Osmium tetroxide-(QN)2 PHAL in an ionic liquid: A highly efficient and recyclable catalyst system for asymmetric dihydroxylation of olefins

Article abstract of DOI:10.1039/b210104c

In Os-catalysed asymmetric dihydroxylation using NMO as a co-oxidant, the combination of an ionic liquid and the new bis-cinchona alkaloid 2 generated in situ from (QN)₂PHAL during reaction provided a simple and practical approach to the recycling of both catalytic components (osmium tetroxide and chiral ligand).

Full text of DOI:10.1039/b210104c

Osmium tetroxide–(QN) PHAL in an ionic liquid: a highly efficient and
2
recyclable catalyst system for asymmetric dihydroxylation of olefins
a
a
a
a
b
Choong Eui Song,* Da-un Jung, Eun Joo Roh, Sang-gi Lee and Dae Yoon Chi
a
Life Sciences Division, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul
30-650, Korea. E-mail: s1673@kist.re.kr; Fax: +82 (0)2 958 5189; Tel: +82 (0)2 958 5143
Department of Chemistry, Inha University, 253 Yonghyundong, Namgu, Inchon 402-751, Korea; Fax: +82
0)32 860 7686; Tel: +82 (0)32 867 5604. E-mail: dychi@inha.ac.kr
1
b
(
Received (in Cambridge, UK) 14th October 2002, Accepted 30th October 2002
First published as an Advance Article on the web 15th November 2002
In Os-catalysed asymmetric dihydroxylation using NMO as
a co-oxidant, the combination of an ionic liquid and the new
bis-cinchona alkaloid 2 generated in situ from (QN) PHAL
2
during reaction provided a simple and practical approach to
the recycling of both catalytic components (osmium tetr-
oxide and chiral ligand).
The Os-catalysed asymmetric dihydroxylation (AD) of olefins
provides one of the most elegant methods for the synthesis of
1
chiral vicinal diols. Although the AD reaction offers a number
of processes that could be applied to the synthesis of chiral
drugs, natural products, fine chemicals, etc., the high cost of
osmium and chiral ligands as well as the high toxicity and
volatility of the osmium component has made their large-scale
industrial application difficult. In order to explore the possibil-
ity of the repetitive use of both catalytic components, several
out with the well-known ligand, 1,4-bis(9-O-dihydroquininyl-
phthalazine [(DHQ) PHAL], under the standard Upjohn
)
2
9
conditions (N-methylmorpholine-N-oxide (NMO) as a co-
oxidant) in the presence of the ionic liquid 1a at 20 °C. As
shown in entries 1, 3, 8 and 9 in Table 1, the results obtained in
the presence of the ionic liquid were quite comparable to those
without an ionic liquid. Especially, when olefin was added in
one portion, the reaction proceeded very fast, and thus, AD
reactions of trans-stilbene and methyl trans-cinnamate in the
presence of the ionic liquid 1 were completed within 20 min
attempts to immobilise this catalytic system have been made.2
–4
Early attempts to immobilise OsO
4
on solid-supported alkaloid
ligands failed due to severe osmium leaching.2 Recently,
Kobayashi reported that microencapsulated OsO in a polymer
4
3
matrix can be used as a recyclable osmium catalyst. However,
high loading (5 mol%) of osmium was required in a typical
dihydroxylation reaction. Very recently, another approach to
(
entry 1 in Table 1) and 4 h (entry 8 in Table 1), respectively.
Moreover, overoxidation of the product diols, a fairly common
side reaction in the Upjohn dihydroxylation, was not observed
in the presence of the ionic liquid 1. Encouraged by this result,
we next performed the following catalyst recycling experiment
2 4 2
immobilise K OsO ·2H O has been achieved by using an ion-
4
exchange technique on various solid supports. Although
recycling experiments using 1 mol% of this type of immobilised
osmium catalysts have been successfully performed for five
cycles, the amount of catalyst required is much higher than that
needed in homogeneous AD reactions. In homogeneous cases,
Table 1 Asymmetric dihydroxylation of olefins in the presence of the ionic
liquid 1a
0.2 mol% of osmium is enough to complete most reactions.
For catalyst recycling, a new approach has recently been
adopted in a number of catalytic reactions involving the use of
Ionic Yield eeb Abs.
Entry Ligand
(DHQ)
Olefin
liquid (%)
(%) config.
room temperature ionic liquids, in particular, consisting of
5
1
,3-dialkylimidazolium cations and their counter anions. In
1c
2
PHAL trans-Stilbene
1a
1a
1a
1b
1a
1a
95
45
94
92
95
89
85 S,S
n.d. S,S
97 S,S
94 S,S
97 S,S
these solvents, catalysts having polar or ionic character can be
immobilised and thus the ionic solutions containing the catalyst
can be easily separated from reagents and products. During our
2
3
4
5
6
7
d
2
(DHQ) PHAL trans-Stilbene
(DHQ)
(QN) PHAL
(QN) PHAL
2
PHAL trans-Stilbene
2
trans-Stilbene
trans-Stilbene
Styrene
b-Methyl-trans-
styrene
6
on going research using room temperature ionic liquids to
2
(QN)
(QN)
2
PHAL
PHAL
72
S
immobilise transition metal-based catalysts, we have found that
the combination of an ionic liquid 1 (1-butyl-3-methylimidazo-
2
1a
1a
1a
1a
92
96
96
96
90 S,S
lium hexafluorophosphate ([bmim][PF
6
], 1a) and 1-butyl-
-methylimidazolium hexafluoroantimonate ([bmim][SbF ],
b), and a new bis-cinchona alkaloid 2 provided a simple and
8e
9
(DHQ)
PHAL Methyl trans-
cinnamate
PHAL Methyl trans-
cinnamate
2
3
1
6
91 2R,3S
95 2R,3S
94 2R,3S
96 2R,3S
7
(DHQ)
2
practical approach to the recycling of both catalytic components
osmium tetroxide and the chiral ligand 2). During our work,
(
10
(QN)
(QN)
(QN)
2
PHAL
2
PHAL
2
PHAL
Methyl trans-
cinnamate
Methyl p-methoxy-
trans-cinnamate
a-Methylstyrene
8
4
two papers on immobilisation of OsO involving an ionic
1
1
2
liquid have quite recently been published for non-asymmetric
dihydroxylation. This prompted us to report our preliminary
results here.
1a
1a
93
98
1
63
S
a
Unless indicated otherwise, all reactions were carried out on a 1 mmol
, 2.5 mol% of chiral ligand,
.5 mmol of NMO and 2 mmol of the ionic liquid 1 in acetone–H O (v/v =
reaction scale of olefin using 1 mol% of OsO
4
1
1
2
b
0+1, 10 mL) at 20 °C. Olefins were added for 12 h. Determined by chiral
c
HPLC. Olefin was added in one portion. Reaction time was 20 min.
d
Reaction was carried out with the recovered ionic liquid phase obtained
To investigate the effect of an ionic liquid on catalysis as well
as recyclability of catalytic components, the AD reactions of
trans-stilbene and methyl trans-cinnamate were initially carried
from the reaction in entry 1 without further addition of OsO
4
and
e
(
DHQ) PHAL. Olefin was added in one portion. Reaction time was 4 h.
2
3
038
CHEM. COMMUN., 2002, 3038–3039
This journal is © The Royal Society of Chemistry 2002

In summary, this work demonstrates that the combination of
an ionic liquid and a new bis-cinchona alkaloid 2 generated in
situ from (QN) PHAL during AD reaction provides a simple
2
and practical approach to the immobilisation of both catalytic
components (osmium and the alkaloid ligand) for AD reactions.
This present method requires neither any additional modifica-
tion of ligand nor high loading of osmium. Moreover,
(
QN)
2
PHAL is more economically preparable than the conven-
PHAL [1,4-bis(9-O-dihy-
tional AD ligands such as (DHQ)
2
droquininyl)phthalazine]. Thus, we hope that the method
described here might open up new perspectives for immobilisa-
tion of catalyst for AD reactions. Further optimisation of the
recyclability of the both catalytic components is currently
underway.
This research was supported by a grant (NRL-program) from
Ministry of Science and Technology in Korea.
Scheme 1
(
entry 2 in Table 1): After completion of the reaction, all the
volatiles were removed under reduced pressure and the chiral
diols produced were extracted with pre-cooled (0 °C) diethyl
ether from the residue. The remained ionic liquid phase was
then subjected without any addition of osmium and ligand to the
next run with a new batch of the olefin and NMO. However,
further re-use of the recovered ionic liquid phase resulted in a
dramatic decrease in the yield (45% after 24 h) of the product
due to severe leaching of both osmium and (DHQ)
during the extraction with ether (entry 2 in Table 1). Leaching
of the catalytic components during the extraction can be
Notes and references
†
Typical procedure of asymmetric dihydroxylation of olefins using
-(QN) PHAL and ionic liquid: A 50 mL flask was charged with
O (10+1, v/v, 30 mL), [bmim][PF ] (1a, 3 mL), OsO (0.72 mL
of 1 wt% of aqueous solution, 0.03 mmol) and (QN) PHAL (116.2 mg, 0.15
mmol). After stirring for 10 min, N-methylmorpholine-N-oxide (NMO,
27.2 mg, 4.5 mmol) was added. trans-Stilbene (540.4 mg, 3 mmol) was
OsO
4
2
2
PHAL
acetone-H
2
6
4
2
5
ascribed to some solubility of (DHQ)
2
PHAL in ether. Since the
then added by a syringe pump for 12 h and the reaction mixture was stirred
at 20 °C for 20 min. All the volatiles were then removed under reduced
pressure and the ionic liquid layer extracted with pre-cooled (0 °C) Et O (3
2
3 30 mL). The combined ether extracts were concentrated to dryness and
the crude product was purified by flash column chromatography on silica
(EtOAc/hexane 1+2) to give 592 mg (92%) of pure 1,2-diphenyl-
1,2-ethanediol as a white solid.
complex formation of OsO and an alkaloid ligand is expected
4
to be reversible, the lowering of the concentration of chiral
ligand in the ionic liquid phase might result in more leaching of
OsO from the ionic liquid phase. Therefore, it is reasonable to
4
assume that the use of an alkaloid ligand, which can be strongly
immobilised in an ionic liquid, can minimise Os leaching during
the extraction of the product. To prove our assumption, we used
Recycling and re-use of OsO
layer recovered from the above experiment was added acetone–H
4
–ligand–ionic liquid: To the ionic liquid
O (10+1,
2
1
(
,4-bis(9-O-quininyl)phthalazine [(QN)
QN) PHAL will be converted to the alkaloid 2 bearing highly
polar residues (four hydroxy groups) during AD reactions of
olefins (Scheme 1). (QN) PHAL is more economically prepar-
able by the reaction of quinine and 1,4-dichlorophathalazine
than the conventional (DHQ)
PHAL.10
The use of (QN) PHAL instead of (DHQ)
2
PHAL] as the ligand.
v/v, 30 mL) and NMO (527.2 mg, 4.5 mmol). trans-Stilbene (540.4 mg, 3
mmol) was then added by a syringe pump for 12 h and the reaction mixture
was stirred at 20 °C. Similar work-up and purification gave 567 mg (88%)
of pure 1,2-diphenyl-1,2-ethanediol. The reaction was repeated for four
times. The results were listed in Table 2.
2
2
2
1 H. C. Kolb, M. S. VanNieuwenhze and K. B. Sharpless, Chem. Rev.,
1994, 94, 2483.
2
2
PHAL afforded
the same yields and ees (entries 4–7 and 10–12 in Table 1) and,
moreover, resulted in drastic improvement in recyclability of
both catalytic components.† The recovered ionic liquid phase
containing osmium and 2 could be recycled several times, even
in the recycle experiments using 0.1 mol% of OsO
In the case of the recycle experiments using 0.1 mol% of OsO
2
For reviews: C. E. Song and S.-g. Lee, Chem. Rev., 2002, 102, 3495; P.
Salvadori, D. Pini and A. Petri, Synlett, 1999, 1181; C. Bolm and A.
Gerlach, Eur. J. Org. Chem., 1998, 21.
3
S. Nagayama, M. Endo and S. Kobayashi, J. Org. Chem., 1998, 63,
4
(Table 2).
6
1
094; S. Kobayashi, M. Endo and S. Nagayama, J. Am. Chem. Soc.,
999, 121, 11229; S. Kobayashi, T. Ishida and R. Akiyama, Org. Lett.,
4
,
the total turnover number (TON) was 2370 (entry 2 in Table 2).
To the best of our knowledge, this is the highest TON value ever
2001, 3, 2649.
4 B. M. Choudary, N. S. Chowdari, M. L. Kantam and K. V. Raghavan,
J. Am. Chem. Soc., 2001, 123, 9220; B. M. Choudary, N. S. Chowdari,
K. Jyothi and M. L. Kantam, J. Am. Chem. Soc., 2002, 124, 5341.
reported under Upjohn conditions. It should also be noted here
that separate experiments with pure 211 gave the same results.
5
For recent reviews on ionic liquids, R. Sheldon, Chem. Commun., 2001,
However, a gradual decrease in catalytic activity and enantiose-
lectivity over successive reactions was observed and thus upon
re-use the reaction time became longer. The loss of activity can
be ascribed to osmium leaching and/or deactivation. However,
2
2
399; P. Wasserscheid and W. Keim, Angew. Chem., Int. Ed. Engl.,
000, 39, 3772; T. Welton, Chem. Rev., 1999, 99, 2071.
6
C. E. Song, W. H. Shim, E. J. Roh, S.-g. Lee and J. H. Choi, Chem.
Commun., 2001, 1122; C. E. Song, C. R. Oh, E. J. Roh and D. J. Choo,
Chem. Commun., 2000, 1743; C. E. Song, W. H. Shim, E. J. Roh and J.
H. Choi, Chem. Commun., 2000, 1695; C. E. Song and E. J. Roh, Chem.
Commun., 2000, 837.
during the extraction of diol with Et
ligand was observed.
2
O, no leaching of the chiral
Table 2 AD reactions of trans-stilbene in the ionic liquid 1a using OsO
as recyclable and reusable catalyst
4
–2
7 Preparation of ionic liquids 2: For 2a P. A. Z. Suarez, J. E. L. Dullius,
S. Einloft, R. F. de Souza and J. Dupont, Polyhedron, 1996, 15, 1217;
The synthesis of 2b was similar to that of 2a with the exception that
Entry
%Yield (%ee)
6 6
NaSbF was used in place of NaPF . The contents of water and chloride
Run 1
Run 2
Run 3
Run 4
Run 5
of 2 used in this work are < 300 ppm and < 30 ppm, respectively.
Q. Yao, Org. Lett., 2002, 4, 2197; R. Yanada and Y. Takemoto,
Tetrahedron Lett., 2002, 43, 6849.
8
a
1
2
a
†
92 (98)
90 (98)
88 (96)
89 (92)
91 (94)
58 (89)
70 (94)
—
50 (94)
—
b
9 V. Van Rheenen, R. C. Kelly and P. Y. Cha, Tetrahedron Lett., 1976, 23,
1973.
Recycle experiments were carried out on a 3 mmol reaction scale of olefin
, 5 mol% of (QN) PHAL, 4.5 mmol of NMO and 3
mL of the ionic liquid 1a in acetone–H O (v/v = 10+1, 30 mL) at 20 °C.
Olefin was added by a syringe pump for 12 h.†. Recycle experiments were
carried out on a 3 mmol reaction scale of olefin using 0.1 mol% of OsO and
PHAL, 4.5 mmol of NMO and 0.3 mL of the ionic liquid
O (v/v = 10+1, 30 mL) at 20 °C. Olefin was added by a
1
0 C. E. Song, J. W. Yang, H. J. Ha and S.-g. Lee, Tetrahedron:
Asymmetry, 1996, 7, 645.
using 1 mol% of OsO
4
2
2
11 13C NMR of two diastereomers of 2 (75.5 MHz, CD
OD): d = 22.6,
4.8, 27.7, 37.8, 43.1, 54.6, 55.4, 60.0, 64.7, 74.0, 76.4, 101.8, 118.5,
22.6, 122.8, 123.0, 127.4, 130.4, 133.5, 144.1, 145.5, 146.9, 156.8,
58.8; d = 22.8, 24.8, 28.1, 38.1, 43.1, 54.4, 55.4, 59.7, 65.2, 74.6, 76.6,
01.8, 118.5, 122.6, 122.8, 123.0, 127.4, 130.4, 133.5, 144.1, 145.5,
46.9, 156.8, 158.8.
b
3
2
1
1
1
1
4
5
mol% of (QN)
2
1
a in acetone–H
2
syringe for 12 h.
CHEM. COMMUN., 2002, 3038–3039
3039