3-Menthoxybiphenyl-4-carboxylic acid: a versatile resolving agent and reagent for determination of the absolute configuration of benzylic alcohols

Article abstract of DOI:10.1016/j.tetasy.2017.05.008

A versatile reagent for the chiral resolution and determination of the absolute configuration of benzylic alcohols, (?)-3-menthoxybiphenyl-4-carboxylic acid, is reported. (?)-3-menthoxybiphenyl-4-carboxylic acid was condensed with racemic benzylic alcohol

Full text of DOI:10.1016/j.tetasy.2017.05.008

Tetrahedron: Asymmetry xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
3-Menthoxybiphenyl-4-carboxylic acid: a versatile resolving agent
and reagent for determination of the absolute configuration of
benzylic alcohols
a
a
a
c
Shunsuke Kuwahara a,b, , Nobuyoshi Tasaki , Yuri Suzuki , Mizuki Nakagawa , Mari Ikeda ,
⇑
Yoichi Habata a,b
a Department of Chemistry, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
b Research Center for Materials with Integrated Properties, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
c Education Center, Faculty of Engineering, Chiba Institute of Technology, 2-1-1 Shibazono, Narashino, Chiba 275-0023, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A versatile reagent for the chiral resolution and determination of the absolute configuration of benzylic
alcohols, (À)-3-menthoxybiphenyl-4-carboxylic acid, is reported. (À)-3-menthoxybiphenyl-4-carboxylic
acid was condensed with racemic benzylic alcohols to yield diastereomeric 3-menthoxybiphenyl-4-car-
boxylic esters, which were separated by reversed-phase HPLC. The absolute configurations of the 3-men-
thoxybiphenyl-4-carboxylic esters were unambiguously determined by exciton-coupled circular
dichroism. Hydrolysis of the 3-menthoxybiphenyl-4-carboxylic esters yielded enantiopure alcohols,
and their absolute configurations were simultaneously determined.
Received 31 March 2017
Revised 1 May 2017
Accepted 9 May 2017
Available online xxxx
Ó 2017 Elsevier Ltd. All rights reserved.
1. Introduction
In order to develop a versatile reagent for the resolution and
determination of the absolute configuration of benzylic and allylic
Chiral benzylic and allylic alcohols are important building
blocks for the preparation of chiral pharmaceuticals, agrochemi-
cals, and functional materials.1–3 The need for enantiopure alcohols
has therefore increased. In general, chiral compounds are prepared
by techniques such as asymmetric synthesis, enzymatic kinetic
resolution, separation by chiral HPLC, and recrystallization of
diastereomeric salts.1 However, these methods do not always pro-
vide the desired enantiomer with 100% enantiopurity. The deter-
mination of the absolute configuration of the prepared chiral
compounds presents another challenge for researchers. Although
X-ray crystallography is a reliable method for the determination
of absolute configuration, it can often be difficult to obtain good
crystals suitable for X-ray analysis. Recently, the 1H NMR aniso-
tropy method has been employed as an empirical method to deter-
mine the absolute configurations of chiral compounds.4–6 We have
previously developed (S)-(+)-2-methoxy-2-(1-naphthyl)propionic
alcohols, we designed a new chiral auxiliary, (À)-3-menthoxy-
biphenyl-4-carboxylic acid (À)-1. The (1R,2S,5R)-(À)-menthoxy
group has been used previously for the resolution of carboxylic
acids, amino acids, phosphinates and silanes by recrystallization
or chromatography.7,9,15–17 In 3-menthoxybiphenyl-4-carboxylic
acid, the (1R,2S,5R)-(À)-menthoxy group is connected to the biphe-
nyl carboxylic acid group, which acts as a chromophore as well as a
linker to the alcohols (Fig. 1).
It is expected that the diastereomeric 3-menthoxybiphenyl-4-
carboxylic esters obtained when 3-menthoxybiphenyl-4-car-
boxylic acid (À)-1 are covalently bonded to racemic benzylic or
allylic alcohols and can be separated by chromatography. Their
absolute configurations could then be determined by exciton-cou-
pled circular dichroism (ECCD),18–29 between the biphenyl chro-
mophore of the 3-menthoxybiphenyl-4-carboxylic part of the
molecule and the chromophore of the alcohol. The advantage of
ECCD is that it can be used to determine absolute configurations
in a non-empirical manner. The chiral alcohols would then finally
be recovered by hydrolysis of the 3-menthoxybiphenyl-4-car-
boxylic esters. Herein we report the development of (À)-1, and
its application in the chiral resolution of benzylic alcohols and
the determination of their absolute configurations.
acid (MaNP acid), which is useful for the resolution of secondary
alcohols and determination of their absolute configurations by
the 1H NMR anisotropy method.7–14
⇑
Corresponding author.
E-mail address: kuwahara@chem.sci.toho-u.ac.jp (S. Kuwahara).
http://dx.doi.org/10.1016/j.tetasy.2017.05.008
0957-4166/Ó 2017 Elsevier Ltd. All rights reserved.
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2
S. Kuwahara et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
the molecule, resulting in the (1S,2R) absolute configuration of
(À)-7a.
Compound (+)-7b exhibits an almost mirror image of the Cotton
effects of (À)-7a in the CD spectrum [kext = 259.8 nm ( 1 = À24.6)
and kext = 220.4 nm ( 2 = +38.8)], indicating that the arrange-
ments of the chromophores in (À)-7a and (+)-7b are symmetrical.
The negative first and positive second Cotton effects indicate that
(+)-7b has the (1R,2S)-absolute configuration.
chiral resolution part
linker part
D
e
O
D
e
chromophore part
λmax 260 nm (ε 99,000)
COOH
(1R,2S,5R)-(–)-1
To confirm the configurational assignment by X-ray crystallog-
raphy, (1S,2R)-(À)-7a was recrystallized from EtOAc to give single
crystals.32 The absolute configuration of the alcohol part of the
molecule was determined to be (S) using the known absolute con-
figuration of the (1R,2S,5R)-(À)-menthol part as an internal refer-
ence. As shown in Figure 3, the long axes in the biphenyl and
naphthyl groups constitute a clockwise screw sense. The dihedral
angles /(C9–O1–C1-H1) and /(O2–C9–O1-C1) are À47.2° and
3.5°, respectively, which indicates that the carbonyl oxygen atom
of the benzoate and the alcoholic methine proton are arranged in
a nearly syn-periplanar conformation in the crystalline state.
Optimized structures of (1S,2R)-(À)-7a and (1R,2S)-(+)-7b
determined by DFT at the B3LYP/6-31G⁄ level of theory,33 also sup-
port the conformations described above (Fig. 4). The absolute twist
of the long axes in the biphenyl and naphthyl groups constitute a
clockwise and counterclockwise screw sense in (1S,2R)-(À)-7a
and (1R,2S)-(+)-7b, respectively. The carbonyl oxygen atom of the
benzoate and the alcoholic methine proton of (1S,2R)-(À)-7a and
(1R,2S)-(+)-7b take the syn-periplanar conformation.
Figure 1. Design of 3-menthoxybiphenyl-4-carboxylic acid (1R,2S,5R)-(À)-1.
2. Results and discussion
3-Menthoxybiphenyl-4-carboxylic acid (À)-1 was synthesized
from commercially available 4-bromo-2-fluorobenzoic acid 2 as
shown in Scheme 1. Nucleophilic aromatic substitution of pro-
tected ester 3 by the (À)-menthoxy nucleophile gave menthoxy
ether (À)-4. Suzuki–Miyaura coupling of (À)-4 and phenylboronic
acid followed by deprotection of the ester afforded (À)-1.
Compound (À)-1 was condensed with racemic benzylic alcohol
( )-trans-6, which is an intermediate used in the preparation of
DNA-binding molecular motors,30 to yield 3-menthoxybiphenyl-
4-carboxylic esters (À)-7a and (+)-7b (Scheme 2). Compounds
(À)-7a and (+)-7b were inseparable by HPLC on silica gel. However,
we found that reversed-phase HPLC using an octadecylsilane col-
umn was capable of baseline separation of (À)-7a and (+)-7b (sep-
aration factor
a = 1.12, Fig. S53 in the Supporting Information).
Enantiopure alcohols (1S,2R)-(+)-6 and (1R,2S)-(À)-6 were
obtained from the corresponding esters (1S,2R)-(À)-7a and
(1R,2S)-(+)-7b, respectively, by hydrolysis with KOH in EtOH/H2O
(Scheme 1). Applications of this technique to other benzylic and
allylic alcohols ( )-8–11 are summarized in Table 1. Each diastere-
omeric mixture of 3-menthoxybiphenyl-4-carboxylic esters was
The CD and UV spectra of (À)-7a and (+)-7b are illustrated in
Figure 2a. The UV spectrum of (À)-7a exhibits intense absorptions
at kmax = 269.2 nm (e 23,600) and 233.4 nm (e 86,000) due to the
p–
p⁄ transition arising from polarization along the long axes in
the biphenyl and naphthyl groups, respectively. These two transi-
tions couple with each other in the CD spectrum of (À)-7a to gen-
separated by HPLC using an octadecylsilane column (a = 1.05–
erate exciton coupling Cotton effects: kext = 258.4 nm (De1 = +28.4)
1.06, Figs. S54–55 in the SI). The diastereopurities of the 3-men-
thoxybiphenyl-4-carboxylic esters were determined to be >99%
by 1H NMR. The amplitude of the CD signals of the 3-menthoxy-
biphenyl-4-carboxylic esters of 6-methoxy-1-tetralol (S)-13a and
(R)-13b was low, and their CD spectra did not show a mirror image
(Fig. S57a in the SI). The difference CD curve was therefore calcu-
and kext = 219.8 nm (
D
e
2 = À36.6). The positive first and negative
second Cotton effects indicate the positive exciton chirality
between the two chromophores. This means that the two long axes
of the chromophores constitute a clockwise screw sense.
The preferred conformation of (À)-7a is illustrated in Figure 2b.
Although there may be some free rotation around the benzoate C–
O bond, it is well known that the benzoate C–O bond is s-trans, and
that the carbonyl oxygen atom of the benzoate is syn-periplanar to
the alcoholic methine proton.10,11,18,19,21,31 The long axis of the
biphenyl chromophore is nearly parallel to the alcoholic C–O bond.
Therefore, the clockwise screw sense of the chromophores of (À)-
7a leads to an (S)-absolute configuration of the alcohol part of
lated to detect the genuine ECCD34
and DD ((R)-13b)–
showed an almost mirror image of the typical ECCD pattern
:
DD
e
=
D
e
((S)-13a)–
D
e
((À)-1)
e
=
D
e
D
e
((À)-1). The difference CD curve
(Fig. S57c in the SI).
The 3-menthoxybiphenyl-4-carboxylic esters of acyclic alcohols
( )-10 and 11 also exhibited the typical ECCD pattern (Figs. S58–59
in the SI). Even if the naphthyl or styryl chromophore rotates
2,4-dimethylpentan-3-ol,
DCC, DMAP, CSA
(–)-menthol,
Br
F
Br
F
NaH
COOH
DMF, 70 oC
CH2Cl2
COOR
2
3
97%
R = 2,4-dimethyl-3-pentyl
phenylboronic acid,
Pd(OAc)2, PPh3,
K2CO3
KOH
(–)-1
94%
DMF, 80 oC
Br
O
O
EtOH,
reflux
COOR
COOR
(–)-4
(–)-5
99%
61%
Scheme 1. Synthesis of 4-menthoxybiphenyl-4-carboxylic acid (À)-1.
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S. Kuwahara et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
3
Br
OH
Br
O
KOH
O
EtOH/H2O
O
(1S,2R)-(+)-6
75%
OH
7a
(1S,2R)-(–)- (1st eluted by HPLC)
1
(–)-
,
Br
43%
DCC, DMAP
CH2Cl2
Br
( )-trans-6
OH
Br
O
KOH
O
EtOH/H2O
O
6
(1R,2S)-(–)-
78%
(1R,2S)-(+)-7b (2nd eluted by HPLC)
35%
Scheme 2. Resolution of 4-menthoxybiphenyl-4-carboxylic acid esters (À)-7a and (+)-7b.
(a)
(b)
CD
O-Ment
O
O
H
Br
Br
Δε
(1S,2R)-(–)-7a
7a
(1S,2R)-(–)-
H
(1R,2S)-(+)-7b
O
Ment-O
O
UV
7b
(1R,2S)-(+)-
λ / nm
Figure 2. (a) CD and UV spectra of (1S,2R)-(À)-7a (red line, 0.20 mM in EtOH) and (1R,2S)-(+)-7b (blue line, 0.22 mM in EtOH). (b) Preferred conformations of (1S,2R)-(À)-7a
and (1R,2S)-(+)-7b.
around the C–C single bond connected to the center stereogenic
carbon, the absolute twist between the biphenyl group and the
chromophore is unchanged (Fig. S60 in the SI).
Allylic alcohol (S)-(À)-11, a key intermediate in the synthesis of
anthracyclin antibiotics,35,36 has previously been prepared with
94%ee, and the absolute configuration was assigned by considering
the mechanism of the asymmetric synthesis. Herein, we have pre-
pared enantiopure (S)-(À)-11 and (R)-(+)-11, and unambiguously
determined their absolute configurations by ECCD.
3. Conclusion
In conclusion, we have reported a versatile reagent, 3-men-
thoxybiphenyl-4-carboxylic acid (À)-1, for the resolution and
determination of the absolute configuration of benzylic alcohols.
Figure 3. ORTEP drawing of (1S,2R)-(À)-7a.
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S. Kuwahara et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
H
O
Ment-O
Br
O
O-Ment
O
O
Br
H
C2
C1
O1
C9
O2
O1
C9
C1
C2
O2
(1S,2R)-(–)-7a
kcal/mol
(1R,2S)-(+)-7b
Total energy
–2656278.7
–2656279.3 kcal/mol
Figure 4. Optimized structures of (1S,2R)-(À)-7a and (1R,2S)-(+)-7b at B3LYP/6-31G* level.
Table 1
Application of the technique to benzylic and allylic alcohols ( )-8–11.
Alcohols
a
Separated esters
kmax/nm (De)
OH
(1S,2S)-12a (1st eluted)
256.6 (+31.0), 219.6 (À7.7)
259.6 (À23.7), 220.6 (+30.8)
Br
1.06
(1R,2R)-12b (2nd eluted)
( )-cis-8
OH
OH
OH
(S)-13a (1st eluted)
(R)-13b (2nd eluted)
278.2 (+2.7), 233.2 (À5.7)a
1.05
1.05
284.4 (À1.1, sh), 233.8 (+5.1)a
OMe
(s)-9
(S)-14a (1st eluted)
(R)-14b (2nd eluted)
264.4 (+11.2), 215.0 (À34.7)
265.0 (À7.4), 216.6 (+22.0)
(s)-10
OMe
OMe
(S)-15a (1st eluted)
(R)-15b (2nd eluted)
284.0 (+3.7), 257.8 (À6.3)
1.05
296.8 (À4.1, sh), 259.0 (+7.8)
(s)-11
a
Difference CD curve: DD
e
=
D
e
((S)-13a)–
D
e
((À)-1) and DDe = De((R)-13b)–De((À)-1).
Diastereomeric mixtures of esters of (À)-1 with racemic benzylic
alcohols ( )-6, 8–11 were separated by reversed-phase HPLC and
the absolute configurations of the esters were unambiguously
determined by ECCD. Enantiopure alcohols 6, 8–11 were obtained
from the corresponding 3-menthoxybiphenyl-4-carboxylic esters
by hydrolysis. Further applications of this technique to other allyl
alcohols and amines are currently in progress.
or film on KBr on a JASCO FT/IR-410 spectrophotometer. 1H NMR
spectra were recorded on Jeol ECP400 (400 MHz) spectrometers.
13C NMR spectra were obtained on Jeol ECP400 (100 MHz) spec-
trometers. All NMR spectroscopic data of CDCl3 solutions are
reported in ppm (d) downfield from TMS. UV and CD spectra were
recorded on JASCO V-650 and JASCO J-820 spectrometers, respec-
tively. CD spectra were recorded with the following measurement
parameters: scan speed, 20 nm/min; resolution, 0.2 nm; band-
width, 1.0 nm; response, 4.0 s; 4–10 accumulations. HPLC separa-
tions were performed on a JASCO PU-2080 instrument equipped
with a JASCO UV-2070 detector with YMC-Pack Pro C18 RS col-
umns (250 Â 10 mm or 250 Â 20 mm, YMC Co., Ltd.). Silica gel 60
F254 precoated plates on glass from Merck Ltd. were used for thin
layer chromatography (TLC).
4. Experimental
4.1. General
All reagents and solvents were commercially available and used
without further purification. IR spectra were obtained as KBr disks
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S. Kuwahara et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
5
4.2. Synthesis of 3-menthoxybiphenyl-4-carboxylic acid
4.2.1. 2,4-Dimethylpentan-3-yl 4-bromo-2-fluorobenzoate 3
NMR (400 MHz, CDCl3) d7.84–7.75 (m, 1H), 7.61–7.54 (m, 2H),
7.51–7.43 (m, 2H), 7.43–7.36 (m, 1H), 7.16–7.12 (m, 1H), 5.00–
4.82 (m, 1H), 4.25 (ddd, J1 = 10.5 Hz, J2 = 10.6 Hz, J3 = 4.2 Hz, 1H),
2.38–2.26 (m, 1H), 2.22–1.94 (m, 3H), 1.78–1.65 (m, 3H), 1.17–
1.04 (m, 2H), 1.02–0.86 (m, 21H), 0.83–0.74 (J = 7.0 Hz, 3H); 13C
NMR (100 MHz, CDCl3) d 167.3, 157.6, 145.8, 140.7, 131.9, 128.8,
127.9, 127.3, 121.4, 118.6, 112.3, 83.1, 77.7, 47.8, 40.0, 34.5, 31.4,
29.6, 25.4, 23.2, 22.1, 20.9, 19.7, 19.6, 17.6, 17.3, 16.1; IR (KBr) mmax
3034, 2981, 2937, 2835, 1719, 1599, 1519, 1484, 1280, 1251, 1089,
A
mixture of 4-bromo-2-fluorobenzoic acid
2
(3.05 g,
13.9 mmol), 2,4-dimethylpentan-3-ol (2.25 g, 19.3 mmol), DCC
(4.27 g, 20.9 mmol), DMAP (0.785 g, 6.43 mmol), and 10-camphor-
sulfonic acid (CSA, 0.407 g, 1.75 mmol) in CH2Cl2 (50 mL) was stir-
red at room temperature overnight. After the addition of a small
amount of water, the mixture was stirred for 1 h, diluted with CH2-
Cl2, and filtered with Celite, which was washed with CH2Cl2. The
organic layer was dried over MgSO4 and evaporated to dryness.
The crude product was purified by column chromatography on sil-
ica gel (hexane/CHCl3, v/v 5:1) to yield ester 3 (4.27 g, 97%) as a
colorless oil: 1H NMR (400 MHz, CDCl3) d 7.83 (t, J = 8.4, 1H),
7.40–7.30 (m, 2H), 4.87 (t, J = 8.8 Hz, 1H), 2.02 (oct, J = 6.5 Hz,
2H), 0.94 (dd, J1 = 6.9 Hz, J2 = 2.6 Hz, 12H); 13C NMR (100 MHz,
CDCl3) d 163.9 (d, J = 3.8 Hz), 161.6 (d, J = 263.0 Hz), 133.2 (d,
J = 2.3 Hz), 127.5 (d, J = 3.1 Hz), 127.4 (d, J = 2.3 Hz), 120.7 (d,
J = 25.2 Hz), 118.3 (d, J = 9.9 Hz), 84.4, 29.6, 19.6, 17.3; IR (neat)
mmax 2966, 2937, 2876, 1714, 1602, 1570, 1482, 1404, 1369,
1285, 1240, 1220, 1143, 1127, 1086, 940, 889, 861, 767, 682,
581, 549 cmÀ1; FAB-MS (matrix: DTT/TG = 1/1) m/z 317 ([M(79Br)
+H]+, 80%), 319 ([M(81Br)+H]+, 80%); Anal. Calcd for C14H18BrFO2:
C, 53.01; H, 5.72. Found. C, 52.80; H, 5.74.
1044, 893, 828 cmÀ1
;
[a
]
D
27 = À74.3 (c 1.08, CHCl3); FAB-MS
(matrix: m-NBA) m/z 451 ([M+H]+, 20%); Anal. Calcd for
C30H42O3: C, 79.96; H, 9.39. Found. C, 79.75; H, 9.41.
4.2.4. (À)-3-Menthoxybiphenyl-4-carboxylic acid 1
mixture of menthyl ether (1R,2S,5R)-(À)-5 (450 mg,
A
0.999 mmol) and KOH (894 mg, 15.9 mmol) in EtOH (5 mL) was
heated at reflux for 4 h. After cooling to room temperature, the
reaction mixture was evaporated under reduced pressure to
remove EtOH. After the addition of water, the mixture was washed
with Et2O. The aqueous layer was acidified with 1 M HCl, and
extracted with Et2O. The organic layer was washed with brine,
dried over anhydrous Na2SO4, and evaporated to dryness. The
crude product was purified by column chromatography on silica
gel (hexane/AcOEt, v/v 3:1) to yield 3-menthoxybiphenyl-4-car-
boxylic acid (1R,2S,5R)-(À)-1 (332 mg, 94%) as colorless needles:
mp 132–133 °C; 1H NMR (400 MHz, CDCl3) d 11.4 (br.s, 1H), 8.26
(d, J = 8.2 Hz, 1H), 7.59 (d, J = 7.0 Hz, 2H), 7.51 (t, J = 7.5 Hz, 2H),
7.45 (d, J = 7.1 Hz, 1H), 7.34 (dd, J1 = 8.1 Hz, J2 = 1.5 Hz, 1H), 7.22
(d, J = 1.3 Hz, 1H), 4.51 (ddd, J1 = 10.6 Hz, J2 = 10.6 Hz, J3 = 4.6 Hz,
1H), 2.25–2.14 (m, 2H), 1.87–1.63 (m, 3H), 1.25–0.80 (m,
J = 12.5 Hz, 12H); 13C NMR (100 MHz, CDCl3) d 165.4, 157.0,
148.2, 139.6, 134.3, 129.1, 128.7, 127.3, 121.2, 117.4, 112.6, 81.2,
48.2, 40.1, 34.0, 31.5, 26.3, 23.6, 21.9, 20.7, 16.6; IR (KBr) mmax
4.2.2. 2,4-Dimethylpentan-3-yl 4-bromo-2-(((1R,2S,5R)-2-
isopropyl-5-methylcyclohexyl)oxy)benzoate (À)-4
At first, NaH (60% dispersion on oil, 0.389 g, 9.73 mmol) was
added to a vigorously stirred solution of (À)-menthol (1.84 g,
11.8 mmol) in dry DMF (5 mL) at 0 °C and then the reaction mix-
ture was stirred at 70 °C for 1 h. After cooling to room temperature,
the reaction mixture was added to a solution of ester 3 (2.88 g,
90.8 mmol) in dry DMF (30 mL) at 0 °C and then the reaction mix-
ture was stirred at room temperature for 3 h. After treatment with
water (50 mL), the mixture was extracted with (hexane/AcOEt, v/v
4:1). The organic layer was washed with brine, dried over anhy-
drous MgSO4, and evaporated to dryness. The crude product was
purified by column chromatography on silica gel (hexane/CHCl3,
v/v 5:1) to yield menthyl ether (1R,2S,5R)-(À)-4 (2.52 g, 61%) as
colorless oil: 1H NMR (400 MHz, CDCl3) d 7.59 (d, J = 8.3 Hz, 1H),
7.11 (d, J = 1.2 Hz, 1H), 7.06 (dd, J1 = 8.3 Hz, J2 = 1.7 Hz, 1H), 4.85
(t, J = 6.3 Hz, 1H), 4.12 (ddd, J1 = 10.5 Hz, J2 = 10.5 Hz, J3 = 4.2 Hz,
1H), 2.30–1.90 (m, 5H), 1.77–1.67 (m, 2H), 1.60–1.41 (m, 2H),
1.35–1.22 (m, 3H), 1.15–0.83 (m, 30H), 0.73 (d, J = 7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3) d 166.8, 157.8, 132.6, 126.5, 122.8,
121.5, 116.7, 83.4, 78.2, 47.7, 39.7, 34.4, 31.4, 29.5, 25.4, 23.1,
22.1, 20.8, 19.6, 19.5, 17.5, 17.2, 16.1; IR (neat) mmax 2960, 2932,
2872, 1730, 1702, 1588, 1564, 1479, 1405, 1387, 1369, 1347,
3212, 2954, 2870, 2849, 1725, 1609, 1559, 1454, 1412, 1197,
974 cmÀ1; FAB-MS (matrix: DTT/TG) m/z 353 ([M+H]+, 50%); [
a]
25
D
À100.9 (c 1.04, CHCl3); Anal. Calcd for C23H28O3: C, 78.38; H,
8.01. Found. C, 78.28; H, 8.03.
4.3. Preparation of ( )-trans-7-bromo-2-methyl-2,3-dihydro-
1H-cyclopenta[a]naphthalen-1-ol
6
and ( )-cis-7-bromo-2-
methyl-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-ol 8
At first, NaBH4 (0.377 g, 9.96 mmol) was added at 0 °C to a solu-
tion of ketone ( )-1630 (0.882 g, 3.21 mmol) in MeOH (21 mL), and
the reaction mixture was stirred at room temperature for 1 h. After
the addition of water, the reaction mixture was evaporated under
reduced pressure to remove MeOH, and extracted with AcOEt. The
organic layer was washed with aqueous NaHCO3, brine, dried over
anhydrous Na2SO4, and evaporated to dryness. The crude product
was purified by column chromatography on silica gel (hexane/
AcOEt, v/v 4:1), and the obtained cis- and trans-alcohols were sep-
arated by HPLC (silica gel, YMC-Pack SIL 06, 250 Â 10 mm, eluent:
hexane/AcOEt, v/v 10:1), yielding ( )-cis-8 (0.327 g, 37%) as the
alcohol eluted first and ( )-trans-6 (0.486 g, 55%) as the alcohol
eluted second.
1321, 1284, 1247, 1229, 1182, 1128, 1096, 1038, 1009, 991, 942,
925, 889, 840, 768, 582 cmÀ1; [
a
]
D
À63.4 (c 1.19, CHCl3); m/z
26
FAB-MS (matrix: m-NBA) m/z 452 ([M(79Br)+H]+, 15%), 455 ([M
(
81Br)+H]+, 15%); Anal. Calcd for C24H37BrO3: C, 63.57; H, 8.22.
Found. C, 63.36; H, 8.23.
4.2.3. 2,4-Dimethylpentan-3-yl 3-{[(1R,2S,5R)-5-methyl-2-
(propan-2-yl)cyclohexyl]oxy}biphenyl-4-carboxylate (À)-5
A mixture of (1R,2S,5R)-(À)-4 (1.42 g, 3.12 mmol), phenyl-
boronic acid (0.512 g, 4.20 mmol), Pd(OAc)2 (0.049 g, 0.22 mmol),
PPh3 (0.247 g, 0.943 mmol), and K2CO3 (1.32 g, 9.54 mmol), in
DMF (15 mL) was stirred at 80 °C for 1d. After cooling to room tem-
perature, water (30 mL) was added. The reaction mixture was
extracted with hexane/AcOEt (v/v 4:1). The organic layer was
washed with aqueous NaHCO3, brine, dried over anhydrous MgSO4,
and evaporated to dryness. The crude product was purified by col-
umn chromatography on silica gel (hexane/CHCl3, v/v 3:1) to yield
phenylbenzoate (1R,2S,5R)-(À)-5 (1.39 g, 99%) as a colorless oil: 1H
4.3.1. ( )-trans-7-Bromo-2-methyl-2,3-dihydro-1H-cyclopenta
[a]naphthalen-1-ol 6
White solid; mp 138–139 °C; 1H NMR (400 MHz, CDCl3) d 8.13
(d, J = 8.9 Hz, 1H), 8.01 (d, J = 2.0 Hz, 1H), 7.67 (d, J = 8.3 Hz, 1H),
7.58 (dd, J1 = 8.9 Hz, J2 = 2.0 Hz, 1H), 7.37 (d, J = 8.3 Hz, 1H), 5.24
(dd, J1 = 8.0 Hz, J2 = 4.2 Hz, 1H), 3.38 (dd, J1 = 16.1 Hz, J2 = 7.6 Hz,
1H), 2.57 (dd, J1 = 16.1 Hz, J2 = 5.5 Hz, 1H), 2.49 (m, 1H), 1.78 (d,
J = 8.2 Hz, 1H), 1.26 (d, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 141.0, 138.6, 134.2, 130.4, 129.9, 129.7, 129.0, 128.4, 125.8,
124.6, 119.0, 83.0, 44.3, 38.8, 18.9; IR (KBr) 3755, 3335, 2931,
Please cite this article in press as: Kuwahara, S.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.05.008

6
S. Kuwahara et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
1635, 1581, 1503, 1455, 1323, 1242, 1151, 1063, 1029, 886, 845,
805, 630 cmÀ1; FAB-MS (matrix: m-NBA) m/z 276 ([M(79Br)]+,
30%), 278 ([M(81Br)]+, 30%); Anal. Calcd for C14H13BrO: C, 60.67;
H, 4.73. Found. C, 60.62; H, 4.73.
J1 = 16.4 Hz, J2 = 2.8 Hz, 1H), 1.90–1.84 (m, 2H), 1.56 (d,
J = 12.6 Hz, 1H), 1.40–1.24 (m, 6H), 0.87–0.74 (m, 4H), 0.64–0.40
(m, 10H); 13C NMR (100 MHz, CDCl3) d 167.2, 158.2, 146.6, 143.4,
140.5, 135.3, 134.2, 132.8, 130.3, 130.0, 129.2, 129.0, 128.9, 128.1,
127.3, 126.4, 124.8, 120.0, 119.0, 118.7, 112.6, 83.6, 77.6, 47.0,
40.2, 39.8, 38.4, 34.0, 31.1, 25.6, 23.0, 21.9, 20.4, 19.6, 16.3; IR
(KBr) mmax 3819, 2732, 3647, 2955, 1693, 1606, 1557, 1505, 1454,
1408, 1309, 1279, 1213, 1140, 1069, 803, 758, 697, 567, 520, 462,
452, 424, 417 cmÀ1; FAB-MS (matrix m-NBA) m/z 610 ([M(79Br)]+,
4.3.2. ( )-cis-7-Bromo-2-methyl-2,3-dihydro-1H-cyclopenta
[a]naphthalen-1-ol 8
White solid; mp 149–150 °C; 1H NMR (400 MHz, CDCl3) d 8.01
(d, J = 2.0 Hz, 1H), 7.98 (d, J = 8.9 Hz, 1H), 7.68 (d, J = 8.3 Hz, 1H),
7.60 (dd, J1 = 8.9 Hz, J2 = 2.0 Hz, 1H), 7.39 (d, J = 8.3 Hz, 1H), 5.48
(t, J = 8.3 Hz, 1H), 3.10 (dd, J1 = 16.1 Hz, J2 = 7.8 Hz, 1H), 2.84 (dd,
J1 = 16.1 Hz, J2 = 8.5 Hz, 1H), 2.66 (m, 1H), 1.46 (d, J = 7.1 Hz, 1H),
1.30 (d, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 142.3, 139.8,
134.1, 130.5, 129.9, 128.8, 128.3, 125.7, 124.5, 119.0, 76.2, 39.2,
39.1, 13.9; IR (KBr) mmax 3191, 2961, 2926, 2899, 1585, 1501,
1435, 1352, 1313, 1259, 1159, 1097, 1071, 1005, 901, 875, 824,
810, 780, 759, 680, 668, 642, 602, 563 cmÀ1; FAB-MS (matrix: m-
NBA) m/z 276 ([M(79Br)]+, 50%), 278 ([M(81Br)]+, 50%); Anal. Calcd
for C14H13BrO: C, 60.67; H, 4.73. Found. C, 60.55; H, 4.74.
3%), 612 ([M(81Br)]+, 3%); [ 25 = +102.5 (c 1.08, CHCl3); Anal. Calcd
a]
D
for C37H39BrO3: C, 72.66; H, 6.43. Found: C, 72.36; H, 6.42.
4.4.2. (À)-3-Menthoxybiphenyl-4-carboxylic acid ester (1S,2S)-
(+)-12a and (1R,2R)-(À)-12b
GP-1 was carried out with alcohol ( )-cis-8 (257 mg,
0.928 mmol), (À)-3-menthoxybiphenyl-4-carboxylic acid acid
(À)-1 (407 mg, 1.15 mmol), DCC (259 mg, 1.27 mmol), and DMAP
(21 mg, 0.17 mmol) in CH2Cl2 (3 mL) at room temperature over-
night. The crude product was purified by column chromatography
on silica gel (hexane/EtOAc, 10:1). The diastereomeric esters
obtained were separated by HPLC on octadecylsilane (YMC-Pack
Pro C18 RS (250 Â 10 mm), eluent: acetonitrile, separation factor
4.4. General procedure for the preparation of (À)-3-
menthoxybiphenyl-4-carboxylic acid esters (GP-1)
a
= 1.06, resolution factor Rs = 1.07), giving (1S,2S)-(+)-12a
4.4.1. (À)-3-Menthoxybiphenyl-4-carboxylic acid esters (1S,2R)-
(À)-7a and (1R,2S)-(+)-7b
(238 mg, 42%) as the ester eluted first and (1R,2R)-(À)-12b
(263 mg, 46%) as the ester eluted second.
A mixture of alcohol ( )-trans-6 (0.159 g, 0.575 mmol), (À)-3-
menthoxybiphenyl-4-carboxylic acid acid (À)-1 (0.264 g,
0.748 mmol), DCC (0.188 g, 0.909 mmol), and DMAP (0.035 g,
0.287 mmol) in CH2Cl2 (2 mL) was stirred at room temperature
overnight. After the addition of a small amount of water, the mixture
was stirred for 2 h, diluted with EtOAc, and filtered with Celite,
which was washed with EtOAc. The organic layer was dried over
anhydrous Na2SO4, and evaporated to dryness. The crude product
was purified by column chromatography on silica gel (hexane/
EtOAc, 20:1). The diastereomeric esters obtained were separated
by HPLC on octadecylsilane (YMC-Pack Pro C18 RS (250 Â 10 mm),
4.4.2.1. (À)-3-Menthoxybiphenyl-4-carboxylic acid ester (1S,2S)-
(+)-12a.
White solid; mp 129–130 °C; 1H NMR (400 MHz,
CDCl3) d 8.02 (d, J = 2.0 Hz, 1H), 7.89 (d, J = 8.9 Hz, 2H), 7.76–7.69
(m, 2H), 7.58–7.48 (m, 3H), 7.47–7.34 (m, 4H), 7.11–7.07 (m,
2H), 7.05 (d, J = 6.4 Hz, 2H), 4.09 (ddd, J = 10.6, 10.6, 4.4 Hz, 1H),,
3.24–3.12 (m, 1H), 2.99–2.85 (m, 2H), 1.98–1.82 (m, 2H), 1.65–
1.57 (m, 2H), 1.37–1.23 (m, 4H), 1.05–0.86 (m, 2H), 0.83–0.56
(m, 12H); 13C NMR (100 MHz, CDCl3) d 167.1, 158.2, 146.5, 143.7,
140.5, 137.0, 134.1, 132.7, 130.3, 130.1, 128.9, 128.8, 128.7,
128.1, 127.3, 126.4, 124.3, 120.3, 119.1, 118.8, 112.9, 77.8, 77.6,
47.0, 40.0, 39.4, 38.3, 34.1, 31.1, 25.6, 23.1, 21.9, 20.6, 16.3, 14.3;
IR (KBr) mmax 2954, 2924, 2864, 1690, 1605, 1557, 1515, 1481,
1454, 1405, 1307, 1270, 1237, 1213, 1139, 1074, 990, 914, 810,
757, 721, 697, 650, 604, 556, 534 cmÀ1; FAB-MS (matrix: DTT:
TG = 1:1) m/z 633 ([M(79Br)+Na]+, 20%), 635 ([M(81Br)+Na]+, 20%);
eluent: acetonitrile, separation factor
a = 1.12, resolution factor
Rs = 1.86), giving (1S,2R)-(À)-7a (0.152 g, 43%) as the ester eluted
first and (1R,2S)-(+)-7b (0.124 g, 35%) as the one eluted second.
4.4.1.1.
(À)-3-Menthoxybiphenyl-4-carboxylic
acid
Colorless needles; mp 145–146 °C; 1H NMR
(ppm) 8.03 (d, J = 1.9 Hz, 1H), 7.84 (d,
ester
(1S,2R)-(À)-7a.
[a]
25 = +89.9 (c 0.68, CHCl3); Anal. Calcd for C37H39BrO3: C, 72.66;
D
(400 MHz, CDCl3)
d
H, 6.43. Found: C, 72.49; H, 6.40.
J = 8.9 Hz, 1H), 7.74 (dd, J1 = 8.3 Hz, J2 = 1.9 Hz, 2H), 7.57–7.52 (m,
2H), 7.46–7.35 (m, 5H), 7.10–7.08 (m, 2H), 6.66 (s, 1H), 4.09
(ddd, J = 10.7, 10.7, 4.4 Hz, 1H), 3.52 (dd, J1 = 16.5 Hz, J2 = 7.8 Hz,
1H), 2.78–2.75 (m, 1H), 2.66 (dd, J1 = 16.5 Hz, J2 = 2.3 Hz, 1H),
1.96–1.93 (m, 2H), 1.62–1.56 (m, 6H), 1.28 (d, J = 7.4 Hz, 3H),
1.09–0.92 (m, 2H), 0.64–0.40 (m, 12H); 13C NMR (100 MHz, CDCl3)
d 167.0, 158.1, 146.2, 143.5, 140.5, 135.1, 134.2, 131.9, 130.4,
130.1, 129.2, 129.1, 128.9, 128.0, 127.3, 126.1, 124.7, 121.1,
119.1, 118.9, 113.2, 83.4, 78.5, 47.5, 40.4, 39.9, 39.7, 34.2, 31.3,
25.7, 23.2, 22.0, 20.6, 19.6, 16.3; IR (KBr) mmax 3420, 3064, 2954,
2868, 1684, 1607, 1557, 1505, 1479, 1450, 1409, 1312, 1279,
1247, 1216, 1140, 1093, 1047, 974, 893, 851, 806, 759, 725, 696,
607, 508, 418 cmÀ1; FAB-MS (matrix m-NBA) m/z 610 ([M(79Br)]+,
4.4.2.2.
(1R,2R)-(À)-12b.
(À)-3-Menthoxybiphenyl-4-carboxylic
acid
ester
White solid; mp 72–73 °C; 1H NMR
(400 MHz, CDCl3) d 8.02 (d, J = 2.0 Hz, 1H), 7.89–7.82 (m, 2H),
7.72 (d, J = 8.3 Hz, 1H), 7.58–7.48 (m, 3H), 7.47–7.34 (m, 4H),
7.11 (dd, J1 = 8.1 Hz, J2 = 1.5 Hz, 2H), 7.07–7.02 (m, 2H), 4.18
(ddd, J = 10.7, 10.7, 4.4 Hz, 1H), 3.26–3.13 (m, 1H), 3.12–2.86 (m,
2H), 1.98–1.85 (m, 1H), 1.87–1.77 (m, 1H), 1.52–1.39 (m, 2H),
1.33–1.15 (m, 4H), 0.92–0.30 (m, 13H); 13C NMR (100 MHz, CDCl3)
d 167.1, 158.2, 146.5, 143.7, 140.5, 137.0, 134.1, 132.7, 130.3,
130.1, 128.9, 128.7, 128.1, 127.3, 126.4, 124.3, 120.3, 119.1,
118.8, 112.9, 77.8, 77.7, 47.0, 40.0, 39.4, 38.3, 34.1, 31.1, 25.6,
23.1, 21.9, 20.6, 16.3, 14.3; IR (KBr) mmax 2955, 2927, 2869, 1962,
1606, 1557, 1505, 1481, 1453, 1407, 1345, 1308, 1279, 1247,
1213, 1140, 1096, 1073, 1048, 991, 913, 893, 803, 757, 723, 697,
554 cmÀ1 FAB-MS (matrix: DTT:TG = 1:1) m/z 633 ([M(79Br)+Na]+,
3%), 612 ([M(81Br)]+, 3%); [
a
]
D
25 = À164.1 (c 1.70, CHCl3); Anal. Calcd
for C37H39BrO3: C, 72.66; H, 6.43. Found: C, 72.42; H, 6.47.
4.4.1.2.
(1R,2S)-(+)-7b.
(À)-3-Menthoxybiphenyl-4-carboxylic
acid
ester
5%), 635 ([M(81Br)+Na]+, 5%); [
Calcd for C37H39BrO3: C, 72.66; H, 6.43. Found. C, 72.66; H, 6.45.
a]
25 = À186.4 (c 0.77, CHCl3); Anal.
D
White solid; mp 75–76 °C; 1H NMR
(400 MHz, CDCl3) d 8.04 (d, J = 2.0 Hz, 1H), 7.90 (d, J = 8.1 Hz, 2H),
7.80 (d, J = 8.9 Hz, 1H), 7.74 (m, J = 8.4 Hz, 1H), 7.55–7.52 (m, 3H),
7.46–7.36 (m, 4H), 7.12 (dd, J1 = 8.1 Hz, J2 = 1.5 Hz, 1H), 7.04 (d,
J = 1.2 Hz, 1H), 6.61 (s, 1H), 4.03 (ddd, J = 10.6, 10.6, 4.2 Hz, 1H),
3.52 (dd, J1 = 16.4 Hz, J2 = 7.4 Hz, 1H), 2.80–2.76 (m, 1H), 2.67 (dd,
4.4.3. (À)-3-Menthoxybiphenyl-4-carboxylic acid esters (S)-(À)-
13a and (R)-(À)-13b
GP-1 was carried out with alcohol ( )-9 (59 mg, 0.33 mmol),
(À)-3-menthoxybiphenyl-4-carboxylic acid acid (À)-1 (145 mg,
Please cite this article in press as: Kuwahara, S.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.05.008

S. Kuwahara et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
7
0.664 mmol), DCC (141 mg, 0.688 mmol), and DMAP (21 mg,
0.17 mmol) in CH2Cl2 (2 mL) at room temperature overnight. The
crude product was purified by column chromatography on silica
gel (hexane/EtOAc, 5:1). The diastereomeric esters obtained were
separated by HPLC on octadecylsilane (YMC-Pack Pro C18 RS
(m, 10H); 13C NMR (100 MHz, CDCl3) d 166.4, 158.0, 146.1, 140.6,
139.4, 133.2, 133.0, 132.1, 128.9, 128.2, 128.1, 128.0, 127.6,
127.3, 126.1, 125.9, 125.1, 124.4, 120.8, 118.7, 112.6, 78.0, 72.9,
47.7, 40.0, 34.3, 31.4, 25.7, 23.3, 22.5, 22.1, 20.8, 16.3; IR (KBr) mmax
3057, 2954, 2927, 2868, 1701, 1606, 1558, 1509, 1482, 1452, 1407,
1308, 1281, 1239, 1214, 1179, 1142, 1061, 1010, 992, 908, 855,
817, 758, 731, 698, 649, 478 cmÀ1; FAB-MS (matrix: m-NBA) m/z
(250 Â 10 mm), eluent: acetonitrile, separation factor
a = 1.05, res-
olution factor Rs = 1.03), giving (S)-(À)-13a (57 mg, 34%) as the
ester eluted first and (R)-(À)-13b (65 mg, 39%) as the one eluted
second.
507 ([M+H]+, 5%); [
a]
25 = +23.1 (c 1.10, CHCl3); Anal. Calcd for
D
C35H38O3: C, 82.97; H, 7.56. Found. C, 82.88; H, 7.47.
4.4.3.1. (À)-3-Menthoxybiphenyl-4-carboxylic acid ester (S)-(À)-
4.4.4.2. (À)-3-Menthoxybiphenyl-4-carboxylic acid ester (R)-
(À)-14b.
Colorless oil; 1H NMR (400 MHz, CDCl3) d 7.95–
13a.
Colorless oil; 1H NMR (400 MHz, CDCl3) d 7.77 (d,
J = 7.8 Hz, 1H), 7.55 (d, J = 7.1 Hz, 2H), 7.46 (m, 2H), 7.41–7.32
(m, 2H), 7.12–7.08 (m, 2H), 6.74 (dd, J1 = 8.4 Hz, J2 = 2.6 Hz, 1H),
6.65 (d, J = 2.6 Hz, 1H), 6.21 (t, J = 3.8 Hz, 1H), 4.15 (ddd,
J1 = 10.6 Hz, J2 = 10.6 Hz, J3 = 4.1 Hz, 1H), 3.79 (s, 3H), 2.92–2.70
(m, 2H), 2.20–1.64 (m, 8H), 1.49–1.21 (m, 4H), 1.12–0.72 (m,
10H), 0.71 (d, J = 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 166.7,
159.2, 157.9, 145.9, 140.6, 139.4, 131.9, 131.3, 128.9, 128.0,
127.3, 127.1, 121.4, 118.7, 113.3, 112.8, 112.4, 78.3, 70.1, 55.2,
47.7, 40.0, 34.4, 31.4, 29.5, 29.3, 25.7, 23.3, 22.1, 20.8, 18.8, 16.3;
IR (neat) mmax 2950, 2867, 1964, 1607, 1558, 1506, 1455, 1406,
1307, 1236, 1215, 1140, 1077, 1040, 990, 900, 844, 813, 771,
719, 698, 673, 663, 649, 638, 623, 603 cmÀ1; FAB-MS (matrix: m-
7.77 (m, 5H), 7.62–7.57 (m, 3H), 7.49–7.45 (m, 4H), 7.39–7.37
(m, 1H), 7.16–7.11 (m, 2H), 6.31 (q, J = 6.6 Hz, 1H), 4.24 (ddd,
J = 10.5, 10.5, 4.1 Hz, 1H), 2.39–2.29 (m, 1H), 2.22–2.17 (m, 1H),
1.77–1.57 (m, 6H), 1.50–1.36 (m, 1H), 1.16–1.02 (m, 2H), 0.96–
0.74 (m, 10H); 13C NMR (100 MHz, CDCl3) d 166.3, 158.1, 146.3,
140.5, 139.5, 133.2, 133.0, 132.5, 128.9, 128.2, 128.04, 127.98,
127.6, 127.3, 126.1, 125.9, 124.9, 124.3, 120.4, 118.7, 112.6, 78.1,
72.8, 48.0, 40.1, 34.4, 31.4, 25.7, 23.3, 22.5, 22.2, 20.8, 16.3; IR
(KBr) mmax 3057, 2954, 2926, 2868, 1698, 1606, 1558, 1509, 1481,
1452, 1407, 1308, 1280, 1248, 1214, 1179, 1142, 1095, 1062,
1011, 992, 910, 855, 817, 758, 747, 732, 698, 648, 604, 478 cmÀ1
;
FAB-MS (matrix: m-NBA) m/z 507 ([M+H]+, 3%); [
a]
25 = À148.4 (c
D
NBA) m/z 512 ([M]+, 10%), 535 ([M+Na]+, 10%); [
a]
D
25 = À59.7 (c
0.71, CHCl3); Anal. Calcd for C35H38O3: C, 82.97; H, 7.56. Found.
C, 82.79; H, 7.51.
1.08, CHCl3); Anal. Calcd for C34H40O4: C, 79.65; H, 7.86. Found.
C, 79.48; H, 7.89.
4.4.5. (À)-3-Menthoxybiphenyl-4-carboxylic acid esters (S)-(À)-
15a and (R)-(À)-15b
4.4.3.2. (À)-3-Menthoxybiphenyl-4-carboxylic acid ester (R)-
(À)-13b.
Colorless oil; 1H NMR (400 MHz, CDCl3) d 7.82 (d,
GP-1 was carried out with alcohol ( )-11 (102 mg, 0.434 mmol),
(À)-3-menthoxybiphenyl-4-carboxylic acid acid (À)-1 (266 mg,
0.754 mmol), DCC (224 mg, 1.09 mmol), and DMAP (58 mg,
0.47 mmol) in CH2Cl2 (2 mL) at room temperature overnight. The
crude product was purified by column chromatography on silica
gel (toluene). The diastereomeric esters obtained were separated
by HPLC on octadecylsilane (YMC-Pack Pro C18 RS
J = 8.3 Hz, 1H), 7.55 (d, J = 7.5 Hz, 2H), 7.46 (m, 2H), 7.41–7.32
(m, 2H), 7.12 (m, 2H), 6.74 (dd, J1 = 8.5 Hz, J2 = 2.6 Hz, 4H), 6.66
(d, J = 2.6 Hz, 1H), 6.23 (t, J = 3.9 Hz, 1H), 4.15 (ddd, J1 = 10.5 Hz,
J2 = 10.5 Hz, J3 = 4.1 Hz, 1H), 3.79 (s, 3H), 2.92–2.70 (m, 2H),
2.30–1.80 (m, 6H), 1.90–1.60 (m, 2H), 1.451.22 (m, 4H), 1.10–
0.72 (m, 14H); 13C NMR (100 MHz, CDCl3) d 166.7, 159.2, 158.2,
146.1, 140.6, 139.5, 132.2, 131.4, 128.9, 128.0, 127.4, 127.3,
121.2, 118.8, 113.3, 113.1, 112.3, 78.5, 70.0, 55.2, 47.6, 39.9, 34.4,
31.4, 29.5, 29.3, 25.7, 23.2, 22.1, 20.8, 18.8, 16.3; IR (neat) mmax
2952, 2868, 1719, 1692, 1608, 1558, 1504, 1481, 1453, 1407,
1308, 1272, 1252, 1215, 1142, 1124, 1098, 1077, 1057, 1040,
990, 902, 862, 812, 758, 698, 665, 604 cmÀ1; FAB-MS (matrix: m-
(250 Â 10 mm), eluent: acetonitrile, separation factor
a = 1.05, res-
olution factor Rs = 1.54), giving (S)-(À)-15a (72 mg, 30%) as the
ester eluted first and (R)-(À)-15b (79 mg, 32%) as the ester eluted
second.
4.4.5.1. (À)-3-Menthoxybiphenyl-4-carboxylic acid ester (S)-(À)-
NBA) m/z 535 ([M+Na]+, 2%); [
Calcd for C34H40O4: C, 79.65; H, 7.86. Found. C, 79.45; H, 7.87.
a]
25 = À51.5 (c 0.57, CHCl3); Anal.
15a.
Colorless oil; 1H NMR (400 MHz, CDCl3) d 7.80 (d,
D
J = 8.3 Hz, 1H), 7.67–7.55 (m, 2H), 7.51–7.45 (m, 2H), 7.44–7.37
(m, 1H), 7.17–7.12 (m, 2H), 6.94–6.91 (m, 1H), 6.71 (d, J = 8.9 Hz,
1H), 6.66 (d, J = 8.9 Hz, 1H), 5.78 (q, J = 4.5 Hz, 1H), 4.24 (ddd,
J1 = 10.6 Hz, J2 = 10.6 Hz, J3 = 4.1 Hz, 1H), 3.79 (s, 6H), 2.92–2.72
(m, 2H), 2.44–2.26 (m, 3H), 2.24–2.10 (m, 1H), 1.80–1.40 (m,
7H), 1.21–1.01 (m, 2H), 0.99–0.70 (m, 10H); 13C NMR (100 MHz,
CDCl3) d 166.3, 157.9, 150.4, 149.7, 145.9, 140.7, 139.5, 131.3,
128.9, 128.0, 127.3, 124.5, 123.9, 121.2, 118.6, 117.7, 112.5,
110.0, 108.6, 78.1, 73.9, 56.1, 56.0, 47.8, 40.0, 34.4, 31.4, 25.7,
23.3, 22.5, 22.1, 20.8, 20.7, 19.0, 16.3; IR (neat) mmax 2953, 2928,
2868, 2832, 1723, 1698, 1606, 1558, 1482, 1453, 1406, 1307,
1257, 1214, 1142, 1093, 1047, 1009, 991, 851, 758, 719, 698,
667 cmÀ1; FAB-MS (matrix: DTT:TG = 1:1) m/z 568 ([M]+, 4%);
4.4.4. (À)-3-Menthoxybiphenyl-4-carboxylic acid esters (S)-(+)-
14a and (R)-(À)-14b
GP-1 was carried out with alcohol ( )-10 (90 mg, 0.52 mmol),
(À)-3-menthoxybiphenyl-4-carboxylic acid acid (À)-1 (353 mg,
1.00 mmol), DCC (400 mg, 1.95 mmol), and DMAP (29 mg,
0.24 mmol) in CH2Cl2 (3 mL) at room temperature overnight. The
crude product was purified by column chromatography on silica
gel (hexane/EtOAc, 10:1). The diastereomeric esters obtained were
separated by HPLC on octadecylsilane (YMC-Pack Pro C18 RS
(250 Â 10 mm), eluent: acetonitrile, separation factor
a = 1.05, res-
olution factor Rs = 0.91), giving (S)-(+)-14a (84.4 mg, 45%) as the
ester eluted first and (R)-(À)-14b (76.9 mg, 41%) as the ester eluted
second.
[
a
]
25 = À16.6 (c 0.45, CHCl3); Anal. Calcd for C37H44O5: C, 78.14;
D
H, 7.80. Found. C, 77.98; H, 7.80.
4.4.4.1. (À)-3-Menthoxybiphenyl-4-carboxylic acid ester (S)-(+)-
4.4.5.2. (À)-3-Menthoxybiphenyl-4-carboxylic acid ester (R)-
14a.
White solid; mp 116.1–116.5 °C; 1H NMR (400 MHz,
(À)-15b.
Colorless oil; 1H NMR (400 MHz, CDCl3) d 7.85 (d,
CDCl3) d 7.93–7.89 (m, 1H), 7.85–7.81 (m, 4H), 7.60–7.56 (m,
3H), 7.51–7.44 (m, 4H), 7.39–7.37 (m, 1H), 7.14–7.12 (m, 2H),
6.30 (q, J = 6.5 Hz, 1H), 4.22 (ddd, J = 10.6, 10.6, 4.6 Hz, 1H), 2.32–
2.24 (m, 1H), 2.17–2.12 (m, 1H), 1.73 (d, J = 6.6 Hz, 1H), 1.68–
1.60 (m, 2H), 1.47–1.39 (m, 2H), 1.12–0.99 (m, 2H), 0.89–0.74
J = 8.4 Hz, 1H), 7.62–7.53 (m, 2H), 7.51–7.43 (m, 2H), 7.42–7.36
(m, 1H), 7.16–7.10 (m, 2H), 6.95–6.90 (m, 1H), 6.70 (d, J = 8.9 Hz,
1H), 6.65 (d, J = 8.9 Hz, 1H), 5.87 (q, J = 6.5 Hz, 1H), 4.23 (dd,
J1 = 10.4 Hz, J2 = 10.4 Hz, J3 = 4.0 Hz, 1H), 3.79 (s, 3H), 3.78 (s, 3H),
2.94–2.69 (m, 2H), 2.44–2.27 (m, 3H), 2.25–2.14 (m, 1H), 1.79–
Please cite this article in press as: Kuwahara, S.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.05.008

8
S. Kuwahara et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
1.41 (m, 7H), 1.20–0.82 (m, 9H), 0.76 (d, J = 6.9 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 166.2, 158.1, 150.4, 149.7, 146.1, 140.7,
139.5, 132.4, 128.9, 128.0, 127.3, 124.5, 123.9, 120.7, 118.6,
117.6, 112.4, 110.0, 108.6, 78.0, 73.8, 56.1, 56.0, 47.9, 40.0, 34.4,
31.4, 25.6, 23.3, 22.5, 22.2, 20.8, 20.7, 19.0, 16.3; IR (neat) mmax
2953, 2928, 2869, 2829, 1698, 1606, 1558, 1482, 1453, 1407,
1308, 1257, 1214, 1142, 1093, 1048, 1009, 991, 850, 758, 699,
666 cmÀ1; FAB-MS (matrix: DTT:TG = 1:1) m/z 568 ([M]+, 2%);
J = 8.8 Hz, 3H), 7.67 (d, J = 8.4 Hz, 1H), 7.59 (dd, J1 = 8.8 Hz,
J2 = 2.0 Hz, 2H), 7.39 (d, J = 8.4 Hz, 1H), 5.54–5.40 (m, 1H), 3.10
(dd, J1 = 16.0 Hz, J2 = 7.8 Hz, 2H), 2.84 (dd, J1 = 16.0 Hz, J2 = 8.4 Hz,
2H), 2.72–2.59 (m, 1H), 1.50–1.42 (m, 1H), 1.30 (d, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) d 142.3, 139.8, 134.1, 130.5,
129.9, 128.8, 128.4, 125.7, 124.5, 119.0, 76.3, 39.2, 39.1, 13.9; IR
(KBr) mmax 3184, 2961, 2925, 2896, 1585, 1500, 1455, 1435, 1351,
1313, 1259, 1158, 1097, 1071, 1004, 900, 875, 824, 810, 758,
[a
]
D
25 = À118.9 (c 0.62, CHCl3); Anal. Calcd for C37H44O5: C, 78.14;
668, 642, 613, 602, 588, 573, 561 cmÀ1; FAB-MS (matrix: DTT:
TG = 1:1) m/z 276 ([M(79Br)]+, 50%), 278 ([M(81Br)]+, 50%); [
a]
=
25
H, 7.80. Found. C, 77.98; H, 7.80.
D
+105.6 (c 0.72, CHCl3); Anal. Calcd for C14H13BrO: C, 60.67; H,
4.5. General procedure for the preparation of enantiopure
alcohols (GP-2)
4.73. Found: C, 60.47; H, 4.75.
4.5.4. (1R,2R)-(À)-7-Bromo-2-methyl-2,3-dihydro-1H-cyclopenta
[a]naphthalen-1-ol 8
4.5.1. (1S,2R)-(+)-7-Bromo-2-methyl-2,3-dihydro-1H-cyclopenta
[a]naphthalen-1-ol 6
GP-2 was carried out with ester (1R,2R)-(À)-12b (29 mg,
0.047 mmol) and KOH (49 mg, 0.87 mmol) in EtOH (1 mL) under
refluxing overnight. The crude product was purified by column
chromatography on silica gel (hexane/AcOEt, v/v 5:1) to yield alco-
hol (1R,2R)-(À)-8 (10 mg, 77%) as colorless needles: mp 153–
154 °C; 1H NMR (400 MHz, CDCl3) d 8.01 (d, J = 2.0 Hz, 4H), 7.98
(d, J = 8.8 Hz, 3H), 7.67 (d, J = 8.4 Hz, 1H), 7.59 (dd, J1 = 8.8 Hz,
J2 = 2.0 Hz, 2H), 7.39 (d, J = 8.4 Hz, 1H), 5.54–5.40 (m, 1H), 3.10
(dd, J1 = 16.0 Hz, J2 = 7.8 Hz, 2H), 2.84 (dd, J1 = 16.0 Hz, J2 = 8.4 Hz,
2H), 2.72–2.59 (m, 1H), 1.50–1.42 (m, 1H), 1.30 (d, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) d 142.3, 139.8, 134.1, 130.5,
129.9, 128.8, 128.4, 125.7, 124.5, 119.0, 76.3, 39.2, 39.1, 13.9; IR
(KBr) mmax 3183, 2961, 2926, 2896, 1585, 1501, 1435, 1313, 1158,
1097, 1071, 1005, 901, 875, 824, 810, 758, 668, 643, 602, 575,
A mixture of ester (1S,2R)-(À)-7a (0.551 g, 0.900 mmol) and
KOH (894 mg, 15.9 mmol) in EtOH (20 mL) was heated under
refluxing for 1 d. After cooling to room temperature, the reaction
mixture was evaporated under reduced pressure to remove EtOH.
After the addition of water, the mixture was extracted with Et2O,
washed with brine, dried over anhydrous Na2SO4, and evaporated
to dryness. The crude product was purified by column chromatog-
raphy on silica gel (hexane/AcOEt, v/v 5:1) to yield alcohol (1S,2R)-
(+)-6 (0.188 g, 75%) as colorless needles: mp 133–135 °C; 1H NMR
(400 MHz, CDCl3) d 8.09 (d, J = 8.9 Hz, 1H), 7.99 (d, J = 2.0 Hz, 1H),
7.64 (d, J = 8.4 Hz, 1H), 7.56 (dd, J1 = 8.9 Hz, J2 = 2.0, 1H), 7.34 (d,
J = 8.4 Hz, 1H), 5.20 (dd, J1 = 7.4 Hz, J2 = 4.3 Hz, 1H), 3.34 (dd,
J1 = 16.0 Hz, J2 = 7.8 Hz, 1H), 2.55 (dd, J1 = 16.0 Hz, J2 = 5.5 Hz, 1H),
2.50–2.40 (m, 1H), 1.89 (d, J = 7.8 Hz, 1H), 1.24 (d, J = 7.0 Hz, 3H);
13C NMR (100 MHz, CDCl3) d 141.0, 138.6, 134.2, 130.4, 129.7,
129.0, 128.4, 125.8, 124.6, 119.0, 83.0, 44.3, 38.8, 18.9; IR (KBr)
mmax 3852, 3734, 3340, 2933, 1634, 1582, 1504, 1455, 1323,
532 cmÀ1
;
FAB-MS
(matrix:
DTT:TG = 1:1)
m/z
276
([M(79Br)]+, 40%), 278 ([M(81Br)]+, 40%); [
a]
25 = À108.9 (c 0.43,
D
CHCl3); Anal. Calcd for C14H13BrO: C, 60.67; H, 4.73. Found: C,
60.43; H, 4.75.
1151, 1063, 1029, 886, 847, 806, 631 cmÀ1; FAB-MS (matrix DTT/
TG = 1:1) m/z 276 ([M(79Br)]+, 40%), 278 ([M(81Br)]+, 40%); [
a]
=
4.5.5. (S)-(+)-6-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ol 9
GP-2 was carried out with ester (S)-(À)-13a (20 mg,
0.039 mmol) and KOH (41 mg, 0.73 mmol) in EtOH (1 mL) under
refluxing overnight. The crude product was purified by column
chromatography on silica gel (hexane/AcOEt, v/v 2:1) to yield alco-
hol (S)-(+)-9 (4.9 mg, 71%) as colorless oil; 1H NMR (400 MHz,
CDCl3) d 7.34 (d, J = 8.5 Hz, 1H), 6.77 (dd, J1 = 8.5 Hz, J2 = 2.7 Hz,
1H), 6.63 (d, J = 2.7 Hz, 1H), 4.75 (m, 1H), 2.85–2.63 (s, 2H), 2.02–
1.84 (m, 3H), 1.82–1.70 (m, 1H), 1.62 (m, 1H); 13C NMR
(100 MHz, CDCl3) d 158.9, 138.6, 131.3, 130.1, 113.4, 112.5, 67.7,
55.2, 32.4, 29.6, 18.6; IR (neat) mmax 3435, 2996, 2933, 2862,
2834, 1608, 1577, 1501, 1455, 1332, 1315, 1274, 1254, 1235,
1154, 1123, 1109, 1062, 1038, 1010, 982, 872, 834, 811, 772,
20
D
+45.5 (c 1.04, CHCl3); Anal. Calcd for C14H13BrO: C, 60.67; H,
4.73. Found: C, 60.42; H, 4.75.
4.5.2. (1R,2S)-(À)-7-Bromo-2-methyl-2,3-dihydro-1H-cyclopenta
[a]naphthalen-1-ol 6
GP-2 was carried out with ester (1R,2S)-(+)-7b (0.286 g,
0.468 mmol) and KOH (0.524 g, 9.35 mmol) in EtOH (15 mL) under
refluxing for 1 d. The crude product was purified by column chro-
matography on silica gel (hexane/AcOEt, v/v 5:1) to yield alcohol
(1R,2S)-(À)-6 (0.101 g, 78%) as colorless needles: mp 134–135 °C;
1H NMR (400 MHz, CDCl3) d 8.09 (d, J = 8.9 Hz, 1H), 7.99 (d,
J = 2.0 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.56 (dd, J1 = 8.9 Hz,
J2 = 2.0, 1H), 7.35 (d, J = 8.4 Hz, 1H), 5.20 (dd, J1 = 7.4 Hz,
J2 = 4.3 Hz, 1H), 3.35 (dd, J1 = 16.0 Hz, J2 = 7.8 Hz, 1H), 2.55 (dd,
J1 = 16.0 Hz, J2 = 5.5 Hz, 1H), 2.50–2.40 (m, 1H), 1.85 (d, J = 7.8 Hz,
1H), 1.24 (d, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 141.0,
138.6, 134.3, 130.5, 129.7, 129.0, 128.4, 125.8, 124.6, 119.0, 83.0,
44.3, 38.8, 18.9; IR (KBr) mmax 3746, 3331, 2931, 2898, 1648,
1581, 1502, 1457, 1323, 1242, 1151, 1063, 1029, 885, 845, 806,
562 cmÀ1; FAB-MS (matrix DTT/TG = 1:1) m/z 276 ([M(79Br)]+,
706, 650 cmÀ1; [
a]
25 = +23.0 (c 0.19, CHCl3); Anal. Calcd for
D
C11H14O2: C, 74.13; H, 7.92. Found. C, 73.86; H, 7.95.
4.5.6. (R)-(À)-6-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ol 9
GP-2 was carried out with ester (R)-(À)-13b (22 mg,
0.043 mmol) and KOH (57 mg, 1.0 mmol) in EtOH (1 mL) under
refluxing overnight. The crude product was purified by column
chromatography on silica gel (hexane/AcOEt, v/v 2:1) to yield
alcohol (R)-(À)-9 (6.0 mg, 76%) as colorless oil; 1H NMR
(400 MHz, CDCl3) d 7.34 (d, J = 8.5 Hz, 1H), 6.77 (dd, J1 = 8.5 Hz,
J2 = 2.7 Hz, 1H), 6.63 (d, J = 2.7 Hz, 1H), 4.75 (m, 1H), 2.85–2.63
(s, 2H), 2.02–1.84 (m, 3H), 1.82–1.70 (m, 1H), 1.62 (m, 1H);
13C NMR (100 MHz, CDCl3) d 158.9, 138.6, 131.3, 130.1, 113.4,
112.5, 67.7, 55.2, 32.4, 29.6, 18.6; IR (neat) mmax 3402, 2997,
2934, 2863, 2835, 1609, 1578, 1503, 1456, 1332, 1316, 1274,
1254, 1235, 1156, 1123, 1110, 1064, 1037, 1009, 982, 912,
40%), 278 ([M(81Br)]+, 40%); [
Calcd for C14H13BrO: C, 60.67; H, 4.73. Found: C, 60.58; H, 4.75.
a]
D
20 = À48.6 (c 0.47, CHCl3); Anal.
4.5.3. (1S,2S)-(+)-7-Bromo-2-methyl-2,3-dihydro-1H-cyclopenta
[a]naphthalen-1-ol 8
GP-2 was carried out with ester (1S,2S)-(+)-12a (198 mg,
0.323 mmol) and KOH (332 mg, 5.93 mmol) in EtOH (4 mL) at
reflux overnight. The crude product was purified by column chro-
matography on silica gel (hexane/AcOEt, v/v 5:1) to yield alcohol
(1S,2S)-(+)-8 (71 mg, 79%) as colorless needles: mp 153–154 °C;
1H NMR (400 MHz, CDCl3) d 8.01 (d, J = 2.0 Hz, 4H), 7.98 (d,
863, 834, 817, 773, 706, 655 cmÀ1; [
Anal. Calcd for C11H14O2: C, 74.13; H, 7.92. Found. C, 73.96; H,
a
]
D
25 = À22.5 (c 0.19, CHCl3);
7.91.
Please cite this article in press as: Kuwahara, S.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.05.008

S. Kuwahara et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
9
4.5.7. (S)-(À)-1-(Naphthalen-2-yl)ethanol 10
Acknowledgments
GP-2 was carried out with ester (S)-(+)-14a (198 mg,
0.323 mmol) and KOH (98 mg, 1.7 mmol) in EtOH (1 mL) under
refluxing overnight. The crude product was purified by column
chromatography on silica gel (hexane/AcOEt, v/v 5:1) to yield alco-
hol (S)-(À)-10 (14 mg, 75%) as white solid; mp 64–65 °C; 1H NMR
(400 MHz, CDCl3) d 7.86–7.79 (m, 4H), 7.53–7.42 (m, 3H), 5.07 (q,
J = 6.4 Hz, 1H), 1.94 (br.s, 1H), 1.58 (d, J = 6.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 143.1, 133.3, 132.9, 128.3, 127.9, 127.7,
126.2, 125.8, 123.8, 70.6, 25.1; IR (KBr) mmax 3320, 3051, 2970,
2877, 1599, 1363, 1272, 1172, 1124, 1075, 1023, 949, 902, 861,
822, 771, 742, 559, 482 cmÀ1; FAB-MS (matrix: DTT:TG = 1:1) m/
This work was supported by JSPS KAKENHI Grant Number
JP25410100, and the MEXT-Supported Program for the Strategic
Research Foundation at Private Universities (2012–2016) for S.K.
A. Supplementary data
Supplementary data (1H and 13C NMR spectra, HPLC chro-
matogram, CD and UV spectra, and crystallographic data.) associ-
ated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetasy.2017.05.008.
z 172 ([M]+, 40%); [
a
]
D
25 = À46.4 (c 0.25, CHCl3); Anal. Calcd for
C12H12O: C, 83.69; H, 7.02. Found. C, 83.50; H, 7.05.
References
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2012.
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Tetrahedron: Asymmetry 2000, 11, 1249–1253.
4.5.8. (R)-(+)-1-(Naphthalen-2-yl)ethanol 10
GP-2 was carried out with ester (R)-(À)-14b (39 mg,
0.077 mmol) and KOH (62 mg, 1.1 mmol) in EtOH (1 mL) under
refluxing overnight. The crude product was purified by column
chromatography on silica gel (hexane/AcOEt, v/v 5:1) to yield alco-
hol (R)-(+)-10 (11 mg, 85%) as white solid; mp 64–65 °C; 1H NMR
(400 MHz, CDCl3) d 7.86–7.79 (m, 4H), 7.53–7.42 (m, 3H), 5.07
(q, J = 6.4 Hz, 1H), 1.94 (br.s, 1H), 1.58 (d, J = 6.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3) d 143.1, 133.3, 132.9, 128.3, 127.9, 127.7,
126.2, 125.8, 123.8, 70.6, 25.1; IR (KBr) mmax 3328, 3053, 2971,
2924, 2879, 1600, 1507, 1449, 1364, 1271, 1217, 1172, 1125,
1073, 1023, 1000, 949, 902, 859, 821, 771, 743, 659, 620557,
481 cmÀ1; FAB-MS (matrix: DTT:TG = 1:1) m/z 172 ([M]+, 40%);
8. Taji, H.; Kasai, Y.; Sugio, A.; Kuwahara, S.; Watanabe, M.; Harada, N.; Ichikawa,
A. Chirality 2002, 14, 81–84.
9. Kasai, Y.; Taji, H.; Fujita, T.; Yamamoto, Y.; Akagi, M.; Sugio, A.; Kuwahara, S.;
Watanabe, M.; Harada, N.; Ichikawa, A.; Schurig, V. Chirality 2004, 16, 569–585.
10. Kasai, Y.; Sugio, A.; Sekiguchi, S.; Kuwahara, S.; Matsumoto, T.; Watanabe, M.;
Ichikawa, A.; Harada, N. Eur. J. Org. Chem. 2007, 1811–1826.
11. Kuwahara, S.; Naito, J.; Yamamoto, Y.; Kasai, Y.; Fujita, T.; Noro, K.; Shimanuki,
K.; Akagi, M.; Watanabe, M.; Matsumoto, T.; Ichikawa, A.; Harada, N. Eur. J. Org.
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12. Sekiguchi, S.; Akagi, M.; Naito, J.; Yamamoto, Y.; Taji, H.; Kuwahara, S.;
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2324.
[a]
25 = +37.8 (c 0.40, CHCl3); Anal. Calcd for C12H12O: C, 83.69; H,
D
7.02. Found. C, 83.41; H, 7.06.
4.5.9. (S)-(À)-1-(5,8-Dimethoxy-3,4-dihydronaphthalen-2-yl)
ethanol 11
13. Yamamoto, Y.; Akagi, M.; Shimanuki, K.; Kuwahara, S.; Watanabe, M.
Tetrahedron: Asymmetry 2014, 25, 1456–1465.
GP-2 was carried out with ester (S)-(À)-15a (29 mg,
0.050 mmol) and KOH (43 mg, 0.77 mmol) in EtOH (1 mL) under
refluxing overnight. The crude product was purified by column
chromatography on silica gel (hexane/AcOEt, v/v 2:1) to yield alco-
hol (S)-(À)-11 (10.5 mg, 84%) as white solid; mp 85–86 °C; 1H NMR
(400 MHz, CDCl3) d 6.80–6.77 (m, 1H), 6.70 (d, J = 8.9 Hz, 1H), 6.66
(d, J = 8.9 Hz, 1H), 4.52–4.40 (m, 1H), 3.79 (s, 6H), 2.89–2.69 (m,
2H), 2.40–2.14 (m, 2H), 1.60 (d, J = 3.5 Hz, 1H), 1.36 (d, J = 6.5 Hz,
1H); 13C NMR (100 MHz, CDCl3) d 150.4, 149.6, 144.0, 124.6,
124.0, 115.4, 109.8, 108.6, 71.5, 56.0, 56.0, 22.1, 21.4, 20.9; IR
(KBr) mmax 3389, 2937, 2888, 2832, 1593, 1482, 1463, 1437, 1365,
1337, 1294, 1256, 1219, 1176, 1098, 1062, 1029, 987, 958, 882,
848, 791, 772, 718, 571 cmÀ1; FAB-MS (matrix: DTT:TG = 1:1) m/
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z 235 ([M+H]+, 70%); [
a]
25 = À23.3 (c 0.17, CHCl3); Anal. Calcd for
D
C14H18O3: C, 71.77; H, 7.74. Found. C, 71.53; H, 7.76.
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4.5.10. (R)-(+)-1-(5,8-Dimethoxy-3,4-dihydronaphthalen-2-yl)
ethanol 11
GP-2 was carried out with ester (R)-(À)-15b (30 mg,
0.054 mmol) and KOH (45 mg, 45 mmol) in EtOH (1 mL) under
refluxing overnight. The crude product was purified by column
chromatography on silica gel (hexane/AcOEt, v/v 2:1) to yield alco-
hol (R)-(+)-11 (11.5 mg, 92%) as white solid; mp 85–86 °C; 1H NMR
(400 MHz, CDCl3) d 6.80–6.77 (m, 1H), 6.70 (d, J = 8.9 Hz, 1H), 6.66
(d, J = 8.9 Hz, 1H), 4.52–4.40 (m, 1H), 3.79 (s, 6H), 2.89–2.69 (m,
2H), 2.40–2.14 (m, 2H), 1.60 (d, J = 3.5 Hz, 1H), 1.36 (d, J = 6.5 Hz,
1H); 13C NMR (100 MHz, CDCl3) d 150.4, 149.6, 144.0, 124.6,
124.0, 115.4, 109.8, 108.6, 71.5, 56.0, 56.0, 22.1, 21.4, 20.9; IR
(KBr) mmax 3385, 2937, 2888, 2831, 1593, 1482, 1463, 1437, 1365,
1337, 1294, 1256, 1219, 1176, 1098, 1062, 1029, 958, 882, 848,
791, 718, 561 cmÀ1; FAB-MS (matrix: DTT:TG = 1:1) m/z 235 ([M
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10418.
+H]+, 100%);
[a]
25 = +26.7 (c 0.57, CHCl3); Anal. Calcd for
D
C14H18O3: C, 71.77; H, 7.74. Found. C, 71.58; H, 7.75.
Please cite this article in press as: Kuwahara, S.; et al. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.05.008