Heterogeneous organocatalysis for the asymmetric desymmetrization of meso-cyclic anhydrides using silica gel-supported bis-cinchona alkaloids

Article abstract of DOI:10.1016/j.tet.2004.10.046

The silica gel-supported bis-cinchona alkaloid 1a was prepared and found to be an efficient heterogeneous chiral organocatalyst with high catalytic activities, enantioselectivities (up to 92% ee), and recyclability for the asymmetric desymmetrization of m

Full text of DOI:10.1016/j.tet.2004.10.046

Tetrahedron 60 (2004) 12051–12057
Heterogeneous organocatalysis for the asymmetric
desymmetrization of meso-cyclic anhydrides using silica
gel-supported bis-cinchona alkaloids
†
Hyun Sook Kim, Yu-Mi Song, Jin Seok Choi, Jung Woon Yang and Hogyu Han
†
*
Department of Chemistry, Korea University, 1 Anam-dong, Seoul 136-701, South Korea
Received 26 August 2004; revised 15 October 2004; accepted 15 October 2004
Available online 28 October 2004
Abstract—The silica gel-supported bis-cinchona alkaloid 1a was prepared and found to be an efficient heterogeneous chiral organocatalyst
with high catalytic activities, enantioselectivities (up to 92% ee), and recyclability for the asymmetric desymmetrization of meso-cyclic
anhydrides with alcoholysis.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
achieved by using the commercially available bis-cinchona
alkaloids such as 1,4-bis(dihydroquinidinyl)anthraquinone
(DHQD)2AQN 1 (Scheme 1).6c For the first time, this
method overcomes the frequently encountered problem of
the high loading of cinchona alkaloids to obtain high
enantioselectivity in such reactions.
Enantioselective desymmetrization of meso compounds
using enzymatic1 and non-enzymatic2 methods has proven
to be a powerful synthetic means of preparing enantiomeri-
cally enriched products where multiple stereocenters can be
introduced in one step, enabling the conversion of cheap
starting materials into more expensive ones. The non-
enzymatic method reported by Oda3 and Aitken4 employed
a catalytic amount of inexpensive and readily available
cinchona alkaloids for the asymmetric methanolysis of
meso-cyclic anhydrides to afford chiral hemiesters in good
to excellent yields and moderate enantiomeric excesses.
Based on the findings of Oda and Aitken groups, Bolm and
co-workers developed a more enantioselective methanolysis
of meso-cyclic anhydrides by using a stoichiometric
quantity of cinchona alkaloids.5
Very recently, we reported the immobilization of the bis-
cinchona alkaloid, 1,4-bis(dihydroquininyl)anthraquinone
(DHQ)2AQN 2, onto silica gel and its use for the
asymmetric desymmetrization of meso-cyclic anhydrides
(Fig. 1).7 The resulting heterogeneous chiral organocatalyst
2a gave moderate enantioselectivities (up to 84% ee) in
those reactions. Reuse of this heterogeneous organocatalyst
invariably gave a small reduction in ee values and
conversions and thereby showed some stability under the
reaction conditions. Although the results obtained using
organocatalyst 2a were somewhat satisfactory, a similar
study using its counterpart 1a would offer an opportunity to
compare their enantioselectivity for the desymmetrization
of meso-cyclic anhydrides and thus to observe a true
diastereomeric effect stemming from the pseudo-enantio-
meric alkaloid 1a.
Recently, Deng and co-workers found that commercially
available modified cinchona alkaloids are able to function as
effective chiral Lewis-base/nucleophilic organic catalysts.6
These organocatalysts allow desymmetrization and
(dynamic) kinetic resolution of cyclic anhydrides, cyanation
of ketones, and conjugate addition of thiols to cyclic enones
with high enantioselectivity. Among them, a highly
enantioselective organocatalytic desymmetrization of
prochiral meso-cyclic anhydrides with methanolysis is
Here, we report the preparation of the silica gel-supported
organocatalyst, SGS-(DHQD)2AQN 1a, and its use for the
asymmetric desymmetrization of meso-cyclic anhydrides.
For comparison studies, the more flexible organocatalysts
1b and 2b were also prepared, where only one of dihydro-
quinidine (DHQD) or dihydroquinine (DHQ) moieties in 1
and 2 was tethered to silica gel by use of their derivatives 8
and 9 containing quinidine (QD) and quinine (QN),
Keywords: Asymmetric organocatalysis; Heterogeneous chiral organoca-
talyst; Desymmetrization; Cinchona alkaloid; Cyclic anhydride.
* Corresponding author. Tel.: C82 2 3290 3134; fax: C82 2 3290 3121;
e-mail: hogyuhan@korea.ac.kr
† These authors contributed equally to this work.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.10.046

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H. S. Kim et al. / Tetrahedron 60 (2004) 12051–12057
Scheme 1. Structures of the bis-cinchona alkaloids, (DHQD)2AQN 1 and (DHQ)2AQN 2, and their use for the asymmetric desymmetrization reaction of meso-
cyclic anhydrides with methanol.
respectively. We found that 1a showed higher enantio-
selectivities compared to 2a and their flexible derivatives 1b
and 2b. In addition, organocatalyst 1a could be recycled five
times without any significant loss of catalytic activity and
enantioselectivity.
performed at K30 8C for 72 h because the higher tempera-
ture resulted in a decrease in optical yield and the lower
temperature slowed down the reaction rate. In reactions with
organocatalyst 1a (5 mol%), the best enantioselectivity
(88% ee) was attained by using the 0.05:1 mixture of
methanol and toluene/CCl4 (1:1) at K30 8C (Table 1, entry
3). In particular, SGS-(DHQD)2AQN 1a was superior to
SGS-(DHQ)2AQN 2a for the asymmetric desymmetrization
of 10a (Table 1, entries 1–3 vs 7–9). These results are
consistent with those obtained by Oda,3b Aitken,4b Bolm,5c
Bigi10 who pointed out that diastereomeric quinidine, a
pseudo-enantiomer of quinine, afforded the ring opening
product with slightly higher enantioselectivity.
A comparison between rigid and flexible organocatalysts
(1a, 2a vs 1b, 2b) shows that the rigidity of the active site
seems to be crucial to the enantioselectivity and stability of
the catalytic system (Table 1, entries 1, 7 vs 10, 11).
2. Results and discussion
To synthesize the silica gel-supported organocatalyst 1a, we
started with 1,4-bis(quinidinyl)anthraquinone (QD)2AQN 4,
a homogeneous analogue of 1. Alkaloid 4 was prepared by
nucleophilic substitution of 1,4-difluoroanthraquinone (3)
with the lithium salt of quinidine in THF at room
temperature (Scheme 2).8 The desired silica gel-supported
bis-cinchona alkaloid 1a was prepared by reacting chiral
monomer 4 with mercaptopropylsilanized silica gel in the
presence of a,a0-azoisobutyronitrile (AIBN) as a radical
initiator in CHCl3.9 The nitrogen analysis of 1a confirmed
6.09 wt% incorporation of monomeric alkaloid 4 onto silica
gel (0.0711 mmol/g). Organocatalysts 1b, 2a, and 2b were
prepared in a similar manner.
The highest enantioselectivity (92% ee) was obtained by a
one-pot conversion of meso-cyclic anhydride 10b with
organocatalyst 1a (20 mol%) into the corresponding
desymmetrized mono ester acid 11b in the 0.1:1 mixture
of methanol and diethyl ether at K10 8C (Table 2, entry 2).
In contrast, meso-cyclic anhydrides 10c–e afforded very low
conversions despite excellent ee values: 10c gave 11c in 9%
conversion and 83% ee; 10d gave 11d in 8% conversion and
77% ee. The low reactivity of meso-cyclic anhydrides 10c–e
could probably be due to their steric effects in the
heterogeneous asymmetric desymmetrization reactions.
We also investigated the effect of various nucleophiles on
the asymmetric desymmetrization reactions by replacing
methanol with ethanol or 2-propanol. As a result, ethanol
In a first series of experiments, we examined the
desymmetrization of meso-cyclic anhydride 10a in various
solvents using 1a as an organocatalyst and methanol as a
nucleophile under heterogeneous conditions (Scheme 3).
Our results are summarized in Table 1. To optimize the
reaction conditions, the influence of catalyst amount, the
nucleophile to solvent ratio (MeOH/solvent), and tempera-
ture on the efficiency of the process was investigated, with
particular regard to enantioselectivity. The reaction was

H. S. Kim et al. / Tetrahedron 60 (2004) 12051–12057
12053
Figure 1. Structures of the silica gel-supported bis-cinchona alkaloids, SGS-(DHQD)2AQN 1a and 1b and SGS-(DHQ)2AQN 2a and 2b.
and 2-propanol as nucleophiles exhibited lower reactivity
and enantioselectivity compared to methanol (Table 2,
entries 1 vs 6, 7).
decrease in enantioselectivity (92–89% ee) and catalytic
activity (73–70% conversion). A gradual decrease in the
enantioselectivity and catalytic activity of the silica gel-
supported organocatalyst 1a with repetitive use was likely
attributed to its slight solubility in methanol and thereby
somewhat leaching from the reaction mixture (ca. 1% for
each cycle).
Finally, the recyclability of silica gel-supported organoca-
talysts was also examined by carrying out the reaction with
1a (20 mol%) in the 0.1:1 mixture of methanol and diethyl
ether at K10 8C for 72 h (Table 3). To our delight, excellent
enantioselectivity was retained throughout the successive
recycling of organocatalysts. Organocatalyst 1a could be
separated from the reaction mixture by simple filtration and
reused for five consecutive reactions without any significant
In summary, we succeeded in a heterogeneous organocata-
lytic asymmetric methanolysis of various meso-cyclic
anhydrides in diethyl ether using the silica gel-supported
chiral organocatalyst 1a to afford the corresponding chiral

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H. S. Kim et al. / Tetrahedron 60 (2004) 12051–12057
Scheme 2. Synthesis of SGS-(DHQD)2AQN 1a and 1b and SGS-(DHQ)2AQN 2a and 2b: (a) quinidine (XOH) or quinine (YOH), n-BuLi, THF, K50 8C to rt,
(4, 71%; 5, 76%), or XOH, NaH, DMF, rt, (4, 72%); (b) hydroquinidine (X0OH) or hydroquinine (Y0OH), NaH, DMF, rt, (6, 45%; 7, 68%); (c) XOH or YOH,
NaH, DMF, rt, (8, 77%; 9, 98%); (d) mercaptopropylsilanized silica gel (SGS-SH), AIBN, CHCl3, 80 8C, (1a, 0.0711 mmol/g; 2a, 0.0733 mmol/g; 1b,
0.0604 mmol/g; 2b, 0.0630 mmol/g).
hemiesters with excellent enantioselectivities in moderate
conversions. In such reactions, the rigidity of the organo-
catalyst appears to be an important parameter. Furthermore,
the immobilized chiral organocatalyst 1a could be reused
several times without any significant decrease in catalytic
activity and enantioselectivity. Our process therefore retains
the ease of catalyst removal/recycling as well as the efficient
reaction protocol.
shifts (d) are reported in parts per million (ppm) with
reference to tetramethylsilane or solvent and coupling
constants (J) are reported in hertz (Hz). High-resolution
mass spectra (HRMS) were recorded on a JEOL JMS-
AM505WA mass spectrometer using a fast atom bombard-
ment (FAB) technique. Optical rotations (a) were deter-
mined on a Rudolph AUTOPOL III automatic polarimeter.
Elemental analysis was performed on a CE EA1110
elemental analyzer. GC analysis was performed on a
Younglin Acme 6000 GC system. HPLC analysis was
performed on a Waters 600 HPLC system equipped with a
2487 dual l absorbance detector. Thin-layer chromato-
graphy (TLC) was performed on silica gel 60 F254 precoated
plates (0.25 mm thickness, Merck). Flash chromatography
was carried out on silica gel 60 (230–400 mesh, Merck).
Bis-cinchona alkaloids 4, 5, 8, and 9 were prepared by
3. Experimental
3.1. General
1H and 13C NMR spectra were recorded on a Bruker Avance
500 or a Varian Mercury 300 NMR spectrometer. Chemical

H. S. Kim et al. / Tetrahedron 60 (2004) 12051–12057
12055
Scheme 3. Desymmetrization of meso-cyclic anhydrides 10a–e with alcoholysis in diethyl ether using 1a, 1b, 2a, or 2b as a organocatalyst followed by
conversion of the resulting hemiesters 11a–g and ent-11a into the corresponding amide–esters 12a–g and ent-12a, respectively.
Table 1. Effects of various heterogeneous organocatalysts and solvents on conversions and ee values in the desymmetrization reaction of cis-1,2-
cyclohexanedicarboxylic anhydride 10a with methanola
Entry
Anhydride
Product
Catalystb (mol%)
Solvent
Conversionc (%)
eed (%)
Configuratione
1
2
3
4
5
6
7
8
10a
10a
10a
10a
10a
10a
10a
10a
10a
10a
10a
11a
11a
11a
11a
11a
11a
ent-11a
ent-11a
ent-11a
11a
1a (5)
1a (5)
1a (5)
1a (5)
1a (5)
1a (5)
2a (5)
2a (5)
2a (5)
1b (5)
2b (5)
Diethyl ether
THF
Toluene/CCl4 (1:1)
Toluene
EtOAc
t-Butyl methyl ether
Diethyl ether
THF
Toluene/CCl4 (1:1)
Diethyl ether
Diethyl ether
76
44
78
9
80
88
88
67
70
86
64
63
46
67
43
1R,2S
1R,2S
1R,2S
1R,2S
1R,2S
1R,2S
1S,2R
1S,2R
1S,2R
1R,2S
1S,2R
5
47
65
16
67
58
45
9
10
11
ent-11a
a MeOH (nucleophile)/solvent (ca. 0.05:1 (v/v)), reaction temperature (K30 8C), reaction time (72 h).
b SGS-(DHQD)2AQN 1a and 1b, SGS-(DHQ)2AQN 2a and 2b.
c Determined by GC analysis of an enantiomeric mixture for 11a or ent-11a on a Chiraldex G-TA column (30 m!0.25 mm).
d Determined by HPLC analysis of a diastereomeric mixture for 12a or ent-12a on a Hypersil silica column (4.6!200 mm, 5 mm).6c,7
e The absolute configuration of 11a and ent-11a was determined as described.5,7
Table 2. Desymmetrization of meso-cyclic anhydrides 10a-e with alcoholysis in diethyl ether using heterogeneous organocatalyst 1aa
Entry
Anhydride
Product
Catalystb (mol%)
Time (h)
Conversionc,d (%)
eee (%)
Configurationf
1
2
3
4
5
6
7
10a
10b
10c
10d
10e
10a
10a
11a
11b
11c
11d
11e
11fg
11gh
1a (20)
1a (20)
1a (20)
1a (20)
1a (20)
1a (20)
1a (20)
48
72
72
72
72
72
72
82
73
9
8
22
7
89
92
83
77
43
82
53
1R,2S
1R,2S
2R,3S
2R,3S
3S
1R,2S
1R,2S
6
a MeOH (nucleophile)/Et2O (solvent) (ca. 0.1:1 (v/v)), reaction temperature (K10 8C).
b SGS-(DHQD)2AQN 1a.
c Determined by GC analysis of an enantiomeric mixture for 11a, 11f, or 11g on a Chiraldex G-TA column (30 m!0.25 mm).
d Determined by GC analysis of an enantiomeric mixture for each of 11b–e on a HP-1 column (30 m!0.32 mm!0.25 mm).
e Determined by HPLC analysis of a diastereomeric mixture for each of 12a–g on a Hypersil silica column (4.6!200 mm, 5 mm).6c,7
The absolute configuration of 11a–g was determined as described.5,7
f
g EtOH instead of MeOH as a nucleophile.
h i-PrOH instead of MeOH as a nucleophile.

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H. S. Kim et al. / Tetrahedron 60 (2004) 12051–12057
Table 3. The recyclability of the heterogeneous bis-cinchona alkaloid-
based organocatalyst 1a in the asymmetric desymmetrization reaction of
10b with methanola
3.2. General procedure for the asymmetric methanolysis
of meso-cyclic anhydrides 10a–e
ee (%) with consecutive use of recycled organocatalyst 1a
Described for the reaction of cis-1,2-cyclohexanedi-
carboxylic anhydride 10a in the mixture of methanol (ca.
60 equiv) and diethyl ether (5 mL per 0.1 mmol anhydride)
at an approximate ratio of ca. 0.05:1 (v/v).
Recycle
ee (%)
Conversion (%)
1st
92
73
2nd
91
72
3rd
93
70
4th
86
71
5th
89
70
a Asymmetric desymmetrization reaction using 20 mol% silica gel-
supported chiral organocatalyst 1a was carried out in the 0.1:1 mixture
of methanol and diethyl ether at K10 8C for 72 h.
After a suspension containing cis-1,2-cyclohexanedicar-
boxylic anhydride 10a (12 mg, 0.0778 mmol) and
SGS-(DHQD)2AQN 1a (54.7 mg, 5 mol%) in dry diethyl
ether (3.9 mL) at K30 8C was stirred for 10 min under Ar,
dry MeOH (195 mL, 4.81 mmol) was added. After stirring at
K30 8C for 72 h, the reaction mixture was filtered, and then
the filtrate was concentrated in vacuo. The crude residue
was purified by flash chromatography (EtOAc/n-hexaneZ
1:2) to afford an enantiomeric mixture for 11a as a colorless
oil. For determining conversion efficiency, GC analysis of
an enantiomeric mixture for 11a was performed prior to
work-up. The filtrate for GC analysis was prepared by
filtering the reaction mixture followed by washing with
EtOAc.
modified procedures.8 Reagent-grade chemicals were
purchased from Aldrich, Fluka, Junsei, and TCI and used
as received unless otherwise specified.
3.1.1. Mercaptopropylsilanized silica gel (SGS-SH).
Dried silica gel 60 (230–400 mesh, 14.0 g) was treated
with (3-mercaptopropyl)trimethoxysilane (61.3 mL) in
anhydrous pyridine/toluene (1:1) (59.0 mL). After stirring
at 90 8C for 24 h, the slurry was cooled to room temperature,
filtered, washed with MeOH and CHCl3, and dried in vacuo
for 24 h to afford derivatized silica gel (15.6 g) containing
3.59 wt% S, corresponding to 1.12 mmol of S per g of
derivatized silica gel. Element analysis (wt%): C 6.81, H
1.60, S 3.59.
GC analysis of an enantiomeric mixture for 11a, 11f, or 11g
obtained by use of 1a was performed on a Chiraldex G-TA
column (Advanced Separation Technology, 30 m!
0.25 mm) under the condition: initial temperature, 130 8C;
initial time, 10.0 min; 2.0 8C/min gradient; final tempera-
ture, 170 8C, 17 psi. Retention time (min): 11a, tRZ32.44,
tRZ32.58 (major); 11f, tRZ30.26; 11g, tRZ30.27. GC
analysis of an enantiomeric mixture for each of 11b–e was
performed on a HP-1 column (Hewlett Packard, 30 m!
0.32 mm!0.25 mm) under the condition: initial tempera-
ture, 50 8C; initial time, 5.0 min; 15.0 8C/min gradient; final
temperature, 170 8C, 17 psi. Retention time (min): 11b, tRZ
9.75; 11c, tRZ10.78; 11d, tRZ10.83; 11e, tRZ10.77.
3.1.2. SGS-(DHQD)2AQN 1a. To a suspension of SGS-SH
(2.64 g, 2.95 mmol) in CHCl3 (60 mL) was added 4 (1.20 g,
1.41 mmol) and a,a0-azoisobutyronitrile (AIBN, 120 mg,
0.731 mmol). After stirring at reflux for 48 h under Ar, the
slurry was cooled to rt, filtered, exhaustively washed with
MeOH and CH2Cl2, and dried in vacuo to give 1a (2.74 g).
Element analysis (wt%) of 1a: C 10.00, H 1.82, N 0.40, S
3.44.
3.3. General procedure for the ee determination of
hemiesters 11a–g (described for cis-1,2-cyclohexane-
dicarboxylic acid monomethyl ester 11a)
3.1.3. SGS-(DHQD)2AQN 1b. To a suspension of SGS-SH
(1.31 g, 1.46 mmol) in CHCl3 (60 mL) was added 8 (1.50 g,
1.75 mmol) and AIBN (125 mg, 0.760 mmol). After stirring
at reflux for 48 h under Ar, the slurry was cooled to rt,
filtered, exhaustively washed with MeOH and CH2Cl2, and
dried in vacuo to give 1b (1.33 g). Element analysis (wt%)
of 1b: C 9.45, H 1.81, N 0.34, S 3.54.
The enantiomeric excess of the product was determined by
HPLC analysis of a diastereomeric mixture for the
corresponding amide–ester 12a prepared from an enantio-
meric mixture for hemiester 11a according to the literature
procedure.6c,7
To a filtrate containing an enantiomeric mixture for cis-1,2-
cyclohexanedicarboxylic acid monomethyl ester 11a
(36.4 mg, 0.195 mmol) in CH2Cl2 (9.8 mL) at room
temperature was added 1-ethyl-3-(3-dimethylaminopropyl)-
carbodiimide hydrochloride (EDCI, 44.9 mg, 0.234 mmol).
After stirring for 10 min, 4-(dimethylamino)pyridine
(DMAP, 7.2 mg, 58.6 mmol) and (R)-(C)-1-(1-naphthyl)-
ethylamine (34.7 mL, 0.215 mmol) were added to the
mixture. After stirring at room temperature for 5 h,
the reaction mixture was extracted with CH2Cl2/H2O. The
combined organic layers were dried over Na2SO4 and then
concentrated in vacuo. The crude residue was purified by
flash chromatography (EtOAc/n-hexaneZ1:2) to afford a
diastereomeric mixture for 12a as a yellow oil. For
determining the ee value, HPLC analysis of a diastereo-
meric mixture for 12a was performed prior to column
3.1.4. SGS-(DHQ)2AQN 2a. To a suspension of SGS-SH
(2.09 g, 2.34 mmol) in CHCl3 (60 mL) was added 5 (1.0 g,
1.17 mmol) and AIBN (100 mg, 0.609 mmol). After stirring
at reflux for 48 h under Ar, the slurry was cooled to rt,
filtered, exhaustively washed with MeOH and CH2Cl2, and
dried in vacuo to give 2a (2.2 g). Element analysis (wt%) of
2a: C 10.18, H 1.69, N 0.41, S 3.44.
3.1.5. SGS-(DHQ)2AQN 2b. To a suspension of SGS-SH
(1.31 g, 1.46 mmol) in CHCl3 (60 mL) was added 9 (1.50 g,
1.75 mmol) and AIBN (125 mg, 0.760 mmol). After stirring
at reflux for 48 h under Ar, the slurry was cooled to rt,
filtered, exhaustively washed with MeOH and CH2Cl2, and
dried in vacuo to give 2b (1.35 g). Element analysis (wt%)
of 2b: C 10.15, H 1.78, N 0.35, S 3.03.

H. S. Kim et al. / Tetrahedron 60 (2004) 12051–12057
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Trans. 1 1999, 1765–1784. (b) Spivey, A. C.; Andrews, B. I.
Angew. Chem. Int. Ed. 2001, 40, 3131–3134.
purification. The diastereomeric mixture was dissolved in
EtOAc and diluted with n-hexane for HPLC analysis.
3. (a) Hiratake, J.; Yamamoto, Y.; Oda, J. J. Chem. Soc., Chem.
Commun. 1985, 1717–1719. (b) Hiratake, J.; Inagaki, M.;
Yamamoto, Y.; Oda, J. J. Chem. Soc., Perkin Trans. 1 1987,
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HPLC analysis of a diastereomeric mixture for each of
12a–g was performed on a Hypersil silica column (Thermo,
4.6!200 mm, 5 mm) with UV monitoring at 280 nm and a
flow rate of 1.0 mL/min under isocratic conditions: 12a,
n-hexane/2-propanolZ97/3, tRZ8.20 (major), tRZ11.09;
12b, n-hexane/2-propanolZ97/3, tRZ10.74 (major), tRZ
13.89; 12c, n-hexane/2-propanolZ97/3, tRZ16.75 (major),
tRZ22.47; 12d, n-hexane/2-propanolZ97/3, tRZ14.86
(major), tRZ18.32; 12e, n-hexane/2-propanolZ96/4, tRZ
24.54, tRZ26.80 (major); 12f, n-hexane/2-propanolZ97/3,
tRZ6.98 (major), tRZ8.67; 12g, n-hexane/2-propanolZ97/
3, tRZ8.52 (major), tRZ11.30.
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Acknowledgements
This work was financially supported by the Basic Research
(Grant No. R01-2003-000-11623-0) and CRM programs
from KOSEF. Fellowship support from the BK21 program
(H.S.K., Y.-M.S., J.S.C., and J.W.Y.) is gratefully
acknowledged.
7. Song, Y.-M.; Choi, J. S.; Yang, J. W.; Han, H. Tetrahedron
Lett. 2004, 45, 3301–3304.
References and notes
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1. For an overview of enzymatic asymmetric desymmetrization
reactions, see: Wong, C.-H.; Whitesides, G. M. In Enzymes in
Synthetic Organic Chemistry; Elsevier Science: Oxford, 1994;
Vol. 12, pp 41–130.
10. Bigi, F.; Carloni, S.; Maggi, R.; Mazzacani, A.; Sartori, G.;
Tanzi, G. J. Mol. Catal. A 2002, 182–183, 533–539.
2. For recent reviews on non-enzymatic asymmetric desymme-
trization reactions, see: (a) Willis, M. C. J. Chem. Soc., Perkin