Chiral preparation of C2-symmetric 4-cyclopentene-1,3-diol

Article abstract of DOI:10.1055/s-2002-31949

Optically pure C₂-symmetric 4-cyclopentene-1,3-diol has been prepared in both enantiomeric forms from racemic (3aS*,4R*,7S*,7aS*)-3a,4,7,7a-tetrahydro-4,7- methano-1H-inden-1-one by employing lipase-mediated kinetic resolution as the key step. As a result, the known (3aS*,4R*,7S*,7aS*)-3a,4,7,7a-tetrahydro-4,7- methano-1H-inden-1-one is transformed into (1′S*,3′S*,3′aR*,4′S*, 7′R*,7′aS*)- 2′,3′,3′a,4′,7′,7′a-hexahydro-3′- hydroxy-4′,7′-methano-1′H-inden-1′-yl benzoate, via stereo- and regioselective hydride reduction of epoxy ketone and sequential benzoylation, which is resolved under transesterification conditions in the presence of lipase. The hydride reduction of benzoate and acetate gives the corresponding chiral diols, which are further transformed into both enantiomers of C₂-symmetric 4-cyclopentene-1,3-diol via a retro-Diels-Alder reaction.

Full text of DOI:10.1055/s-2002-31949

PAPER
1027
Chiral Preparation of C2-Symmetric 4-Cyclopentene-1,3-diol
C
hi ra
l
Prepara
e
t ion of C2
-
i
k
tric 4-Cyclo
o
Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Fax +81(22)2752013; E-mail: inomata@tohoku-pharm.ac.jp
Received 5 February 2002; revised 5 April 2002
alcohol 4 with 90% ee, via [2,3]-sigmatropic rearrange-
ment of sulfoxide 5 as the key step. In that communica-
tion, (+)–2 was immediately trapped with diphenyl
disulfide to convert it into a chiral epoxide synthon 6 for
Abstract: Optically pure C2-symmetric 4-cyclopentene-1,3-diol
has been prepared in both enantiomeric forms from racemic
(3aS*,4R*,7S*,7aS*)-3a,4,7,7a-tetrahydro-4,7-methano-1H-inden-
1-one by employing lipase-mediated kinetic resolution as the key
step. As a result, the known (3aS*,4R*,7S*,7aS*)-3a,4,7,7a-tetrahy- the synthesis of prostaglandin E2 intermediate
(Scheme 2).7 Thus, (+)- and (–)-2 have never been isolat-
ed in optically pure forms. Because of the symmetrical
form of C2 and allylic trans-diol functionalities in 2, high
potentiality would be expected in the chiral synthesis of
cyclopentanoids. So, an efficient chiral preparation of 2 in
both enantiomeric forms would be required. We report
herein an efficient chiral preparation of both enantiomers
dro-4,7-methano-1H-inden-1-one
is
transformed
into
(1 S*,3 S*,3 aR*,4 S*,7 R*,7 aS*)- 2 ,3 ,3 a,4 ,7 ,7 a-hexahydro-3 -
hydroxy-4 ,7 -methano-1 H-inden-1 -yl benzoate, via stereo- and
regioselective hydride reduction of epoxy ketone and sequential
benzoylation, which is resolved under transesterification conditions
in the presence of lipase. The hydride reduction of benzoate and ac-
etate gives the corresponding chiral diols, which are further trans-
formed into both enantiomers of C2-symmetric 4-cyclopentene-1,3-
diol via a retro-Diels–Alder reaction.
of
2
starting
from
the
known
racemic
(3aS*,4R*,7S*,7aS*)-3a,4,7,7a-tetrahydro-4,7-methano-
1H-inden-1-one 78,9 by employing a lipase-mediated ki-
netic transesterification10 as the key step.11
Key words: enzymes, stereoselective synthesis, Diels–Alder reac-
tions, diols, epoxides
4-Cyclopentene-1,3-diol1 serves as an important precur-
sor for enantiocontrolled syntheses of a variety of biolog-
ically active natural and synthetic compounds, especially
prostanoids2 and carbocyclic nucleosides.3 In connection
with cyclopentanoid synthesis, much effort has been made
to develop efficient preparations and practical uses of
AcO
Baker's yeast
(−)−2
AcO
(±)−3
meso-4-cyclopentene-1,3-diol (1) (Figure 1). Many asym- Scheme 1
metric procedures have been developed on the basis of the
desymmetrization of 1.4
Dienone ( )-7 was first transformed into racemic epoxy
ketone 8 by the established method, which was reported
by Chapman.12 Treatment of 8 with LAH in refluxing
THF gave trans–diol 9 as a single isomer in high yield via
stereoselective 1,2-reduction of ketone and regioselective
epoxide ring-opening.13 Zwanenburg reported that this re-
duction at a lower temperature yielded the corresponding
epoxy alcohol with a trace amount of diol 9.14 To distin-
guish between the two alcohol functionalities in the mol-
ecule, diol 9 was exposed to NBS to block the endo-
oriented alcohol regioselectively by generating the single
bromo ether 10, whose remaining alcohol was protected
with a benzoyl group to furnish benzoate 11, in 54% yield
from 8. Treatment of 11 with zinc in the presence of
HOAc in EtOH regenerated olefin and alcohol functional-
ity to furnish endo-alcohol ( )-12 (Scheme 3).
HO
HO
OH
HO
HO
(+)−2
OH
(−)−2
1
Figure 1
But, because of the difficulty of stereoselectively con-
structing trans-diol functionalities on a cyclopentene ring,
no efficient chiral preparation of C2-symmetric 4-cyclo-
pentene-1,3-diol (2) has been reported, except for a report
by Kurozumi5 and one by Fuchs.6 Kurozumi et al. report-
ed that asymmetric hydrolysis of a stereoisomeric mixture
of diacetate 3 using baker’s yeast furnished (–)-2 in 7–
17% yield with 10–32% optical purity (Scheme 1). On the
other hand, Fuchs et al. obtained (+)–2 from chiral sulfide
Treatment of the racemic alcohol ( )-12 with vinyl acetate
in organic solvent in the presence of lipase15 at 37 °C
yielded the acetate (+)-13 and unreacted starting alcohol
(+)-12, which were readily separated by silica gel column
chromatography (Scheme 4, Table). Alcohol (+)-12 was
converted to the corresponding acetate (–)-13 to deter-
mine its optical purity. Both the ee of (+)- and of (–)-13
were determined by HPLC analysis using a chiral column
Synthesis 2002, No. 8, 04 06 2002. Article Identifier:
1437-210X,E;2002,0,08,1027,1032,ftx,en;F01402SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1028
S. Kimura et al.
PAPER
O
HO
HO
HO
HO
HO
SC6H5
SC6H5
SC6H5
[2,3]
[O]
O
(+)−2
4
5
6
Scheme 2
ref. 12
LiAlH4
NBS
OH
THF
reflux
(77%)
CH2Cl2
0 °C
O
HO
O
O
(87%)
(±)-9
(±)-7
8
BzCl
Et3N
Br
Br
Zn
DMAP
HOAc
OH
OBz
OBz
CH2Cl2
0 °C
(81%)
EtOH
reflux
(73%)
O
O
HO
(±)-12
11
10
Scheme 3
(Chiralcel OD). As shown in the Table, when a catalytic good solvents for this reaction, because the reaction in ei-
amount of lipase PS-D or lipase AK-20 was used with vi- ther case proceeded very slowly and gave the acetate (+)-
nyl acetate in t-BuOMe, acetate (+)-13 and alcohol (+)-12 13 in lower yield (entries 3 and 4). When some other lipas-
were obtained in good recovery with moderate ee (entries es were used, such as lipase AS and lipase AYS, no reac-
1, 2 and 7). THF and diisopropyl ether (IPE) were not tion occurred (entries 5 and 6). Next, we demonstrated the
Table Lipase-Mediated Asymmetric Esterification of ( )-12
Entry
Scale
(g)
Lipase
Vinyl Acetate
(mol equiv)
Solvent
Time
(h)
Yielda (%) (ee)b
(weight%)
(+)-12
(+)-13
48 (90)
45 (97)
18 (89)
1 (99)
1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
25.0
PS-Dc)
PS-D
PS-D
PS-D
ASd
(10)
(10)
1.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.8
0.8
t-BuOMe
t-BuOMe
IPE
82
57
57
57
57
57
57
48
24
24
48 (82)
2
51 (82)
3
(10)
76 (21)
4
(10)
THF
82 (1)
5
(10)
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
t-BuOMe
no reaction
no reaction
54 (32)
6
AYSe
AK-20f
PS-D
PS-D
PS-D
(10)
7
(10)
45 (23)
54 (92)
46 (96)
52 (95)
8
(100)
(100)
(100)
45 (93)
9
48 (92)
10
40 (95)
a Isolated yield.
b HPLC analysis of acetate (+)- and (–)-13.
c Pseudomonas cepasia, immobilized on diatomaceous earth (AMANO).
d Aspergillus niger (AMANO).
e Candida rugosa (AMANO).
f Pseudomonas fluorescens (AMANO).
Synthesis 2002, No. 8, 1027–1032 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Chiral Preparation of C2-Symmetric 4-Cyclopentene-1,3-diol
1029
vinyl acetate
lipase
OAc
(±)-12
OBz
solvent
37 °C
RO
OBz
AcCl, Et3N
DMAP
CH2Cl2
(66%)
(+)-13
(+)-12 : R = H
(−)-13 : R = Ac
Scheme 4
amounts of lipase and vinyl acetate in the reaction. As en- have just begun to investigate the practical uses of the pre-
try 8 shows, when 100 weight% of lipase PS-D with 1.0 pared enantiopure 2 as a chiral building block.
mol equiv of vinyl acetate was used, both (+)-12 and (+)-
13 were obtained in good yield with high ee. The most ef-
Melting points are uncorrected. IR spectra were recorded on a JAS-
CO-FT-IR-5000 spectrometer. 1H NMR spectra were recorded on a
ficient reaction condition, using lipase PS-D with 0.8 mol JEOL-EX-270 (270 MHz) spectrometer and on a JEOL-GSX-400
(400 MHz) spectrometer. Mass spectra were recorded on a JEOL-
DX-303 spectrometer. Enantiomeric excess was determined using a
Waters-HPLC 600 instrument equipped with a chiral column. Opti-
cal rotations were measured with a JASCO-DIP-370 digital pola-
equiv of vinyl acetate in t-BuOMe, yielded (+)-13 and (+)-
12 in 46% yield with 96% ee and 48% yield with 92% ee,
respectively (entry 9). Under this reaction condition, the
same result was obtained when 25 g of ( )-12 was used as
rimeter.
a starting material (entry 10).
( )-(1S*,3S*,3aR*,4S*,7R*,7aS*) -2,3,3a,4,7,7a-Hexahydro-4,7-
methano-1H-indene-1,3-diol [( )-9]
To a stirred suspension of LiAlH4 (10.34 g, 0.27 mol) in THF (300
mL) was added keto epoxide 8 (36.8 g, 0.23 mol) in THF (400 mL)
over 25 min at 0 °C. After further stirring at 80 °C for 6 h, the reac-
tion was quenched by adding 28% aq ammonia and Celite at 0 °C.
Acetate (+)-13 and alcohol (+)-12 were easily converted
to (+)- and (–)-diol 9 by LAH reduction, respectively.
Fortunately, chiral diol 9 was readily recrystallized from
i-PrOH and hexane to give enantiopure materials. Thus,
the enantiopure diol 9 was obtained in both enantiomeric
forms. The optical purity of (+)- and (–)-9 was determined After further stirring for 2 h at r.t., the mixture was filtered through
a Celite pad, and the filtrate was extracted with THF (5 300 mL).
The extract was washed with brine (100 mL), dried (MgSO4), and
evaporated under reduced pressure. The residue was recrystallized
from MeOH to give the diol 9.
by HPLC using a chiral column (Chiralcel OD), after the
conversion to corresponding dibenzoate 14. Next, (+)-
and (–)-diol 9 were heated in refluxing diphenyl ether16 in
the presence of sodium hydrogen carbonate17 to give (+)-
Yield: 29 g, 77%; colorless crystals; mp 134–136 °C.
IR (film): 3182 cm–1.
and (–)-diol 2, respectively, via retro-Diels–Alder reac-
tions (Scheme 5).
1H NMR (270 MHz, CDCl3–CD3OD): = 1.32–1.36 (1 H, m),
In conclusion, we have established an efficient chiral
1.43–1.47 (1 H, m), 1.69–1.88 (2 H, m), 2.18–2.33 (2 H, br s), 2.64
preparation of 2 in both enantiomeric forms by employing
lipase-mediated kinetic transesterification as the key step.
On the basis of the C2 symmetry and allylic trans–diol
functionalities in 2, this study may have established the
enantiocontrolled syntheses of natural and unnatural
products involving prostanoids and aminopentitols. We
(1 H, dd, J = 8.6, 4.5 Hz), 2.94–3.02 (3 H, m), 3.79 (1 H, d, J = 5.3
Hz), 4.56 (1 H, td, J = 17.2, 8.3 Hz), 6.00 (1 H, dd, J = 5.6, 3.1 Hz),
6.28 (1 H, dd, J = 5.6, 2.8 Hz).
13C NMR (270 MHz, CDCl3–CD3OD): = 45.08, 45.16, 45.31,
51.23, 52.38, 55.80, 72.66, 73.09, 133.68, 137.63.
MS: m/z = 166 (M+), 66 (100%).
HRMS: m/z Calcd for C10H12O2: 166.0994. Found: 166.0976.
For R = H
NaHCO3
Anal. Calcd for C10H12O2: C, 72.26; H, 8.49. Found: C, 72.11; H,
8.78.
LiAlH4
(−)-2
OR
(+)-12
THF
0 °C
(88 %)
Ph2O
reflux
(41%)
RO
( )-(1S*,3S*,3aS*,4R*,5S*,6S*,7S*,7aR*)-6-Bromo-3,5-epoxy-
2,3,3a,4,5,6,7,7a-octahydro-4,7-methano-1H-inden-1-ol (10)
To a stirred solution of ( )-9 (42.2 g, 0.25 mol) in CH2Cl2 (250 mL)
was added NBS (56.0 g, 0.31 mol) portionwise over 10 min at 0 °C.
After stirring at the same temperature for 30 min, the reaction mix-
ture was diluted with CH2Cl2 (100 mL), washed with sat. aq
NaHCO3 (100 mL), aq Na2S2O3 (10%, 100 mL) and brine (100 mL),
dried (MgSO4), and evaporated under reduced pressure. The residue
was recrystallized from hexane–Et2O to give the bromo ether 10.
BzCl
(−)-9 : R = H
(−)-14 : R = Bz
Et3N
DMAP
(85%)
For R = H
NaHCO3
LiAlH4
OR
(+)-13
(+)-2
THF
0 °C
Ph2O
reflux
(45%)
(64%)
OR
Yield: 54.0 g (87%); colorless crystals; mp 74–75 °C.
IR (film): 3210 cm–1.
BzCl
(+)-9 : R = H
Et3N
DMAP
(+)-14 : R = Bz
1H NMR (270 MHz, CDCl3): = 1.59 (1 H, br s), 1.77–1.81 (1 H,
(84%)
m), 1.90 (1 H, td, J = 15.3, 5.4 Hz), 2.30 (1 H, d, J = 11.2 Hz), 2.55–
Scheme 5
Synthesis 2002, No. 8, 1027–1032 ISSN 0039-7881 © Thieme Stuttgart · New York

1030
S. Kimura et al.
PAPER
2.63 (3 H, m), 2.77–2.83 (1 H, m), 2.97–3.04 (1 H, m), 3.81 (1 H, d,
J = 2.3 Hz), 4.36–4.46 (1 H, m), 4.47–4.51 (2 H, m).
Anal. Calcd for C17H18O3: C, 75.53; H, 6.71. Found: C, 75.52; H,
6.53.
13C NMR (270 MHz, CDCl3): = 38.78, 45.55, 48.06, 48.39, 49.54,
56.17, 56.71, 72.67, 84.52, 89.03.
MS: m/z = 246 (M+ + 2), 244 (M+), 165, 99 (100%).
HRMS: m/z Calcd for C10H1379BrO2: 244.0099 (M+). Found:
244.0113; calcd for C10H1381BrO2: 246.0079 (M+ + 2). Found:
246.0086.
Asymmetric Transesterification of ( )-12; Typical Procedure
A solution of alcohol ( )-12 (25.0 g, 92.6 mmol) and vinyl acetate
(6.8 mL, 74.1 mmol) in t-BuOMe (500 mL) was suspended with li-
pase PS-D (Pseudomonas sp. AMANO, 25.0 g) and the suspension
was stirred at 37 °C for 24 h. After filtration through a Celite pad,
the filtrate was evaporated under reduced pressure. The residue was
chromatographed (silica gel 400 g; hexane–EtOAc, 8:1 v/v) to give
the acetate (+)-13 (15.1 g, 52%) as a colorless oil and alcohol (+)-
12 (10.0 g, 40%) as colorless crystals.
Anal. Calcd for C10H13BrO2: C, 49.00; H, 5.35. Found: C, 48.86; H,
5.23.
( )-(1 S*,3 S*,3 aR*,4 R*,5 S*,6 S*,7 S*,7 aR*)-6 -Bromo-3 ,5 -
epoxy-2 ,3 ,3 a,4 ,5 ,6 ,7 ,7 a-octahydro-4 ,7 -methano-1 H-in-
den-1 -yl Benzoate (11)
A solution of bromo ether 10 (59.6 g, 0.24 mol) in CH2Cl2 (600 mL)
was stirred with Et3N (37.1 mL, 0.27 mol), DMAP (34.0 g, 0.27
mol) and benzoyl chloride (BzCl, 30.9 mL, 0.27 mol) at 0 °C for 3
h. The reaction mixture was washed with aq. HCl (10%, 300 mL),
sat. aq NaHCO3 (300 mL) and brine (300 mL), dried (MgSO4) and
evaporated under reduced pressure. The residue was recrystallized
from hexane–EtOAc to give benzoate 11.
(+)-(1 R,3 R,3 aS,4 R,7 S,7 aR)-3 -Acetoxy-2 ,3 ,3 a,4 ,7 ,7 a-
hexahydro-4 ,7 -methano-1 H-inden-1 -yl Benzoate [(+)-13]
[ ]D21+49.5 (c 1.00, CHCl3).
IR (film):1717, 1735 cm–1.
1H NMR (270 MHz, CDCl3): = 1.44–1.45 (1 H, m), 1.47–1,48 (1
H, m), 1.93–2.08 (1 H, m), 2.09 (3 H, s), 2.10–2.21 (1 H, m), 2.83–
2.88 (2 H, m), 3.13–3.15 (1 H, m), 3.23 (1 H, dt, J = 8.2, 4.0 Hz),
4.97 (1 H, d, J = 6.1 Hz), 5.34 (1 H, td, J = 10.1, 8.6 Hz), 6.15 (1 H,
dd, J = 5.5, 3.0 Hz), 6.22 (1H, dd, J = 5.5, 3.0 Hz), 7.40–7.46 (2 H,
m), 7.52–7.58 (1 H, m), 7.99–8.03 (2 H, m).
13C NMR (400 MHz, CDCl3): = 21.05, 39.65, 45.59, 45.74, 49.00,
52.02, 53.14, 75.45, 76.27, 128.34, 129.53, 130.47, 132.93, 133.90,
137.63, 166.01, 170.89.
Yield: 68.0 g (81%); colorless crystals; mp 90–91 °C.
IR (film): 1714 cm–1.
1H NMR (270 MHz, CDCl3): = 1.81 (1 H, dd, J = 11.1, 0.8 Hz),
2.16 (1 H, td, J = 15.7, 5.8 Hz), 2.34 (1 H, d, J = 10.9 Hz), 2.68–
2.80 (3 H, m), 2.81–2.88 (1 H, m), 2.99–3.06 (1 H, m), 3.95 (1 H, d,
J = 2.3 Hz), 4.53–4.57 (2 H, m), 5.30–5.36 (1 H, m), 7.41–7.47 (2
H, m), 7.53–7.64 (1 H, m), 7.99–8.03 (2 H, m).
13C NMR (270 MHz, CDCl3): = 38.77, 44.47, 45.52, 48,43, 49.70,
54.09, 55.97, 75.96, 83.86, 89.07, 128.40, 129.53, 130.13, 133.07,
166.37.
MS: m/z = 312 (M+), 187, 66 (100%).
HRMS: m/z Calcd for C19H20O4: 312.1362. Found: 312.1357.
Anal. Calcd for C19H20O4: C, 73.06; H, 6.45. Found: C, 72.10; H,
6.51.
Optical purity was determined to be 95% ee by HPLC using a
chiral column with chiral stationary phase (Chiralcel OD; hex-
ane–i-PrOH, 25:1 v/v).
MS: m/z = 350 (M+ + 2), 348 (M+), 228, 269, 105 (100%).
HRMS: m/z Calcd for C17H1779BrO3: 348.0361 (M+). Found:
348.0323; calcd for C17H1781BrO3: 350.0341 (M+ + 2). Found:
350.0440.
(+)-(1 S,3 S,3 aR,4 S,7 R,7 aS)-2 ,3 ,3 a,4 ,7 ,7 a-Hexahydro-3 -
hydroxy-4 ,7 -methano-1 H-inden-1 -yl Benzoate [(+)-12]
Mp 88 °C; [ ]D22+13.8 (c 1.00, CHCl3).
Anal. Calcd for C17H17BrO3: C, 58.47; H, 4.91. Found C, 58.16; H,
4.55.
The spectroscopic data were identical to those of ( )-12. Optical pu-
rity was determined to be 95% ee by HPLC using a chiral column
with chiral stationary phase (Chiralcel OD; hexane–i-PrOH, 25:1 v/
v) after the following conversion into acetate (–)-13.
( )-(1 S*,3 S*,3 aR*,4 S*,7 R*,7 aS*)-2 ,3 ,3 a,4 ,7 ,7 a-Hexahy-
dro-3 -hydroxy-4 ,7 -methano-1 H-inden-1 -yl Benzoate [( )-12]
A solution of benzoate 11 (75.0 g, 0.21 mol) in HOAc (61.4 mL)
and EtOH (1000 mL) was stirred at 90 °C with zinc dust (140.0 g,
0.21 mol) for 4 h. After cooling, the mixture was filtered through a
Celite pad and the filtrate was evaporated under reduced pressure.
The residue was diluted with EtOAc (500 mL), washed with sat. aq
NaHCO3 (300 mL) and brine (300 mL), dried (MgSO4) and evapo-
rated under reduced pressure. The residue was recrystallized from
hexane–EtOAc to give alcohol ( )-12.
(–)-(1 S,3 S,3 aR,4 S,7 R,7 aS)-3 -Acetoxy-2 ,3 ,3 a,4 ,7 ,7 a-
hexahydro-4 ,7 -methano-1 H-inden-1 -yl Benzoate [(–)-13]
A solution of alcohol (+)-12 (0.10 g, 0.37 mmol) in CH2Cl2 (5 mL)
was stirred at 0 °C with Et3N (57 L, 0.41 mmol), DMAP (52 mg,
0.43 mmol) and AcCl (29 L, 0.41 mmol) for 2 h. The reaction mix-
ture was diluted with CH2Cl2 (15 mL), washed with aq HCl
(10%,10 mL), sat. aq NaHCO3 (10 mL) and brine (10 mL), dried
(MgSO4) and evaporated under reduced pressure. The residue was
chromatographed (silica gel 20 g; hexane–EtOAc, 10:1 v/v) to give
acetate (–)-13.
Yield: 42.3 g (73%); colorless crystals; mp 98 °C.
IR (film): 3240 cm–1.
1H NMR (270 MHz, CDCl3): = 1.35–1.42 (2 H, m), 1.48–1.52 (1
H, m), 1.86–1.97 (1 H, m), 2.05–2.17 (1 H, m), 2.81–2.86 (1 H, m),
3.00–3.07 (2 H, m), 3.12–3.15 (1 H, m), 4.58–4.70 (1 H, m), 4.92 (1
H, d, J = 6.1 Hz), 6.17 (1 H, dd, J = 5.5, 3.1 Hz), 6.34 (1 H, dd,
J = 5.5, 2.5 Hz), 7.40–7.47 (2 H, m), 7.52–7.59 (1 H, m), 7.99–8.03
(2 H, m).
13C NMR (400 MHz, CDCl3): = 42.98, 45.33, 45.55, 51.44, 52.48,
53.52, 73.13, 77.23, 128.32, 129.51, 130.64, 132.86, 134.26,
137.73, 166.10.
Yield: 76 mg (66%); colorless oil; [ ]D22 –49.5 (c 1.00, CHCl3).
The spectroscopic data were identical to those of (+)-13.
(–)-(1S,3S,3aR,4S,7R,7aS)-2,3,3a,4,7,7a-Hexahydro-4,7-metha-
no-1H-indene-1,3-diol [(–)-9]
To a stirred suspension of LiAlH4 (1.01g, 26.7 mmol) in THF (100
mL) was added alcohol (+)-12 (6.0 g, 22.2 mmol) in THF (50 mL)
at 0 °C over 30 min, and the mixture was stirred for 1.5 h. The reac-
tion was quenched by adding of 28% aq ammonia and Celite. After
further stirring for 12 h at r.t., the mixture was filtered through a
Celite pad, and the filtrate was extracted with THF (5 100 mL ).
MS: m/z = 270 (M+), 148, 66 (100%).
HRMS: m/z Calcd for C17H18O3: 270.1256. Found: 270.1226.
Synthesis 2002, No. 8, 1027–1032 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Chiral Preparation of C2-Symmetric 4-Cyclopentene-1,3-diol
(1R,3R)-4-Cyclopentene-1,3-diol [(+)-2]
1031
The extract was dried (MgSO4) and evaporated under reduced pres-
sure. The residue was chromatographed (silica gel 200 g; hexane–
EtOAc, 1:1 v/v) to give diol (–)-9 (3.23 g, 88%) as colorless
crystals. Diol (–)-9 (3.2 g, 95% ee) was recrystallized from hexane–
i-PrOH to give optically pure diol (–)-9 (1.2 g), whose optical purity
was determined to be >99% ee by HPLC using a chiral column with
chiral stationary phase (Chiralcel OD; hexane–i-PrOH, 99:1 v/v) af-
ter the following conversion into dibenzoate (–)-14.
A suspension of (+)-9 (500 mg, 3.01 mmol) and NaHCO3 (1.91 g,
22.6 mmol) in Ph2O (5 mL) was sonicated under bubbling argon gas
for 20 min. The suspension was stirred at 280 °C for 3 h. After cool-
ing, the mixture was directly chromatographed (silica gel 30 g; hex-
ane–EtOAc, 10:1 v/v) to give diol (+)-2.
Yield: 141 mg (47%); colorless crystals; mp 67–69 °C;
[ ]D27+228.1 (c 1.04, MeOH), {lit.5 (antipode): [ ]D –237
(MeOH)}.
Mp 123–126 °C; [ ]D24 – 29.3 (c 1.00, MeOH).
The spectroscopic data were identical to those of ( )-9.
IR (film): 3250 cm–1.
1H NMR (270 MHz, CDCl3–CD3OD): = 2.04 (2 H, t, J = 5.1 Hz),
4.99 (2 H, t, J = 5.1, 1.0 Hz), 5.99 (2 H, d, J = 1.0 Hz).
13C NMR (270 MHz, CDCl3–CD3OD): = 43.60, 75.73, 136.90.
MS: m/z = 100 (M+), 99 (M+ – 1), 43 (100%).
(+)-(1R,3R,3aS,4R,7S,7aR)-2,3,3a,4,7,7a-Hexahydro-4,7-meth-
ano-1H-indene-1,3-diol [(+)-9]
To a stirred suspension of LiAlH4 (2.27 g, 60.0 mmol) in THF (200
mL) was added the acetate (+)-13 (15.6 g, 50.0 mmol) in THF (100
mL) at 0 °C over 30 min. The mixture was stirred at that tempera-
ture for 3 h. The reaction was quenched by adding 28% aq ammonia
and Celite. After further stirring for 12 h at r.t., the mixture was fil-
tered through a Celite pad, and the filtrate was extracted with THF
(5 100 mL). The extract was dried (MgSO4) and evaporated under
reduced pressure. The residue was chromatographed (silica gel 200
g; hexane–EtOAc, 1:1 v/v) to give diol (+)-9 (5.32 g, 64%) as col-
orless crystals. The diol (+)-9 (0.72 g, 95% ee) was recrystallized
from hexane–i-PrOH to give optically pure diol (+)-9 (0.40 g),
whose optical purity was determined to be >99% ee by HPLC using
a chiral column with chiral stationary phase (Chiralcel OD; hexane–
i-PrOH, 99:1 v/v) after the following conversion into dibenzoate
(+)-14.
HRMS: m/z Calcd for C5H8O2: 100.0524. Found: 100.0524.
Anal. Calcd for C5H8O2: C, 59.98; H, 8.05. Found: C, 60.18; H,
8.34.
(1S,3S)-4-Cyclopentene-1,3-diol [(–)-2]
In the same manner as described for (+)-2, (–)-9 gave (–)-2.
23
Yield: 123 mg (41%); colorless crystals; mp 68–69 °C; [ ]D
–
233.8 (c 0.95, MeOH), {lit.5 [ ]D –237 (MeOH)}.5
The spectroscopic data were identical to those of (+)-2.
Acknowledgements
Mp 123–126 °C;[ ]D26 + 30.3 (c 1.00, MeOH).
We thank Prof. K. Ogasawara, Tohoku University, for many useful
suggestions. We also thank Nisshin Flour Milling Co., Ltd., Japan,
for financial support (to K. I.).
The spectroscopic data were identical to those of ( )-9.
(–)-(1 S,3 S,3 aR,4 S,7 R,7 aS)–3 -Benzoyloxy-2 ,3 ,3 a,4 ,7 ,7 a-
hexahydro-4 ,7 -methano-1 H-inden-1 -yl Benzoate [(–)-14]
To a stirred solution of diol (–)-9 (100 mg, 0.60 mmol) with Et3N
(0.19 mL, 1.33 mmol) and DMAP (169 mg, 1.39 mmol) in CH2Cl2
was added BzCl (0.15 mL, 1.33 mmol) at 0 °C. After stirring at r.t.
for 1 h, the reaction mixture was diluted with CH2Cl2 (15 mL),
washed with aq HCl (10%, 15 mL), sat. aq NaHCO3 (15 mL) and
brine (15 mL), dried (MgSO4) and evaporated under reduced pres-
sure. The residue was chromatographed (silica gel 15 g; hexane–
EtOAc, 20:1 v/v) to give dibenzoate (–)-14.
References
(1) Kobayashi, Y. Trends in Organic Chemistry 1998, 7, 27.
(2) Noyori, R.; Suzuki, M. Angew. Chem. Int. Ed. Engl. 1984,
23, 847.
(3) Borthwick, A. D.; Biggadike, K. Tetrahedron 1992, 48, 571.
(4) Schoffers, E.; Golebiowski, A.; Johnson, C. R. Tetrahedron
1996, 52, 3769.
(5) Miura, S.; Kurozumi, S.; Toru, T.; Tanaka, T.; Kobayashi,
M.; Matsubara, S.; Ishimoto, S. Tetrahedron 1976, 32, 1893.
(6) Saddler, J. C.; Donaldson, R. E.; Fuchs, P. L. J. Am. Chem.
Soc. 1981, 103, 2110.
(7) Donaldson, R. E.; Fuchs, P. L. J. Am. Chem. Soc. 1981, 103,
2108.
(8) (a) Rosenblum, M. J. Am. Chem. Soc. 1957, 79, 3179.
(b) Non-hazardous synthesis of racemic dienone 7, see:
Takano, S.; Moriya, M.; Tanaka, K.; Ogasawara, K.
Synthesis 1994, 687.
(9) An exploitation of dienone 7 as a chiral synthon, see the
following reviews: (a) Ogasawara, K. Pure Appl. Chem.
1994, 66, 2119. (b) Ogasawara, K. J. Syn. Org. Chem. Jpn.
1996, 54, 29.
Yield: 191 mg (85%); colorless oil; [ ]D22 –81.3 (c 1.00, CHCl3).
IR (film): 1707 cm–1.
1H NMR (270 MHz, CDCl3): = 1.39 (1 H, d, J = 8.2 Hz), 1.48 (1
H, td, J = 10.2, 1.7 Hz), 2.09–2.19 (1 H, m), 2.32 (1 H, dd, J = 14.7,
8.4 Hz), 2.90–2.95 (2 H, m), 3.17–3.20 (1 H, m), 3.36 (1 H, dt,
J = 8.7, 4.0 Hz), 5.04 (1 H, d, J = 6.3 Hz), 5.61 (1 H, td, J = 10.1,
8.4 Hz), 6.20 (1 H, dd, J = 5.6, 3.0 Hz), 6.32 (1 H, dd, J = 5.6, 3.0
Hz), 7.42–7.51 (4 H, m), 7.54–7.65 (2 H, m), 8.01–8.10 (4 H, m).
13C NMR (270 MHz, CDCl3): = 39.85, 45.67, 45.83, 49.25, 52.09,
53.24, 76.02, 76.39, 128.36, 128.49, 129.56, 129.59, 130.30,
130.47, 132.96, 133.02, 134.13, 137.73, 166.07, 166.32.
MS: m/z = 374 (M+), 130, 105 (100%).
(10) A pertinent monograph, see: Enzyme Catalysis in Organic
Synthesis; Drauz, K.; Waldmann, H., Eds.; VCH: Weinheim,
1995.
HRMS: m/z Calcd for C24H22O4: 374.1518. Found: 374.1526.
Anal. Calcd for C24H22O4: C, 76.99; H, 5.92. Found: C, 76.87; H,
5.90.
(11) Preliminary results of this work were presented at The 5th
International Symposium on Biocatalysis and
Biotransformation, Darmstadt: Germany, September 2-7,
2001, see abstracts p. 353.
(+)-(1 R,3 R,3 aS,4 R,7 S,7 aR)-3 -Benzoyloxy-2 ,3 ,3 a,4 ,7 ,7 a-
hexahydro-4 ,7 -methano-1 H-inden-1 -yl Benzoate [(+)-14]
In the same manner as described for (–)-14, (+)-9 gave (+)-14.
Yield: 189 mg (84%); colorless oil; [ ]D24 +79.3 (c 1.00, CHCl3).
(12) Chapman, O. L.; Hess, T. C. J. Org. Chem. 1979, 44, 962.
(13) Quite recently, a similar regio- and stereoselective reduction
of keto epoxide has been reported, see: Mehta, G.; Kumaran,
R. S. Tetrahedron Lett. 2001, 42, 8097.
The spectroscopic data were identical to those of (–)-14.
Synthesis 2002, No. 8, 1027–1032 ISSN 0039-7881 © Thieme Stuttgart · New York

1032
S. Kimura et al.
PAPER
(14) Dols, P. P. M. A.; Arnouts, E. G.; Rohaan, J.; Klunder, A. J.
H.; Zwanenburg, B. Tetrahedron 1994, 50, 3473.
(15) All of the lipases we used were commercially available from
Amano Enzyme Inc., Japan. The origin of each lipase is
summarized in the Table.
(16) Takano, S.; Moriya, M.; Ogasawara, K. Synlett 1993, 601.
(17) cf: Kamikubo, T.; Ogasawara, K. J. Chem. Soc., Chem.
Commun. 1995, 1951.
Synthesis 2002, No. 8, 1027–1032 ISSN 0039-7881 © Thieme Stuttgart · New York