Clean osmium-catalyzed asymmetric dihydroxylation of olefins in ionic liquids and supercritical CO2 product recovery

Article abstract of DOI:10.1039/b411325j

The combination of ionic liquids (ILs) as solvents in the asymmetric Sharpless dihydroxylation (AD) with the use of ScCO₂ in the separation process allows a very simple, efficient, clean and robust system for the reuse of the AD catalytic system, which also does not need the use of organic solvents either for the reaction or for the separation of products and allows the isolation of the diol, in high yield and enantiomeric excess and basically without contamination with osmium.

Full text of DOI:10.1039/b411325j

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Clean osmium-catalyzed asymmetric dihydroxylation of olefins in ionic
liquids and supercritical CO product recovery{
2
a
Lu ´ı s C. Branco, Ana Serbanovic, Manuel Nunes da Ponte* and Carlos A. M. Afonso*
b
a
ac
Received (in Cambridge, UK) 26th July 2004, Accepted 27th September 2004
First published as an Advance Article on the web 25th November 2004
DOI: 10.1039/b411325j
The combination of ionic liquids (ILs) as solvents in the
asymmetric Sharpless dihydroxylation (AD) with the use of
extraction of the product with supercritical CO that follows
2
introduces, in principle, easy product recovery and catalyst recycle.
Provided that the AD reaction proceeds efficiently in ILs, the
2
scCO in the separation process allows a very simple, efficient,
application of this concept requires that scCO
towards the reaction products, and that it will not extract the
catalyst. The solvent power of scCO is easily tuneable, because it
2
will be selective
clean and robust system for the reuse of the AD catalytic
system, which also does not need the use of organic solvents
either for the reaction or for the separation of products and
allows the isolation of the diol, in high yield and enantiomeric
excess and basically without contamination with osmium.
2
depends essentially on its density, which varies rapidly with
pressure and temperature. The strategy in this work was to try and
2
use scCO at the lowest possible density where it can still dissolve
Osmium-catalyzed asymmetric dihydroxylation (AD) of olefins is
one of the most reliable methods for the preparation of chiral
vicinal diols, which act as intermediaries in the syntheses of many
biologically active substances. The obstacles to its large-scale
application in the pharmaceutical and fine chemicals industries
remain the osmium catalyst’s high cost, toxicity and potential
product contamination. To address this problem, several groups
have investigated the possibility of immobilizing the osmium
to some extent the reaction products, but does not carry any
catalyst out of the ionic liquid solution. In these high selectivity
conditions, the lower solubility of the product in scCO can be
2
compensated by extracting with higher amounts of the super-
critical solvent.
The AD reaction was performed with the substrates 1-hexene
and styrene, using the catalytic system consisting of
2 2 2 4
(DHQD) PHAL (1.0 mol%) and K OsO (OH) (0.5 mol%) and
1
2
catalyst by microencapsulation, anchoring it to porous resins, or
3
by ion exchange on various solid supports. However, none of
the co-oxidants K Fe(CN) and N-methylmorpholine oxide
3
6
(NMO). Under these conditions, a range of ILs based on the
7
methylimidazolium [mim], dimethylimidazolium [bdmim] and
8
tetraalkyldimethylguanidinium [dmg] cations were screened.
these methods proved successful to recover and reuse the catalyst
for a larger number of cycles, and to prevent catalyst leaching.
Recently, a novel way to immobilize the osmium and chiral
ligand catalyst system was achieved by using ionic liquids (ILs) as
co-solvents to the traditional reaction solvent, consisting of
4 2 8 4 6
From those ILs, [C mim]NTf , [C mim]BF , [bdmim]PF ,
[bdmim]BF and [bdmim]NTf
4
2
allowed the formation of the diol
in high yields (87–98%) and enantiomeric excesses (e.e.) (90–97%),
4
t-BuOH/water and acetone/water.
using NMO as the co-oxidant.{ Similar results were also
Herein we report on extended research of catalyst immobiliza-
tion in ionic liquids only, without any other reaction solvents, by
obtained for other olefins and using the ligands (DHQD)
(DHQD) PHAL, (DHQD) AQN and (DHQ) PHAL.{ It is also
important to mention that in previously reported methods using
2
PYR,
2
2
2
combining it with supercritical CO extraction, in order to enhance
2
4,9
product quality, minimize osmium catalyst loss and make its reuse
NMO as co-oxidant, it was always necessary to add the olefin
slowly in order to achieve high e.e. In contrast, in this work, with
the above-mentioned ILs as reaction media, high e.e. were
observed by adding the olefin at once. This advantage is due to
the low solubility of the olefin in the ILs, since we observed the
formation of a second phase of the olefin, which slowly disappears
during the reaction.
2 2
possible. The combination of supercritical CO (scCO ) with ionic
liquids (ILs) as an alternative reaction medium has recently
5
become an intensive focus of research. In fact, the remarkable
properties of both solvents can bring numerous advantages to
chemical processes. Due to their ionic nature and negligible vapour
2
pressure, ionic liquids exhibit no appreciable solubility in scCO ; at
the same time, scCO is remarkably soluble in most ionic liquids,
2
Optimised results obtained for several representative olefins in
and can be used to extract numerous organic substances from
6
them without any IL contamination in the final product. As it is
4 2 2
the selected ILs [C mim]NTf and [bdmim]NTf are presented in
Table 1.{ They clearly show yields and e.e. which are better, or
similar to those reported using the optimised solvent systems
possible to achieve homogeneous catalysis, with high selectivity
and atom efficiency, by immobilising the catalyst in an IL, the
9
4
consisting of organic solvent/water or ILs as a co-solvent.
The use of NMO in opposition to K Fe(CN) is advantageous
3
6
for the removal of the reaction products from the IL, since NMO
can be extracted from the IL phase using a non-aqueous solvent.
{
Electronic supplementary information (ESI) available: results of the AD
reaction using different ILs, co-oxidants, ligands and substrates, schematic
diagram of the apparatus used in scCO extraction, general experimental
2
3 6
In the case of K Fe(CN) , further extraction of the IL with water is
information and spectral data of initial and reused room temperature ionic
liquid. See http://www.rsc.org/suppdata/cc/b4/b411325j/
*mnp@dq.fct.unl.pt (Manuel Nunes da Ponte)
carlosafonso@ist.utl.pt (Carlos A. M. Afonso)
required, which implies additional leaching of the osmium
4
catalyst. The reuse of the IL and the catalytic system was
tested for 1-hexene using the above optimised conditions for
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 107–109 | 107

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a
Table 1 Asymmetric dihydroxylation of olefins using ionic liquids as reaction media
Styrene
yield (ee)
a-methylstyrene
yield (ee)
1-hexene
yield (ee)
1-methylcyclohexene
yield (ee)
trans-stilbene
yield (ee)
trans-5-decene
yield (ee)
Ionic liquid
[
C
4
mim]NTf
2
2
92 (93)
92 (98)
92 (89)
94 (89)
96 (97)
93 (95)
99 (98)
92 (93)
97 (67)
94 (85)
94 (99)
89 (98)
[
bdmim]NTf
a
Reaction conditions: (0.5 mmol), K
2
OsO
2
(OH)
4
(0.5 mol%), (DHQD)
2
PHAL (1.0 mol%), NMO (1 mol equiv.), IL (1.0 mL), rt, 24 h.
[
C
4
mim]NTf
mixture was extracted with diethyl ether. We observed that this
system is extremely robust ([C mim]NTf : run 1, yield 5 98%,
e.e. 5 96%; run 14, yield 5 92%, e.e. 5 92%; [bdmim]NTf : run 1,
2
and [bdmim]NTf
2
. After each cycle, the reaction
Table 2 Mass and yield of 1,2-hexanediol extracted, enantiomeric
excess and osmium content for recycling experiments on osmium
catalyst, immobilized in ionic liquid [C mim]NTf
4
2
4
2
a
a
b
Run
Extract [mg]
Yield [%]
ee [%]
Os content [%]
2
yield 5 94%, e.e. 5 93%; run 13, yield 5 93%, e.e. 5 92%; run 14,
yield 5 88%, e.e. 5 87%) and after new addition of the catalyst
and ligand in run 15, the reaction restored again the high profile
1
2
3
4
5
6
7
8
230 (37)
255 (23)
258 (17)
266 (6)
272
252
235
205 (14)
174
74 (12)
82 (7)
83 (5)
86 (2)
88
81
76
66 (5)
56
94
93
95
95
96
91
92
87
80
0.28
0.21
0.30
0.30
0.34
0.30
0.38
0.30
0.40
4 2
for the maximum of sixteen runs tested ([C mim]NTf : yield 5 97%,
e.e. 5 97%; [bdmim]NTf : yield 5 94%, e.e. 5 94%).{ However,
2
the osmium content in the crude ethereal phase of each cycle has
been found in the range of 1–2% of the initial amount of osmium
catalyst, which would lead to some contamination of the product
stream.
9
a
The results in brackets represent the product mass and extraction
yield, after the second volume of screw injector was introduced.
The osmium content in the extract for all runs is in the range of
b
The concept of scCO
2
extraction was tested for 1-hexene as a
the detection limit of the method used (ICP).
substrate model, using the same experimental conditions described
above. After the reaction was finished, the reaction mixture was
transferred to the scCO
injector pump, high-pressure cell and a cold trap.{ When two
volumes of screw injector pump filled with CO were passed
), the extraction was
2
extraction apparatus, consisting of screw
The results of recycling experiments on osmium catalyst
immobilized in [C mim]NTf are presented in Table 2.
4
2
2
For some extraction cycles (runs 1, 2, 3, 4 and 8 in Table 2), the
3
through the system (120 cm ; 1.72 mol of CO
2
sample was also collected at the point when the first volume of
3
(60 cm , 0.86 mol of CO
considered finished. The ethanol samples were collected, and
divided into two equal parts. One was used for the determination
of the osmium content by ICP and the other was used for the
isolation of the 1,2-(R)-hexanediol and for the e.e. determination.
screw injector pump filled with CO
2
2
) was
passed through the system, in order to check how much of the
product is extracted with this quantity of scCO
suggest that most of the product is recovered with the first 60 cm
of CO (CO /product molar ratio y400).{
2
. The results
3
2
The initial round of scCO extraction experiments was
2
2
performed in [bdmim]BF at 40 uC and four different pressures
4
The product is obtained in high yield (above 80% until run 6)
(100, 120, 140 and 200 bar). The results indicate that lowering the
and enantiomeric excess (above 90% until run 8), with the lowest
4
reported catalyst leaching.
pressure of CO has a dramatic effect on the osmium content of
2
the extracts. While 24.22% initial osmium content in the cell was
extracted at 200 bar, only 0.34% (close to the detection limit of the
analytical method) was measured at 100 bar.
In summary, performing dihydroxylation in ILs provides a very
efficient, simple and robust method for the immobilisation of the
catalytic system in the AD reaction and when combined with an
scCO2 extraction system allows a cleaner process with high
product quality, as well as easy product recovery.
A second round of experiments was then performed, at 100 bar,
with four additional ionic liquids ([C mim]BF , [C mim]BF ,
8
4
10
4
[
bdmim]NTf
osmium catalyst extracted were very small, up to a maximum of
.69% of the initial osmium content of the cell. For [C mim]NTf
and [C mim]BF , high yields and e.e. were obtained, together with
2 4 2
, and [C mim]NTf ). For all five ILs, the amounts of
We thank Funda c¸ a˜ o para a Ci eˆ ncia e a Tecnologia (Lisbon,
Portugal) and FEDER (projects: POCTI/EQU/35437/1999 and
POCTI/QUI/38269/2001, and doctoral grants: SFRH/BD/6792/
0
4
2
10
4
2001 and SFRH/BD/10623/2002) for financial support.
low osmium content.{ Hence they were used in the third round of
experiments, where successive reaction–extraction cycles were
performed with the same ionic liquid + osmium catalyst mixture.
In each new cycle, the substrate and co-oxidant were added to the
a
Lu ´ı s C. Branco, Ana Serbanovic, Manuel Nunes da Ponte* and
Carlos A. M. Afonso*
a
REQUIMTE, Departamento de Qu ´ı mica, Faculdade de Ci eˆ ncias e
b
a
ac
Tecnologia, Universidade Nova de Lisboa, 2829-516, Caparica,
Portugal. E-mail: mnp@dq.fct.unl.pt; Fax: 00 351 21 2948550;
Tel: 00 351 21 2948300 ext. 10934
2
IL phase, that remains in the cell after scCO extraction.
The succession was stopped only when the accumulation of the
salt NMO rendered the solution too viscous for the reaction to
take place within a feasible time interval. Still, after washing the
mixture with water and diethyl ether, the reaction medium can be
restored,{ and its reuse can be resumed.
b
ITQB, Universidade Nova de Lisboa, Apartado 127, 2780-901, Oeiras,
Portugal
c
CQFM, Departamento de Engenharia Qu ´ı mica, Instituto Superior
T e´ cnico, 1049-001, Lisboa, Portugal. E-mail: carlosafonso@ist.utl.pt;
Fax: 351 218417122; Tel: 351 218417627
1
08 | Chem. Commun., 2005, 107–109
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