entries
9–14), were added to the system, but most of them provided
much worse results. When F3CO2H, H2SO4 or HCl were used,
the yield of 4aa decreased sharply and only trace amounts of the
product were found by TLC. Interestingly, when CH3CO2H was
added, the yield of 4aa was increased to 89%. Solvent effects
were also investigated. Reactions in a polar solvent, such as
CH3CN, DMF and DMSO, afforded good results, while non-
polar solvents, such as toluene or ClCH2CH2Cl, deteriorated the
yields.
With the establishment of a viable reaction system, we set out
to explore the scope of this sequential process (the results were
indicated in Scheme 1). In order to explore the scope of the
cyclization reaction, a variety of electron-deficient alkynes and
Based on the control experiments, a possible mechanism is
depicted in Scheme 3. Firstly, DABCO-promoted nucleoaddition
of 2a to 1b formed intermediate A which is activated by CuO/
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Fig. 3 Photographs showing the separation of catalyst.
Table 2 The catalyst reusea
Entry
Catalyst
Run
Yieldb (%)
1
2
3
4
5
6
CuO/CNTs
1
2
3
4
5
6
89
89
89
88
87
85
CuO/CNTs (reuse)
CuO/CNTs (reuse)
CuO/CNTs (reuse)
CuO/CNTs (reuse)
CuO/CNTs (reuse)
a Reaction conditions: 1a (1.0 mmol), 2a (1.1 mmol), 10% mol AcOH,
DMF 3.0 mL, at 60 °C for 6 h. b GC-yield.
Scheme 2 Control experiment.
CNTs and H+ to give adduct B. The coordination of H+ to the
carbonyl group lowers the electron density of the carbon–oxygen
double bond, which makes the nucleophilic attack of the
α-carbon toward the carbonyl carbon generate intermediate C.
Finally, the desired product was obtained by hydration of inter-
mediate C.
In conclusion, we have synthesized carbon nanotube sup-
ported CuO and developed a highly active, easily recoverable,
and practical heterogeneous catalyst for cyclization reactions,
which provides efficient access to the construction of highly sub-
stituted furans from electron-deficient alkynes and α-hydroxy
ketones. In particular, the performance of the catalyst fully pro-
moted the transformation and shortened reaction times due to the
excellent electrical conductivity of the carbon nanotubes. In
addition, further studies will focus on utilizing this
Scheme 1 CuO/CNTs-catalyzed synthesis of furans.
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Acknowledgements
The work was financially Supported by Foundation for Distin-
guished Young Talents in Higher Education of Guangdong,
China (LYM11083), National Natural Science Foundation of
China (20932002 and 21172076), National Basic Research
Program of China (973 Program) (2011CB808600), Doctoral
Fund of the Ministry of Education of China (20090172110014),
and
Guangdong
Natural
Science
Foundation
(10351064101000000).
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