Unexpected chemoselectivity in the rhodium-catalyzed transfer hydrogenation of α,β-unsaturated ketones in ionic liquids

Article abstract of DOI:10.1039/b913305d

Chalcone and some other α,β-unsaturated ketones were subjected to transfer hydrogenation catalyzed by the dimer [Rh(cod)Cl]₂ and the Wilkinson's catalyst in imidazolium-, ammonium- and phosphonium-based ionic liquids. In certain ionic liquids,

Full text of DOI:10.1039/b913305d

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www.rsc.org/greenchem | Green Chemistry
Unexpected chemoselectivity in the rhodium-catalyzed transfer
hydrogenation of a,b-unsaturated ketones in ionic liquids
Zolt a´ n Ba a´ n,a,b Zolt a´ n Finta, Gy o¨ rgy Keglevich and Istv a´ n Hermecz*
a
b
a
Received 6th July 2009, Accepted 16th September 2009
First published as an Advance Article on the web 1st October 2009
DOI: 10.1039/b913305d
Chalcone and some other a,b-unsaturated ketones were
subjected to transfer hydrogenation catalyzed by the dimer
4
Table 1 Transfer hydrogenation of chalcone in [bmim][BF ] with
a
Pd(OAc)
2
or RhCl(PPh
3 3
) as catalyst
[
Rh(cod)Cl] and the Wilkinson’s catalyst in imidazolium-,
2
Entry
Catalyst
Conversion%
ammonium- and phosphonium-based ionic liquids. In
certain ionic liquids, the reduction of chalcone gave 1,3-
diphenylpropan-1-one chemoselectively, in contrast with
molecular solvents, which resulted in the formation of
2
a
3a
2
5
30
0
0
1
2
3
4
5
6
2 mol% Pd(OAc)
5 mol% Pd(OAc)
10 mol% Pd(OAc)2
2 mol% RhCl(PPh
5 mol% RhCl(PPh
10 mol% RhCl(PPh
2
2
57
85
70
15
16
74
3
)
)
3
3
1
,3-diphenylpropan-1-ol. An accelerated reaction rate was
observed in [emim][BuSO ] and [emin][HeSO ]. The ob-
served chemoselectivity could be maintained applying a
molar equivalent excess of [bmim][BF ] to chalcone
3
4
4
3
)
3
0
a
Reaction conditions: 1a (0.2 mmol), HCO
2
NH
4
(0.8 mmol),
5
4
◦
[
bmim][BF
4
] (1 ml), 60 C, 3 h.
in 2-PrOH. This phenomenon suggests that there is an
interaction between the chalcone carbonyl group and the
ionic liquid which prevents reduction of the carbonyl group.
compounds has also been examined in ionic liquids with this
11
new Pd/MgLa catalyst.
The catalyst [Rh(cod)Cl] dissolved in an ionic liquid was
2
successfully recycled at least three times, in contrast with
Wilkinson’s catalyst, which lost its activity on recycling.
Results and discussion†‡
In the present paper we report our results relating to the
chemoselective rhodium-catalyzed transfer hydrogenation of
a,b-unsaturated ketones, with different ionic liquids as solvent.
For the initial investigation, we selected chalcone 1a as a model
compound under similar reaction conditions applied earlier for
Introduction
In recent years, ionic liquids have attracted considerable atten-
tion as green, efficient and environmentally friendly reaction
media for the future. This is due mainly to their appreciable
1
7
the transfer hydrogenation of cinnamic acid derivatives.
Under these conditions, the transfer hydrogenation of chal-
advantages, such as extremely low vapor pressure, good solvent
power, high thermal stability and tunable physical properties.
Accordingly, it is not surprising that a wide range of organic
chemical reactions have recently been successfully performed in
cone was examined over Pd(OAc)
2
and Wilkinson’s catalyst
, a mixture of 1,3-
in [bmim][BF ] (Scheme 1). Over Pd(OAc)
4
2
2
diphenylpropan-1-one 2a and 1,3-diphenylpropan-1-ol 3a was
obtained (Table 1, entries 1–3). Surprisingly, in the case of
Wilkinson’s catalyst, the transfer hydrogenation was chemose-
lective, but 2a was formed in only a moderate conversion (entries
ionic liquids.
Catalytic transfer hydrogenation is a well-known protocol
whereby organic compounds can be hydrogenated without
the use of special equipment or molecular hydrogen gas. The
combination of transfer hydrogenation with non-volatile, non-
flammable ionic liquids furnishes an environmentally safe and
4
and 5).
3-10
friendly alternative to classical hydrogenation.
We earlier successfully achieved the transfer hydrogenation
of a,b-unsaturated carboxylic acids over Pd catalysts in the
presence of HCO
based ionic liquids. A new Pd/MgLa mixed oxide catalyst was
also effectively used in this type of transfer hydrogenation.
2
7
NH
4
as hydrogen donor in imidazolium-
Scheme 1
Since the conversion of the chemoselective transfer hydro-
11
The transfer hydrogenolysis of some halogenated aromatic
genation was merely moderate, even with 10 mol% Wilkinson’s
catalyst (entry 6), we increased the reaction temperature to
90 C. Practically 100% conversion could be achieved within
a
◦
Chinoin Ltd., H-1045 T o´ u 1-5., Budapest, Hungary.
E-mail: istvan-ext.hermecz@sanofi-aventis.com; Fax: 36 15052632;
Tel: 36 15052865
3
0 min at this temperature (Table 2, entry 1).
We also screened some other hydrogen donors in [bmim][BF ]
4
b
Department of Organic Chemistry and Technology, Budapest University
ionic liquid, but only relatively low chemoselective conversions
were observed in 30 min (Table 2). As concerns the tested formate
of Technology and Economics H-1111, M u˝ egyetem rkp 3-9, Budapest,
Hungary
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a
Table 2 Transfer hydrogenation of chalcone in [bmim][BF
4
] in the
Table 4 Transfer hydrogenation of chalcone in ionic liquids
a
presence of different hydrogen donors
Entry Ionic liquid
Reaction time (min) Conversion%
Entry
Hydrogen donor
Conversion%
2
a
3a
0
0
0
0
26
0
3
6
0
0
0
0
0
0
0
2
>99
64
54
40
45
37
55
a
3a
0
0
0
0
0
0
0
1
2
3
4
5
6
7
8
9
1
1
1
1
1
[emim][EtSO
[emim][BuSO
[emim][HeSO
4
]
90
15
15
30
240
240
240
240
240
15
84
1
2
3
4
5
6
7
HCO
HCO
HCO
HCO
HCO
HCO
2
2
2
2
2
2
NH
Na
K
H : Et
H : Et
H : Et
4
4
]
>99
>99
>99
74
0
88
4
]
[bmim][BF
[bmim]Cl
4
]
3
3
3
N 1 : 1
N 2 : 1
N 5 : 2
[bmim][AlCl
[emim][PF
4
]
6
]
2-propanol (Na
2
CO
3
)
[bmim][PF
[hmim][PF
6
]
]
93
60
6
a
TM
Reaction conditions: 1a (0.2 mmol), RhCl(PPh
3
)
3
(0.02 mmol), H-
0
1
2
3
4
ECOENG-500
>99
>99
55
>99
>99
0
◦
donor (0.8 mmol), [bmim][BF
4
] (1 ml), 90 C, 30 min.
[P14,6,6,6][Cl
30
[P14,6,6,6][PF
[P14,6,6,6][BF
[P4,4,4,4][BF
6
]
]
]
240
240
90
4
4
a
Table 3 Transfer hydrogenation of chalcone in molecular solvents
15
[P1,i4,i4,i4][TsO]
240
a
Reaction conditions: 1a (0.2 mmol), RhCl(PPh
3
)
3
(0.02 mmol),
Entry
Molecular solvent
Conversion%
◦
NH
4
CO
2
H (0.8 mmol), ionic liquid (1 ml), 90 C.
2
a
3a
12
31
8
31
14
>99
30
1
2
3
4
5
6
EtOH
DMF
DMSO
THF
hexane
2-PrOH (Na
2-PrOH (Na
88
69
92
69
86
0
TM
2
and 3), furthermore in ECOENG-500 , an ammonium-
based ionic liquid (entry 10). Chemoselectivity was also achieved
in the phosphonium-based ionic liquids (entries 11–14). It is
interesting that the phosphonium-based ionic liquid containing
2
2
CO
CO
3
3
)
)
b
7
70
-
Cl afforded 2a chemoselectively with a high reaction rate (entry
a
Reaction conditions: 1a (0.2 mmol), RhCl(PPh
3
)
3
(0.02 mmol),
1
1), whereas no chemoselectivity was previously observed in
◦
b
HCO
of RhCl(PPh ) .
2
NH
4
(0.8 mmol), [bmim][BF
4
] (1 ml), 90 C, 30 min. 0.004 mmol
[
bmim]Cl (entry 5).
3 3
For the further investigation of the chemoselectivity attained
in the ionic liquids, we attempted to reduce the previously
prepared 2a under the same conditions in one of the most active
ionic liquids (Scheme 2). No further hydrogenation of 2a to
salts and 2-PrOH as hydrogen donors, mixtures of HCO
2
H
and Et N were found to be too reactive, resulting in intensive
3
3
a was observed in [emim][BuSO ] even within 2 days, which
4
gas formation and the reaction became uncontrollable. An
attempt was made to decrease this hyperactivity of the hydrogen
donor by applying lower reaction temperatures, but without any
success.
confirmed the chemoselectivity previously experienced in this
ionic liquid.
The chemoselective rhodium-catalyzed transfer hydrogena-
◦
tion at 90 C for 30 min was studied in different molecular
solvents (Table 3) and ionic liquids (Table 4) to clarify the
effects of the reaction medium on the chemoselectivity. In these
investigations HCO
the molecular solvents under these conditions, a mixture of
a and 3a was obtained in all cases (Table 3, entries 1–5).
2
NH
4
was utilized as hydrogen donor. In
Scheme 2
2
For a better understanding we decided to investigate the
chemoselectivity in different mixtures of the molecular solvent
When 2-PrOH was applied as solvent and hydrogen donor,
the reduction was quicker, and 3a resulted in high conversion
2-PrOH and the ionic liquid [bmim][BF
4
] (Table 5). In the pure
(
entry 6). When the amount of the catalyst was reduced to
ionic liquid (entry 1), HCO NH was applied as hydrogen donor,
2
4
2
mol%, the reaction rate decreased and a mixture of 2a and
in all other cases, 2-PrOH was used. When the volumetric
ratio was 2 : 8 the amount of 2-PrOH was not sufficient
to serve adequately as hydrogen donor (entry 2). When the
volumetric ratio of 2-PrOH was increased, the reaction resulted
chemoselectively in 2a (entries 3–5). When there was less than
10 vol% ionic liquid in the mixture, the chemoselectivity was lost
and 3a also appeared (entries 6 and 7). The product distribution
was inverted when the amount of ionic liquid was decreased
further (entry 8).
3a was obtained (entry 7).
In addition, the transfer hydrogenation of chalcone 1a was
investigated in different ionic liquids (Table 4).
No transfer hydrogenation occurred in [bmim][AlCl ] or
4
[
P
1,i4,i4,i4][TsO] (Table 4, entries 6 and 15), and no chemoselectivity
was observed in [bmim]Cl, [emim][PF ] or [bmim][PF ] (entries
, 7 and 8). In contrast with imidazoliun-based ionic liquids
6
6
5
-
containing [PF ] and a shorter alkyl chain (entries 7 and 8),
6
chemoselective transfer hydrogenation was observed in
hmim][PF ] with a lower reaction rate (entry 9). A higher
reaction rate and chemoselectivity were observed in the ionic
The molar ratio of the ionic liquid present in the solvent
mixture to chalcone 1a indicated that ~ 5 molar equivalents of
ionic liquid (20 vol%, entry 5) shoud be present in the solution to
maintain chemoselective reduction. When the amount of ionic
[
6
+
-
-
liquids involving [emim] and [BuSO
4
]
or [HeSO ] (entries
4
1
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a
Table 5 Transfer hydrogenation of chalcone in 2-PrOH + [bmim][BF
4
]
4
Table 6 Transfer hydrogenation of chalcone in [bmim][BuSO ]
a
mixtures
Entry
Derivative
Conversion%
Molar ratio
Entry [bmim][BF
Volumetric ratio 2-PrOH :
4
] : 1a [bmim][BF
4
]
Conversion%
2b–g
>99
>99
>99
>99
98
3b–g
1
2
3
4
4-chlorochalchone 1b
4¢-chlorochalchone 1c
4-methoxychalcone 1d
4¢methoxychalcone 1e
benzylideneacetone 1f
cyclohexene-2-one 1g
0
0
0
0
0
0
2
a
3a
0
0
0
0
0
4
4
96
1
2
3
4
5
6
7
8
9
~ 27 : 1
~ 21 : 1
~ 16 : 1
~ 10 : 1
~ 5 : 1
~ 2.5 : 1
~ 1.3 : 1
~ 0.5 : 1
0 : 1
0 : 10
2 : 8
4 : 6
6 : 4
8 : 2
>99
0
b
40
45
64
71
81
4
5
6
>99
a
Reaction conditions: 1b–g (0.2 mmol), RhCl(PPh
4
3
)
3
(0.01 mmol),
9 : 1
◦
b
NH
CO
2
H (0.8 mmol), [bmim][BuSO
4
] (1 ml), 90 C, 15 min. Reaction
9.5 : 0.5
9.8 : 0.2
10 : 0
time of 30 min was needed.
0
>99
a
Reaction conditions: 1a (0.2 mmol), RhCl(PPh
3
)
3
(0.02 mmol),
◦
Table 7 Transfer hydrogenation of chalcone in ionic liquids with
a
NH
4
CO
2
H (0.8 mmol), [bmim][BF
4
] (1 ml), 90 C, 30 min.
[
2
Rh(cod)Cl] catalyst
Entry Ionic liquid
Reaction time (min) Conversion%
liquid was only ~ 0.5 equivalents relative to chalcone 1a (2 vol%,
entry 8), the reaction selectivity was lost, and mainly 3a was
obtained.
In light of these results, we assume that ionic liquids
participate in a specific interaction with chalcone 1a that
prevents reduction of the carbonyl group if sufficient ionic
liquid (~5 molar equivalents) is present in the solvent mixture
2
a
3a
0
0
0
0
4
0
0
0
11
>99
0
9
32
50
1
2
3
5
6
7
8
9
1
11
12
1
1
1
[emim][EtSO4]
[emim][BuSO
[emim][HeSO
240
90
90
73
84
82
>99
89
75
91
70
89
0
4
]
]
4
[bmim][BF
[bmim]Cl
4
]
90
240
240
240
240
90
240
240
240
90
[emim][PF
[bmim][PF
[hmim][PF
6
]
]
]
(
entry 5). This interaction is still predominant when the ionic
6
6
liquid is present in a molar ratio of ~1.3–2.5, 2a being the main
component in the reaction mixtures (entries 6 and 7). Further
decrease of the molar ratio of the ionic liquid in the mixture,
however resulted in loss of the chemoselectivity (entry 8).
As regards the ionic liquids tested, one of the best results
TM
0
ECOENG-500
[P14,6,6,6][Cl
[P14,6,6,6][PF
[P14,6,6,6][BF
[P4,4,4,4][BF
[P1,i4,i4,i4][TsO]
6
]
]
>99
91
68
50
3
4
5
4
4
]
240
was achieved in [bmim][BuSO
chemical properties (density, viscosity and polarity) to those
of [bmim][BF ] (Table 4, entry 2). As the reaction took place
4
], which has very similar physico-
a
Reaction conditions:1a (0.2 mmol), [Rh(cod)Cl]
0.8 mmol Et
2
(0.02 mmol), HCO
2
H
◦
(
3
N (0.32 mmol), ionic liquid (1 ml), 90 C.
4
chemoselectively within 15 min we examined the effect of
reducing the amount of catalyst applied. When the quantity
of catalyst was halved to 0.01 mmol (5 mol%), no significant
changes were observed relative to 10 mol% within 15 min.
In the transfer hydrogenation of other chalcone derivatives,
this reduced amount of Wilkinson’s catalyst was used in
vacuum and further chalcone 1a and HCO
source were added. In this second use of the system, a conversion
of only 35% was achieved within 4 h.
2
NH as hydrogen
4
We also tested the applicability of [Rh(cod)Cl] in this chemos-
2
elective transfer hydrogenation. The same chemoselectivity was
observed in most of the ionic liquids as with Wilkinson’s
catalyst, but a longer reaction period (90 min) and a more
[
bmim][BuSO ] ionic liquid.
4
active hydrogen source (mixture of HCO
2
H and NEt ) were
3
necessary (Table 7). The following differences were observed: in
contrast to Wilkinson’s catalyst, chemoselectivity occurred also
-
in all ionic liquids containing [PF
6
] anion (enties 7–9, and 12),
TM
Scheme 3
The results of the transfer hydrogenation of chalcone deriva-
tives are listed in the Table 6 (Scheme 3). The aromatic
substituted chalcones 1b–g (entries 1–4) were chemoselectively
hydrogenated within 15 min, similarly to chalcone. In the case of
b,c no dehydrohalogenation was observed. Benzylideneacetone
f (entry 5) and cyclohexen-2-one 1g (entry 6) were also chemos-
electively hydrogenated. For benzylideneacetone, a reaction time
of 30 min was required to achieve good conversion.
while no chemoselectivity took place in ECOENG-500 , and
phosphonium based ionic liquids, except [P14,6,6,6][PF ] (entries
10, 11, 13–15). This catalyst likewise worked well with all of the
previously tested chalcone derivatives in [bmim][BF ].
The possibility of recycling was examined in a similar way as
with Wilkinson’s catalyst (though in more cycles); the results are
presented in Table 8.
On extraction with 2-PrOH, a decrease in catalytic activity was
observed in each recycling cycle since the reaction time required
to reach 90% conversion increased, first to 6 h and then to
11 h, (entries 2 and 3). Better results were obtained with toluene
extraction. The catalyst activity was found to be decreased only
in the second cycle, with a necessary reaction time of 4 h (entry
4). In the subsequent cycles involving toluene extraction, the
6
4
2
1
The possibility of recycling Wilkinson’s catalyst was examined
with chalcone 1a in [bmim][BF
4
] in the presence of HCO
2
NH .
4
The product could be extracted with 2-PrOH from this ionic
liquid. Ionic liquid containing the catalyst was dried under
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Table 8 Recycling of [bmim][BF
4
] + [Rh(cod)Cl]
2
system in chalcone
Acknowledgements
a
hydrogenation
One of the authors (ZB) is grateful for a scholarship from sanofi-
aventis.
Entry Extraction solvent Cycle Reaction time (h) Conversion 2a
1
2
3
4
5
6
7
2-PrOH
2-PrOH
2-PrOH
toluene
toluene
toluene
toluene
1
2
3
1
2
3
4
1.5
6
11
1.5
4
4
4
>90
>90
>90
>90
>90
>90
>90
Notes and references
†
General procedure: 0.2 mmol of substrate was added to a previously
prepared solution of 1 ml ionic liquid and 0.02 mmol of catalyst.
0
.8 mmol of hydrogen source was added to the mixture, which was then
◦
heated and stirred at 90 C. The reaction mixture was analyzed by HPLC
with reference substances to determine the reaction time and conversion.
The product was isolated by toluene extraction. Imidazolium-based
ionic liquids were purchased from Solvent-Innovation GmbH, and all
others from Sigma-Aldrich. The ionic liquids were used without further
a
Reaction conditions:1a (0.2 mmol), [Rh(cod)Cl]
0.8 mmol), Et N (0.32 mmol), [bmim][BF
2
(0.02 mmol), HCO
2
H
◦
(
3
4
] (1 ml), 90 C.
purification.
TM
catalytic activity was stabilized at this decreased level (entries 5–
). Under these conditions, the system was successfully recycled
‡ ECOENG-500 :PEG-5 cocomonium methylsulfate, product of
Solvent-Innovation GmbH.
7
three times.
1 T. Welton, Chem. Rev., 1999, 99, 2071–2084.
2
P. Wasserscheid and T. Welton, Ionic Liquids in Synthesis, Wiley-
VHC, Weinheim, 2008.
C. Comyns, N. Karodia, S. Zeler and J. Andersen, Catal. Lett., 2000,
67, 113–115.
Conclusions
3
Chemoselective rhodium-catalyzed transfer hydrogenation of
chalcone and some other a,b-unsaturated ketones was achieved
in certain ionic liquids in contrast with molecular solvents. An
4
5
H. Berthold, T. Schotten and H. H o¨ nig, Synthesis, 2002, 1607–1610.
T. J. Geldbach and P. J. Dyson, J. Am. Chem. Soc., 2004, 126, 8114–
8
115.
accelerated reaction rate was observed in [emim][BuSO
emin][HeSO ]. In a mixture of molecular solvent (2-PrOH)
and ionic liquid ([bmim][BF ]), an excess of at least 5 molar
4
] and
6 I. Kawasaki, K. Tsunoda, T. Tsuji, T. Yamaguchi, H. Shibuta, N.
Uchida, M. Yamashita and S. Ohta, Chem. Commun., 2005, 2134–
[
4
2
136.
4
7
Z. Ba a´ n, Z. Finta, Gy. Keglevich and I. Hermecz, Tetrahedron Lett.,
005, 46, 6203–6204.
8 J.-M. Joerger, J-M. Paris and M. Vaultier, ARKIVOC, 2006, (iv),
52–160.
J. M. Brunel, Synlett, 2007, 330–332.
equivalents of the ionic liquid relative to the substrate was found
to be essential to ensure the chemoselectivity. Whereas recycling
of Wilkinson’s catalyst in an ionic liquid was unsuccessful, the
system involving [Rh(cod)Cl] as catalyst could be successfully
recycled at least three times when the product was extracted with
toluene.
2
1
9
2
1
0 J. M. Brunel, Tetrahedron, 2007, 63, 3899–3906.
11 Z. Ba a´ n, A. Pottor, A. Cwik, Z. Hell, Gy. Keglevich, Z. Finta and I.
Hermecz, Synth. Commun., 2008, 38, 1601–1609.
1
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