Preparation of chiral trans-5-substituted-acenaphthene-1,2-diols by baker's yeast-mediated reduction of 5-substituted-acenaphthylene-1,2-diones

Article abstract of DOI:10.1016/j.tetasy.2010.04.048

A series of trans-5-substituted-acenaphthene-1,2-diols were obtained in 21-72% yield with 97-100% ee by baker's yeast-mediated reduction of the corresponding acenaphthylene-1,2-diones, in the presence of DMSO as a co-solvent and under vigorous agitation.

Full text of DOI:10.1016/j.tetasy.2010.04.048

Tetrahedron: Asymmetry 21 (2010) 825–830
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Tetrahedron: Asymmetry
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Preparation of chiral trans-5-substituted-acenaphthene-1,2-diols by baker’s
yeast-mediated reduction of 5-substituted-acenaphthylene-1,2-diones
a
a
a
b,
*
Lixiao Wang a, Xingyong Wang a, Jingnan Cui a, , Weimin Ren , Nan Meng , Jingyun Wang , Xuhong Qian
*
a State Key Laboratory of Fine Chemicals, Dalian University of Technology, 158 Zhongshan Rd., 116012 Dalian, China
b State Key Lab. Bioreactor Engineering, Shanghai Key Lab. Chemical Biology, School of Pharmacy, East China University of Science and Technology,
PO Box 544, 130 Meilong Road, Shanghai 200237, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of trans-5-substituted-acenaphthene-1,2-diols were obtained in 21–72% yield with 97–100% ee
by baker’s yeast-mediated reduction of the corresponding acenaphthylene-1,2-diones, in the presence of
DMSO as a co-solvent and under vigorous agitation. The absolute configuration of (ꢀ)-trans-5-methoxy-
acenaphthene-1,2-diol trans-3b and (ꢀ)-trans-5-bromo-acenaphthene-1,2-diol trans-3c was assigned as
(S,S) and (ꢀ)-trans-5-thiomorpholin-acenaphthene-1,2-diol trans-3d was established as (R,R) by exciton-
coupled circular dichroism.
Received 18 March 2010
Accepted 22 April 2010
Available online 1 June 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
bromization of 1a. Substitution of 1c gave 1d in 75% yield, and 1e
was obtained by diazotization and reduction of 1c in 45% yield.
Acenaphthene-1,2-diol derivatives are important structural
units in biologically active compounds1 and functional materials,2,3
and also widely used as synthetic intermediates.4,5 However, enan-
tiomerically pure acenaphthene-1,2-diols have been scarcely used
due to a lack of their efficient synthesis. As a powerful tool for
enantioselective synthesis, enzymes provide a solution to this
problem. Ziffer et al. have prepared enantiomerically pure ace-
naphthene-1,2-diol by hydrolysis of the corresponding racemic
diacetate compound using Rhizopus nigricans.6 In recent work, we
have successfully reduced a series of substituted acenaphthylene-
1,2-diones 1 to the corresponding chiral substituted 2-hydroxy-
acenaphthylen-1-ones 2 using baker’s yeast via control of the
reaction time.7 Herein, we report the preparation of chiral 5-
substituted-acenaphthene-1,2-diols 3 by baker’s yeast-mediated
reduction of the corresponding substituted acenaphthylene-1,2-
diones (Scheme 1), and for the first time assigned the absolute con-
figuration of some products by exciton-coupled circular dichroism.
2.2. Choosing the optimal experimental conditions
In previous work, we have achieved the first example of using
baker’s yeast-mediated reduction of highly sterically hindered
and hydrophobic fluorenones in which an orbital shaker was
replaced by a mechanical stirrer in order to further improve mass
transfer.8 Acenaphthylene-1,2-diones 1 are also highly sterically
hindered and hydrophobic, so a mechanical stirrer was used as a
mass transfer driver in this reaction. Initially 1a was chosen as a
model to explore the feasibility of the reaction. In a typical exper-
iment, substrate 1a was added to the baker’s yeast suspension and
the reaction mixture was stirred by a mechanical stirrer with the
stirring speed at 600 rpm. Based on monitoring of the reaction pro-
cess by HPLC, di-alcohol 3a was generated together with mono-
alcohol 2a from the beginning of the reaction and the substrate
1a was consumed to about 70% in the initial 4 h of reaction time.
At the same time, the content of 2a reached its maximum value
(about 50%) and this content remained for the next 6 h. The con-
tent of trans-3a increased dramatically after 12 h, while the con-
tent of cis-3a increased gradually. When the reaction proceeded
for 48 h, 1a and 2a were almost consumed, and the content of
trans-3a was over 85% and cis-3a was about 5% only. It indicated
that the selectivity of the reduction towards trans-3a was higher
than that towards cis-3a. This situation is similar with the yeast-
2. Results and discussion
2.1. Preparation of the substrates
The substrates 1b–e were prepared from 1a as shown in
Scheme 2. Nitration and substitution of acenaphthylene-1,2-dione
1a gave 1b in 40% yield, and 1c could be obtained in 90% yield by
mediated reduction of aliphatic
a-diketones in which the trans
configuration was also predominant.9
In our previous work, using an organic solvent (DMSO or DMF)
as the co-solvent was found to not only improve the conversion,
* Corresponding authors. Tel.: +86 411 39893872; fax: +86 411 83673488 (J.C.).
E-mail address: jncui@dlut.edu.cn (J. Cui).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.04.048

826
L. Wang et al. / Tetrahedron: Asymmetry 21 (2010) 825–830
O
O
O
HO
HO
OH
HO
OH
baker's yeast
baker's yeast
+
R
R
R
R
1
2
cis-3
trans-3
e
,
S
: R = NH2
a: R = H, b: R = OMe, c: R = Br, d: R = N
Scheme 1.
O
O
O
O
O
O
MeOH
KOH
NaNO3
H2SO4
OCH3
O
NO2
1a
1a
1b
O
O
O
HN
S
Br2
CuI, K2CO3
N
S
Br
1c
1d
O
O
O
O
NaN3
DMF
toluene
reflux
1c
N3
NH2
1e
Scheme 2.
but also enhance the enantioselectivities and regioselectivities in
baker’s yeast-mediated reduction of fluorenones and acenaphthyl-
ene-1,2-diones 1.7,8 Therefore, the effects of DMSO and DMF as
substrate co-solvents were investigated in this reduction system.
As shown in Table 1, using DMF as the substrate co-solvent in-
creased the enantioselectivity from 87% to 91% ee, but decreased
the yield from 85% to 42%. On the other hand, using DMSO gave
trans-3a with 97% ee and the yield was kept at 74%. The enhanced
enantioselectivity was possibly caused by the sulfur atom in
DMSO, which could modify enantiofacial discrimination in baker’s
yeast-mediated reduction.10,11
Table 1
Effect of co-solvent on the conversion and ee in the reduction of acenaphthylene-1,2-
dione 1a using baker’s yeasta
Entry
Co-solvent
Conv.b%
cis-3a Yieldc
%
trans-3a
Yieldc
%
eed
%
[a]
D
e
1
2
3
No
DMF
DMSO
98
98
100
5
35
23
85
42
74
87
91
97
ꢀ20.7
ꢀ21.1
ꢀ24.1
a
Reaction conditions: substrate (100 mg), water (100 mL), co-solvent (10 mL),
dry baker’s yeast (10.0 g), sucrose (3.0 g), reaction time 48 h, at 30 °C.
b
The conversion was determined by HPLC using a Zorbax RX-SIL column based
on the consumed substrate.
c
Isolated yield.
2.3. Exploration of the reaction
d
The ee was determined by HPLC using a chiral AD-H column.
The [a] was determined by WZZ-2S spectropolarimeter (c 0.28–0.32, CHCl3),
e
D
In order to explore the reaction scope, a series of 5-substituted-
acenaphthylene-1,2-diones 1b–e were synthesized and then
examined under the optimized conditions. As shown in Table 2,
as with 1a, the substrates 1b–d could also be reduced to the corre-
sponding cis- and trans-diols, and diols with the trans configuration
were the dominant product; this may be a result of the thermody-
20 °C.
namic stability of the trans configuration. Importantly, the trans-
diols were highly enantiomerically pure (>97% ee), no matter what
the electronic properties of the substituted group in the 5-position.

L. Wang et al. / Tetrahedron: Asymmetry 21 (2010) 825–830
827
Table 2
Reduction of 5-substituted-acenaphthylene-1,2-dione 1 using baker’s yeasta
Substrate
R
Conv.b
%
2/3
cis-3
trans-3
Yieldc
%
eed
%
[a
]
D
R/S
Yieldc
%
eed
%
[a
]
D
R/S
f
f
1a
1b
1c
H
OCH3
Br
100
92
100
0/100
5/95
3/97
23
23
14
—
54
2
—
+3.0
+3.4
—
—
—
72
56
60
97
100
99
ꢀ24.1
ꢀ24.2
+15.1e
1S,2S
1S,2S
1S,2S
1d
1e
60
98
10/90
95/5
10
—
30
—
+5.5
—
—
—
21
—
100
—
ꢀ29.6
—
1R,2R
N
NH2
S
—
a
b
c
d
e
f
Reaction conditions: substrate (100 mg), water (100 mL), DMSO (10 mL), dry baker’s yeast (10.0 g), sucrose (3.0 g), reaction time 48 h, at 30 °C.
The conversion was determined by HPLC using a Zorbax RX-SIL column based on the consumed substrate.
Isolated yield.
The ee was determined by HPLC using a chiral AD-H column.
The [
The [
a
a
]
]
was determined by WZZ-2S spectropolarimeter (c 0.35–0.38, EtOAc, 20 °C).
was determined by WZZ-2S spectropolarimeter (c 0.24–0.28, CHCl3, 20 °C).
D
D
On the other hand, the cis-diols were obtained with low enantiose-
lectivities. In previous research, substrate 1e could be reduced to
2e with 93% ee in the presence of DMF as the co-solvent.7 However,
substrate 1e could hardly afford the corresponding diols in our
experiment, probably due to the high electron density of the
substituted group, which inhibited the activity of reductases to-
wards the carbonyl group of 2e. Similar results were observed for
1b and 1d, which also bore an electron-donating group in the 5-po-
sition, reductases towards the carbonyl group of 2b and 2d exhib-
iting lower activities than 2a and 2c.
Chiral trans-bis-p-N,N-dimethylaminobenzoyloxy-1,2-dihydro-
5-substituted-acenaphthenes (trans-4b–d) were prepared from
the corresponding chiral trans-diols as shown in Scheme 3. To be-
gin with, the stereochemistry of trans-3a was reexamined by ECCD.
As shown in Figure 1, the strong CD peaks at 308 and 329 nm for
trans-4a, which had arisen from coupling between the two p-
N,N-(dimethylamino)benzoate groups, indicated a positive first
Cotton effect.12–14 According to the ECCD rules, the positive first
100
trans-4a
2.4. The absolute stereochemistry determination
trans-4b
trans-4c
trans-4d
It had been reported that (+)-trans-acenaphthene-1,2-diol has
an (1R,2R) configuration.6 Therefore, the (ꢀ)-trans-1a obtained in
our reduction system should be determined to be an (1S,2S) config-
50
0
uration. Unfortunately, there was no reported [a] for the newly
D
synthesized chiral diols 3b–d, so we turned to other methods for
configuration assignment.
For the most part, the absolute configuration of alpha-diols
could be achieved with exciton-coupled circular dichroism
(ECCD).12–14 Briefly, the ECCD method relies on the coupling of
the electric transition dipole moments of two or more chromoph-
ores held in space in a chiral fashion.15 The sign of the resultant
ECCD couplet reflects the helicity of the interacting chromophores
and consequently the chirality of the derivatized system. It was not
possible to assign the absolute configuration of alpha-diols directly
by ECCD because of a lack of chromophores. This can be accom-
plished via derivatization of the diol group with benzoates (or
other similar chromophores).
-50
250
300
350
400
wavelength/nm
Figure 1. ECCD spectrum (5 ꢁ 10ꢀ5 mol/L in methanol) of trans-4a, -4b, -4c and -
4d.
NMe2
Me2N
HO
OH
O
Cl
O
O
O
O
AgCN
tolunen, rt
+
NMe2
R
R
trans-4
trans-3
S
a: R = H, b: R = OMe, c :R = Br, d: R = N
Scheme 3.

828
L. Wang et al. / Tetrahedron: Asymmetry 21 (2010) 825–830
Cotton effect requires a clockwise sense of the spatial arrange-
ment between the two coupling chromophores.12–14 The absolute
stereochemical of trans-4a was established as (1S,2S), which was
4. Experimental and characterization
4.1. Experimental details
consistent with the previous assignment of tran-3a by [a] com-
D
parison, and the spatial arrangement of two bis-(N,N-dimethyl-
amino)-benzoyl chromophores was shown in Figure 2.
Baker’s yeast was produced by Angel Yeast Co., Ltd. All solvents
were analytical grade unless specified. Normal phase HPLC analysis
was performed on an Agilent 1100 series. The chiracel AD-H col-
umn was produced by Daicel chemical Industries, Ltd. The
length/internal diameter of column was 250/4.6 mm, and all the
reagents of mobile phase were chromatographic pure. 1H NMR
and 13C NMR were recorded on Varian INOVA 400 MHz or Bruker
Avance II 400 MHz. Chemical shifts are reported in parts per mil-
lion (d) downfield from TMS. Optical rotations were determined
by WZZ-2S. ECCD was measured with J-810.
Me
N
Me
O
O
O
O
4.2. Experimental procedure for the synthesis of substrates 1b–e
Me
N
4.2.1. 5-Methoxy-acenaphthylene-1,2-dione 1b
Powdered NaNO3 2.94 g (34.6 mmol) was slowly added into a
mixture of acenaphthylene-1,2-dione 6.00 g (32.9 mmol) in
15 mL of concentrated sulfuric acid and the reaction mixture was
stirred for 2 h in an ice-water-bath. The mixture was slowly trans-
ferred into crushed ice. After filtration and dryness, crude 5-nitro-
acenaphthylene-1,2-dione was obtained.20
Me
Figure 2. Assignment of the absolute configuration of trans-4a based on the
observed positive chirality (positive first Cotton effect at 308 nm and 329 nm)
which needed a clockwise sense (1S,2S) of spatial arrangement between the two (p-
N,N-dimethylamino)-benzoyl chromophores.
A mixture of crude 5-nitro-acenaphthylene-1,2-dione 1.00 g
and KOH 0.25 g (4.46 mmol) in 30 mL of methanol was refluxed
for 2.0 h. After the solvent was removed from the reaction mixture,
the crude product was purified by silica gel column chromatogra-
phy using CH2Cl2 as an eluent to afford the pure 5-methoxy-ace-
naphthylene-1,2-dione 1b as a yellow solid in 40% yield. 1H NMR
(400 MHz, DMSO-d6): 8.38 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.0 Hz,
1H), 8.04 (d, J = 6.8 Hz, 1H), 7.84 (t, J = 7.8 Hz, 1H), 7.35 (d,
J = 8.0 Hz, 1H), 3.35 (s, 3H); 13C NMR (400 MHz, DMSO-d6): 189.1,
186.0, 160.1, 146.7, 128.4, 128.1, 127.5, 124.8, 122.3, 122.2,
107.6, 57.1; IR (KBr, cmꢀ1): 1719, 1248; HRMS-EI (70 eV) m/z, calcd
for C13H8O3 212.0473, found 212.0473; mp: 230.3–231.5 °C.
Based on the same principle, the absolute configuration of
trans-3b and -3c could be determined to be (1S,2S) because
trans-4b and -4c exhibited a positive first Cotton effect. Contrary
to others, the CD curve of trans-4d presented a negative first cotton
effect at 348 nm and 320 nm, which required an anticlockwise
sense of spatial arrangement between the two bis-(p-N,N-dimeth-
ylamino)-benzoyl chromophores. Thus it can be concluded that
trans-3d had an absolute configuration of (1R,2R). Due to the low
enantiomeric excess of cis-3b, -3c and -3d obtained by the yeast
reduction, the absolute configuration of cis-3b, -3c and -3d cannot
be given at this time.
4.2.2. 5-Bromo-acenaphthylene-1,2-dione 1c21
2.5. Proposed mechanism for reductases
A mixture of acenaphthylene-1,2-dione 20 g (109.8 mmol) and
bromine liquid (20 mL) was refluxed for 2 h. Off-gas was absorbed
by saturated NaOH solution. After the mixture had cooled, satu-
rated Na2S2O3 solution was slowly added until the colour of the
reaction mixture changed from red to colourless. Then the reaction
mixture was poured into 700 mL of water and some primrose pre-
cipitates were separated out. After filtration, the filter cake was
recrystallized in glacial acetic acid for four times and a yellow nee-
dle crystalloid was afforded in 90% yield. 1H NMR (400 MHz,
DMSO-d6): 8.39 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 7.6 Hz, 1H), 8.15 (d,
J = 7.2 Hz, 1H), 8.04 (t, J = 7.8 Hz, 1H), 7.96(d, J = 7.6 Hz, 1H); 13C
NMR (400 MHz, DMSO-d6): 187.2, 187.1, 144.7, 132.4, 131.0,
It has been demonstrated that there are several reductases in
baker’s yeast cells and each of the reductase exhibits high enanti-
oselectivity towards different substrates.16–19 Based on these facts,
it could be assumed that there are two kinds of reductases, reduc-
tase-(R) and -(S), towards the first carbonyl group of substituted
acenaphthylene-1,2-diones 1 and four kinds of reductases, reduc-
tase-(R,R), -(S,S), -(R,S) and -(S,R), towards the second residual car-
bonyl group of substituted 2-hydroxyacenaphthylen-1-ones 2,
although it is worthy of a further test by isolating the reductases
from the cells of baker’s yeast. In the reduction of substituted ace-
naphthylene-1,2-diones by baker’s yeast, the low enantiomeric
excess of 2-hydroxyacenaphthylen-1-one7 and cis-acenaphthene-
1,2-diol reveals that both reductase-(R) and -(S) and both reduc-
tase-(R,S) and -(S,R) work actively at the same time, respectively.
The very high enantioselectivity of trans-diols exhibits either
reductase-(S,S) or reductase-(R,R) work only towards different
substrates.
130.5, 130.1, 129.9, 129.3, 126.9, 122.6, 122.5; IR (KBr, cmꢀ1
)
1726, 766; HRMS-EI (70 eV) m/z, calcd for C12H6O2 259.9473, found
259.9475; mp: 236.0–236.8 °C (Lit.22 238 °C).
4.2.3. 5-Thiomorpholin-acenaphthylene-1,2-dione 1d
A mixture of 5-bromo-acenaphthylene-1,2-dione 1c (1.30 g,
5 mmol), K2CO3 (1.38 g, 10.0 mmol), CuI (190 mg, 1.0 mmol) and
thiomorpholine (1.50 ml, 7.5 mmol) in 50 mL of DMF was stirred
for 30 min at room temperature and then heated to 130 °C for
1.5 h under N2 protection. After the mixture was cooled to ambient
temperature, it was poured into 500 mL of water and some red pre-
cipitates were separated out. After filtration, the filter cake was
dried under an infrared dryer. The crude mixture was purified by
silica gel column chromatography using CH2Cl2 as the eluent to
afford the pure 5-thiomorpholin-acenaphthylene-1,2-dione 1d as
a red solid in 75% yield. 1H NMR (400 MHz, CDCl3): 8.22 (d,
3. Conclusions
We have reported a method to obtain a series of substituted
trans-acenaphthene-1,2-diols with very high enantiomeric excess
by baker’s yeast-mediated reduction of the corresponding ace-
naphthylene-1,2-diones. As the second example for baker’s yeast-
catalyzed reduction of rigid and polycyclic aromatic ketones, the
research extends the substrates of the enzymatic reductions
further.

L. Wang et al. / Tetrahedron: Asymmetry 21 (2010) 825–830
829
J = 8.8 Hz, 1H), 8.07 (d, J = 7.6 Hz, 1H), 8.02 (d, J = 6.8 Hz, 1H), 7.76 (t,
J = 8.0 Hz, 1H), 7.25 (d, J = 8.0 Hz, 1H), 3.65 (t, J = 5.2 Hz, 4H), 2.99 (t,
J = 4.8 Hz, 4H); 13C NMR (100 MHz, CDCl3): 189.5, 186.2, 155.7,
148.0, 129.5, 128.8, 127.2, 126.2, 124.0, 123.4, 121.9, 116.1, 54.7,
28.1; IR (KBr, cmꢀ1): 1717, 1318; HRMS-EI (70 eV) m/z, calcd for
C16H13NO2S 283.0667, found 283.0677; mp: 190.6–192.7 °C.
(s, 3H); 13C NMR (100 MHz, DMSO-d6): 154.1, 144.6, 137.2, 136.7,
127.7, 122.6, 121.7, 121.6, 119.5, 106.8, 73.8, 72.4, 56.1; IR (KBr,
cmꢀ1): 3359; HRMS-EI (70 eV) m/z, calcd for C13H12O3 216.0786,
found 216.0790; mp: 170.1–171.5 °C (Lit.25 172–173 °C).
½
a 2D0
ꢂ
¼ þ3:0 (c 0.38, EtOAc); The enantiomeric excess was deter-
mined by HPLC with a chiral AD-H column, (n-hexane/isopropyl
alcohol = 85:15, UV detection at 254 nm, flow rate = 1.0 mL/min),
retention time: (ꢀ)-cis-3b = 10.86 min, (+)-cis-3b = 12.21 min.
4.2.4. 5-Amino-acenaphthylene-1,2-dione 1e
A
mixture of 5-bromo-acenaphthylene-1,2-dione 1c (2.0 g,
7.7 mmol) and NaN3 (0.9 g, 13.8 mmol) in 30 mL of DMF was stirred
at100 °C for5 min. When thereaction mixture was cooled to ambient
temperature, it was poured into 50 mL of water and a yellow precip-
itatewasseparatedout. Afterfiltration, thefiltercakewasdriedunder
vacuum dryer to give crude 5-azido-acenaphthylene-1,2-dione.
The crude 5-azido-acenaphthylene-1,2-dione (0.8 mg, 3.6 mmol)
in 60 mL of toluene was kept at reflux for 36 h. When the reaction
mixture was cooled to ambient temperature, some brown precipi-
tates were separated out. After filtration, the filter cake was dried
under vacuum dryer. The crude 5-amino-acenaphthylene-1,2-dione
was purified by silica gel column chromatography using CH2Cl2 as
the eluent to give pure 5-amino-acenaphthylene-1,2-dione 1e in
45% yield. 1H NMR (400 MHz, DMSO-d6): 8.45 (d, J = 8.4 Hz, 1H),
7.89 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 6.8 Hz, 1H), 7.64 (t, J = 7.6 Hz,
1H), 7.31 (s, 2H), 6.90 (d, J = 8.0 Hz, 1H); 13C NMR (400 MHz,
DMSO-d6): 191.9, 183.1, 152.5, 148.9, 128.5, 127.6, 126.0, 125.9,
121.5, 118.3, 117.0, 109.6; IR (KBr, cmꢀ1): 3456, 3363, 1592, 1344;
mp >200 °C.
4.3.4. trans-(1S,2S)-5-Methoxy-acenaphthene-1,2-diol trans-3b
1H NMR (400 MHz, DMSO-d6): 7.83 (d, J = 8.4 Hz, 1H), 7.52 (t,
J = 7.6 Hz, 1H), 7.43 (d, J = 7.2 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H),
6.98 (d, J = 7.6 Hz, 1H), 5.75 (d, J = 6.8 Hz, 1H), 5.64 (d, J = 6.8 Hz,
1H), 5.14 (d, J = 6.8 Hz, 1H), 5.10 (d, J = 6.8 Hz, 1H), 3.95 (s, 3H);
13C NMR (100 MHz, DMSO-d6): 157.4, 137.0, 131.0, 127.4, 124.5,
123.8, 123.3, 122.8, 122.2, 103.4, 85.3, 83.5, 56.3; IR (KBr, cmꢀ1):
3296; HRMS-EI (70 eV) m/z, calcd for C13H12O3 216.0786, found
216.0788; mp: 158.5–160.5 °C (Lit.25 155–156 °C). ½a 2D0
¼ ꢀ24:2
ꢂ
(c 0.26, CHCl3). The anantiomeric excess was determined by HPLC
with a chiral AD-H column, (n-hexane/isopropyl alcohol = 90:10,
UV detection at 254 nm, flow rate = 1.0 mL/min), retention time:
(S,S)-trans-3b = 19.50 min, (R,R)-trans-3b = 20.58 min.
4.3.5. cis-5-Bromo-acenaphthene-1,2-diol cis-3c
1H NMR (400 MHz, DMSO-d6): 7.87 (d, J = 7.2 Hz, 1H), 7.82 (d,
J = 8.4 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.59 (d, J = 6.8 Hz, 1H), 7.42
(d, J = 7.2 Hz, 1H), 5.39–5.25 (m, 4H); 13C NMR (100 MHz, DMSO-
d6): 145.2, 144.8, 136.3, 131.3, 129.8, 129.3, 122.7, 122.0, 121.9,
117.6, 72.2, 72.1; IR (KBr, cmꢀ1): 3335; HRMS-EI (70 eV) m/z, calcd
for C12H9BrO2 263.9786, found 263.9783; mp: 180.0–183.2 °C.
4.3. Experimental procedure for 3a–3d
A mixture of dry baker’s yeast (10.0 g) and sucrose (3.0 g) in
water (100 mL) was stirred at 30 °C for 0.5 h. Then the substrate
(100 mg) dissolved in the organic solvent of DMSO (10 mL) was
added to the mixture and vigorous stirring (600 rpm) was contin-
ued at the same temperature (30 °C) for 48 h. After removal of the
baker’s yeast by filtration, the filtrates were extracted with ethyl
acetate (3 ꢁ 100 mL). The separated organic phase was dried over
anhydrous MgSO4 and concentrated under reduced pressure. The
crude products were purified by chromatography on a silica gel
column (CH2Cl2/MeOH = 20:1) to afford the pure 1,2-dihydroxy
product as the white solid.
½
a 2D0
ꢂ
¼ þ3:4 (c 0.38, EtOAc). The anantiomeric excess was deter-
mined by HPLC with a chiral AD-H column, (n-hexane/isopropyl
alcohol = 90:10, UV detection at 254 nm, flow rate = 1.0 mL/min),
retention time: (+)-racemic-cis-3c = 12.34 min, (ꢀ)-racemic-cis-
3c = 14.03 min.
4.3.6. trans-(1S,2S)-Bromo-acenaphthene-1,2-diol trans-3c
1H NMR (400 MHz, DMSO-d6): 7.87 (d, J = 7.6 Hz, 1H), 7.82 (d,
J = 8.0 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.55 (d, J = 6.8 Hz, 1H), 7.38
(d, J = 7.6 Hz, 1H), 6.00 (d, J = 6.0 Hz, 2H), 5.18 (s, 1H), 5.13 (s, 1H);
13C NMR (100 MHz, DMSO-d6): 144.8, 144.5, 136.6, 131.8, 130.4,
129.7, 123.1, 121.7, 121.6, 118.0, 82.6, 82.1. IR (KBr, cmꢀ1): 3333;
HRMS-EI (70 eV) m/z, calcd for C12H9BrO2 263.9786, found
4.3.1. cis-Acenaphthene-1,2-diol cis-3a
1H NMR (400 MHz, DMSO-d6): d 7.77 (d, J = 8.0 Hz, 2H), 7.57 (t,
J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 5.29 (s, 2H); 13C NMR
(100 MHz, DMSO-d6): 149.0, 146.7, 138.7, 128.3, 124.1, 120.8,
72.0; IR (KBr, cmꢀ1): 3333; HRMS-EI (70 eV) m/z, calcd for
C12H10O2 186.0681, found 186.0681; mp: 170.8–172.4 °C (Lit.23
208–209 °C).
263.9783; mp: 165.0–170.2 °C (Lit.26 216–217 °C); ½a 2D0
¼ þ15:1
ꢂ
(c 0.35, EtOAc). The anantiomeric excess was determined by HPLC
with a chiral AD-H column, (n-hexane/isopropyl alcohol = 90:10,
UV detection at 254 nm, flow rate = 1.0 mL /min), retention time:
(S,S)-trans-3c = 12.66 min, (R,R)-trans-3c = 14.52 min.
4.3.7. cis-5-thiomorpholin-acenaphthene-1,2-diol cis-3d
4.3.2. trans-(1S,2S)-Acenaphthene-1,2-diol trans-3a
1H NMR (400 MHz, DMSO-d6): 7.80 (d, J = 8.4 Hz, 1H), 7.55 (t,
J = 6.8 Hz, 1H), 7.45 (d, J = 6.8 Hz, 1H), 7.38 (d, J = 7.2 Hz, 1H),
7.11 (d, J = 7.2 Hz, 1H), 5.28–5.14 (m, 4H), 3.29 (t, J = 4.4 Hz 4H),
2.90 (t, J = 4.4 Hz, 4H); 13C NMR (100 MHz, DMSO-d6): 148.4,
145.0, 139.3, 136.9, 127.5, 125.6, 121.0, 120.8, 120.7, 116.6, 73.1,
72.0, 55.0, 27.7. IR (KBr, cmꢀ1): 3412; HRMS-EI (70 eV) m/z, calcd
for C16H17NO2S 287.0980, found 287.0990; mp: 153.5–154.5 °C.
1H NMR (400 MHz, DMSO-d6): 7.76 (d, J = 8.0 Hz, 2H), 7.57 (t,
J = 7.8 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 5.18 (s, 2H); 13C NMR
(100 MHz, DMSO-d6): 143.8, 135.4, 130.3, 128.3, 123.9, 120.0,
82.4; IR (KBr, cmꢀ1): 3266; HRMS-EI (70 eV) m/z, calcd for
C12H10O2 186.0681, found 186.0683; mp: 153.7–154.6 °C (Lit.24
160–163 °C). ½a 2D0
¼ ꢀ24:1 (c 0.28, CHCl3); The enantiomeric ex-
ꢂ
cess was determined by HPLC with a chiral AD-H column (n-hex-
ane/isopropyl alcohol = 85:15, UV detection at 254 nm, flow
rate = 1.0 mL /min), retention time: (S,S)-trans-3a = 8.06 min,
(R,R)-trans-3a = 10.49 min.
½
a 2D0
ꢂ
¼ þ5:5 (c 0.36, EtOAc). The enantiomeric excess was deter-
mined by HPLC with a chiral AD-H column, (n-hexane/isopropyl
alcohol = 80:20, UV detection at 254 nm, flow rate = 1.0 mL/min),
retention time: (ꢀ)-cis-3d = 15.22 min, (+)-cis-3d = 16.32 min.
4.3.3. cis-5-Methoxy-acenaphthene-1,2-diol cis-3b
4.3.8. trans-(1S,2S)-5-thiomorpholin-acenaphthene-1,2-diol
trans-3d
1H NMR (400 MHz, DMSO-d6): 7.84 (d, J = 8.0 Hz, 1H), 7.52 (t,
J = 7.6 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 6.98
(d, J = 7.6 Hz, 1H), 5.29–5.20 (m, 2H), 5.12 (d, J = 6.8 Hz, 2H), 3.95
1H NMR (400 MHz, DMSO-d6): 7.80 (d, J = 8.4 Hz, 1H), 7.55 (t,
J = 6.8 Hz, 1H), 7.41 (d, J = 6.8 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H),

830
L. Wang et al. / Tetrahedron: Asymmetry 21 (2010) 825–830
7.11 (d, J = 7.6 Hz, 1H), 5.77 (d, J = 6.8 Hz, 1H), 5.69 (d, J = 6.8 Hz,
1H), 5.13 (d, J = 6.8 Hz, 1H), 5.09 (d, J = 6.4 Hz, 1H), 3.29 (t,
J = 3.6 Hz, 4H), 2.89 (t, J = 3.6 Hz, 4H); 13C NMR (100 MHz, DMSO-
d6): 148.3, 144.2, 138.7, 136.7, 127.5, 125.5, 120.6, 120.2, 120.1,
116.6, 82.8, 81.8, 54.9, 27.7; IR (KBr, cmꢀ1): 3294, 1019; HRMS-EI
(70 eV) m/z, calcd for C16H17NO2S 287.0980, found 287.0987; mp:
129.7, 125.0, 123.5, 123.4, 120.5, 111.1, 81.0, 80.6, 40.3; IR (KBr,
cmꢀ1): 1705, 1606, 1271, 1180, 1091; HRMS-ESI (M+H)+ m/z, calcd
for C30H28BrN2O4 559.1232, found 559.1208; mp: 176.3–176.9 °C.
½
a 2D0
ꢂ
¼ þ429 (c 0.27, CHCl3).
4.4.4. trans-(1R,2R)-Bis-p-N,N-dimethylaminobenzoyloxy-1,2-
dihydro-5-thiomorpholinacenaphthene trans-4d
144.4–147.4 °C. ½a D20
¼ ꢀ29:6 (c 0.24, CHCl3) The anantiomeric ex-
ꢂ
cess was determined by HPLC with a chiral AD-H column, (n-hex-
ane/isopropyl alcohol = 80:20, UV detection at 254 nm, flow
rate = 1.0 mL /min), retention time: (R,R)-trans-3d = 10.96 min,
(S,S)-trans-3d = 12.83 min.
The same treatment of trans-3d gave trans-4d in 39% yield; 1H
NMR (400 MHz, CDCl3): 7.94 (d, J = 9.2 Hz, 5H), 7.68 (d, J = 7.6 Hz,
1H), 7.62 (d, J = 7.6 Hz, 1H), 7.57 (t, J = 8.0 Hz, 1H), 7.18 (s, 1H),
6.96 (s, 1H), 6.89 (s, 1H), 6.65 (d, J = 8.4 Hz, 4H), 3.44 (s, 4H), 3.03
(s, 12H), 2.96 (s, 4H); 13C NMR (100 MHz, CDCl3): 166.8, 166.7,
153.5, 149.9, 140.0, 139.3, 134.6, 131.7, 127.8, 126.4, 123.1,
122.8, 122.2, 117.0, 116.6, 110.8, 81.6, 80.9, 55.3, 40.2, 28.6; IR
(KBr, cmꢀ1): 1701, 1607, 1274, 1182, 1100; HRMS-ESI (M+Na)+
m/z, calcd for C34H35N3O4NaS 604.2246, found 604.2225; mp:
4.4. Experimental procedure for 4a–4d
4.4.1. trans-(1S,2S)-Bis-p-N,N-dimethylaminobenzoyloxy-1,2-
dihydroacenaphthene trans-4a
A
mixture of trans-3a (18 mg, 0.1 mmol), p-N,N-dim-
101.9–103.2 °C. ½a D20
¼ þ237 (c 0.19, CHCl3).
ꢂ
ethylaminobenzoyl chloride (73 mg, 0.4 mmol) and AgCN (60 mg,
0.4 mmol) in toluene (10 mL) was stirred at rt for 48 h. The reac-
tion mixture was diluted with CH2Cl2 (100 mL) and filtered. The fil-
ter was dried by anhydrous MgSO4. Evaporation of the solvent gave
a yellow solid which was purified by silica gel column chromatog-
raphy using a mixture of n-hexane and EtOAc (4:1) as eluent. The
pure trans-4a was afforded as the white solid (25 mg) in 52% yield;
1H NMR (400 MHz, CDCl3): 7.95 (d, J = 8.8 Hz, 4H), 7.82 (d,
J = 8.0 Hz, 2H), 7.68 (d, J = 7.2 Hz, 2H), 7.57 (t, J = 6.8 Hz, 2H), 6.99
(s, 2H), 6.61 (d, J = 8.8 Hz, 4H), 3.00 (s, 12H); 13C NMR (100 MHz,
CDCl3): 166.7, 153.4, 139.5, 137.7, 131.6, 130.8, 128.4, 125.4,
122.5, 116.4, 110.6, 81.2, 40.0; IR (KBr, cmꢀ1): 1695, 1610, 1276,
1183, 1091; HRMS-ESI (M+H)+ m/z, calcd for C30H29N2O4
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (90713030; 20876025) and the National Basic Research Pro-
gram of China (2009CB724706).
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481.2127, found 481.2147; mp: 168.5–170.7 °C. ½a D20
¼ þ672 (c
ꢂ
0.10, CHCl3).
4.4.2. trans-(1S,2S)-Bis-p-N,N-dimethylaminobenzoyloxy-1,2-
dihydro-5-methoxyacenaphthene trans-4b
The same treatment of trans-3b gave trans-4b in 44% yield. 1H
NMR (400 MHz, CDCl3): 8.05 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 8.8 Hz,
4H), 7.69 (d, J = 7.2 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.54 (t,
J = 7.6 Hz, 1H), 6.97 (s, 1H), 6.87 (d, J = 4.4 Hz, 2H), 6.63(d,
J = 8.8 Hz, 4H), 4.01 (s, 3H), 3.02 (s, 12H); 13C NMR (100 MHz,
CDCl3): 166.8, 166.6, 155.3, 153.4, 139.2, 138.9, 131.7, 131.6,
131.4, 127.5, 123.2, 123.1, 122.9, 121.0, 116.9, 116.7, 110.8,
106.1, 81.9, 81.0, 55.8, 40.1; IR (KBr, cmꢀ1): 1701, 1607, 1271,
1180, 1092; HRMS-ESI (M+Na)+ m/z, calcd for C31H30N2O5Na
533.2052, found 533.2037; mp: 78.8–79.1 °C. ½a D20
¼ þ480 (c
ꢂ
0.15, CHCl3).
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4.4.3. trans-(1S,2S)-Bis-p-N,N-dimethylaminobenzoyloxy-1,2-
dihydro-5-bromoacenaphthene trans-4c
The same treatment of trans-3c gave trans-4c in 54% yield. 1H
NMR (400 MHz, CDCl3): 8.01 (d, J = 8.0 Hz, 1H), 7.94 (d, J = 8.8 Hz,
4H), 7.81 (d, J = 7.2 Hz, 1H), 7.74 (d, J = 6.8 Hz, 1H), 7.68 (t,
J = 8.0 Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 6.97 (s, 1H), 6.89 (s, 1H),
6.65 (d, J = 8.4 Hz, 4H), 3.03 (s, 12H); 13C NMR (100 MHz, CDCl3):
166.5, 166.4, 153.3, 139.8, 139.4, 138.6, 131.7, 131.6, 130.3,