Asymmetric dihydroxylation catalyzed by ionic polymer-supported osmium tetroxide

Article abstract of DOI:10.1016/j.tetlet.2005.04.113

Osmium tetroxide was immobilized onto a short-length PEGylated ionic polymer, which exhibited excellent catalytic performance in OsO4-catalyzed asymmetric dihydroxylation. The resulting polymer was recycled five times without any loss of yield or enantioselectivity. In addition to the immobilization of osmium, the polymer also exhibited an ability to immobilize a significant amount of chiral ligand.

Full text of DOI:10.1016/j.tetlet.2005.04.113

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4491–4493
Asymmetric dihydroxylation catalyzed by ionic
polymer-supported osmium tetroxide
Byoung Se Lee, Suresh Mahajan and Kim D. Janda*
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute,
10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Received 22 March 2005; revised 13 April 2005; accepted 20 April 2005
Available online 17 May 2005
Abstract—Osmium tetroxide was immobilized onto a short-length PEGylated ionic polymer, which exhibited excellent catalytic per-
formance in OsO4-catalyzed asymmetric dihydroxylation. The resulting polymer was recycled five times without any loss of yield or
enantioselectivity. In addition to the immobilization of osmium, the polymer also exhibited an ability to immobilize a significant
amount of chiral ligand.
Ó 2005 Elsevier Ltd. All rights reserved.
Economic and environmental considerations continue
to provide impetus for the recycling of homogeneous
metal catalysts via immobilization.1 As polymer-sup-
ported metal catalysts can be recovered from reaction
mixtures by simple filtration and recycled, product con-
tamination by the catalyst is far less of a concern than
when homogeneous catalysts are used. The osmium-cat-
alyzed asymmetric dihydroxylation (AD) of olefins is
one of the most widely used methods for the synthesis
of chiral vicinal diols.2 Although the AD reaction offers
an elegant approach that can be applied to the synthesis
of chiral drugs, natural products, and fine chemicals, the
high cost of osmium and chiral ligands, as well as the
high toxicity and possible contamination of osmium cat-
alysts restricts its use in the industry.
lized in the form of an osmium bisdiolate complex
through reaction with olefin-containing solid sup-
ports,5,6 and immobilized osmium in the form of
K2OsO4Æ2H2O using an ion exchange resin.7 Clearly,
while important strides have been made in this area,
additional research efforts are warranted.
Recently, we reported the immobilization of ytterbium
triflate (Yb(OTf)3) on a series of ionic polymers. The
optimal polymer-catalyst combination found was suc-
cessfully recycled 10 times without any loss of activity
or catalyst leaching when it was examined in the context
of b-amino ketone synthesis.8 Within this letter, we pro-
vided evidence that unlike other immobilization mecha-
nisms (vide supra), our technique was dependent on ion-
(induced) dipole interactions between the ionic polymer
and the metal–ligand complex. Herein, we extend the
application of our ionic polymers to the immobilization
of OsO4 and its use in the AD reaction.
Immobilization of osmium-chiral ligand complexes has
been attempted by several groups using both soluble
and insoluble polymers and silica gel.3 However, com-
plete recovery and re-use of osmium metal was not
achieved because of weak affinity of the immobilized
ligands for osmium metal. To circumvent this problem,
Kobayashi et al. applied a microencapsulation tech-
nique using soluble polystyrene affording recyclable
OsO4.4 Other techniques include OsO4 directly immobi-
Ionic polymers 3a–d containing a mesylate anion were
prepared by quarternization of poly(4-vinylpyridine/
styrene) (xP/S), where superscript x denotes pyridine
content, x = 1 0 (1a), 20 (1b), 30 (1c), 50 (1d) with
tri(ethylene glycol) monomesylate monomethyl ether
(MsO-PEG3-OMe) at 80 °C (Scheme 1). Our previous
work had shown that short-length PEG (specifically
x
PEG2) attached to the P/S polymer provides distinct
Keywords: PEGylated ionic polymer; Osmium tetroxide; Asymmetric
dihydroxylation.
advantages in immobilizing metal species, preventing
catalyst leaching and improving resin swelling.8 How-
ever, since the hydroxylation reaction requires the use
*
Corresponding author. Tel.: +1858 784 2551; fax: +1858 784
2592; e-mail: kdjanda@scripps.edu
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.04.113

4492
B. S. Lee et al. / Tetrahedron Letters 46 (2005) 4491–4493
tion with acetonitrile solvent (1:9) was selected as the
solvent of choice as this ionic polymer showed better
swelling in acetonitrile than acetone, which resulted in
high olefin conversion. Investigations were also con-
ducted with K3Fe(CN)6 as a co-oxidant and K2CO3;
surprisingly, no hydroxylation reaction took place,
probably due to the low solubility of K3Fe(CN)6 and
K2CO3. As the four OsO4-immobilized ionic polymers
4a–d had been prepared, we also undertook experimen-
tation to determine the optimal polymer for the hydrox-
ylation reaction by assessing these resins using H2O–
acetonitrile (1:9) as the solvent system (Table 1). After
12 h, % conversion was determined by HPLC, resin
(4c) [30P/S-PEG3][BF4](OsO4) proved to have the best
activity. Gratifyingly, this finding concurs with our pre-
vious study of ionic polymer-supported Yb(OTf)3.
Scheme 1. Preparation of ionic polymers.
The resin (4c) [30P/S-PEG3][BF4](OsO4) was engaged for
the AD reaction of 5 using (DHQH)2PHAL ligand for
chiral induction (Table 2). Importantly, we observed that
the reaction time was reduced by a factor of three in the
presence of the chiral ligand; presumably, this was due to
the fact that OsO4-catalyzed dihydroxylation is known
to be accelerated by ligand interaction.9 High enantiose-
lectivity (96–97% ee) was also observed in this reaction.
With regards to recycling, the resin was used four times
by recovering the catalyst via simple filtration at the con-
clusion of the reaction. Although the activity of the cat-
alyst was slightly decreased after reuse of the resin (note
extended reaction times), the desired diol was
of polar solvents, we investigated polymers with higher
PEG content. Polymers containing six PEG units were
sticky to handle and therefore we settled on polymers
containing three PEG units, since these provided ease
of handling and sufficient swelling in polar solvents.
The mesylate ionic polymers were treated with ammo-
nium tetrafluoroborate (NH4BF4) for quantitative anion
exchange of mesylate with BF4À, which was confirmed
by IR spectrosÀco1 py (OMsÀ; 1174, 1039 cmÀ1 and
À
BF4
; 1 031 c)m. Immobilization of OsO4 was
achieved by shaking a suspension of OsO4 and the
BF4 ionic polymer in acetonitrile/water. After 24 h, the
now black resins were filtered and washed with acetoni-
trile and THF. Both weight increase of the resins and
UV analysis (250 nm) of the filtrate revealed that all
the osmium was immobilized onto the ionic polymer.
The final loading of OsO4 was therefore calculated to
be 0.19 mmol/g.
Table 2. Asymmetric dihydroxylation with recycled 4c resina
Run
Time (h)
Conversion (%)
ee (%)b
1
2
3
4
5
3
99
99
96
96
4
6
99
97
Resin (4b) [20P/S-PEG3][BF4](OsO4) (2 mol % as OsO4)
was used in the dihydroxylation of trans-stilbene-4-car-
boxaldehyde (5) in several solvent systems to determine
optimal conditions using 1.5 equiv of N-methylmorpho-
line oxide as a co-oxidant (Table 1). Water in combina-
1
0
2
99
99
97
96
1
a Asymmetric dihydroxylation of 5 was carried out using (DHQD)2
PHAL ligand.
bDetermined by chiral HPLC analysis.
Table 1. Dihydroxylation of 5 with resins (4a–d) in various solventsa
Entry
Resin
Time (h)
Solvent
Conversion (%)
1
2
3
4
5
6
7
8
9
4b
4b
4b
4b
4b
4a
4b
4c
4d
24
24
24
24
24
1
H2O–acetone–CH3CN (1:1:1)
H2O–CH3CN (1:1)
H2O–CH3CN (1:2)
13
1
4
H2O–CH3CN (1:4)
H2O–CH3CN (1:9)
14
70
27
33
99
76
2
2
2
2
2O–CH3CN (1:9)
2O–CH3CN (1:9)
2O–CH3CN (1:9)
2O–CH3CN (1:9)
H
H
H
H
1
1
1
a All reactions were carried out with 5 (0.1mmol), 4a–d (2 mol %) and NMO (0.15 mmol) in solvent (1.5 mL); all data within Table 1 are %
conversion of 5 as determined by HPLC.

B. S. Lee et al. / Tetrahedron Letters 46 (2005) 4491–4493
4493
Table 3. Asymmetric dihydroxylation of several olefins with recycled
4c resina
Research Institute, and Jason Moss for critical reading
of the manuscript.
Entry Olefins
Yield (%)b ee (%)c
1Styrene
97
88
Supplementary data
2
3
4
5
4-Methoxystyrene
trans-Stilbene
88
96
99
98
97
99
The supplementary data describing the experimental
procedures for the preparation of resins and their appli-
cations in the AD reaction are available online with the
paper in ScienceDirect at doi:10.1016/j.tetlet.
2005.04.113.
trans-4-Stilbene carboxaldehyde 99
Methyl-trans-cinnamate 89
a All reactions were carried out with the olefins (1.0 mmol), 4c
(2 mol %), (DHQD)2 PHAL (3 mol % for first use, 1.4 mol % for
cycles 2–5), and NMO (1.5 mmol) for 6–24 h at room temperature.
b Isolated yield.
c Determined by chiral HPLC analysis.
References and notes
consistently obtained in excellent conversion/yield (99%)
and enantioselectivity (96–97% ee). Notably, when the
reaction was performed without additional chiral ligand
after the first use, 88% ee was obtained. This result
implies that a significant amount of (DHQH)2PHAL
ligand might also be immobilized onto the ionic polymer
in the form of an osmium–ligand complex. These prom-
ising findings allowed us to reduce the amount of the
(DHQH)2PHAL ligand to 0.7 equiv relative to OsO4
without any reduction of enantioselectivity. The filtrates
from recycled reactions were analyzed for osmium metal
by ICP-AES analysis to quantitate catalyst retention and
leaching. A small amount of osmium metal was found in
the filtrates (4%, 5%, 4%, 3%, and 3%).
1. Leadbeater, N. E.; Marco, M. Chem. Rev. 2002, 102, 3217.
2. (a) Johnson, R. A.; Sharpless, K. B. In Catalytic Asym-
metric Synthesis, 2nd ed.; Ojima, I., Ed., VCH: Weinheim,
2000, p 357; (b) Tori, S.; Liu, P.; Bhuvaneswari, N.;
Amatore, C.; Jutand, A. J. Org. Chem. 1996, 61, 3055; (c)
Lohray, B. B.; Nandanan, E.; Bhushan, V. Tetrahedron:
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To demonstrate the utility of resin 4c, the AD reaction
was performed using other olefins, and the results are
summarized in Table 3.10 The results as shown in Table
3 were obtained using a single catalyst that was recov-
ered after each use (between different olefins), thus dem-
onstrating recyclability of the immobilized catalyst
without cross-contamination. All corresponding diols
were obtained in good yield and enantioselectivity.
4. (a) Nagayama, S.; Endo, M.; Kobayashi, S. J. Org. Chem.
1998, 63, 6094; (b) Kobayashi, S.; Endo, M.; Nagayama,
S. J. Am. Chem. Soc. 1999, 121, 11229.
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Lett. 2002, 4, 4685.
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Grobet, P. J.; Jacobs, P. A. Angew. Chem., Int. Ed. 2001,
40, 586.
In summary, we have applied short-length PEGylated
ionic polymers to immobilize osmium tetroxide by the
interaction between ions and induced dipole of OsO4
in the same manner as ionic liquids. The resulting
OsO4-immobilized ionic polymers are air-stable, nonvol-
atile, and much easier to handle and recycle than soluble
OsO4. [30P/S-PEG3][BF4](OsO4) (4c) resin showed excel-
lent catalytic performance in the AD reaction of various
olefins and could be recycled several times without any
loss of yield or enantioselectivity. Significant immobili-
zation of the chiral ligand was observed, which allowed
reduction of the ligand, hence reduction in costs of sub-
sequent reactions using the same immobilized catalyst.
Investigations into improved ionic polymers where me-
tal leaching is reduced will be reported in due course.
7. (a) Choudary, B. M.; Chowdari, N. S.; Kantam, M. L.;
Raghavan, K. V. J. Am. Chem. Soc. 2001, 123, 9220; (b)
Choudary, B. M.; Chowdari, N. S.; Jyothi, K.; Kantam,
M. L. J. Am. Chem. Soc. 2002, 124, 5341.
8. Lee, B. S.; Mahajan, S.; Janda, K. D. Tetrahedron Lett.
2005, 46, 807.
9. Jacobsen, E. N.; Marko, I.; France, M. B.; Svendsen, J. S.;
Sharpless, K. B. J. Am. Chem. Soc. 1989, 111, 737.
10. Typical procedure for asymmetric dihydroxylation of
various olefins: To
a
suspension of [30P/S-PEG3]-
[BF4](OsO4) (4c) (110 mg, 2 mol %) and NMO (176 mg,
1.50 mmol) in H2O–acetonitrile (1:9) (12 mL), 300 lL
(3 mol %) of 0.1M solution of (DHQD) 2 PHAL in
acetonitrile was added. After shaking for 30 min, olefin
(1.00 mmol) was added. The mixture was shaken until the
reactant olefin was entirely consumed (monitored by
TLC). The reaction mixture was filtered with a plastic
syringe equipped with a polyethylene frit. The crude
mixture was purified by flash column chromatography.
The filtered resin was washed with acetonitrile three times
and dried under reduced pressure. This recovered resin
was reused in the same procedure with 140 lL (1.4 mol %)
of 0.1M solution of (DHQD) 2PHAL in acetonitrile.
Acknowledgments
We gratefully acknowledge financial support from The
Skaggs Institute for Chemical Biology and The Scripps