Ionic liquid/water as a recyclable medium for Tsuji-Trost reaction assisted by microwave

Article abstract of DOI:10.1016/j.tetlet.2005.04.002

An efficient microwave protocol is described for allylic substitution with various carbon and heteronucleophiles catalyzed by Pd(OAc)₂/TPPTS in an [EMIm]BF₄/H₂O medium. The ionic liquid/water containing catalyst system can be recycled eight times without loss of activity.

Full text of DOI:10.1016/j.tetlet.2005.04.002

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3469–3472
Ionic liquid/water as a recyclable medium for
Tsuji–Trost reaction assisted by microwave
Meng-chun Liao, Xin-hua Duan and Yong-min Liang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
Received 9 December 2004; revised 30 March 2005; accepted 1 April 2005
Abstract—An efficient microwave protocol is described for allylic substitution with various carbon and heteronucleophiles catalyzed
by Pd(OAc)2/TPPTS in an [EMIm]BF4/H2O medium. The ionic liquid/water containing catalyst system can be recycled eight times
without loss of activity.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The Tsuji–Trost reaction is a reliable and widely used
method for constructing C–C, C–N, and C–O bonds
in organic syntheses, with high chemo-, regio-, and
stereoselectivities.1 The reaction often employs Pd(0)
complexes and activated allyl alcohol derivatives, in
particular, allylic halides, acetates, and carbonates. A
variety of nucleophiles such as, carbanions,2,3 amines,2,4
sulfides,2,5 and sulfinates,2,6 have been shown to couple
efficiently with palladium p-allyl complexes. In recent
years, allylic substitutions catalyzed by Pd(0) in water
or an aqueous–organic medium have been reported.7
a variety of possible ꢀgreenꢁ solvent alternatives for cat-
alytic reactions, room-temperature ionic liquid (RTIL)
reaction media continue to be an area of increasing re-
search activity.9 Ionic liquids of the dialkylimidazolium
class may simplify metal catalyst recycling techniques
and allow to developsome new reaction protocols due
to their high polarity and special properties. The rising
number of publications is indicative of the potential
of RTILs as ꢀneoteric solventsꢁ for various chemical
reactions.
Since the appearance of microwave assisted synthesis in
1986,10 this technique has been accepted as a common
method for reducing reaction time by several orders of
magnitude and for increasing yields of product com-
pared to conventional methods.11 The ionic liquids are
also suitable for microwave chemistry.12 We have
focused on the application of the Tsuji–Trost reaction
in a mixture of water and ionic liquid ([EMIm]BF4),13
The chemical and pharmaceutical industry is under an
accelerating pressure to find environmentally friendly
organic reaction methodologies. Because water is one
of the most suitable solvents for realizing safe, harmless,
economical, and environmentally friendly processes for
the production of fine chemicals, organic reactions in
water have recently attracted much attention.8 Among
Pd(OAc)2/TPPTS=1:4, 5% mol
MW, 400W, [EMIm]BF4/H2O
Nu
R
OAc +
R
Nu
R=Ph(1a); H(1b).
OAc
N
N
P
[EMIm]BF4=
1c=
TPPTS=
-
BF4
SO3Na
3
Scheme 1.
*
Corresponding author. Tel.: +86 931 8912593; fax: +86 931 8912582; e-mail: liangym@lzu.edu.cn
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.04.002

3470
M. Liao et al. / Tetrahedron Letters 46 (2005) 3469–3472
a new ꢀgreenꢁ solvent, which has a wide solubility to
organic materials and inorganic materials. Herein, we
reported allylic substitution with various carbon and
heteronucleophiles catalyzed by palladium(0)-TPPTS
assisted by microwave irradiation. The reaction has a
great advantage in terms of catalyst recycling, since
the product could be readily separated from the
[EMIm]BF4/H2O containing catalysts via simple extrac-
tion with a conventional organic solvent (see Scheme 1).
TPPTS, no reaction proceeded. Using [EMIm]BF4/
H2O instead of [EMIm]BF4, the desired product was ob-
tained in good yield. The water plays presumably an
important role in the process because of good water solu-
bility to Pd(OAc)2 and TPPTS. Control experiments
indicated that, in the absence of TPPTS, no product
was observed. Furthermore, the different ratios of
[EMIm]BF4 and H2O in the reaction were investigated.
It is found that the ratio from 1:1 to 1:2 did not affect
the yield. The effect of MW power level on this reaction
was examined too (Table 1). An efficient power reduced
the reaction time from 11 min to 3.5 min. So we chose
the power 400 W as operation parameter for follow-up
experiments.
Firstly, the reaction of cinnamyl acetate with sodium
azide was carried out in ionic liquid ([EMIm]BF4), in
the presence of a catalytic amount of Pd(OAc)2 and
The results concerning the reaction of allylic acetate with
various nucleophiles catalyzed by palladium(0)-TPPTS in
an ionic liquid/water medium via assisted by microwave
irradiation are summarized in Table 2. All are a-products
with E-configuration except entry 12. Reaction of com-
pounds 1a, b, or c with sodium azide (entry 1) or p-toluene
sulfinate (entries 2, 10, 12), which are soluble in water,
Table 1. Reaction at different MW power levelsa
Power (W)
Time (min)
80
11
160
8
240
6
320
5
400
3.5
a Pd(OAc)2 (5.6 mg, 0.025 mmol), TPPTS (56.8 mg, 0.1 mmol)),
[EMIm]BF4 (1 ml), H2O (2 ml), cinnamyl acetate (88 mg, 0.5 mmol),
NaN3 (48.75 mg, 0.75 mmol).
Table 2. Reaction of allylic substrates with various nucleophilesa
Allylic
Nucleophile
NaN3
Base
Product
Time (min)
3.5
Yield (%)b
75
1
2
1a
None
Ph
N3
1a
1a
NaSO2Ph
None
Et3N
1.5
3
99
93
Ph
Ph
SO2Ph
OC2H5
O
O
O
O
3c
4c
5c
OC2H5
O
O
1a
1a
None
Et3N
None
10
4
0
OC2H5
O
O
O
Ph
99
Ph
Ph
HNEt2
O
6d
7d
8d
9d
10c
1a
1a
1a
1a
1b
None
None
None
None
None
3.5
5.5
4.5
10
95
83
95
80
99
Ph
Ph
NEt2
HN
HN
HN
O
N
O
Ph
Ph
N
N
NaSO2Ph
2
SO2Ph
O
Ph
O
O
11c
1b
1c
DBU
None
9
81
Ph
O
SO2Ph
12c
NaSO2Ph
2.5
97
a Reaction conditions: Pd(OAc)2 (5.6 mg, 0.025 mmol), TPPTS (56.8 mg, 0.1 mmol), H2O (2 ml), [EMIm]BF4 (1 ml), allylic acetate (0.6 mmol),
nucleophile (0.5 mmol), base (1.5 equiv), MW (400 W).
b Isolated yields. All products were identified by NMR and mass spectrometry.
c Allylic acetate (0.5 mmol) and nucleophile (0.6 mmol) were employed.
d [EMIm]BF4 (1 ml), H2O (4 ml).

M. Liao et al. / Tetrahedron Letters 46 (2005) 3469–3472
3471
OAc
Pd(OAc)2/TPPTS=1:4, 5% mol
2a
2b
Nu
+
+
SO2Ph
PhO2S
3b
MW, 400W, [EMIm]BF4/H2O
3a
AcO
From 2a
From 2b
97% 3a:3b=1/10
98% 3a:3b=1/10
Scheme 2.
Table 3. Recycle of [EMIm]BF4/H2O reaction mediuma
Isolated yield (%)
References and notes
Run1b Run2 Run3 Run4 Run5 Run6 Run7 Run8
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a Pd(OAc)2 (5.6 mg, 0.025 mmol), TPPTS (56.8 mg, 0.1 mmol),
[EMIm]BF4 (1 ml), H2O (2 ml), cinnamyl acetate (88 mg, 0.5 mmol),
and NaSO2PhÆ2H2O (100 mg, 0.5 mmol).
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gave the corresponding allyl azide or sulfone in good
yields using this system. Alkylation of acetate needed
the presence of a base such as triethylamine (entries 3
and 5) or better DBU (1,8-diazabicyclo [5,4,0] undec-7-
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even after prolonging reaction time to 10 min in the ab-
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1a leading to the products of corresponding monoalkyla-
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rate decreased largely due to the steric hindrance.
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1
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Catalyst recycling studies were also carried out. After
extraction with diethyl ether to separate the product
from the catalyst, the resulting [EMIm]BF4/H2O was
pumped for several minutes and reused for the next reac-
tion directly. The resulting [EMIm]BF4/H2O containing
the Pd catalyst can be reused successfully eight times
without any reduction of its catalytic activity (Table 3).
In summary, we have developed a facile methodology to
assist Tsuji–Trost reaction via palladium(0)/TPPTS-cat-
alyzed in ionic liquid/water by using microwave irradia-
tion. The ꢀgreenꢁ solvent is harmless, economical, and
environmentally friendly. The catalyst system was very
easy to separate from the reaction product, so it can
be used repeatedly. The microwave irradiation is very
favorable for Tsuji–Trost reactions in [EMIm]BF4/
H2O and it assists this reaction greatly.
Acknowledgements
The authors thank the NSF-20021001, NSF-20172024,
and the ꢀHundred Scientist Programꢁ from the Chinese
Academy of Sciences for the financial support.

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M. Liao et al. / Tetrahedron Letters 46 (2005) 3469–3472
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14. General procedure: 0.025 mmol Pd(OAc)2 and 0.1 mmol
TPPTS were added to a mixture of [EMIm]BF4 (1 ml) and
H2O (2 ml) in a sealed vessel. The mixture was stirred until
Pd(OAc)2 soluted completely. Then 0.6 mmol cinnamyl
acetate (1a), 0.5 mmol acetoacetate and 0.75 mmol Et3N
(1.5 equiv) were added into the vessel. After flushed with
argon for 1 min, the vessel was put into a beaker and then
placed in the center of a microwave apparatus (domestic
microwave). The reaction mixture is irradiated by micro-
waves (400 W) for 20 s. After the reaction vessel was cooled
down to room temperature, it is irradiated for 20 s again.
When the reaction was completed, the product was
extracted by diethyl ether (3 · 10 ml). The Pd(0)-TPPTS
was kept in [EMIm]BF4/H2O. The diethyl ether layer was
combined and concentrated in vacuum. The product was
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132.7, 128.5 (2C), 127.4, 126.1 (2C), 125.7, 61.4, 59.5, 31.5,
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