An efficient and heterogeneous recyclable palladium catalyst for chemoselective conjugate reduction of α,β-unsaturated carbonyls in aqueous medium

Article abstract of DOI:10.1039/c1gc15050b

An highly efficient PS-Pd-NHC catalytic system has been developed for chemoselective conjugate reduction of α,β-unsaturated carbonyl compounds providing good to excellent conversion with remarkable chemoselectivity (up to 100%). The developed protocol is more advantageous due to use of HCOONa as hydrogen source, environmentally benign water as solvent and effective catalyst recyclability.

Full text of DOI:10.1039/c1gc15050b

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COMMUNICATION
An efficient and heterogeneous recyclable palladium catalyst for
chemoselective conjugate reduction of a,b-unsaturated carbonyls in aqueous
medium†
Dattatraya B. Bagal, Ziyauddin S. Qureshi, Kishor P. Dhake, Shoeb R. Khan and Bhalchandra M. Bhanage*
Received 14th January 2011, Accepted 28th March 2011
DOI: 10.1039/c1gc15050b
An highly efficient PS-Pd-NHC catalytic system has been
developed for chemoselective conjugate reduction of a,b-
unsaturated carbonyl compounds providing good to ex-
cellent conversion with remarkable chemoselectivity (up to
phosphine ligands, which have been quantified via theoretical
calculation for different metals. Therefore, the binding between
the NHC and transition metal is much stronger, as well as
being chemically and thermally more inert towards cleavage than
that of other metal complexes. Recently, polymer-supported
palladium-N-heterocyclic carbene (PS-Pd-NHC) catalyst have
been explored for Suzuki and carbonylative Suzuki coupling
1
00%). The developed protocol is more advantageous due
to use of HCOONa as hydrogen source, environmentally
benign water as solvent and effective catalyst recyclability.
12
reactions, as it offers several advantages like reuse of expensive
transition metals and ligands with a possibility to prevent the
contamination of ligand residue in products. However, to the
best of our knowledge, no such polymer-supported catalytic
system has yet been explored for the conjugate reduction of
a,b-unsaturated carbonyls.
In recent years, selective hydrogenation of a,b-unsaturated
carbonyls has attracted great attention because of its wide
applications in synthesis of fine chemicals and pharmaceutical
1,2
compounds. For these types of conversion, use of molecular
hydrogen as a reducing agent is the most commonly used
3
method, however use of transfer hydrogenation method is a
In continuation of our ongoing research on development
more attractive alternative which can be efficiently performed
without the use of sophisticated instruments (autoclave) or
molecular hydrogen gas.
of new facile protocol for the hydrogenation reactions with
13
transition metal catalysts, we herein report a complete green
and convenient strategy for chemoselective transfer hydrogena-
tion of a,b-unsaturated carbonyl compounds by using PS-Pd-
NHC catalytic system as a versatile catalyst in aqueous media
(Scheme 1).
4
A selective hydrogenation reaction of a,b-unsaturated car-
bonyl compounds is a challenging task and many transition
5
6
7
8
metals such as rhodium, ruthenium, palladium, iridium
9
and other metal complexes were used for this transformation.
However, despite of their potential utility, the above-mentioned
methods suffer from one or more drawbacks such as use
of expensive ligands, low chemoselectivity, use of hazardous
organic solvents, difficulties associated with catalyst-product
separation thereby limiting their general applications. Therefore,
the efforts to develop an heterogeneous and reusable catalytic
system which can efficiently catalyse chemoselective transfer
hydrogenation of a,b-unsaturated carbonyls is highly desirable.
Recently, N-heterocyclic carbene as a ligand have found
potential applications in homogeneous transition metal
Scheme 1 Chemoselective transfer hydrogenation of a,b-unsaturated
carbonyls.
10,11
Results and discussion
catalysis,
because of their effective binding ability to any
transition metal irrespective of their oxidation states. NHC
ligand reveals very high dissociation energies compared to
In order to optimize the reaction conditions, initial studies
were conducted using PS-Pd-NHC as a choice of catalyst,
HCOONa as a hydrogen source and water as a solvent for
the chemoselective transfer hydrogenation of benzylideneace-
tophenone as a model reaction. Various reaction parameters
such as catalyst screening, catalyst loading, effect of different
hydrogen source, effect of solvent, effect of hydrogen donor
concentration, reaction temperature and time were studied and
the results obtained are summarized in Table 1 and 2.
Department of Chemistry, Institute of Chemical Technology
(
Autonomous), Matunga, Mumbai, 400 019, India. E-mail:
bhalchandra_bhanage@yahoo.com, bm.bhanage@ictmumbai.edu.in;
Fax: +91 22 2414 5614; Tel: +91 22 3361 1111/2222
†
Electronic supplementary information (ESI) available: Experimental
details and characterization data of selected products. See DOI:
0.1039/c1gc15050b
1
1
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Table 1 Effect of catalyst on the transfer hydrogenation of a,b-
lower yield of desired product were observed (Table 3, entries
a
unsaturated carbonyl compound
1–2), whereas the reaction worked efficiently in polar protic
solvent such as water (Table 3, entry 3), as compared to the
other organic polar protic solvents such as ethanol (65%) and
methanol (21%) (Table 3, entries 4–5). The reaction system
was also studied in polar aprotic solvents such as DMF (50%)
and DCM (10%) but lower yield of the desired product were
obtained (Table 3, entries 6–7). We also examined the effect
of mixed solvent system (Table 3, entries 8–9): a mixture of
water and ethanol (9 : 1) gives 94% conversion, whereas water
and DMF (9 : 1) gives 76% conversion of the desired product
within 12 h. So it is notable that the conversion was improved
significantly on going from organic solvent to water in the
presence of PS-Pd-NHC catalyst as water being an environmen-
tally benign solvent, which offers an unpredictable effect on the
rate and selectivity of organic reactions through hydrophobic
interactions.
Catalyst loading Conversion Selectivity
Entry Catalyst
(mol%)
(%)
(2a : 3a)
Catalyst screening
1
2
3
4
5
PS-Pd-NHC
10% Pd/C
(PS-TPP-Pd)
Pd(OAc)
Pd(TMHD)
2
2
2
2
2
99
99 : 1
—
—
97 : 3
—
Traces
Traces
10
2
2
Traces
Catalyst Loading
6
7
8
PS-Pd-NHC
PS-Pd-NHC
PS-Pd-NHC
0.5
1
1.5
63
74
99
97 : 3
98 : 2
99 : 1
a
Reaction conditions: benzylideneacetophenone (1 mmol), HCOONa
◦
(
3 mmol), water (10 mL), temperature (100 C), time (12 h).
The effect of HCOONa as a hydrogen source; using 1.5 mmol
of HCOONa provided 71% conversion and 98% selectivity
of the desired product (Table 3, entry 10), while 3 mmol of
HCOONa reveals 99% conversion with 99% chemoselectivity
towards the expected product (Table 3, entry 11). With further
increase in the amount of HCOONa no profound increase in
results were observed (Table 3, entry 12). In order to examine
the effect of temperature on reaction outcome, reactions were
Table 2 Effect of different hydrogen donors on transfer hydrogenation
a
of a,b-unsaturated carbonyl compound
b
Entry
Hydrogen donor
Conversion (%)
Selectivity
1
2
3
4
HCOONa
HCOOK
HCOONH
HCOOH+Et
99
91
32
54
99 : 1
97 : 3
98 : 2
94 : 6
4
◦
3
N (1 : 1)
carried out at different temperatures ranging from 60–100 C
◦
(
Table 3, entries 13–15). It was observed that at 60 C the yield
a
Reaction conditions: benzylideneacetophenone (1 mmol), PS-Pd-NHC
1.5 mol %), hydrogen donor (3 mmol), solvent (10 mL), temperature
100 C), time (12 h). conversion based on GC analysis.
of the desired product was low whereas with the increase in
(
(
◦
b
◦
temperature up to 100 C, 99% conversion of the desired product
was obtained within 12 h. Hence, the best optimised reaction
parameters for chemoselective transfer hydrogenation of 1 mmol
of benzylideneacetophenone are: PS-Pd-NHC: 1.5 mol %,
solvent: water (10 mL), HCOONa: 3 mmol, temperature: 100 C,
time: 12 h.
Initially to compare the activity of PS-Pd-NHC catalyst
we screened various heterogeneous palladium complexes such
as, 10% Pd/C and PS-TPP-Pd (Table 1, entries 1–3), also
◦
homogeneous complexes such as Pd(OAc)
2
and Pd(TMHD)
2
To broaden the scope and generality of the developed PS-Pd-
NHC catalysed transfer hydrogenation system, we investigated
the effect on various a,b-unsaturated ketones, aldehydes, amides
and ester (Table 4, entries 1–15). The conjugate reduction of a,b-
unsaturated carbonyls provided the corresponding 1,4-reduced
products in good yields (Table 4, entry 1) and it was observed
that both electron-donating and electron-withdrawing aromatic
substituted enones were well tolerated under present reaction
conditions. Electron-donating aromatic substituted enone pro-
vided excellent yield of the corresponding products (Table 4,
entries 2–4). The benzylideneacetone (Table 4, entry 5) and
cyclohexen-2-one (Table 4, entry 6) were also chemoselectively
hydrogenated with ease, while the conjugate reduction of a,b-
unsaturated aldehydes also provided the corresponding reduced
aldehydes in appreciable yield (Table 4, entry 7). The present
catalytic system also worked well with the electron withdrawing
aromatic substituted enones providing good conversions and
chemoselectivity (Table 4, entries 8–9). In general, we observed
that yield for the chemoselective transfer hydrogenation of
electron donating groups are higher than that of corresponding
electron withdrawing substituted enones. Moreover, we also
studied the effect of our developed catalyst for hydrogenation of
heterocyclic enones which provided good to excellent conversion
of desired product (Table 4, entries 10–11). Also, the selective
transfer hydrogenation of multiple bonds in the presence of
(
Table 1, entries 4–5) but amongst them polymer-supported
heterogeneous PS-Pd-NHC complex was found to the best
catalyst providing 99% conversion with excellent selectivity
towards the desired product in aqueous media (Table 1,
entry 1).
In transition metal-catalyzed transfer hydrogenation reac-
tions, the amount of catalyst employed proves to be an important
aspect, considering which efforts were made to determine the
optimum concentration of the catalyst. We studied the catalyst
loading ranging from 0.5 to 2 mol% where increase in initial
catalyst concentration up to 1.5 mol% has increased the yield of
desired product (Table 1, entries 6–8) while further increase in
the amount of catalyst had no profound effect on the yield of
the desired product (Table 1, entry 1).
Next we have studied the effect of different hydrogen source
(
9
Table 2, entries 1–4), it was observed that HCOONa gives
9% conversion with excellent chemoselectivity, HCOOK also
give good conversion (91%), while in case of HCOONH and
N (1 : 1) gives lower yield of the desired
4
mixture of HCOOH + Et
product.
3
The effect of solvent on transfer hydrogenation of a,b-
unsaturated carbonyls was studied and it was observed that
nature of solvent affected the conversion of the reaction. In
non-polar solvents like toluene (30%) and hexadecane (15%)
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a
Table 3 Effect of reaction parameters on transfer hydrogenation of benzylideneacetophenone
◦
b
Entry
Solvent
HCOONa (mmol)
Temp. ( C)
Time (h)
Conv. (%)
Selectivity (2a : 3a)
Effect of solvent
1
2
3
4
5
6
7
Toluene
3
3
3
3
3
3
3
100
100
100
78
65
100
35
12
12
12
12
12
12
12
30
15
99
65
21
50
10
96 : 4
95 : 5
99 : 1
97 : 3
97 : 3
98 : 2
97 : 3
Hexadecane
Water
EtOH
MeOH
DMF
DCM
Effect of mixed solvent system
8
9
Water + EtOH (9 : 1)
Water + DMF (9 : 1)
3
3
100
100
12
12
94
76
99 : 1
98 : 2
Effect of hydrogen donor concentration
1
1
1
0
1
2
Water
Water
Water
1.5
3
5
100
100
100
12
12
12
71
99
92
98 : 2
99 : 1
97 : 3
Effect of temperature
1
1
1
3
4
5
Water
Water
Water
3
3
3
60
80
100
12
12
12
55
85
99
98 : 2
98 : 2
99 : 1
Effect of Time
1
1
1
1
6
7
8
9
Water
Water
Water
Water
3
3
3
3
100
100
100
100
6
8
12
16
62
73
99
99
99 : 1
99 : 1
99 : 1
97 : 3
a
◦
Reaction conditions: benzylideneacetophenone (1 mmol), PS-Pd-NHC (1.5 mol %), HCOONa (3 mmol), solvent (10 mL), temperature (100 C),
b
time (12 h). Conversion based on GC analysis.
aromatic ketone was studied and achieved with ease (Table 4,
entry 12).
Furthermore, the applicability of PS-Pd-NHC catalyst on
different functional groups like amides and esters were inves-
tigated. The aliphatic a,b-unsaturated amide furnished 83%
conversion with 100% selectivity (Table 4, entry 13), whereas
aromatic a,b-unsaturated amide provided 45% conversion with
1
00% selectivity (Table 4, entry 14). In case of aromatic enoates,
the corresponding saturated esters was obtained with 43%
conversion and 100% selectivity of desired product (Table 4,
entry 15). Hence, in general these results reveals the ease with
which an recyclable heterogeneous polymer bound Pd-NHC
catalyst can facilitate the conjugate reduction of a,b-unsaturated
carbonyl derivatives.
Fig. 1 Recyclability study of PS-Pd-NHC catalyst in aqueous medium.
Reaction conditions: benzylideneacetophenone (1 mmol), HCOONa
◦
(3 mmol), catalyst (1.5 mol %), water (10 mL), temperature (100 C).
Conversion and selectivity determined by GC and GC-MS analysis.
In order to make our catalytic system more economical, we
focused on reusability of PS-Pd-NHC catalyst for hydrogena-
tion reaction. As shown in Fig. 1, catalyst was recycled for
standard reaction of benzylideneacetophenone in the presence
of HCOONa in aqueous medium. The catalyst exhibited
remarkable activity for the first two consecutive recycles while
slight decrease in conversion was observed during third and
fourth recycle without affecting chemoselectivity. The decrease
in yield for third and forth cycle may be because of hand-
ling loss of catalyst. The leaching of palladium in solution
was checked by ICP-AES analysis of the reaction mixture
and the palladium content was found below detectable level
(0.01 ppm), which revealed no significant leaching of palladium
catalyst.
Conclusions
In conclusion, the present study reports a development of highly
efficient protocol for chemoselective conjugate reduction of a,b-
unsaturated carbonyl compounds in aqueous media using PS-
Pd-NHC as an heterogeneous recyclable catalyst. The catalyst
1
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a
Table 4 Chemoselective transfer hydrogenation of a,b-unsaturated carbonyl compounds
Entry
1
Substrate
Product
Conversion (%)
99
Selectivity (2a : 3a)
99 : 1
2
99
94 : 6
3
4
99
94
97 : 3
98 : 2
5
6
7
8
9
87
98
86
94
97 : 3
94 : 6
91 : 9
86 : 14
87
99
78
99
83 : 17
94 : 6
99 : 1
93 : 7
1
1
1
0
1
2
b
1
1
3
4
83
45
100 : 0
100 : 0
1
5
43
100 : 0
a
◦
b
Reaction conditions: chalcone (1.0 mmol), PS-Pd-NHC (1.5 mol %), HCOONa (3 mmol), water (10 mL), temperature (100 C), time (12 h). 6 mmol
of HCOONa require for complete reduction.
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system was optimized with respect to various parameters and
was widely applicable for chemoselective conjugate reduction
of various electron-donating and -withdrawing substrates, with
different functionalities like aldehydes, ketones, amides and
esters affording good to excellent conversion with appreciable
selectivity (up to 100%) of the desired products. The catalyst
can be easily recycled by simple filtration process up to four
consecutive recycle without loss in any activity and selectivity.
The developed protocol with use of water as a solvent and
recyclable catalytic system introduces a success towards green
approach in organic synthesis.
catalyst was then dried under reduced pressure and kept for
activation at 80 C for a period of 4 h prior to the next
recycle. The dried catalyst was then used for catalyst recyclability
experiment and it was observed that the recovered catalyst could
be reused for four consecutive cycles affording good conversion
with appreciable chemoselectivity.
◦
Acknowledgements
The author (DBB) is greatly thankful to the UGC-SAP
(
University Grant Commission, India) for providing the
fellowship.
Experimental
References
All chemicals and reagents were purchased from firms of
repute with their highest purity available and were used
without further purification. Polymer-supported palladium-N-
heterocyclic carbene complex (PS-Pd-NHC) used was prepared
according to the reported procedure in the literature. Loading
of palladium catalyst on chloromethyl polystyrene resin support
1
E. Keinan and N. Greenspoon, J. Am. Chem. Soc., 1986, 108, 7314;
H. Lee and M. An, Tetrahedron Lett., 2003, 44, 2775.
G. Neri, L. Mercadante, A. Visco and S. Galvagno, Catal. Lett.,
1994, 29, 379.
2
12
3 A. Mori, Y. Miyakawa, E. Ohashi, T. Haga, T. Maegawa and H.
Sajiki, Org. Lett., 2006, 8, 3279.
4
A. Fujii, S. Hashiguchi, N. Uematsu, T. Ikariya and R. Noyori, J. Am.
Chem. Soc., 1996, 118, 2521; F. Su, L. He, Ji Ni, Y. Cao, H. He and
K. Fan, Chem. Commun., 2008, 3531; S. Hashiguchi, A. Fujii, J.
Takehara, T. Ikariya and R. Noyori, J. Am. Chem. Soc., 1995, 117,
was evaluated by ICP-AES analysis and was found to be about
1
0
.29 mmol g- of support.
7
562.
Experimental procedure for chemoselective conjugate reduction
of a,b-unsaturated carbonyl
5
X. Li, L. Li, Y. Tang, L. Zhong, L. Cun, J. Zhu, J. Liao and J. Deng,
J. Org. Chem., 2010, 75, 2981; Z. Baan, Z. Finta, G. Keglevich and
I. Hermecz, Green Chem., 2009, 11, 1937.
In a 10 mL deionised water, 1 mmol of corresponding a,b-
unsaturated carbonyl compound, 3 mmol of HCOONa and
polymer-supported Pd-NHC catalyst (50 mg, 0.015 mmol) were
added and the reaction mixture was stirred at 100 C for 12 h.
The progress of the reaction was monitored using GC analysis
6 Y. Sasson and J. Blum, Tetrahedron Lett., 1971, 12, 2167; Y. Sasson
and J. Blum, J. Org. Chem., 1975, 40, 1887; G. Descotes and D. Sinou,
Tetrahedron Lett., 1976, 17, 4083; T. Doi, T. Fukuyama, J. Horiguchi,
T. Okamura and I. Ryu, Synlett, 2006, 721; C. Mebi, R. Nair and B.
Frost, Organometallics, 2007, 26, 429.
◦
7 Z. Baan, Z. Finta, G. Keglevich and I. Hermecz, Tetrahedron Lett.,
2
005, 46, 6203; A. mori, Y. Miyakawa, E. Ohashi and T. Haga, Org.
(
Perkin Elmer, Clarus 400) (BP-10 GC column, 30 m ¥ 0.32 mm
ID, film thickness 0.25 mm). On completion, the products were
extracted with ethyl acetate, dried over Na SO and the solvent
Lett., 2006, 8, 3279; P. Four and F. Guibe, Tetrahedron Lett., 1982,
2
3, 1825; E. Keinan and N. Greenspoon, Tetrahedron Lett., 1985, 26,
2
4
1
353; E. Keinan and N. Greenspoon, J. Am. Chem. Soc., 1986, 108,
was evaporated under vacuum. The obtained crude product was
then purified by column chromatography using silica gel, (100–
7314; H. Otsuka, E. Shirakawa and T. Hayashi, Chem. Commun.,
2
Catal., 2006, 348, 354.
007, 1819; A. Sharma, V. Kumar and A. K. Sinha, Adv. Synth.
2
9
00 mesh size) with petroleum ether/ethyl acetate (PE–EtOAc,
5 : 05) as eluent to afford pure product. All the products are
8
S. Sakaguchi, T. Yamaga and Y. Ishii, J. Org. Chem., 2001, 66, 4710;
J. Blum, Y. Sasson and S. Iflah, Tetrahedron Lett., 1972, 13, 1015; Y.
Himeda, N. Onozawa-Komatsuzaki, S. Miyazawa, H. Sugihara, T.
Hirose and K. Kasuga, Chem.–Eur. J., 2008, 14, 11076; Wei-Jing Lu,
Yun-Wei Chen and Xue-Long Hou, Angew. Chem., Int. Ed., 2008,
1
well known and were confirmed by H NMR (Varian Mercury,
1
3
4
00 MHz NMR Spectrometer), C NMR spectra (75.43 MHz),
GC-MS (Shimadzu GC-MS QP 2010) (Rtx-17, 30 m ¥ 25 mm
4
7, 10133.
-
1
◦
ID, film thickness 0.25 mm df) (column flow 2 mL min , 80 C
9 A. Kosal and B. Ashfeld, Org. Lett., 2010, 12, 44; E. Keinan and D.
Perez, J. Org. Chem., 1987, 52, 2576; D. Hays, M. Scholl and G. Fu,
J. Org. Chem., 1996, 61, 6751.
0 W. Herrmann, Angew. Chem., Int. Ed., 2002, 41, 1290; K. Ofele,
J. Organomet. Chem., 1968, 12, 42; H. Wanzlick and H. Schonherr,
Angew. Chem., 1968, 80, 154.
1 J. W. Sprengers, J. Wassenaar, N. D. Clement, K. J. Cavell and C. J.
Elsevier, Angew. Chem., Int. Ed., 2005, 44, 2026; P. Hauwert, R.
Boerleider, S. Warsink, J. J. Weigand and C. J. Elsevier, J. Am. Chem.
Soc., 2010, 132, 16900.
◦
◦
-1
to 240 C at 10 C min . rise.) and IR (Perkin-Elmer FT-IR)
spectroscopic techniques.
1
1
Recyclability study
The reaction was carried out as mentioned above in typical
experimental procedure. However after completion of reaction,
the reaction mixture was cooled to room temperature, the
product was extracted in ethyl acetate and the aqueous layer
containing catalyst was filtered (catalyst particles are suspended
in aqueous layer), the filtered catalyst was washed vigorously
with distilled water (5 ¥ 10 mL) and methanol (5 ¥ 10 mL) to
remove all traces of product or reactant present. The filtered
1
1
2 Z. S. Qureshi, K. M. Deshmukh, P. J. Tambade and B. M. Bhanage,
Synthesis, 2011, 2, 243; J. Byun and Y. Lee, Tetrahedron Lett., 2004,
4
4
5, 1837; J. Kim, B. Jun, J. Byun and Y. Lee, Tetrahedron Lett., 2004,
5, 5827.
3 M. D. Bhor, A. G. Panda, S. R. Jagtap and B. M. Bhanage, Catal.
Lett., 2008, 124, 157; M. D. Bhor, M. J. Bhanushali, N. S. Nandurkar
and B. M. Bhanage, Catal. Commun., 2007, 8, 2064.
1
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This journal is © The Royal Society of Chemistry 2011