An improved catalytic system for recycling OsO4 and chiral ligands in the asymmetric dihydroxylation of olefins

Article abstract of DOI:10.1016/j.tetasy.2004.01.011

A recyclable catalytic system for the asymmetric dihydroxylation of olefins was developed by using a mono-quaternized bis-cinchona alkaloid ligand 3 and OsO₄ combined with PEG or an ionic liquid. Both the catalytic components could be recovered and reused in five consecutive reactions without any additional OsO₄ or ligand. The catalytic system is effective in the AD reactions of seven olefins.

Full text of DOI:10.1016/j.tetasy.2004.01.011

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 743–746
An improved catalytic system for recycling OsO and chiral ligands
4
in the asymmetric dihydroxylation of olefins
Ru Jiang, Yongqing Kuang, Xiaoli Sun and Shengyong Zhang*
Department of Chemistry, Fourth Military Medical University, Xi’an 710032, PR China
Received 9 December 2003; accepted 5 January 2004
Abstract—A recyclable catalytic system for the asymmetric dihydroxylation of olefins was developed by using a mono-quaternized
bis-cinchona alkaloid ligand 3 and OsO combined with PEG or an ionic liquid. Both the catalytic components could be recovered
4
and reused in five consecutive reactions without any additional OsO
of seven olefins.
4
or ligand. The catalytic system is effective in the AD reactions
ꢀ
2004 Published by Elsevier Ltd.
1
. Introduction
reaction media due to the low solubility of the ligand in
ether and the special encapsulating effect of the ionic
liquid and PEG on osmium tetroxide. Unfortunately,
leaching of both catalytic components was inevitable
during extraction of the product with ether, because the
ligand can dissolve in ether to some extent and bring out
some osmium by complexation. Sharpless et al. once
reported that only one of the two quinuclidine nitrogen
atoms of the bis-cinchona alkaloid ligand complexed
with osmium tetroxide. Quaterization of another
quinuclidine nitrogen atom did not affect the catalytic
The osmium-catalyzed asymmetric dihydroxylation
AD) of olefins using cinchona alkaloid derived ligands
is recognized as a very efficient method for the prepa-
ration of a wide range of enantiomerically pure vicinal
(
1
diols. Although the AD reaction can be widely 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 restricted its use in industry.
There has been a growing interest for exploring the
8
activity and enantioselectivity. We assumed that mono-
repetitive use of both the catalytic components (OsO
and chiral ligand) over the past few years. Attachment
of the ligand to a soluble or insoluble support cova-
4
quaternization of the bis-cinchona alkaloid ligand might
minimize the solubility of the ligand in ether due to its
ionic character. Song et al. adopted 1,4-bis(9-O-quini-
2
lently or the immobilization of osmium tetroxide based
3
2
nyl) phthalazine[(QN) PHAL] 1 as chiral ligand instead
4
on microencapsulation, ion-exchange techniques, and
5
of the well-known 1,4-bis(9-O-dihydroquininyl)phthal-
azine [(DHQ) PHAL] ligand in the AD reaction with an
osmylation of resins has made it possible to recover and
reuse the ligand or osmium, but has failed to recycle the
two catalytic components at the same time. Very
2
6
ionic liquid as the reaction medium. They proved that 1
was converted to the bis-cinchona alkaloid 2 bearing
four hydroxyl groups during the catalytic reaction. With
highly polar residues, ligand 2 improved the recyclability
of both catalytic components while affording the same
6
recently, an ionic liquid and poly(ethylene glycol)
7
(
PEG, MW 400) have been employed as reaction media
as well as immobilizing agents for the catalyst in AD
reactions. When the reaction was finished, the product
diol could be extracted with ether, while most of the
alkaloid ligand and osmium tetroxide remained in the
2
yields and ees as (DHQ) PHAL. Moreover, 1 is more
economically preparable. Taking this into consider-
ation, we designed a mono-quaterized bis-cinchona
alkaloid ligand 3, which combines the ionic character
and high polarity (Scheme 1). Here we report the syn-
thesis of 3 and its successful use in the AD reaction with
PEG or ionic liquid as the medium. This catalytic system
provides a simple and efficient approach to the recycling
*
0
Corresponding author. Tel.: +86-029-3376945; fax: +86-029-33744-
0; e-mail: syzhang@fmmu.edu.cn
7
4
of both OsO and chiral ligand.
957-4166/$ - see front matter ꢀ 2004 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2004.01.011

744
R. Jiang et al. / Tetrahedron: Asymmetry 15 (2004) 743–746
OH
HO
-
Br
N
N
N N
N
N
N N
HO
N
N N
OH
N
O
O
O
O
O
O
H
H
H
H
H
H
MeO
OMe
MeO
OMe
MeO
OMe
N
N
N
N
N
N
1
2
3
Scheme 1.
2
. Results and discussion
acetone–H O (v/v, 10:1) combined with PEG as the
2
medium of the AD reaction, and added the olefins
slowly by a syringe pump during a period of 10 h. Sat-
isfactory results were obtained for most of the selected
olefins (Table 1). We also found that low temperature
(0 ꢁC) increased enantioselectivity (Table 2).
9
The synthesis of 1 was reported by Song et al. in 1996.
We prepared 1 in 85% yield with an improved procedure
by using NaH as base instead of KOH. 1 was quatern-
ized by refluxing with benzyl bromide in THF to give
ligand 3 (Scheme 2).
Table 2. Influence of temperature on asymmetric dihydroxylation of
olefins using ligand 3 and OsO in PEG
N
N
4
Quinine
Benzyl bromide
THF
Cl
Cl
1
3
Entry Olefin
Temperature Yield
ꢁC)
Ee (%)
NaH, DMF
(
(%)
1
2
3
4
b-Methyl-trans-styrene
b-Methyl-trans-styrene 25
Ally naphthyl ether
Ally naphthyl ether
0
79
80
85
88
96
85
37
28
Scheme 2. Synthesis of ligand 3.
0
25
In our initial studies, we performed the AD reaction of
trans-stilbene according to the literature by using OsO
4
(
(
0.5 mol %) and chiral ligand 3 (2.0 mol %) in 1 mL PEG
MW 400), with NMO as co-oxidant, and trans-stilbene
The recyclability of osmium and chiral ligand 3 in the
PEG system was next examined. We chose trans-stilbene
as the substrate. After completion of the reaction, all the
volatiles were removed under reduced pressure and the
chiral diol extracted with tert-butyl methyl ether. No
7
being added in one portion. 94% ee and 91% isolated
yield were obtained (entry 2, Table 1). When the system
was applied to other olefins, the enantioselectivity
decreased dramatically (entries 4, 7 and 9, Table 1). We
found that trans-stilbene crystals dissolved slowly during
the reaction, similar to the way when the substrate was
added slowly. Results were different for liquid olefins,
which dissolved completely as soon as being added into
PEG. A high concentration of the substrate resulted in a
decrease of the enantioselectivity. As a result we chose
10
OsO detected in the ether layer by iodometry and the
4
remaining PEG layer could be recycled five times with-
out any further addition of OsO and ligand (Table 3).
4
Table 3. AD reactions of trans-stilbene in PEG using OsO
a
3 as a recoverable and reusable catalyst
4
and ligand
Run
1
2
3
4
5
a
Table 1. AD reaction of olefins using ligand 3 and OsO
4
in PEG
Yield (%)
Ee (%)
88
95
85
91
84
95
80
88
78
87
b
Entry
1
Olefin
Yield (%)
Ee (%)
trans-Stilbene
trans-Stilbene
88
91
82
70
78
89
87
89
78
88
90
95
94
95
77
96
96
73
78
62
80
37
a
Recycle experiments were carried out on a 2 mmol reaction scale of
olefin using 0.5 mol % of OsO , 2.0 mol % of ligand 3, 2.6 mmol of
NMO and 2 mL of PEG (400 MW) in acetone–H O (v/v, 10:1, 20 mL)
at 0 ꢁC. Olefins were added by a syringe pump for 10 h.
c
2
4
3
Ethyl trans-cinnamate
Ethyl trans-cinnamate
Methyl trans-cinnamate
b-Methyl-trans-styrene
b-Methyl-trans-styrene
a-Methystyrene
a-Methystyrene
Styrene
Ally naphthyl ether
2
c
4
5
6
c
7
Encouraged by these promising results, we examined
further the catalytic efficiency of 3 and the recyclability
in the ionic liquid 1-butyl-3-methylimidazolium hexa-
8
c
9
1
1
0
1
fluoro-phosphate [bmim][PF ]. Again trans-stilbene was
6
chosen as the standard substrate. The AD reaction was
carried out under the same conditions as in the PEG
system (OsO , 0.5 mol %, ligand 3, 2.0 mol %). The
a
Unless otherwise indicated, all reactions were carried out on a 1 mmol
reaction scale of olefin using 0.5 mol % of OsO , 2.0 mol % of 3,
.3 mmol of NMO and 1 mL PEG in 10 mL acetone–H O (v/v, 10:1)
at 0 ꢁC (the AD reactions of trans-cinnamates were carried out at
5 ꢁC). Olefins were added for 10 h.
The diols ee was determined by chiral HPLC.
Olefins were added in one portion at 25 ꢁC.
4
4
1
2
recovered ionic liquid phase containing osmium and 3
could only be recycled three times. When 1.5 mol % of
OsO was used, both the OsO and 3 could be easily
2
b
c
4
4
recovered and reused in five consecutive reactions

R. Jiang et al. / Tetrahedron: Asymmetry 15 (2004) 743–746
745
without any additional OsO
However, quantitative analysis of OsO
showed that a small amount of OsO (<2% of the total
4
amount) was transferred into the ether layer during the
extraction of diol with tert-butyl methyl ether.
4
or ligand (Table 4).
by iodometry
was necessary when recycling the catalyst even for
the fifth run. The system is effective in the AD reactions
of a range of olefins. Further study is currently in
progress.
4
a
4. Experimental
Table 4. Reusability of OsO
4
and ligand 3 in ionic liquid
Run
4.1. General
1
2
3
4
5
1
Yield (%)
Ee (%)
86
95
88
94
91
90
82
86
80
81
H NMR spectra were recorded on a Bruker AV-400
as solvents. High perfor-
spectrometer, with CDCl
3
a
mance liquid chromatography (HPLC) was performed
by Agilent 1100 interfaced to a HP 71 series computer
workstation with Daicel Chiralcel OJ-H, OD-H, OB-H
chiral column. Optical rotations were obtained on a
Perkin-Elmer 343 polarimeter.
Recycle experiments were carried out on a 2 mmol reaction scale of
olefin using 1.5 mol % of OsO , 2.0 mol % of ligand 3, 2.6 mmol of
NMO and 2 mL of [bmim][PF ] in acetone–H O (v/v, 10:1, 20 mL) at
ꢁC. Olefins were added by a syringe pump for 10 h.
4
6
2
0
In order to widen the scope and application of the cat-
alytic system, various substrates were subjected for
AD reactions under these conditions (OsO , 1.5 mol %,
4.2. Preparation of 1
4
ligand 3, 2.0 mol %). The results are summarized in Table
5
A 50 mL three-necked round-bottom flask was charged
with quinine (2.5 g, 7.7 mmol), 1,4-dichlorophthalazine
. In most cases, the desired diols were formed in high
yields and ees. We also found that the enantioselectivity
improved considerably when tetraethylammonium ace-
tate (TEAA) was added in the AD reaction of 1,2-
disubstituted olefins (entries 2, 4, and 7, Table 5). This
proves that the hydrolysis of the osmate ester is accel-
erated with the use of TEAA to afford high ee. These are
(
0.76 g, 3.85 mmol), NaH (0.9 g, 38.5 mmol) and dry
DMF (20 mL) under nitrogen. The mixture was stirred
at 70 ꢁC until TLC indicated that quinine had disap-
peared. The resulting mixture was cooled to room
temperature, filtered and concentrated in vacuo. The
residue was recrystallized with ethyl acetate giving 2.5 g
4
in agreement with the earlier observations.
1
of white powder 1 (85% yield). H NMR: d ¼ 8:65 (d,
J ¼ 5:2 Hz, 2H), 8.31–8.33 (m, 2H), 7.94–8.00 (m, 4H),
7
7
.58 (s, 2H), 7.43 (d, J ¼ 4 Hz, 2H), 7.36–7.38 (m, 2H),
.03 (s, 2H), 5.78–5.87 (m, 2H), 4.99 (m, 4H), 3.93 (s,
Table 5. AD reaction of olefins using ligand 3 and OsO
a
4
in ionic
liquid
6H), 3.50 (d, J ¼ 6:4 Hz, 2H), 3.02–3.14 (m, 4H), 2.60
13
(
(
m, 4H), 2.27 (s, 2H), 1.50–1.89 (m, 10H). C NMR
100 MHz, CDCl
Entry Olefin
Yield (%)
Ee (%)
3
) d ¼ 157:7, 156.4, 147.4, 144.8, 144.6,
1
2
3
4
5
6
7
8
9
1
trans-Stilbene
trans-Stilbene
86
88
73
74
67
82
80
89
85
91
95
>99
94
1
1
41.9, 132.4, 131.6, 127.2, 122.8, 122.5, 121.9, 116.6,
14.4, 102.2, 60.2, 56.8, 55.7, 42.7, 39.9, 29.3, 27.9, 27.8.
b
b
Ethyl trans-cinnamate
Ethyl trans-cinnamate
Methyl trans-cinnamate
b-Methyl-trans-styrene
b-Methyl-trans-styrene
a-Methystyrene
þ
MS (FAB): 775.1 (M+H ). ½aꢀ ¼ +244.6 (c 1, CHCl
3
).
91
D
94
92
b
95
66
4.3. Preparation of 3
Styrene
Ally naphthyl ether
81
35
Benzyl bromide (0.34 g, 2 mmol) in dry THF (10 mL)
was added dropwise into a solution of 1 (1.55 g, 2 mmol)
in dry THF (10 mL) under reflux. The mixture was
further refluxed for 3 h, and the solvent was removed in
vacuo, with the resulting residue purified by flash col-
0
a
Unless indicated otherwise, all reactions were carried out on 1 mmol
reaction scale of olefin using 1.5 mol % of OsO , 2.0 mol % of 3,
] in 10 mL acetone–H O (v/v,
0:1) at 0 ꢁC (the AD reactions of trans-cinnamates were carried out
4
1
.3 mmol of NMO and 1 mL [bmim][PF
6
2
1
umn chromatography (CHCl
0.89 g of 3 as a light yellow solid (47% yield). H NMR:
3
/MeOH 10:1) to give
at 25 ꢁC). Olefins were added for 10 h.
1
b
1
mmol TEAA was added.
d ¼ 7:24–8:69 (m, 21H), 5.84 (m, 2H), 4.99–5.31 (m,
6
3
(
H), 4.18 (s, 3H), 3.89 (s, 3H), 3.58 (m, 3H), 3.17 (m,
H), 2.61 (s, 4H), 1.81–2.28 (m, 9H), 1.28 (s, 1H), 1.25
13
s, 1H). C NMR (100 MHz, CDCl ) d ¼ 158:8, 157.8,
3
3. Conclusion
157.5, 155.6, 147.3, 146.7, 144.6, 144.1, 141.6, 138.9,
135.9, 133.8, 133.7, 131.7, 131.6, 130.6, 129.2, 127.1,
We have synthesized a mono-quaternized bis-cinchona
alkaloid ligand 3 and applied it in the AD reaction of
olefins with PEG or ionic liquid as medium. This cata-
lytic system provides a simple and efficient approach to
the recovery and reuse of both catalytic components
126.5, 126.1, 123.4, 123.0, 122.7, 122.3, 122.0, 119.5,
118.5, 114.6, 102.0, 101.4, 69.3, 66.7, 63.4, 60.1, 59.7,
56.7, 56.5, 55.7, 51.7, 42.7, 39.6, 37.8, 21.9, 29.7, 27.8,
27.6, 27.25, 25.5, 23.9, 22.7, 22.4. HRMS (ESI): calcd
ꢁ
1
for [M)Br ]: 865.4440, found 865.4435. ½aꢀ ¼ +249.6
D
(
osmium and ligand). No additional osmium or ligand
(c 1, EtOH).

746
R. Jiang et al. / Tetrahedron: Asymmetry 15 (2004) 743–746
4.4. Typical procedure for asymmetric dihydroxylation
reaction in PEG
Acknowledgements
We thank the National Natural Science Foundation of
China (NSFC) for financial support. (Nos.: 2037208,
20002008, 20302014.)
A 25 mL flask was charged with acetone–H
2
O (10:1, v/v,
(19 mg,
.020 mmol), OsO (1.25 mg, 0.005 mmol). After stirring
8
0
mL), PEG (400 MW 1 mL), ligand
3
4
for 10 min, NMO (176 mg, 1.3 mmol) was added. The
mixture was cooled to 0 ꢁC and the olefin (1 mmol)
dissolved in acetone–H O (10:1, v/v, 2 mL) was added
2
by a syringe pump for 10 h. After completion of the
reaction, all the volatiles were removed under reduced
pressure and tert-butyl methyl ether added into the flask
and the mixture was stirred for 5 min. The ether layer
was separated and the procedure repeated (3 · 5 mL).
The combined ether layers were washed with water and
brine and dried over anhydrous Na SO . After remov-
References and notes
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2
4
5
ing the solvent, the crude product was purified by flash
column chromatography on silica to give the diol. The
PEG layer containing OsO and ligand 3 was reused for
3
4
5
2
4
the next reaction.
4
2003, 1312.
685; Jo, C. H.; Han, S.-H.; Yang, J. W. Chem. Commun.
4.5. Typical procedure for asymmetric dihydroxylation
reaction in ionic liquid
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Chem. Commun. 2002, 3038; Branco, L. C.; Afonso, C. A.
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A 25 mL flask was charged with acetone–H O (10:1, v/v,
2
7
8
9
8
mL), [bmim][PF
6
]
(1 mL), ligand
3
(19 mg,
.020 mmol), OsO (3.75 mg, 0.015 mmol). After stirring
0
for 10 min, NMO (176 mg, 1.3 mmol) was added. The
4
mixture was cooled to 0 ꢁC and the olefin (1 mmol)
dissolved in acetone–H O (10:1, v/v, 2 mL) was added
2
by a syringe pump for 10 h. The procedure for the work-
up is the same as that for PEG system.
10. Nagayama, S.; Endo, M.; Kobayashi, S. J. Org. Chem.
1998, 63, 6094.