Solvent-free hydroalkylation of olefins with 1,3-diketones catalyzed by phosphotungstic acid

Article abstract of DOI:10.1016/j.tetlet.2008.06.029

An efficient and convenient method for the direct hydroalkylation of styrene and norborene with 1,3-diketones has been developed by using 12-phosphotungstic acid as an eco-friendly, and air- and moisture-tolerable catalyst. Reactions proceeded without any solvent, providing a clean access to alkylated 1,3-diketones.

Full text of DOI:10.1016/j.tetlet.2008.06.029

Tetrahedron Letters 49 (2008) 5090–5093
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Solvent-free hydroalkylation of olefins with 1,3-diketones catalyzed
by phosphotungstic acid
a
a
b,
Guan-Wu Wang a, , Ye-Bing Shen , Xue-Liang Wu , Lei Wang
*
*
a Hefei National Laboratory for Physical Sciences at Microscale, Joint Laboratory of Green Synthetic Chemistry, and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, PR China
b Department of Chemistry, Huaibei Coal Teachers College, Huaibei, Anhui 235000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and convenient method for the direct hydroalkylation of styrene and norborene with 1,3-
diketones has been developed by using 12-phosphotungstic acid as an eco-friendly, and air- and mois-
ture-tolerable catalyst. Reactions proceeded without any solvent, providing a clean access to alkylated
1,3-diketones.
Received 3 April 2008
Revised 31 May 2008
Accepted 6 June 2008
Available online 12 June 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Solvent-free
Hydroalkylation
Olefin
1,3-Diketone
Phosphotungstic acid
The construction of carbon–carbon bonds is among the most
important concerns in modern organic chemistry.1 The alkylation
of 1,3-dicarbonyl compounds is one of the most common methods
for carbon–carbon bond formation. Traditionally, however, organic
halides are employed as typical electrophiles in these reactions,
and a stoichiometric amount of bases, which would generate unde-
sired byproducts and decrease the atom economy, is required.2
Nowadays, an emphasis in green chemistry is to develop environ-
mentally benign routes, which hold significant potential for reduc-
tion of byproduct and waste, and lowering of energy cost.3
Therefore, the catalytic direct alkylation of 1,3-dicarbonyl com-
pounds with alkenes would provide a greener alternative.
In 1993, a pioneer work on ruthenium-catalyzed hydroarylation
of alkenes was accomplished by Murai and co-workers.4 After that,
extensive studies have been focused on the exploration of efficient
catalytic system to promote the addition of active methylene com-
pounds to alkenes. Widenhoefer and co-workers reported an
elegant palladium-catalyzed intramolecular hydroalkylation of
alkenyl 1,3-diketones to form 2-acylcyclohexanones,5 which was
later improved by employing lanthanide triflates as additives.6
Che and co-workers described a Au(I) complexes-catalyzed intra-
molecular addition of b-ketoamide to unactivated alkenes.7
Furthermore, platinum- or palladium-catalyzed intermolecular
additions of ethylene and propylene with 1,3-diketones has also
been realized.8 Hartwig and co-workers disclosed the palladium-
catalyzed addition of the
a-C–H bond of monocarbonyl and 1,3-
dicarbonyl compounds to conjugated dienes.9 Trost and co-work-
ers reported an elegant asymmetric hydroalkylation reaction of
allenes with pronucleophiles.10 Very recently, Li and co-workers
developed a new system for the highly effective intermolecular
addition of active methylene compounds to alkenes by using gold
and silver as the catalysts.11 Since then, various Lewis acids such as
bismuth triflate,12 ferric chloride,13 indium chloride,14 Lewis acidic
ruthenium complex,15 a combination of gallium triflate and triflic
acid,16 as well as Brønsted acid such as proton-exchanged mont-
morillonite17 have been employed to facilitate this transformation.
On the other hand, heteropoly acids (HPAs) such as 12-phos-
photungstic acid (PWA) and 12-phosphomolybdic acid (PMA),
which are often regarded as green catalysts for their commercial
availability, stability, reutilization, and clean reaction processes,18
are promising and highly active solid acids as an alternative to tra-
ditional metal catalysts.19
Moreover, solvent-free reactions have been paid more and more
attentions recently, often providing clean, efficient, and high-yield-
ing organic processes in modern synthetic chemistry.20 Recently,
we reported a highly efficient C–N bond formation reaction pro-
moted by PWA.21 In our continuous interest in solvent-free organic
reactions,22 herein, we demonstrate a convenient hydroalkylation
reaction of styrene and norbornene with 1,3-dicarbonyl com-
pounds mediated by PWA without any solvent.
* Corresponding authors. Tel./fax: +86 551 360 7864 (G.-W.W.).
E-mail address: gwang@ustc.edu.cn (G.-W. Wang).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.06.029

G.-W. Wang et al. / Tetrahedron Letters 49 (2008) 5090–5093
5091
Table 1
Initial studies were conducted using 1,3-diphenylpropane-1,3-
dione (1a) and styrene (2) as a prototype reaction. Various reaction
conditions of this transformation were extensively investigated
with the results summarized in Table 1. The PWA-catalyzed sol-
vent-free reaction at 20 °C only afforded trace product (entry 1).
Elevating the reaction temperature increased the yields obviously
(entries 2–5). When the reaction was performed under neat condi-
tion at 80 °C, to our delight, it proceeded mildly and rapidly, deliv-
ering the final adduct in excellent yield (94%) within 4 h (entry 5).
Further elevating the temperature was not beneficial, affording the
product in a slightly decreased yield (entry 6). When PMA was em-
ployed as catalyst, a lower yield was obtained (entry 7). Then var-
ious solvents were examined to facilitate this transformation. Only
trace product (entry 8) was detected when the reaction was per-
formed in CH3NO2, which was used as a privileged solvent in inter-
molecular hydroalkylation reactions.11a,12,14 1,2-Dichloroethane,
another common solvent, afforded the adduct in 42% after reflux-
ing for 4 h (entry 9). When 1,1,2,2-tetrachloroethane was
employed, the yield decreased dramatically (entry 10). While
CH3CN and n-heptane gave only trace product, a complex mixture
was observed in toluene (entries 11–13). Other solvents were also
investigated, including THF, EtOAc, DMF, DMSO, PEG-400, and H2O.
However, no reaction was observed in all these cases (entries
14–19).
Optimizing reaction conditions of direct hydroalkylation reaction of styrene with 1,3-
diphenylpropane-1,3-dionea
O
O
O
HPA
Ph
+
Ph
Ph
conditions, 4 h
O
Ph
1a
2a
3a
Entry
Solvent
T/°C
Yieldb (%)
1
2
3
4
5
Neat
Neat
Neat
Neat
Neat
Neat
Neat
CH3NO2
DCE
20
40
60
70
80
100
80
80
Reflux
80
Reflux
80
80
Reflux
Reflux
80
80
80
80
Trace
48
65
87
94
90
60
Trace
42
20
Trace
Trace
Complex
NRc
NRc
NRc
NRc
NRc
NRc
6
7d
8
9
10
11
12
13
14
15
16
17
18
19
TCE
CH3CN
n-Heptane
Toluene
THF
EtOAc
DMF
DMSO
PEG-400
H2O
With the optimized conditions in hand, next we investigated
the scope of 1,3-diketone substrates in the hydroalkylation reac-
tion of styrene and norbornene.23 The results are summarized in
Table 2. The reaction of symmetric 1,3-diarylpropane-1,3-diones
with para-substituents on the phenyl moiety (1b, 1c) with styrene
at 80 °C was investigated, furnishing the final adducts in slightly
decreased yields compared with 1,3-diphenylpropane-1,3-dione
a
Unless otherwise specified, all the reactions were performed with 0.25 mmol
(56.1 mg) of 1a, 0.87 mmol (90.6 mg) of 2, and 5 mg of PWA in neat or the presence
of 2 mL of indicated solvent.
b
Isolated yield.
No reaction.
PMA was used as the catalyst.
c
d
Table 2
PWA-catalyzed hydroalkylation reactions of styrene and norbornene with 1,3-diketonesa
Entry
1,3-Diketone
Alkenes
Time (h)
4
Product
Yieldb (%)
94
O
O
1
O
O
2a
1a
3a
Cl
O
O
O
2
2a
2.5
92
O
Cl
Cl
Cl
1b
3b
O
O
O
3
2a
3.5
89
O
1c
3c
O
O
O
O
4c
2a
3
75
1d
3d
(continued on next page)

5092
G.-W. Wang et al. / Tetrahedron Letters 49 (2008) 5090–5093
Table 2 (continued)
Entry
1,3-Diketone
Alkenes
Time (h)
3
Product
Yieldb (%)
O
O
5
2a
90 (60:40)d
O
O
Cl
Cl
1e
3e
O
O
O
O
6
7
2a
3
4
91 (55:45)d
1f
3f
O
O
O
O
96
2b
1a
3g
Cl
O
O
O
O
8
2b
2.5
2.5
4
92
93
85
Cl
Cl
1b
Cl
3h
O
O
O
O
9
2b
1c
3i
O
O
O
O
O
10
2b
O
O
1g
O
3j
Cl
O
O
O
11
2b
2b
2.5
O
94 (50:50)d
Cl
1e
3k
O
O
O
O
12
3
90 (65:35)d
1f
3l
a
Unless otherwise specified, all the reactions were performed with 0.25 mmol of 1, alkene 2 (0.87 mmol of 2a or 0.32 mmol of 2b), and 5 mg of PWA at 80 °C without any
solvent. Only the exo product could be formed in the reaction of 2b.
b
Isolated yield.
c
Reaction was performed at 120 °C.
d
The ratio of diastereoisomers was determined by 1H NMR spectroscopy.

G.-W. Wang et al. / Tetrahedron Letters 49 (2008) 5090–5093
5093
Table 3
Supplementary data
The reusability of PWA in the hydroalkylation of styrene with 1,3-diphenylpropane-
1,3-dionea
Spectroscopic and analytical data for compounds 3b, 3c, 3e, 3h,
3i, and 3j. Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2008.06.029.
Cycle
1
2
3
Time (h)
4
4
90
4
87
Yieldb (%)
92
a
References and notes
All the reactions were performed with 0.25 mmol of 1a, 0.87 mmol of styrene
2a, and 5 mg of PWA at 80 °C.
b
Isolated yield.
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1a (entries 2 and 3 vs entry 1). The electronic factor of the substit-
uents exhibited an insignificant influence on the reactivity of 1,3-
diketones (entries 2 and 3). When acetylacetone was heated with
styrene at 80 °C, the corresponding product was isolated in low
yield. Elevating the temperature to 120 °C proved helpful, the reac-
tion completed in 2 h, affording product 3d in 75% yield (entry 4).
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the corresponding adducts in high yields as mixtures of insepara-
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reaction conditions was investigated subsequently (entries 7–12).
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in high yields, ranging from 85% to 96% after heating at 80 °C for
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with asymmetric 1,3-diphenylpropane-1,3-dione 1e afforded the
product in 94% yield as a 50:50 mixture of diastereoisomers (entry
11). When 1-phenylbutane-1,3-dione 1f was employed as the sub-
strate, a similar reactivity was observed and the product was iso-
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The advantage of PWA could be further demonstrated by its
reutilization in this transformation. Upon completion of the hydro-
alkylation of styrene with 1,3-diketone 1a, dichloromethane was
added to the reaction mixture, and the thus precipitated PWA
was collected by filtration. The recovered PWA was reused to
catalyze the reaction with the results listed in Table 3. Gratifyingly,
the recovered PWA could be reused for at least three times without
the loss of activity apparently.
In conclusion, we have demonstrated an efficient methodology
for the solvent-free direct hydroalkylation reactions of styrene and
norbornene with 1,3-dicarbonyl compounds catalyzed by PWA.
The reactions proceeded in excellent yields, could be performed
in air, and avoided the usage of toxic organic solvent. Moreover,
the short reaction time, simplicity, practicability, simple workup,
as well as the use of a small amount and recycling of readily avail-
able, reactive, non-moisture-sensitive, and non-toxic PWA as the
catalyst in an environmentally benign process make the current
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23. General procedure for the PWA-catalyzed direct hydroalkylation of alkenes with
1,3-diketones: To a small vial were added 1,3-diketone 1 (0.25 mmol), alkene 2
(0.87 mmol for styrene; 0.32 mmol for norbornene), and 12-phosphotungstic
acid (5 mg). The vial was sealed and the reaction mixture was allowed to heat
at 80 °C for the indicated time (monitored by TLC). Upon completion, 5 mL of
CH2Cl2 was added, then the reaction mixture was filtered to recover PWA and
the organic solution was evaporated to dryness in vacuo. The residue was
separated on a silica gel column with petroleum ether/ethyl acetate 4:1 as the
eluent to afford the desired product 3.
Acknowledgments
The authors are grateful for the financial support from National
Natural Science Foundation of China (No. 20772117) and Anhui
Provincial Bureau of Education.