Osmium catalyzed asymmetric dihydroxylation of methyl trans-cinnamate in ionic liquids, followed by supercritical CO2 product recovery

Article abstract of DOI:10.1016/j.jorganchem.2005.04.025

In this work, osmium-catalyzed asymmetric dihydroxylation (AD) of methyl trans-cinnamate was studied. Osmium and chiral ligand catalysts were immobilized in ionic liquid only, without any other reaction solvents, while the recovery of the product was perf

Full text of DOI:10.1016/j.jorganchem.2005.04.025

Journal of Organometallic Chemistry 690 (2005) 3600–3608
www.elsevier.com/locate/jorganchem
Osmium catalyzed asymmetric dihydroxylation of methyl
trans-cinnamate in ionic liquids, followed by
supercritical CO2 product recovery
a
b
c,
*
Ana Serbanovic , Luis C. Branco , Manuel Nunes da Ponte * b,1, Carlos A.M. Afonso
a
ITQB, Universidade Nova de Lisboa, Apartado 127, 2780-901 Oeiras, Portugal
´ ˆ
REQUIMTE, CQFB, Departamento de Quımica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
b
c
´ ´
CQFM, Departamento de Engenharia Quımica, Instituto Superior Tecnico, Complexo 1, Av. Rovisco Pais, 1049-001Lisboa, Portugal
Received 16 February 2005; accepted 12 April 2005
Available online 8 June 2005
Abstract
In this work, osmium-catalyzed asymmetric dihydroxylation (AD) of methyl trans-cinnamate was studied. Osmium and chiral
ligand catalysts were immobilized in ionic liquid only, without any other reaction solvents, while the recovery of the product
was performed by extraction with supercritical CO2, and compared with results obtained by extractions with organic solvents such
as hexane and diethyl ether. In supercritical CO2 extraction experiments, optimal extraction pressure was found and ionic liquid
chosen, so that the highest reaction yields coupled with lowest osmium content in the crude product can be achieved. Finally, recycle
experiments of the same (ionic liquid + catalytic system) mixture were successfully conducted. Application of ionic liquids and
supercritical CO2 in osmium catalyzed AD allows for the isolation of the diol basically without contamination with osmium, in high
yield and enantiomeric excess, and it makes possible the efficient reuse of ionic liquid solvent and the catalytic system.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Asymmetric dihydroxylation; Ionic liquids; Supercritical CO2; Taxol side chain; Catalyst reuse; Osmium contamination
1. Introduction
advantageous for the efficient synthesis of 3 [3a]. The
Sharpless asymmetric dihydroxylation is a very robust
methodology for the synthesis of a diverse range of chi-
ral 1,2-diols in one step from the corresponding olefins
[4]. However, the extension of this reaction to large-scale
processes still suffers from several drawbacks – the high
cost of the osmium and chiral ligands and the high tox-
icity of the osmium, which can contaminate the chiral
product [5].
Several approaches have been developed in order to
reuse the catalytic system [6], such as immobilization
of chiral ligands onto soluble and insoluble polymers.
However, this approach has shown the need of long syn-
thesis of each chiral ligand, reduction of the enantiose-
lectivity, and/or uncompleted recovery and reuse of the
osmium-ligand catalytic system, due to the occurrence
N-Benzoyl-(2R,3S)-3-phenylisoserine 3 is an impor-
tant unit of the C-13 side chain of the taxol (paclitaxel)
family for the antitumor activity [1]. The synthesis of 3
has become of high interest [2], and a considerable num-
ber of asymmetric oxidation methodologies on the sub-
strate trans-cinnamate unit have been applied [3].
Among them, the Sharpless asymmetric dihydroxyla-
tion (AD) and aminohydroxylation (AA) are the most
*
Corresponding author. Tel.: +351 218417627; fax: +351 218417122/
64455.
E-mail addresses: mnp@dq.fct.unl.pt (M. Nunes da Ponte),
carlosafonso@ist.utl.pt (C.A.M. Afonso).
1
Tel.: +351 21 2948353; fax: +351 21 2948550.
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.04.025

A. Serbanovic et al. / Journal of Organometallic Chemistry 690 (2005) 3600–3608
3601
of osmium leaching [7]. Other efficient approaches have
O
OH O
AD
been described: microencapsulation of osmium catalyst
in polystyrene [8], polyurea (achiral version) [9], anchor-
ing in poly(ethylene glycol) matrixes [10], silica tetrasub-
stituted olefins [11], ion exchangers [12], nanocrystaline
magnesium oxide [13] anchoring in Amberlite contain-
ing residual vinyl groups [14], gold colloids [15], biphasic
system containing dendrimer-bound (achiral version)
[16] or fluorous (achiral version) [17] osmium catalyst.
More recently, another simple and efficient approach
for the immobilization of the (non-chiral) osmium [18]
and chiral ligand [19] has been reported by using room
temperature ionic liquids (ILs) as co-solvents to the tra-
ditional reaction solvent systems, consisting of t-BuOH/
water or acetone/water, including the use of H2O2 as co-
oxidant in the presence of OsO4, N-methylmorpholine
oxide (NMO) and flavin as the catalyst system [20].
Moreover, extensive research of osmium catalyst immo-
bilization in ionic liquids only, without any other reac-
tion solvents, followed by supercritical CO2 extraction,
has been conducted in our laboratories [21].
Room temperature ionic liquids are a relatively new
and peculiar media that has been intensely studied dur-
ing the last decade and applied in different areas, such as
electrochemical transformations, fuel cells, solar cells,
analytical and preparative separation and nanochem-
istry [22]. ILs are also appealing as reaction media in or-
ganic chemistry, with special focus in organometallic
catalysis, organocatalysis and biocatalysis [23]. During
the last years, it has been demonstrated that ILs are in
fact a unique alternative reaction media for a consider-
able range of catalytic reactions [23], with many exam-
ples of similar or better enantioselectivites to the ones
in traditional organic solvents.
Their non-volatility, as well as the possibility to mod-
ulate the solubility properties relative to either common
organic solvents, water, catalysts, organic reactants or
products by appropriate combination of the cation
and anion, allow for a very simple, robust and efficient
method for catalyst reuse, simply by immobilizing the
catalyst in the IL under homogeneous conditions.
For the success of this approach, it is necessary that
the catalyst has a strong affinity to the IL phase, while
very low or no affinity for the solvent (including scCO2
[24] or membrane technology [25]) used to extract the
product from the IL phase. It is also crucial for the cat-
alyst to be effective in the IL reaction medium, especially
in the case of asymmetric catalysis.
Ph
O
Ph
O
in Ionic Liquid
OH
1
2
O
Ph
NH
O
R
Ph
O
OH
3
Taxol Side Chain
Scheme 1.
solvent power is a function of density, it is possible to
tune it by a small modification of those variables. This
property, combined with other advantages mentioned
above, makes scCO2 attractive for solubility-based sep-
aration processes. At least two major reviews and a
book have recently been published on scCO2 application
in chemical synthesis and processing [26].
The combination of supercritical CO2 with ionic liq-
uids as alternative reaction medium has recently become
an intensive focus of research [27]. In fact, the remark-
able properties of both solvents can bring numerous
advantages to chemical processes. Due to their ionic nat-
ure and negligible vapour pressure, ionic liquids exhibit
no appreciable solubility in scCO2; at the same time,
scCO2 is remarkably soluble in most ionic liquids, and
can be used to extract numerous organic substances
from them without any IL contamination in the final
product [28].
Several reactions with organometallic catalysts have
been performed in IL-scCO2 systems [29]. We reported
for the first time this system being used for osmium cat-
alyzed AD reaction [21].
In line with our ongoing interest in the development
of new ILs [30], their application in separation technol-
ogy [27c,31], and their use as an efficient reaction med-
ium for catalyst immobilization [19a,c,32], and
encouraged by the results obtained for the AD reaction
on the model substrate 1-hexene [21], we applied this
methodology to the important substrate methyl trans-
cinnamate 1. The importance of this substrate lies in
the fact that it allows for the preparation of the diol 2,
a known efficient precursor for the synthesis of the taxol
side chain 3 (Scheme 1).
2. Results and discussion
Supercritical CO2 (scCO2) is the most commonly used
supercritical fluid, due to its advantageous properties –
relatively low and easily reachable critical parameters
(tc = 31 ꢁC, pc = 73.8 bar), non-flammability, low cost
and low toxicity (threshold limit value – TLV =
5000 ppm). One of the most distinctive properties of a
supercritical gas is that the density is very sensitive even
to slight pressure and temperature changes. Since the
Herein, we present the extension of the research per-
formed previously by our group, which proved the
advantages of running AD reaction in ILs only, fol-
lowed by extraction of the product with scCO2. The
model substrate in these studies was 1-hexene. In this
work, we performed a series of experiments of AD

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A. Serbanovic et al. / Journal of Organometallic Chemistry 690 (2005) 3600–3608
Table 1
Asymmetric dihydroxylation of methyl trans-cinnamate 1 using ionic liquids as solvent and co-solventa
Solvent system
Yield (%) (e.e. (%))b
K3Fe(CN)6
NMO
PHAL
PYR
PHAL
PYR
[C4mim]PF6/H2O (1:2)
[C8mim]PF6/H2O (1:2)
[C4mim]PF6/H2O/t-BuOH (1:1:2)
[C8mim]PF6/H2O/t-BuOH (1:1:2)
[C4mim]PF6
95 (81)
85 (68)
82 (75)
80 (70)
88 (83)
94 (84)
83 (66)
65 (80)
51 (76)
88 (80)
78 (93)
67 (73)
83 (66)
87 (62)
68 (90)
78 (85)
87 (79)
65 (91)
66 (92)
85 (84)
66 (62)
82 (83)
86 (91)
83 (92)
85 (72)
79 (66)
82 (69)
83 (62)
87 (80)
86 (87)
60 (61)
70 (92)
65 (79)
80 (79)
70 (76)
93 (78)
84 (66)
81 (65)
84 (72)
89 (89)
[C8mim]PF6
[C4mim][NTf2]
[C4mim]BF4
[bdmim]BF4
t-BuOH/H2O (1:2)
a
Reaction conditions: 1 (0.55 mmol), K3Fe(CN)6 (3 mol equiv.) or NMO (1.3 mol equiv.), K2OsO2(OH)4 (0.5 mol%), (DHQD)2PHAL or
(DHQD)2PYR (1 mol%), solvent system (1–2 mL), RT, 24 h.
b
Isolated yield (%) and enantiomeric excess (%) (e.e. in brackets) of the diol 2; in bold are presented the best three results using IL as solvent or co-
solvent.
reactions for the substrate methyl trans-cinnamate 1,
with ionic liquids acting either as co-solvent or only
solvent. The reaction is followed by extraction of the
product by either organic solvents or supercritical CO2.
Ionic liquids [C4mim]PF6, [C4mim]BF4, [C4mim]
[NTf2], [C8mim]PF6 and [bdmim]BF4 were selected as
potential candidates for further experiments, on the ba-
sis of previous study of the AD reaction in ILs for a
range of aryl and alkyl-olefins [21].
it is also necessary to extract the IL with water in order
to remove the inorganic salts, which implies additional
leaching of the osmium catalyst [19c].
AD reaction can also be efficiently performed using
IL as the only solvent used, giving better or similar
yields and e.e.s for a range of substrates to those re-
ported using the optimised solvent system consisting of
organic solvent/water [4] or IL as a co-solvent [19]. In
our previous experiments with 1-hexene, the IL and
the catalytic system was reused for 14 times by extrac-
tion with diethyl ether without considerable loss of yield
(6%) and e.e. (4%) and the osmium content in the prod-
uct was in the range of 1–2% of the initial amount of the
osmium catalyst. Additionally, when NMO was used as
a co-oxidant, high e.e.s were observed by adding the ole-
fin at once, which is due to low solubility of the olefin in
the IL [21], allowing to suppress the secondary catalytic
cycle [4a,33].
The reuse of the IL and catalytic system for the AD
of methyl trans-cinnamate 1 was tested by performing
extraction with either organic solvents hexane and
diethyl ether, or scCO2. The co-oxidant used for these
comparative experiments was NMO, while the ionic liq-
uids chosen were [C8mim]PF6 and [bdmim]BF4, those
that gave the best perfomance in the preliminary studies.
In the case of extraction with organic solvents, after
each cycle the organic phases were removed, and more
substrate 1 and co-oxidant NMO was added to the IL
phase. The combined organic phases were equally di-
vided in two parts. One part was used for the determina-
tion of the osmium content by ICP and the other was
further purified by flash chromatography for the deter-
mination of the yield and e.e.
In Table 1, the results obtained for methyl trans-
1 are presented, using K2OsO2(OH)4
cinnamate
(0.5 mol%), two chiral ligands (DHQD)2PHAL or
(DHQD)2PYR (1.0 mol%), and the co-oxidants
K3Fe(CN)6 or N-methylmorpholine oxide (NMO).
For systems consisting of IL as a co-solvent (IL/water
or IL/water/t-BuOH), higher yields were obtained using
K3Fe(CN)6 as co-oxidant, while higher enantiomeric ex-
cesses were generally observed using NMO. When IL
was used as the only solvent, the results clearly show
that the observed yields and enantiomeric excesses
(e.e.s) are more dependent on the combination of IL,
chiral ligand and co-oxidant. However, for each chiral
ligand and co-oxidant, similar or even better yield and
e.e. was obtained than in the case of the conventional
t-BuOH/H2O (1:2) solvent (results in bold vs. last row).
In our previous study of AD of 1-hexene in ionic li-
quid as co-solvent, we were able to reuse the IL and
the osmium-chiral ligand catalytic system for nine times
with low reduction of the yield (8%) and enantioselectiv-
ity (e.e., 5%) by careful extraction of the reaction media
with the appropriate organic solvent. Under those con-
ditions the osmium content in the recovered chiral diol
was always less than 3% of initial amount [19a,c].
The use of NMO instead of K3Fe(CN)6 is advanta-
geous for the removal of the reaction products from
the IL, since all products can be removed using non-
aqueous solvents. In case of the co-oxidant K3Fe(CN)6
In Table 2, the observed results are presented. It is
clear that the IL-catalytic system is also extremely ro-
bust for the substrate 1 (run 1, yield 79%, e.e. 78%;
run 6, yield 79%, e.e. 81%). The isolated yields for each

A. Serbanovic et al. / Journal of Organometallic Chemistry 690 (2005) 3600–3608
3603
Table 2
Reuse of the catalyst system for the AD reaction of methyl trans-cinnamate 1 in [C8mim]PF6 using NMO as co-oxidant and extraction with Et2O or
hexanea
Run
Et2O
Hexane
Yield (%)b (e.e. (%))
Os content (%)c
Yield (%)b (e.e. (%))
Os content (%)c
1
2
3
4
5
6
79 (78)
72 (79)
75 (83)
70 (81)
77 (85)
79 (81)
52d (82)
<0.05
<0.05
<0.05
0.08
41 (82)
45 (77)
48 (78)
64 (76)
67 (80)
61 (78)
142d (77)
<0.05
<0.05
<0.05
<0.05
<0.05
<0.05
–
<0.05
<0.05
–
a
Reaction conditions: 1 (0.55 mmol), NMO (1.3 mol equiv.), K2OsO2(OH)4 (0.5 mol%), (DHQD)2PYR (1 mol%), [C8mim]PF6 (2 mL), RT, 24 h,
followed by extraction with Et2O or hexane (2 · 5 mL), removed the organic solvent and reload with substrate 1 and NMO.
Isolated yield and enantiomeric excess (e.e. in brackets) of the diol 2 (%).
b
c
Percentage of osmium relative to initial amount detected by ICP in the combined organic phase (detection limit 0.05%).
After purification by flash chromatography, more diol 2 was isolated from the remaining ionic liquid (61 mg (52%) by extraction with Et2O and
168 mg (142%) by extraction with hexane).
d
run obtained by extraction with Et2O and hexane are for
all cycles, respectively, 8.7% and 23.7% in average lower
than the observed one when the product 2 was removed
from the IL reaction mixture without solvent extraction
(Table 1, yield of 93%). In fact, after solvent extraction
of the last cycle, the IL retained 52% and 142% of diol 2.
This demonstrates that the AD reaction keeps the effi-
ciency during the reuse experiments, but the removal
of the product is not complete by extraction with Et2O
and very inefficient when using the less polar solvent
hexane. However, very importantly, the osmium content
in the crude organic phases of each cycle has been found
below the detection limit (less than 0.05%), for reuse sys-
tems extracted with either Et2O or hexane.
In the study with 1-hexene, scCO2 was proved a fea-
sible solvent for product extraction, and the catalytic
system was reused eight times [21a]. The erosion of
yields and e.e.s was higher than when using diethyl ether
as extraction solvent, but more importantly, the osmium
content in the product was the lowest one reported (less
than 0.4% of initial osmium catalyst amount).
scCO2 is denser, and hence has better solvent power.
On lowering the pressure, scCO2 density and solvent
power decrease, enhancing its selectivity. By changing
system pressure it is therefore possible to decrease the
solubility of a catalyst and selected solutes/by-products
in CO2, lowering (in case of organometallic catalysts,
even to the limit of detection) their content in the con-
densed phase, and enhancing the product quality. The
strategy should be to try and use scCO2 at the lowest
possible density, where it can still dissolve reaction prod-
ucts, but does not carry any catalyst out of the ionic li-
quid solution.
Extraction experiments with 1-hexene proved that
lowering CO2 pressure has a dramatic effect on the os-
mium content of the extracts, and that it is necessary
to work at as low pressure as possible [21] (for 1-hex-
ene, 100 bar). The product 2 of methyl trans-cinna-
mate 1 is less soluble in CO2 than 1,2-hexanediol,
therefore higher extraction pressure should be needed.
The extraction of the AD reaction in ILs for substrate
1 by scCO2 was performed using the apparatus are pre-
sented in Figs. 1 and 2.
The initial round of scCO2 extraction experiments
was performed in two different ionic liquids [bdmim]BF4
and [C8mim]PF6, at 40 ꢁC and two different pressures
(100 and 125 bar). This was done in order to find opti-
mal extraction pressure and choose ionic liquid for fur-
ther recycle experiments, so that the highest reaction
yields coupled with lowest osmium content can be
achieved.
Provided that the AD reaction proceeds efficiently in
ILs, the application of IL-scCO2 concept requires that
scCO2 will be selective towards the reaction products,
and that it will not extract the catalyst. Selectivity of
supercritical CO2 as an extraction medium can be tuned
by changing operating pressure. At higher pressures,
Fig. 1. Apparatus used for supercritical CO2 extraction: high pressure
cell (1), water bath (2), mixing plate (3), cold traps (4).

3604
A. Serbanovic et al. / Journal of Organometallic Chemistry 690 (2005) 3600–3608
CO2
2
3
5
1
scCO2
+ diol
scCO2
4
Fig. 2. Schematic diagram of the apparatus used in scCO2 extraction experiments: (1) CO2 screw injector pump; (2) constant temperature water bath;
(3) high-pressure cell; (4) magnetic stirrer; (5) cold trap.
Table 3
Mass of extracted product 2, yield and osmium content for extraction
experiments with ionic liquids [C8im]PF6 and [bdmim]BF4, at two
Table 4
Mass of extracted product, yield, enantiomeric excess and osmium
content for recycling experiments of osmium catalyst, immobilized in
a
a
different pressures of scCO2
ionic liquid [C8im]PF6 extracted with scCO2
scCO2 pressure
Extract (mg)b
Yield (%)b
Os content (%)c
Run
Extract (mg)b
Yield (%)b
e.e. (%)b
Os content (%)c
[C8 mim][PF6]
100 bar
125 bar
1
2
3
4
5
6
a
198
91
87
89
88
90
85
77
83
85
84
80
84
<0.05
<0.05
40
109
44
88
<0.05
<0.05
188 (180)
193 (193)d
191 (170)d
196 (177)d
185 (168)d
<0.05
<0.03
<0.03(0.06)d
<0.03
[bdmim][BF4]
100 bar
125 bar
a
66
93
63
86
0.23
0.16
Reaction conditions:
1 (1.1 mmol), NMO (1.3 mol equiv.),
Reaction conditions:
1 (1.1 mmol), NMO (1.3 mol equiv.),
K2OsO2(OH)4 (0.5 mol%), (DHQD)2PYR (1 mol%), IL (2 mL), RT,
24 h, followed by extraction scCO2 at 125 bar, 40 ꢁC, and reload of
substrate 1 and NMO.
K2OsO2(OH)4 (0.5 mol%), (DHQD)2PYR (1 mol%), IL (2 mL), RT,
24 h, followed by extraction with scCO2 at 40 ꢁC.
Isolated mass and yield of the diol 2.
b
b
Isolated mass, yield and observed e.e. of the diol 2.
c
Percentage of osmium relative to initial amount detected by ICP in
the extracted scCO2 phase (detection limit 0.05%).
c
Percentage of osmium relative to initial amount detected by ICP in
the extracted scCO2 phase. The detection limits of 0.05% and 0.03%
were achieved, respectively, for runs 1–3 and 4–6.
d
The results in brackets represent the mass of product after 60 cm3
This was confirmed in our experiments: higher yields
of more than 80% were achieved only at 125 bar,
while at 100 bar they were much lower, as presented
in Table 3. On the other hand, osmium content in
the extract was still low, even at 125 bar. In case of
[C8mim]PF6 it was below the detection limit of the
ICP method (0.05%) at both 100 and 125 bar of
CO2 pressure, while for [bdmim]BF4, there was some,
even though small, amount of osmium detected in the
samples (Table 3). Supercritical CO2 extraction from
the ionic liquid [C8mim]PF6 proved therefore to be
more selective. For this reason, [C8mim]PF6 was cho-
sen for the study of the reuse of the ionic liquid + cat-
alyst system.
In the second round of extraction experiments, suc-
cessive reaction-extraction cycles were performed with
the same ionic liquid + osmium-chiral ligand catalyst
solution. In each new cycle, the substrate and co-oxidant
were added to the IL phase that remains in the cell after
scCO2 extraction. After the reaction time has passed, a
new scCO2 extraction would be performed. The results
of recycling experiments of osmium catalyst immobi-
lized in [C8im]PF6 are presented in Table 4.
of CO2 at 125 bar and 40 ꢁC was introduced.
run 3) is extracted when 60 cm3 of CO2 at 40 ꢁC and
125 bar are passed through the system. Since the density
of scCO2 at these conditions is around 730 kgmÀ3, the
quantity used for extraction corresponds to 1 mol of
CO2, and the CO2/product molar ratio of around 900.
This high value is a necessary consequence of the high
selectivity towards the product. This is obtained for all
cycles in high yield (around 90%) and enantiomeric ex-
cess (above 80%), and remarkably without contamina-
tion with osmium (lower than the ICP detection limit,
0.03% and 0.05%). For the production of the diol 2 by
the AD reaction in IL, it is clearly more advantageous
to perform the product extraction by scCO2 than by
common organic solvents, because the extraction is
more efficient and no contamination of osmium in the
product is still achieved.
3. Conclusions
The results show that most of the product (180 mg
out of 188 mg extracted in run 2, the whole amount in
Performing asymmetric dihydroxylation of methyl
trans-cinnamate 1 in ILs has proved to be a very efficient,

A. Serbanovic et al. / Journal of Organometallic Chemistry 690 (2005) 3600–3608
3605
simple and robust method for the immobilisation of the
catalyst system in the AD reaction. When combined with
scCO2 extraction system, it allows a cleaner process with
high product quality, as well as easy product recovery.
(1.0 mol%) and the catalyst K2OsO2(OH)4 (0.5 mol%)
were added. The olefin methyl trans-cinnamate 1,
(90 mg, 0.55 mmol) was then added at once, and the
reaction mixture stirred at room temperature during
24 h. The obtained mixture was extracted with dichlo-
romethane (3 · 25 mL) and the resulting solution was
dried (MgSO4), evaporated in vacuo and purified by
TLC or flash chromatography. In the case of mono-
phasic system using only ionic liquid, the reaction
mixture was dissolved in a small amount of dichloro-
methane (2 mL) and purified by flash chromatography
(eluent: ethyl acetate/1-hexane (1:3)) to give the corre-
sponding diol 2 as a white solid. The enantiomeric ex-
cess (e.e.) was determined by HPLC analysis [eluent:
hexane/iPrOH 90:10; flow rate: 1.0 mL/min]: tR =
17.0 min (minor); tR = 23.0 min (major); spectral data
are identical to authentic sample and to those previ-
ously reported [12a].
4. Experimental
4.1. General
The following chemicals were purchased from
Aldrich or Fluka and used as supplied: methyl trans-cin-
namate 1, K2CO3, K2OsO2(OH)4, K3[Fe(CN)6],
(DHQD)2PHAL, (DHQD)2PYR, t-butanol and
osmium ICP standard. All aqueous solutions were
prepared using distilled water. The ILs 1-n-butyl-
3-methylimidazolium hexafluorophosphate ([C4mim]
PF6), 1-n-butyl-3-methylimidazolium tetrafluoroborate
([C4mim]BF4), 1-n-butyl-3-methylimidazolium bis(trif-
luoromethylsulfonyl)imide ([C4mim][NTf2]), 1-n-octyl-
3-methylimidazolium hexafluorophosphate ([C8mim]
PF6) and 1-n-butyl-2,3-methylimidazolium tetrafluoro-
borate ([bdmim]BF4) were prepared according to re-
ported procedures [34]. 1H, and 13C NMR spectra
were recorded on a Bruker AMX 400 spectrometer.
Chemical shifts are reported downfield in parts per mil-
lion (ppm) from a tetramethylsilane reference for 1H and
13C NMR. IR spectra were recorded on a Mattson
Instruments model Satellite FTIR as thinly dispersed
films. HPLC analyses were performed using Merck &
Hitachi components L-600A, L-4250, T-6300, D-6000
and Dionex components P680 and UVD340S using Dai-
cel Chiralcel OD column at room temperature. Induc-
tively Coupled Plasma spectroscopy (ICP) analysis
were performed by the Analytical services laboratory
of REQUIMTE using JOBIN YVON-HORIBA, ULTI-
MA model, a free-running 27.0 MHz generator operat-
ing 1250 W.
4.1.2. General procedure used for the AD reaction
presented in Table 1 using NMO as a co-oxidant
A 5 mL flask was charged with NMO (100 mg;
1.3 mol equiv.); using a biphasic system ionic liquid/
water (0.5:1.0 mL; 1:2), or a monophasic system: ionic
liquid/water/t-butanol (0.5:0.5:1.0 mL; 1:1:2) or ionic
liquid (1.0 mL) under stirring were added the ligand
(DHQD)2PHAL or (DHQD)2PYR (1.0 mol%) and the
catalyst K2OsO2(OH)4 (0.5 mol%). The olefin methyl
trans-cinnamate 1 (90 mg, 0.55 mmol) was then added
at once, and the reaction mixture stirred at room tem-
perature during 24 h. The obtained mixture was ex-
tracted with dichloromethane (3 · 25 mL) and the
resulting solution was dried (MgSO4), evaporated in va-
cuo and purified by TLC or flash chromatography. In
the case of monophasic system using only ionic liquid,
the reaction mixture was dissolved in a small amount
of dichloromethane (2 mL) and purified by flash
chromatography (eluent: ethyl acetate/1-hexane (1:3))
to give the corresponding diol 1 as a white solid. The
enantiomeric excess (e.e.) was determined by HPLC as
described above.
Flash chromatography was carried out using an MN-
Kiesel-gel 60 M gel (230–400 mesh ASTM, Art. 815381).
All eluents were distilled prior to use. Preparative and
analytical thin layer chromatography (TLC) was carried
out using, respectively, MN Kieselgel G/UV254 (Art.
816320) glass-backed plates and MN Alugramꢂ SIL
G/UV254 (Art. 818133). The plates were visualised using
ultraviolet light (254 nm) or using phosphomolybdic
acid.
4.1.3. General procedure for the reuse of the
K2OsO2(OH)4/(DHQD)2PYR/IL system and NMO as
co-oxidant and extraction with Et2O or hexane (Table 2)
A 5 mL flask was charged with NMO (100 mg;
1.3 mol equiv.); [C8mim]PF6 (2 mL), and under stirring
the ligand [(DHQD)2PYR] (4.5 mg; 1 mol%) and the
catalyst K2OsO2(OH)4 (1.0 0.1 mg; 0.5 mol%) were
added. Methyl trans-cinnamate 1 (90 mg, 0.55 mmol)
was then added at once, and the resulting mixture stirred
for 24 h at room temperature. The ionic liquid was ex-
tracted with diethyl ether (2 · 5 mL) or hexane
(2 · 5 mL) and the combined organic phase was divided
in two equal parts. One part was dried (MgSO4), evap-
orated in vacuo and purified by flash chromatography
4.1.1. General procedure used for the AD reaction
presented in Table 1 using K3Fe(CN)6 as co-oxidant
A
5 mL flask was charged with K3[Fe(CN)6]
(495 mg; 1.5 mmol); K2CO3 (210 mg; 1.5 mmol); using
a biphasic system ionic liquid/water (0.5:1.0 mL; 1:2),
or a monophasic system: ionic liquid/water/t-butanol
(0.5:0.5: 1.0 mL; 1:1:2) or ionic liquid (1.0 mL) under
stirring the ligand (DHQD)2PHAL or (DHQD)2PYR

3606
A. Serbanovic et al. / Journal of Organometallic Chemistry 690 (2005) 3600–3608
(eluent: ethyl acetate/hexane (1:3)). The other part was
evaporated in vacuo, diluted with water (5 mL) and
the osmium content was analysed by inductively coupled
plasma spectroscopy (ICP) (k = 228.226 nm) using a cal-
ibration curve based on standard solutions prepared
from Os standard for ICP (Fluka, 1000 ppm). Then,
more methyl trans-cinnamate 1 (90 mg, 0.55 mmol),
NMO (100 mg; 1.3 mol equiv.) was added to the recy-
cled ionic liquid and the cycle was repeated. After cycle
6, the ionic reaction mixture was purified by flash chro-
matography using the same procedure described above
(4.1.2), giving, respectively, 61 mg (52%) and 168 mg
(142%) of diol 2 for the AD reaction resulted of extrac-
tion with Et2O and hexane.
when the system equilibrated, scCO2 extraction at con-
stant pressure was performed. The samples were col-
lected as described above. Fresh quantity of NMO
co-oxidant (200 mg, 1.3 mol equiv.) and substrate 1
(180 mg, 1.1 mmol) were added to the ionic liquid phase
that remains in the high pressure cell after the extrac-
tion. After the reaction time of 24 h, the new scCO2
extraction at 125 bar was carried out.
Acknowledgements
ˆ
This work was funded by Fundac¸a˜o para a Ciencia e a
Tecnologia (Lisbon, Portugal) and FEDER (Projects
Refs. POCTI/EQU/35437/1999 and POCTI/QUI/38269/
2001, and Doctoral Grants SFRH/BD/6792/2001 and
SFRH/BD/10623/2002). We gratefully acknowledge Sol-
chemar company (http://www.solchemar.com) for pro-
viding some of the ionic liquids.
4.1.4. AD reaction in ionic liquids [C8im]PF6 or
[bdmim]BF4, using K2OsO2(OH)4/(DHQD)2PYR or
(DHQD)2PHAL system and NMO as a co-oxidant,
followed by scCO2 extraction at two different pressures
Ionic liquids [C8mim]PF6 or [bdmim]BF4 (2 mL),
with (DHQD)2PYR or (DHQD)2PHAL ligand, respec-
tively,
(1 mol%),
K2OsO2(OH)4
(2.0 0.1 mg;
References
0.5 mol%), NMO (200 mg; 1.3 mol equiv.) and substrate
methyl trans-cinnamate 1 (180 mg, 1.1 mmol) were
added into the high pressure cell. The reaction was car-
ried out for 24 h at atmospheric pressure and room tem-
perature. After the reaction was finished, the high
pressure cell was connected to the scCO2 extraction
apparatus that consists of screw injector pump, water
bath and two cold traps for collecting samples (Fig. 1).
The water bath was heated to 40 ꢁC, and supercritical
CO2 at either 100 or 125 bar was added. When the sys-
tem equilibrated, scCO2 extraction at constant pressure
was performed. The cold traps were cooled with (liquid
nitrogen + ethanol) mixture, and ethanol samples col-
lected at different points of extraction. This was done
in order to determine the amount of CO2 needed to ex-
tract most of the product. Samples were then divided in
two equal parts. One was used for the determination of
the osmium content by ICP, and the other for the isola-
tion of the product and for the determination of the
enantiomeric excess as described before.
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