A novel microencapsulated osmium catalyst using cross-linked polystyrene as an efficient catalyst for asymmetric dihydroxylation of olefins in water

Article abstract of DOI:10.1002/adsc.200505032

A novel microencapsulated osmium catalyst (PSresin-MC Os) was developed using cross-linked polystyrene. The concept of this method may go beyond that of microencapsulation. The catalyst was successfully used in asymmetric dihydroxylation in water, and it was recovered quantitatively by simple filtration and reused several times without loss of activity. The shape of the catalyst was maintained even after several uses. Moreover, no leaching of the Os component was detected.

Full text of DOI:10.1002/adsc.200505032

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A Novel Microencapsulated Osmium Catalyst Using
Cross-Linked Polystyrene as an Efficient Catalyst for
Asymmetric Dihydroxylation of Olefins in Water
Tasuku Ishida, Ryo Akiyama, Shu¯ Kobayashi*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
Fax: (þ81)-3-5684-0634, e-mail: skobayas@mol.f.u-tokyo.ac.jp
Received: January 21, 2005; Accepted: April 8, 2005
Abstract: A novel microencapsulated osmium cata-
lyst (PSresin-MC Os) was developed using cross-
linked polystyrene. The concept of this method
may go beyond that of microencapsulation. The cat-
alyst was successfully used in asymmetric dihydroxy-
lation in water, and it was recovered quantitatively
by simple filtration and reused several times without
loss of activity. The shape of the catalyst was main-
tained even after several uses. Moreover, no leaching
of the Os component was detected.
to prepare microencapsulated catalysts using cross-
linked polystyrene. In this paper, we describe the use
of cross-linked polymers for the preparation of a micro-
encapsulated osmium catalyst.[8] The concept of this
method may go beyond that of microencapsulation.[9]
The use of cross-linked polymers is quite unusual be-
cause microcapsules are generally formed from linear
polymers, and indeed, only few successful examples to
prepare microcapsules using cross-linked polymers
were reported before this work.[8] Contrary to this, we
thought that microcapsules might be formed even
from cross-linked polymers if the polymers were flexible
and swollen well. A polystrene-1% divinylbenzene
(DVB) cross-linked polymer (polystyrene-resin) was
prepared using suspension polymerization. Polystyr-
ene-resin (1.00 g) thus prepared was combined with
OsO4 (200 mg) in THF, and the mixture was stirred for
Keywords: asymmetric dihydroxylation; microencap-
sulation; osmium tetroxide; polymer-supported
Osmium tetroxide (OsO4) is among the most effective 24 h at 658C. After cooling, MeOHwas added, and
catalysts for the dihydroxylation of olefins.[1] In particu- the resulting resin was filtered, washed with MeOH,
lar, catalytic asymmetric dihydroxylation of olefins us- and dried. Interestingly, OsO4 (170 mg) was immobi-
ing a catalytic amount of OsO4 with a chiral ligand is of- lized in the polystyrene-resin according to this method
ten used for the synthesis of biologically important nat- (Scheme 1).
ural products and others in the laboratory.[2] However,
The polystyrene-resin based, microencapsulated os-
since OsO4 is expensive, highly toxic, and is easily sub- mium catalyst (PSresin-MC Os) thus prepared was
limed, its use for the synthesis of medicines and fine then observed using the scanning electron microscope
chemicals on an industrial scale has been limited. In (SEM) and transmission electron microscope (TEM)
1998, we reported on a linear, polystyrene-based micro- (Figure 1). Itwas exciting to find that very small capsules
encapsulated osmium (PS-MC Os), with which com- (10–20 nm) were formed on the particles of the PSresin
plete recovery and reuse of the osmium catalyst without beads.
leaching of the osmium component were attained.[3,4]
We assumed that these small capsules included Os,
After that, we also developed a new type of microencap- and indeed, the Os energy-dispersive X-ray (EDX)
sulated osmium catalyst based on poly(phenoxyethoxy-
methylstyrene-co-styrene) (PEM-MC Os), and ach-
ieved a more practical asymmetric dihydroxylation of
olefins in H2O-acetone (1/1) with K3Fe(CN)6 as a co-ox-
idant.[5–7] While these catalysts have several advantages
over OsO4, they were found to be soluble in some sol-
vents because they were prepared based on liner poly-
mers. When the catalysts dissolved even partially, leach-
ing of the osmium component occurred. Moreover, the
shapes of the catalysts were sometimes changed to
lumps, which decreased their surface area, thus lowering
the catalytic activity. To address these issues, we decided sulated osmium catalyst.
Scheme 1. Preparation of the polystyrene-resin microencap-
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DOI: 10.1002/adsc.200505032
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Tasuku Ishida et al.
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Figure 1. SEM and TEM images of the polystyrene-resin and PSresin-MC Os; (a) the polystyrene-resin beads, (b) the polystyr-
ene-resin particles inside the beads, (c) the PSresin-MC Os beads, (d) and (e) the PSresin-MC Os particles inside the beads, (f)
TEM image of PSresin-MC Os.
map showed that the capsules were filled with Os (Fig-
ure 2). Thus, the Os component was formed on the par-
ticles of the PSresin beads.
We then examined the catalytic activity of PSresin-
MC Os in the asymmetric dihydroxylation of styrene.
It was found that the asymmetric oxidation proceeded
smoothly in water using PSresin-MC Os, whose activity
was comparable to that of PEM-MC Os.[5b] Moreover, it
was noted that leaching ofthe Os component was not de-
tected by fluorescent X-ray analysis even using cross-
linked polystyrene. The effect of the ratios of DVB in
polystyrene-resins on reactivity and selectivity was
also examined (Table 1). When a polystrene-0.5%
DVB cross-linked polymer was used as polymer back-
bone, a slightly higher activity of the catalyst was noted,
but a small amount of the leaching of the Os component
was observed (entry 1). We assume that the polymer was
physically weaker and was partially destroyed, which led
to the Os leaching. On the other hand, when the amount
of DVB was increased to 2% and 5%, the catalytic activ-
ity was decreased, especially in the reused catalysts. It
was observed that these catalysts did not swell well
with the substrate, and this might lead to lower activity
of the catalyst.
Figure 2. Os EDX mapping image of PSresin-MC Os (the upper
panel is an SEM image about the same point of the mapping).
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Asymmetric Dihydroxylation of Olefins in Water
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Table 1. Effect of the ratio of divinylbenzene.
Entry
DVB [mol %][a]
Yield [%] (ee [%]) {Os leaching [%]}[b]
1st run
2nd run
3rd run
4th run
5th run
1
2
3
4
0.5
1.0
2.0
5.0
92 (79) {1.2}
81 (78) {n.d.}
78 (77) {n.d.}
84 (76) {n.d.}
83 (77) {n.d.}
84 (76) {n.d.}
72 (74) {n.d.}
41 (68) {1.1}
95 (76) {n.d.}
78 (77) {n.d.}
73 (74) {n.d.}
48 (72) {n.d.}
87 (76) {n.d.}
86 (74) {n.d.}
79 (69) {n.d.}
–
96 (73) {0.9}
85 (72) {n.d.}
67 (69) {n.d.}
–
[a]
The ratio of DVB in the polystyrene-resin.
The leaching of the osmium component was determined by fluorescent X-ray analysis (a percentage of the original osmium
[b]
content of the catalyst).
n.d.¼not detected (<0.8%).
By using PSresin-MC Os containing a polystyrene-1% Table 2. Asymmetric dihydroxylation of olefins using PSre-
sin-MC Os.[a]
DVB cross-linked polymer, we tested other substrates,
and the results are summarized in Table 2. When the
amount of the catalyst was decreased to 0.2 mol %, the
reaction also proceeded smoothly to afford the desired
adduct in high yield with high enantioselectivity (en-
try 4). Terminal, trans, and trisubstituted olefins worked
well to provide the corresponding dihydroxylated prod-
ucts in high yields with good to excellent enantioselec-
tivities. In the reaction of 1-phenyl-1-cyclohexene, the
yield and enantiomeric excess were much improved us-
ing PSresin-MC Os compared with those obtained using
PEM-MC Os (entry 11).[5] In all cases, the catalysts were
recovered quantitatively, and reused several times with-
out loss of activity. It is noteworthy that the shape of the
catalyst was retained without forming lumps even after
several uses. In addition, no leaching of the Os compo-
nent was detected by fluorescence X-ray analysis in all
cases.
Entry
1
X
5
Substrate
Yield [%]
81
ee [%][b]
78
2
3
4
5
1
92
82
84
36
75
76
73
68
0.5
0.2
0.05
6
5
85
89
In summary, we have developed a novel microencap-
sulated Os catalyst using cross-linked polystyrene. The
concept of this method may go beyond that of microen-
capsulation. The salient features of this new catalyst are
as follows.
(1) A microencapsulated catalyst is prepared using a
cross-linked polymer. The catalyst is not soluble
in many solvents.
(2) The catalyst is successfully used in asymmetric di-
hydroxylation.
(3) The catalyst is recovered quantitatively by simple
filtration and reused several times without loss of
activity.
7
8
5
5
90
84
79
94
9
10[c]
5
5
99
91
55
61
11
5
82 (26)[d]
94 (86)[d]
[a]
The leaching of the osmium component was not observed
by fluorescent X-ray analysis in all cases.
The enantiomeric excess was determined by HPLC analy-
sis.
(DHQD) AQN was used as a ligand.
PEM-MC Os was used instead of PSresin-MC Os.
[b]
(4) The shape of the catalyst is maintained even after
several uses.
(5) No leaching of the Os component is detected.
(6) Water is used as the sole solvent.
[c]
[d]
2
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Tasuku Ishida et al.
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was determined by HPLC analysis using chiral stationary col-
umns.
In addition to these characteristics, since it is expected
that several other metal catalysts could be immobilized
using the same method, this work should expand the
possibility of providing microencapsulated catalysts
with wide uses in organic synthesis.
References and Notes
[1] Review: M. Schrçder, Chem. Rev. 1980, 80, 187–213.
[2] Reviews: a) H. C. Kolb, M. S. Van Nieuwenhze, K. B.
Sharpless, Chem. Rev. 1994, 94, 2483–2547; b) R. A. John-
son, K. B. Sharpless, in: Catalytic Asymmetric Synthesis,
2nd edn., (Ed.: I. Ojima), Wiley-VCH, Weinheim, 2000,
pp. 357–398.
[3] S. Nagayama, M. Endo, S. Kobayashi, J. Org. Chem. 1998,
63, 6094–6095.
[4] Review: S. Kobayashi, R. Akiyama, Chem. Commun.
2003, 449–460.
Experimental Section
Preparation of Polystyrene-Resin (PS-resin)
Styrene (50.00 g, 480 mmol), divinylbenzene (washed with 1 N
NaOH, 80 wt %; 781.0 mg, 4.8 mmol), polyvinyl alcohol (n¼
ca. 2000; 500.0 mg), and 2,2’-azobis(isobutyronitrile)
(500.0 mg, 3.04 mmol) were combined in H2O-toluene (3/1;
120 mL), and the two-phase mixture was stirred vigorously us-
ing a mechanical stirrer at 908C for 12 h. After cooling to room
temperature, an excess amount of tetrahydrofuran (THF,
200 mL) was added and the mixture was further stirred for
1 h at the same temperature. The heterogeneous mixture was
filtered and the residue was washed with THF. The obtained
polymer was swollen with THFand dropped into a large excess
amount of methanol, and this procedure was repeated twice.
The washed polymer was dried under reduced pressure and
divided into 50–200 mesh sieves to afford the desired polystyr-
ene-resin; yield: 2.96 g (29%).
[5] a) S. Kobayashi, T. Ishida, R. Akiyama, Org. Lett. 2001, 3,
2649–2652; b) T. Ishida, R. Akiyama, S. Kobayashi, Adv.
Synth. Catal. 2003, 345, 576–579.
[6] For other examples of microencapsulated catalysts, see;
a) R. Saladino, V. Neri, A. R. Pelliccia, R. Caminiti, C. Sa-
dum, J. Org. Chem. 2002, 67, 1323–1332; b) S. V. Ley, C.
Ramarao, A.-L. Lee, N. Østergaad, S. C. Smith, I. M. Shir-
ley, Org. Lett. 2003, 5, 185–187; c) M. L. Kantam, B. Ka-
vita, V. Neeraja, Y. Haritha, M. K. Chaudhuri, S. K. Dehu-
ry, Tetrahedron Lett. 2003, 44, 9029–9032; d) R. Naik, P.
Joshi, R. K. Deshpande, Catal. Commun. 2004, 5, 195–
198; e) B. M. Choudary, C. Sridhar, M. Sateesh, B. Sreed-
har, J. Mol. Catal. A: Chem. 2004, 212, 237–243.
[7] Recently several groups have reported recoverable and
reusable osmium-catalyzed reaction systems, see:
a) B. M. Choudary, N. S. Naidu, K. Jyothi, M. L. Kantam,
J. Am. Chem. Soc. 2002, 124, 5341–5349; b) Q. Yao Org.
Lett. 2002, 4, 2197–2199; c) J. W. Yang, H. Han, E. J.
Roh, S. Lee, C. E. Song, Org. Lett. 2002, 4, 4685–4688;
d) K. Huang, H.-W. Liu, X. Dou, M.-Y. Huang, Y.-Y.
Jiang, Polym. Adv. Technol. 2003, 14, 364–368; e) R.
Jiang, Y. Kuang, X. Sun, S. Zhang, Tetrahedron: Asymme-
try 2004, 15, 743–746; f) A. Kçckritz, M. Bartoszek, C.
Dçbler, M. Beller, W. Mägerlein, H.-C. Militzer, J. Mol.
Catal. A: Chemical 2004, 218, 55–66; g) J.-H. Miao, J.-H.
Yang, L.-Y. Chen, B.-X. Tu, M.-Y. Huang, Y.-Y. Jiang, Pol-
ym. Adv. Technol. 2004, 15, 221–224; h) L. C. Branco
C. A. M. Afonso, J. Org. Chem. 2004, 69, 4381–4389.
[8] Recently, Saladino et al. reported “microencapsulated”
methylrhenium trioxide using cross-linked polystyrenes,
see Ref.[6a] In this case, however, activity of the reused cat-
alysts decreased. Ley et al. developed a cross-linked osmi-
um catalyst encapsulated by polymerization of diisocya-
nate to form polyurea.[6b] Also in this case, activity of
reused catalysts decreased in asymmetric dihydroxylation
of olefins, see: A.-L. Lee, S. V. Ley, Org. Biomol. Chem.
2003, 1, 3957–3966.
Preparation of PS-resin Microencapsulated Osmium
Catalyst
The prepared polystyrene-resin (1.00 g) was stirred in THF
(20 mL) at 658C for 1 h, and then OsO4 (0.20 g) was added.
The suspension was stirred for 24 h at 658C, and then methanol
was added slowly at 08C. The mixture was allowed to stand at
room temperature for 12 h, and the catalyst was then washed
with methanol (100 mL). PSresin-MC Os (1.17 g, Os loading:
0.6 mmol/g) was obtained after drying at room temperature
for 48 h. The loading of the osmium component was deter-
mined by X-ray fluorescence analysis of the filtrate.
Typical Experimental Procedure for the Catalytic
Asymmetric Dihydroxylation of Olefins
Olefin (0.55 mmol), PSresin-MC Os (46.0 mg, 5 mol %),
(DHQD)2PHAL (21.5 mg, 5 mol %), K3Fe(CN)6 (543.3 mg,
3.0 equivs.), K2CO3 (228.0 mg, 3.0 equivs.), and Tritonꢁ X-405
(108.3 mg, 10 mol %) were combined in H2O at 308C, and
the heterogeneous slurry was stirred at 308C for 24 h. Aqueous
H2SO4 (2 N, 1.1 mL) was added slowly, and the mixture was fur-
ther stirred for 10 min. Ethanol (10 mL) was added, and the
mixture was stirred for 1 min. PSresin-MC Os was separated
by filtration and washed with water and ethanol, and then
reused. The filtrate was analyzed by fluorescent X-ray analysis
to determine the leaching of the osmium component. The
crude product was purified by chromatography on silica gel
to afford the desired cis-diol. The optical purity of the product
[9] M. Donbrow, Microcapsules and Nanocapsules in Medi-
cine and Pharmacy, CRC Press, Boca Raton, 1992.
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