A soluble block copolymer-supported bis-cinchona alkaloid ligand for the asymmetric dihydroxylation of olefins

Article abstract of DOI:10.1081/SCC-120024740

A soluble block copolymer-supported ligand was prepared via polycondensation of a bis-cinchona alkaloid derivative, polyethylene glycol, and terephthaloyl chloride. Its application in the asymmetric dihydroxylation of olefins delivered very good enantioselectivity.

Full text of DOI:10.1081/SCC-120024740

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
A Soluble Block Copolymer-Supported bis-
Cinchona Alkaloid Ligand for the Asymmetric
Dihydroxylation of Olefins
Yong-Qing Kuang , Sheng-Yong Zhang & Ling-Ling Wei
To cite this article: Yong-Qing Kuang , Sheng-Yong Zhang & Ling-Ling Wei (2003) A Soluble
Block Copolymer-Supported bis-Cinchona Alkaloid Ligand for the Asymmetric Dihydroxylation
of Olefins, Synthetic Communications, 33:20, 3545-3550, DOI: 10.1081/SCC-120024740
To link to this article: http://dx.doi.org/10.1081/SCC-120024740
Published online: 15 Aug 2006.
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 20, pp. 3545–3550, 2003
A Soluble Block Copolymer-Supported
bis-Cinchona Alkaloid Ligand for the
Asymmetric Dihydroxylation of Olefins
*
Yong-Qing Kuang, Sheng-Yong Zhang, and Ling-Ling Wei
Department of Chemistry,
Fourth Military Medical University, Xi’an, China
ABSTRACT
A soluble block copolymer-supported ligand was prepared via
polycondensation of a bis-cinchona alkaloid derivative, polyethylene
glycol, and terephthaloyl chloride. Its application in the asymmetric
dihydroxylation of olefins delivered very good enantioselectivity.
Key Words: Polymer-supported ligand; Asymmetric dihydroxyla-
tion; Cinchona alkaloid; Derivative; Homogeneous catalysis.
*Correspondence: Sheng-Yong Zhang, Department of Chemistry, Fourth
Military Medical University, Xi’an 710032, China; Fax: þ86-29-3246270;
E-mail: syzhang@fmmu.edu.cn.
3545
DOI: 10.1081/SCC-120024740
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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3546
Kuang, Zhang, and Wei
The osmium-catalyzed asymmetric dihydroxylation (AD) and asym-
metric aminohydroxylation (AA) of olefins have found wide applications
in organic synthesis.[1] However, the high cost of osmium and ligands as
well as the high toxicity of osmium compounds has restricted their use in
industry. To solve this problem, several methods have been introduced
for the recovery and reuse of the ligand and/or osmium.[2] Among them,
soluble polymer-supported ligands have attracted much attention for
combinating the advantages of homogeneous catalysis with the easy
separation of a heterogenized ligand.[3] Both mono- and bis-cinchona
alkaloid derivatives have been anchored on a soluble polymer, poly-
ethylene glycol monomethyl ether (HO-PEG-OMe). Although the
monomethylated PEG-bound bis-cinchona alkaloid ligands showed
better enantioselectivity than their mono-cinchona alkaloid counterparts,
especially for terminal olefins, due to the beneficial effect of the binding
pocket of the bis-cinchona alkaloid type ligands,[1a] the former required
much more complicated synthetic manipulations than the latter. Recently
we prepared a new PEG-supported ligand (1 in Sch. 1) by a very
convenient approach, and applied it to the AD reaction of olefins.
Ligand 1 was synthesized via polycondensation of polyethylene
glycol (PEG-4000), terephthaloyl chloride and a bis-cinchona alkaloid
derivative (2 in Sch. 1) in the presence of NEt3. Then it was applied to
t
the AD reaction of six olefins respectively, with BuOH/H2O (1:1) as the
solvent, and K3Fe(CN)6 as the co-oxidant. The ligand is completely
soluble in the reaction media, allowing homogeneous catalysis. After
the reaction was finished, the ligand and the product were extracted
with CH2Cl2 and the organic phase was concentrated. Precipitation
HO
OH
SO
2
SO
N
2
N
N N
----
O
O
----
OH
PEG
H
H
HO
+
ClOC
COCl
+
OCH
3
CH O
3
(MW=4000)
N
N
2
CH Cl
NEt
3
2
2
O
C
O
C
O
C
O
O
PEG
O
C
O
O
SO
SO
2
q
2
p
N
N
N N
O
O
H
H
OCH
3
CH O
3
N
N
1
Scheme 1. Synthesis of ligand 1.

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Soluble Block Copolymer-Supported Ligand
3547
Table 1. Asymmetric dihydroxylation of olefins using ligand 1a.
Entry
1
Olefin
T (ꢀC) t (h) Yieldb (%) eec (%) Configurationd
0
0
24
24
85(91e)
84f
99(99e)
98f
S,S
S,S
2
3
4
0
0
24
24
84(87e)
82(82e)
94(97e)
91(91e)
S
S
87(93e)
84(89e)
R
O
5
0
21
CO Me
2
6
7
r.t.
r.t.
28
28
83
78
95
92
2S,3R
2S,3R
CO Et
2
aThe asymmetric dihydroxylation reactions were run for 21–24 h at 0ꢀC (entries
t
1–5) or for 28 h at room temperature (entries 6 and 7) in BuOH/H2O (1:1),
with K3Fe(CN)6 as the cooxidant; the molar ratio of olefin/ligand/OsO4 ¼
1/0.10/0.005.
bIsolated yields by column chromatography.
cThe ee values were determinated by chiral HPLC analysis of the diols (see Ref.[3e]
for details).
25
dThe absolute configuration of the diols were determined by comparison of ½aꢁD
with the literature values.
eResults for the free ligand 2 from Ref.[4]
fAverage value of five cycles.
upon addition of diethyl ether allowed for excellent recovery of the ligand
(>95%). The AD reaction results for the selected olefins are shown in
Table 1. The enantioselectivity of ligand 1 is comparable to that of the
unbound bis-cinchona alkaloid monomer. For stilbene, recovered ligand
1 was reused a total of five runs. When OsO4 was added as in the first run,
no significant decrease in activity and enantioselectivity was observed.
EXPERIMENTAL
Monomer 2 and naphthyl allyl ether were synthesized according to
published methods.[4,5] Osmium tetroxide was perchased from Aldrich.
Terephthaloyl chloride and methyl sufonamide was perchased from
Acros. All other solvents and chemicals were obtained from commercial
sources and were used without further purification unless otherwise stated.

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3548
Kuang, Zhang, and Wei
1H NMR spectra were recorded on a Varian INOVA 400 spectrometer.
Gel penetrating chromatography (GPC) were performed on Waters
ALC/GPC. Chiral HPLC analyses were carried out using following
columns: Daicel Chiracel OJ (250 ꢁ 4.6 mm); Daicel Chiracel OB-H
(250 mm ꢁ 4.6 mm); Daicel Chiracel OD (250 mm ꢁ 4.6 mm); Daicel
Chiracel OD (50 mm ꢁ 4.6 mm).
Synthesis of ligand 1. In a three-necked flask, which was equipped
with a stirring bar and a reflux condenser, was added 5.6 g (1.4 mmol)
polyethylene glycol (MW ¼ 4000), 4.5 mL NEt3, and 15 mL CH2Cl2. To
this mixture was added portionwise 427 mg (2.1 mmol) terephthaloyl
chloride. A solution of 695 mg (0.70 mol) monomer 2 in 7 mL CH2Cl2
was further added dropwise. The reaction mixture was stirred for 10 h
under reflux and 14 h at room temperature. Then the mixture was
centrifuged and the supernatant liquid separated. Dry and cool Et2O
was slowly added to the supernatant liquid under vigorous stirring
conditions. The precipitate thus obtained was collected on a glass filter,
washed with 95% methanol and Et2O, and dried over P2O5 under vacuo,
giving 6.1 g of polymer (92.8 yield). The amount of monomer 2 moieties
in the polymer 1 was 9.4 wt%, which was determined by 1H NMR.
The average molecular weight was 35,000 (on the base of polystyrene
calibration) and the polydispersity index was 3.84, which were determined
by GPC. 1H NMR (400 MHz, CDCl3): 8.63 (d, J ¼ 4 Hz, 2H), 8.31
(m, 2H), 7.96–8.11 (m, 10H), 7.60 (s, 2H), 7.43 (d, J ¼ 4.4 Hz, 2H), 7.36
(d, J ¼ 9.2 Hz, 2H), 7.03 (d, J ¼ 5.2 Hz, 2H), 4.50 (t, J ¼ 4.6 Hz, 4H), 4.04
(t, J ¼ 5.0 Hz, 4H), 3.40–3.95 (PEG peaks), 3.02–3.25 (m, 12H), 2.38–2.57
(m, 4H), 1.64–1.87 (m, 14H).
Typical procedure for asymmetric dihydroxylation reactions.
K3Fe(CN)6 (0.98 g, 3.0 mmol), K2CO3 (0.41 g, 3.0 mmol), ligand 1
(0.95 g, 0.1 mmol bis-cinchona alkaloid residue) were dissolved in
tBuOH/H2O (1:1, 12 mL) at room temperature, followed by addition of
100 mg mLꢂ1 OsO4 in toluene (13 mL, 0.005 mmol). For trans-1,2-disub-
stituted olefins, CH3SO2NH2 (95 mg, 1.0 mmol) was added. The solution
was cooled to 0ꢀC (with the exception of trans-methyl cinnamate and
trans-ethyl cinnamate, see Entries 6 and 7 in Table 1) and the olefin
(1.0 mmol) was added. The mixture was stirred vigorously at 0ꢀC or
room temperature for 21–28 h. Na2SO3 (1.5 g) was added and the mixture
was allowed to warm to room temperature and stirred for 40–60 min.
CH2Cl2 (10 mL) was added to the reaction mixture, and after separation
of the layers the aqueous phase was further extracted with CH2Cl2
(5 mL ꢁ 3) (if CH3SO2NH2 was used, the combined organic layers were
washed with 2 mol Lꢂ1 NaOH). The combined organic layers were dried
over anhydrous Na2SO4 and concentrated to about half volume. Et2O

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Soluble Block Copolymer-Supported Ligand
3549
was slowly added under vigorous stirring conditions. The precipitate
obtained was collected by filtration, washed with cool Et2O/EtOH
(3:1) and Et2O, and dried over P2O5 in vacuo. The filtrate was evaporated
to give the crude product, which was further purified by column
chromatography to afford the pure diol.
1H NMR of the diols. (1S,2S )(ꢂ)-1,2-Diphenyl-1,2-ethanediol. (CDCl3,
400 MHz): ꢀ 2.54 (brs, 2H), 4.72 (s, 2H), 7.12–7.26 (m, 10H).
(2S )-(Q)-1-Phenyl-1,2-ethanediol. (CDCl3, 400 MHz): ꢀ 3.27 (s, 2H),
3.59–3.72 (m, 2H), 4.76–4.79 (m, 1H), 7.27–7.36 (m, 5H).
(2S )-(Q)-2-Phenyl-1,2-propanediol (CDCl3, 400 MHz): ꢀ 1.53 (s, 3H),
2.21 (s, 2H), 3.62–3.82 (m, 2H), 7.28–7.47 (m, 5H).
(2R)-(R)-3-(1-Naphthoxy)-1,2-propanediol. (CD3OD, 400 MHz): ꢀ
3.73–3.83 (m, 2H), 4.12–4.25 (m, 3H), 6.91 (m, 1H), 7.34–7.48 (m, 4H),
7.78 (m, 1H), 8.30 (m, 1H).
(2S,3R)-(Q)-Methyl-2,3-dihydroxyl-3-phenylpropionate. (CDCl3,
400 MHz): ꢀ 2.90 (brs, 2H), 3.82 (s, 3H), 4.38 (d, J ¼ 2.8 Hz, 1H), 5.03
(d, J ¼ 2.4 Hz, 1H), 7.30–7.41 (m, 5H).
(2S,3R)-(Q)-Ethyl-2,3-dihydroxyl-3-phenylpropionate. (CDCl3,
400 MHz): ꢀ 1.27 (m, 3H), 2.62 (brs, 2H), 4.27 (m, 2H), 4.36 (d,
J ¼ 2.8 Hz, 1H), 5.00 (d, J ¼ 2.8 Hz, 1H), 7.30–7.42 (m, 5H).
ACKNOWLEDGMENT
We thank National Natural Science Foundation of China (NSFC)
for financial support.
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Received in Japan February 28, 2003