Resolution of inherently chiral anti-O,O′-dialkylthiacalix[4]arenes and determination of their absolute stereochemistries

Article abstract of DOI:10.1016/j.tetasy.2008.05.034

Inherently chiral anti-O,O′-dibenzyl- and anti-O,O′-dibutyl-p-tert-butylthiacalix[4]arenes 4 and 6 are resolved as (S)-2-methoxy-2-(naphthalen-1-yl)propionic esters by flash chromatography. The absolute stereochemistries were determined to be (S_a

Full text of DOI:10.1016/j.tetasy.2008.05.034

Tetrahedron: Asymmetry 19 (2008) 1470–1475
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Tetrahedron: Asymmetry
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Resolution of inherently chiral anti-O,O0-dialkylthiacalix[4]arenes and
determination of their absolute stereochemistries
b
b
b
c
Fumitaka Narumi a, , Nobuji Matsumura , Nariaki Sasagawa , Koichi Natori , Takashi Kajiwara ,
*
Tetsutaro Hattori b,
*
a Department of Basic Sciences, School of Science and Engineering, Ishinomaki Senshu University, 1 Shinmito, Minamisakai, Ishinomaki 986-8580, Japan
b Department of Environmental Studies, Graduate School of Environmental Studies, Tohoku University, 6-6-11 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan
c Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki-Aoba, Aoba-ku, Sendai 980-8578, Japan
a r t i c l e i n f o
a b s t r a c t
Inherently chiral anti-O,O0-dibenzyl- and anti-O,O0-dibutyl-p-tert-butylthiacalix[4]arenes 4 and 6 are
resolved as (S)-2-methoxy-2-(naphthalen-1-yl)propionic esters by flash chromatography. The absolute
stereochemistries were determined to be (Sa)-(+)-4 and (Sa)-(+)-6 by X-ray crystallographic analyses.
Ó 2008 Elsevier Ltd. All rights reserved.
Article history:
Received 1 May 2008
Accepted 19 May 2008
Available online 27 June 2008
1. Introduction
achieved by a diastereomeric method.15 However, the racemic syn-
thesis could not be applied to thiacalix[4]arene 1, which, on being
Over the last decade, interest in the development of chiral host
molecules with a calixarene skeleton has increased.1 A variety of
chiral calixarenes have been prepared by introducing chiral sub-
stituents at the lower rim through the phenolic oxygens or at the
para positions, and applied as chromogenic receptors,2 additives
in capillary electrophoresis,3 chiral stationary phases for GC and
HPLC,4 chiral solvating agents for NMR,5 and so on.6 On the other
hand, although a certain number of inherently chiral calixarenes
have been prepared, their chiral recognition abilities have hardly
been investigated, seemingly due to the poor accessibility to this
type of compounds in enantiopure form;7,8 they have, in most
cases, been resolved on an analytical scale by chiral HPLC9 and it
is seldom that resolution techniques easy to scale-up were suc-
cessfully applied to these compounds.8,10
treated in a similar manner, selectively gave syn stereoisomers
(e.g., compounds 5 and 7).14 This was attributed to the bulkiness
of the TIPDS moiety, which allows the attack of an alkyl halide to
an anionic intermediate of the thiacalixarene from only the opposite
side to the TIPDS moiety with respect to the mean plane defined by
the macrocycle, giving a diether of 1,2-alternate conformation. Re-
cently, we found that syn-O,O0-bistriflate ester of thiacalix[4]arene
3, bearing Tf capping groups smaller than TIPDS for two adjacent hy-
droxy groups, can be prepared by a base-catalyzed isomerization of
syn-O,O00-counterpart 2 and shows good anti selectivity in the dial-
kylation.16 With a method for the racemic synthesis in hand, we
herein report the resolution of anti-O,O0-dialkylthiacalix[4]arenes
4 and 6 on a gram-scale by flash chromatography after conversion
into the diastereomeric esters of (S)-2-methoxy-2-(naphthalen-1-
yl)propionic acid [(S)-MNPA].17 Also reported are the absolute ste-
reochemistries determined by X-ray crystallographic analysis. To
the best of our knowledge, this is the first report on the synthesis
of optically active anti-O,O0-dialkylthiacalix[4]arenes.
anti-O,O0-Dialkylthiacalix[4]arenes, for example, compounds 4
and 6, are one of the simplest inherently chiral calixarenes and ex-
pected to show high complexation ability toward metal ions by the
cooperative coordination of the two neighboring hydroxy groups
with the interpositioned epithio linkage to the metal center.11,12
Therefore, the development of a synthetic method toward them is
highly desirable for designing synthetic receptors, as well as meal
catalysts.13 Previously, we succeeded in the synthesis of methy-
lene-bridged analogues, anti-O,O0-dialkylcalix[4]arenes, via 1,2-O-
tetraisopropyldisiloxane (TIPDS)-capping by the O,O0-disiloxylation
of calix[4]arene with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane,
followed by the base-catalyzed dialkylation of the remaining hydro-
xy groups with an alkyl halide, and subsequent deprotection of the
TIPDS moiety.14 The resolution of the resulting diethers could be
2. Results and discussion
2.1. Synthesis and resolution of O,O0-dialkylthiacalix[4]arenes 4
and 6
Racemic diethers 4 and 6 were prepared on a gram-scale,
according to the reported procedure (Scheme 1).16 Commercially
available thiacalix[4]arene 1 was allowed to react with 2.9 mol
equiv of triflic anhydride in the presence of pyridine in dichloro-
methane at room temperature to give syn-O,O00-bistriflate ester
2 (76%), which was isomerized by heating at 60 °C in DMSO
in the presence of 4.4 mol equiv of triethylamine to give
* Corresponding authors. Tel.: +81 225 22 7716; fax: +81 225 22 7746 (F.N.).
E-mail addresses: fnarumi@isenshu-u.ac.jp (F. Narumi), hattori@orgsynth.che.
tohoku.ac.jp (T. Hattori).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.05.034

F. Narumi et al. / Tetrahedron: Asymmetry 19 (2008) 1470–1475
1471
OH
OH
OTf
HO OH
HO
S
OH
S
HO
OH
TfO
OTf
HO
OTf
i
ii
S
S
S
S
S
S
S
S
HO
HO
HO
S
S
S
S
S
S
But
But
ButBut
1
2
3
OH
HO
OH
OH
HO
HO
OR
iii
iv
S
S
S
S
S
S
S
RO
OR
RO
S
S
S
S
S
RO
OR
4
( )- : R = CH2Ph
: R = CH Ph
5
2
6
7
( )- : R = Bu
: R = Bu
Scheme 1. Reagents: (i) triflic anhydride, Py, dichloromethane; (ii) NEt3, DMSO; (iii) benzyl bromide or 1-iodobutane, K2CO3, acetone; (iv) NaOH aq, EtOH, THF.
syn-O,O0-counterpart 3 (92%). The dialkylation was performed by
the treatment of diester 3 with 12 mol equiv of benzyl bromide
in the presence of K2CO3 in refluxing acetone to give a mixture of
three stereoisomers of syn-O,O0-bistriflate ester of O00,O000-dibenzyl-
thiacalix[4]arene,16 which was hydrolyzed without separation un-
der basic conditions to give, after recrystallization, anti-O,O0-
dibenzyl ether ( )-4 in 67% yield. The filtrate was purified by col-
umn chromatography to give syn-O,O0-dibenzyl ether 5 (28%) with
an additional crop of ( )-4 (2%). By using the same dialkylation
procedure, anti- and syn-O,O0-dibutyl ether ( )-6 and 7 were
obtained in 71% and 23% yields, respectively.
treatment of racemic dibenzyl ether ( )-4 with (S)-MNPA in dichlo-
romethane in the presence of N,N0-dicyclohexylcarbodiimide (DCC)
gave a mixture of four possible diastereomeric monoesters 8a–d,
from which ester 8a was successfully separated by flash chroma-
tography in 36% yield (see Section 4). The stereochemistry of ester
8a was determined by an X-ray crystallographic analysis (vide in-
fra). The removal of the MNPA moiety from ester 8a by conversion
into the methyl ester with sodium methoxide gave enantiopure
diether (+)-4 in 95% yield. The resolution of dibutyl ether ( )-6
was achieved by the same procedure (Scheme 2). Flash chromatog-
raphy of a mixture of 9a–d isolated ester 9a (36%), which gave,
after the removal of the MNPA moiety, diether (+)-6 in almost
quantitative yield.
The resolution of diethers ( )-4 and ( )-6 was examined by
using (S)-MNPA as a chiral derivatizing agent (Scheme 2). The
OEs∗
Es∗ O
OH
HO
∗
OH
HO
OEs∗
Es O
i
S
S
S
S
S
S
S
S
( )-4
RO
OR
RO
OR
6
( )-
S
S
S
S
S
S
S
S
RO
OR
RO
OR
8a: R = CH2Ph
9a: R = Bu
8b: R = CH2Ph
9b: R = Bu
8c: R = CH2Ph
9c: R = Bu
8d: R = CH2Ph
9d
: R = Bu
ii
O
Es∗
=
Nap
OMe
OH
OH
S
S
RO
S
S
RO
(+)-4: R = CH2Ph
(+)-6: R = Bu
Scheme 2. Reagents: (i) (S)-MNPA, DCC, PPy, dichloromethane; (ii) sodium methoxide, methanol, water.

1472
F. Narumi et al. / Tetrahedron: Asymmetry 19 (2008) 1470–1475
2.2. Determination of the absolute stereochemistries of
compounds (+)-4 and (+)-6
In our previous paper,15 we reported that the absolute stereo-
chemistries of anti-O,O0-dialkylcalix[4]arenes could be determined
by the CD exciton chirality method:18 The two etherified phenol
units showed an exciton-split CD pattern at the UV band of ca.
230 nm, which represents the axial twist of the two etherified phe-
nol units. However, the CD method could not be applied to thiaca-
lixarene derivatives (+)-4 and (+)-6, because their CD patterns were
ambiguous, presumably due to the auxochromous epithio linkages
(Figs. 1 and 2).
We next tried X-ray crystallographic analysis: The recrystalliza-
tion of ester 8a from chloroform–acetonitrile gave single crystals,
one of which was subjected to X-ray crystallographic analysis.
The crystal of 8a belongs to the monoclinic system with a C2 space
group. In the asymmetric unit, there are two crystallographically
independent molecules, which adopt similar conformations to
each other. Figure 3 shows the X-ray structure of one of the two
independent molecules. Compound 8a adopts a partial-cone con-
formation in the crystal. Interestingly, the benzyl moiety attached
to the inverted phenol unit of the calix macrocycle is included into
the cavity formed by the other three phenol units. As previously re-
ported,15 the axial chirality of anti-O,O0-dialkylcalix[4]arenes can
be defined by the spatial arrangement of the four aromatic carbons
at the ortho-positions to the epithio linkage between the two ethe-
rified phenol units. By this definition, the absolute stereochemistry
of ester 8a, as well as that of dibenzyl ether (+)-4, was assigned to
be (Sa) by using the (S)-MNPA moiety as the internal reference.
A single crystal of ester 9a, obtained by recrystallization from
diethyl ketone–acetonitrile, was analyzed by X-ray diffraction. It
was shown that the crystal belongs to the triclinic system with a
P1 space group. The asymmetric unit contains two independent
molecules of similar conformations, one of which is shown in Fig-
ure 4. Compound 9a adopts a partial-cone conformation and an
acetonitrile molecule is included in the calix cavity. From the X-
Figure 2. CD and UV spectra of dibutyl ether (+)-6 (0.19 mM) in ethanol–dioxane
(9:1) at 25 °C.
Figure 3. X-ray structure of diastereomeric ester 8a.
ray structure, the absolute configuration of ester 9a, as well as that
of dibutyl ether (+)-6, was determined to be (Sa) by using the (S)-
MNPA moiety as the internal reference.
Figure 1. CD and UV spectra of dibenzyl ether (+)-4 (0.18 mM) in ethanol at 25 °C.

F. Narumi et al. / Tetrahedron: Asymmetry 19 (2008) 1470–1475
1473
ice-cold suspension of thiacalix[4]arene 1 (21.6 g, 30.0 mmol) in
anhydrous dichloromethane (40 mL) were added anhydrous pyri-
dine (d = 0.983 g mLꢀ1, 14.5 mL, 0.180 mol) and triflic anhydride
(d = 1.72 g mLꢀ1, 14.5 mL, 88.3 mmol) under nitrogen. After stir-
ring at room temperature for 3 h, the mixture was quenched with
2 M HCl and the mixture extracted with chloroform. The organic
layer was washed with water, dried over MgSO4, and evaporated.
The residue was purified by recrystallization from dichlorometh-
ane–methanol to give syn-O,O00-bistriflate ester 219 (22.6 g, 76%)
as a colorless powder.
A mixture of compound 2 (22.6 g, 22.9 mmol), triethylamine
(d = 0.726 g mLꢀ1
; 14.0 mL, 0.100 mol), and anhydrous DMSO
(300 mL) was heated at 60 °C for 8 h under nitrogen. After cooling,
the reaction was quenched with 2 M HCl (200 mL) to give a precip-
itate, which was collected by filtration, washed successively with
2 M HCl and water, and then dried under an air stream. The crude
product was purified by recrystallization from dichloromethane–
methanol to give syn-O,O0-bistriflate ester 3 (20.7 g, 92%), the spec-
troscopic data of which were identical with those reported
previously.16
4.3. Synthesis of anti-O,O0-dibenzylthiacalix[4]arene ( )-4
This compound was prepared on a large scale according to the
reported procedure.16 To
a solution of compound 3 (9.86 g,
10.0 mmol) in anhydrous acetone (100 mL) were added K2CO3
(16.6 g, 0.120 mol) and benzyl bromide (d = 1.44 g mLꢀ1; 14.0 mL,
0.118 mol), after which the mixture was refluxed for 6 h under
nitrogen. After cooling, the reaction was quenched with 2 M HCl
and the mixture extracted with dichloromethane. The extract
was washed with water, dried over MgSO4, and evaporated. The
residue was recrystallized from methanol to give a mixture of
three stereoisomers of syn-O,O0-bistriflate ester of O00,O000-dibenzyl-
thiacalix[4]arene16 (11.3 g) as a colorless powder, which was dis-
solved in a 1:1 mixture of THF and ethanol (400 mL). To the
solution was added 20 M NaOH (25 mL) after which the mixture
was heated at reflux for 8 h. After cooling, most of the organic sol-
vents were evaporated and the residue extracted with chloroform.
The extract was washed successively with 2 M HCl and water,
dried over MgSO4, and evaporated. The residue was purified by
recrystallization from dichloromethane–methanol to give anti-
O,O0-dibenzyl ether ( )-4 (6.02 g) as a colorless powder. Further-
more, the filtrate was evaporated and the residue purified by col-
umn chromatography with hexane–chloroform (2:1) as an eluent
to give an additional crop (0.22 g) for a total yield of 6.24 g
(69%). The chromatography also isolated the syn-counterpart 5
(2.56 g, 28%,) as a colorless solid. The spectral data of these diethers
were identical with those reported previously.14b
Figure 4. X-ray structure of diastereomeric ester 9a.
3. Conclusion
In conclusion, we have reported a practical method to prepare
enantiopure anti-O,O0-diethers of thiacalix[4]arenes (+)-4 and (+)-
6 on a gram-scale. The synthesis of racemates was achieved by
our recently reported di-O-protection method with Tf moieties.
The racemates could be resolved as the (S)-MNPA esters by flash
chromatography. The absolute stereochemistries were determined
to be (Sa)-(+)-4 and (Sa)-(+)-6 by X-ray analyses.
4. Experimental
4.1. General
Melting points were taken using a Mitamura Riken MP-P or a
Yamato IA-9000 apparatus. Microanalyses were carried out in the
Microanalytical Laboratory of the Institute of Multidisciplinary Re-
search for Advanced Materials, Tohoku University. Optical rota-
4.4. Synthesis of anti-O,O0-dibutylthiacalix[4]arene ( )-6
tions were measured on a JASCO DIP-1000 polarimeter and [
a]
D
values are given in units of 10ꢀ1 deg cm2 gꢀ1 1H and 13C NMR
.
spectra were recorded on a Bruker DPX-400, DRX-500, or JEOL
JNM-ECA300 spectrometer using tetramethylsilane (1H NMR) or
chloroform (13C NMR) as the internal standard and CDCl3 as sol-
vent. J-Values are given in Hertz. Open columns and flash columns
were prepared by using Kanto Kagaku Silica Gel 60N (spherical,
This compound was prepared by the same procedure as men-
tioned for the preparation of compound ( )-4 by using ester 3
(7.88 g, 8.00 mmol), anhydrous acetone (80 mL), K2CO3 (13.3 g,
96.2 mmol), and 1-iodobutane (d = 1.60 g mLꢀ1
;
11.1 mL,
96.3 mmol). The crude product was recrystallized from chloro-
form–ethanol to give anti-O,O0-dibutyl ether ( )-6 (3.61 g) as a
colorless powder. The filtrate was then evaporated and the resi-
due was purified by column chromatography with hexane–chlo-
roform (2:1) as an eluent to give an additional crop (1.13 g) for a
total yield of 4.74 g (71%), mp 217–219 °C (Anal. Calcd for
neutral, 63–210
lm) and Silica Gel 60N (spherical, neutral, 40–
50 m), respectively. Mass spectra were measured on a JEOL
l
JMS-DX602 spectrometer. Triethylamine was distilled from cal-
cium hydride and stored under nitrogen. Other materials were
used as purchased.
C
48H64O4S4: C, 69.19; H, 7.74; S, 15.39. Found: C, 68.89; H,
4.2. Synthesis of syn-O,O0-bistriflate ester of thiacalix[4]arene 3
7.71; S, 15.58.); dH (400 MHz) 0.53 (6H, t, J 7.4, CH2CH3), 0.86–
0.91 (4H, m, CH2CH3), 1.05–1.26 (4H, m, OCH2CH2), 1.25 [18H,
s, C(CH3)3], 1.30 [18H, s, C(CH3)3], 3.70–3.80 (2H, m, OCH2),
4.01–4.11 (2H, m, OCH2), 7.46 (2H, d, J 2.5, ArH), 7.48 (2H, d, J
This compound was prepared on a large scale via syn-O,O00-
bistriflate ester 2, according to the reported procedure.16,19 To an

1474
F. Narumi et al. / Tetrahedron: Asymmetry 19 (2008) 1470–1475
2.5, ArH), 7.51 (2H, d, J 2.5, ArH), 7.58 (2H, d, J 2.5, ArH), 8.53
(2H, s, OH); dC (75 MHz) 13.73, 18.68, 30.92, 31.23, 31.32,
34.07, 34.42, 71.97, 120.28, 120.68, 127.52, 128.30, 129.29,
131.73, 132.09, 133.52, 142.90, 147.27, 155.39, 156.50; m/z
(FAB) 833 [(M+1)+]. This chromatography also isolated syn coun-
terpart 7 (1.55 g, 23%) as a colorless solid, the spectroscopic data
of which were identical with those reported previously.14b
4.6. Resolution of anti-O,O0-dibutyl ether ( )-6
4.6.1. Esterification of dibutyl ether ( )-6 to diastereomeric
monoesters 9a–d
Racemic dibutyl ether ( )-6 was esterified by the same manner
as described for dibenzyl ether
4 by using ( )-6 (4.17 g,
5.00 mmol), anhydrous dichloromethane (50 mL), (S)-MNPA
(2.30 g, 10.0 mmol), 4-PPy (2.22 g, 15.0 mmol), and DCC (3.09 g,
15.0 mmol). The mixture of diastereomeric monoesters 9a–d were
loaded on a flash column and eluted with hexane–chloroform (1:1)
to give, in addition to an inseparable mixture of 9b–d, diastereo-
merically pure 9a (1.86 g, 36%) as a colorless powder, mp 154–
158 °C (dichloromethane–methanol) (Anal. Calcd for C62H76O6S4:
C, 71.22; H, 7.33; S, 12.27. Found: C, 71.00; H, 7.28; S, 12.16);
4.5. Resolution of anti-O,O0-dibenzyl ether ( )-4
4.5.1. Esterification of dibenzyl ether ( )-4 to diastereomeric
monoesters 8a–d
To an ice-cold solution of dibenzyl ether ( )-4 (3.61 g,
4.00 mmol) in anhydrous dichloromethane (40 mL) were added
(S)-MNPA (1.84 g, 8.00 mmol), 4-pyrrolidinopyridine (4-PPy)
(1.78 g, 12.0 mmol), and DCC (2.48 g, 12.0 mmol) under nitrogen.
After stirring at room temperature for 24 h, the mixture was
quenched with 2 M HCl and the mixture extracted with dichlo-
romethane. The extract was washed with 1 M NaOH to recover
unreacted (S)-MNPA, and then with 2 M HCl and water, dried
over MgSO4, and evaporated. The residue was passed through a
short silica gel column with hexane–diethyl ether (4:1) as an
eluent to give a mixture of four diastereomeric monoesters 8a–
d. Flash chromatography of the mixture, eluting with hexane–
chloroform (1:1–2:3), gave an inseparable mixture of 8b–d as
the first fraction, while the second fraction gave diastereomeri-
cally pure 8a (1.59 g, 36%) as a colorless powder, mp 193–
½
a 2D8
ꢁ
¼ ꢀ118:2 (c 1.21, chloroform); dH (300 MHz, CDCl3) 0.75
(9H, s, C(CH3)3), 0.82 (3H, t, J 7.2, CH2CH3), 0.88 (3H, t, J 7.2,
CH2CH3), 1.06 (9H, s, C(CH3)3), 0.96–1.16 (1H, m, OCH2CH2), 1.19
(9H, s, C(CH3)3), 1.21–1.36 (4H, m, CH2CH3), 1.33 (9H, s, C(CH3)3),
1.38–1.71 (3H, m, OCH2CH2), 2.07 (3H, s, CCH3), 3.52 (3H, s,
OCH3), 3.70 (1H, td, J 7.9 and 7.9, OCHCH2), 3.86–3.94 (1H, m,
OCHCH2), 4.03–4.11 (1H, m, OCHCH2), 4.35 (1H, td, J 8.2 and 4.8,
OCHCH2), 7.20 (1H, d, J 2.4, ArH), 7.28 (1H, d, J 2.4, ArH), 7.38
(1H, d, J 2.4, ArH), 7.41 (1H, d, J 2.4, ArH), 7.47 (1H, d, J 2.4, ArH),
7.49–7.57 (4H, m, ArH ꢂ 2 and Naph ꢂ 2), 7.61 (1H, t, J 7.7, Naph),
7.69 (1H, d, J 2.4, ArH), 7.78 (1H, s, OH), 7.88–7.92 (2H, m,
Naph ꢂ 2), 8.14 (1H, d, J 7.2, Naph), 8.75 (1H, d, J 7.5, Naph); dC
(75 MHz) 13.79, 13.90, 18.90, 18.96, 24.88, 30.57, 30.93, 31.08,
31.25, 31.45, 31.88, 33.83, 34.06, 34.17, 34.34, 54.03, 70.78,
74.23, 86.20, 119.91, 122.64, 124.76, 125.07, 125.36, 125.99,
126.24, 127.08, 127.30, 128.04, 128.41, 128.90, 129.25, 129.77,
129.81, 130.35, 131.44, 131.65, 131.89, 132.45, 132.87, 134.30,
134.33, 134.47, 134.85, 135.83, 142.07, 145.83, 147.50, 147.79,
150.01, 156.62, 156.70, 158.43, 171.68; m/z (FAB) 1044 (M+).
195 °C
68H72O6S4: C, 73.34; H, 6.52; S, 11.52. Found: C, 73.33; H,
6.51; S, 11.66.);
¼ ꢀ75:0 (c 1.02, chloroform); dH
(dichloromethane–methanol)
(Anal.
Calcd
for
C
½ ꢁ
a 2D8
(300 MHz) 0.68 [9H, s, C(CH3)3], 0.70 [9H, s, C(CH3)3], 0.84 [9H,
s, C(CH3)3], 1.20 (3H, s, CH3), 1.40 [9H, s, C(CH3)3], 3.43 (3H, s,
OCH3), 4.85 (1H, d, J 12.0, OCH2Ph), 4.86 (1H, d, J 9.6, OCH2Ph),
4.96 (1H, d, J 12.0, OCH2Ph), 5.25 (1H, d, J 9.6, OCH2Ph), 6.02
(2H, d, J 7.6, OCH2Ph), 6.36 (2H, t, J 7.6, OCH2Ph), 6.74 (1H, t, J
7.6, OCH2Ph), 6.92 (1H, d, J 2.4, ArH), 7.12 (1H, d, J 2.4, ArH),
7.18 (1H, d, J 2.4, ArH), 7.23–7.37 (6H, m, ArH ꢂ 3 and Nap ꢂ 3),
7.49–7.58 (5H, m, OCH2Ph ꢂ 3 and Nap ꢂ 2), 7.71 (1H, d, J 2.7,
ArH), 7.81–7.87 (4H, m, ArH ꢂ 1, OCH2Ph ꢂ 2 and Nap ꢂ 1),
8.39 (1H, s, OH), 8.54 (1H, d, J 8.6, Nap); dC (75 MHz) 22.18,
30.41, 30.47, 30.67, 31.52, 33.81, 33.84, 33.97, 34.18, 53.57,
67.38, 86.22, 119.78, 122.06, 124.36, 124.57, 124.90, 125.17,
125.43, 125.82, 126.16, 126.50, 126.72, 127.01, 127.27, 127.45,
127.82, 128.14, 128.56, 128.59, 128.75, 128.85, 128.90, 129.45,
129.94, 130.41, 131.23, 131.29, 133.67, 134.85, 135.09, 135.44,
135.65, 136.77, 137.00, 142.62, 146.95, 148.56, 148.65, 149.74,
154.77, 156.62, 157.63, 171.29.
4.6.2. Hydrolysis of ester 9a to anti-O,O0-dibutyl ether (+)-6
The hydrolysis of ester 9a was carried out by a similar proce-
dure to that described for ester 8a by using 9a (1.72 g, 1.64 mmol),
anhydrous THF (10 mL), and a 28% solution of sodium methoxide
in methanol (10 mL). The crude product was recrystallized from
dichloromethane–methanol to give dibutyl ether (+)-6 (1.33 g,
97%) as a colorless powder, ½a D27
¼ þ16:3 (c 1.00, chloroform).
ꢁ
The enantiomeric purity of the sample was determined to be
99.8% ee by HPLC on a Sumika SUMICHIRAL OA-2000 column
(4.6 mm i.d. ꢂ 25 cm) with hexane–chloroform (9:1, 1.0 mL minꢀ1
)
as the eluent. The retention times for enantiomers (+)- and (ꢀ)-6
were 11.5 and 13.1 min, respectively. The spectroscopic data of
the sample were identical with those of the racemate (vide supra).
4.5.2. Hydrolysis of ester 8a to anti-O,O0-dibenzyl ether (+)-4
To a solution of ester 8a (1.59 g, 1.43 mmol) in anhydrous
THF (5 mL) was added a 28% solution of sodium methoxide in
methanol (10 mL) under nitrogen and the mixture was heated
at reflux. After 4 h, water (1 mL) was added and the mixture re-
fluxed for a further 30 min. After cooling, the organic solvents
were evaporated and the residue extracted with dichlorometh-
ane. The extract was washed successively with 2 M HCl and
water, dried over MgSO4, and evaporated. The residue was puri-
fied by column chromatography with hexane–chloroform (2:1)
as eluent to give dibenzyl ether (+)-4 (1.22 g, 95%,) as a colorless
4.7. X-ray analysis of ester 8a
The single crystals were obtained by the slow diffusion of ace-
tonitrile into a chloroform solution of ester 8a. Data were collected
on a Bruker SMART CCD diffractometer employing graphite mono-
chromated MoK
a radiation (k = 0.71073 Å). The data integration
and reduction were undertaken with SAINT and XPREP.
20 The structure
was solved by the direct methods with SHELXS-9721 and refined by
the full-matrix least squares methods with SHELXL-97.22 Crystal data
and refinement statistics are as follows:
C
140H149Cl6NO12S8,
M = 2506.96, monoclinic, a = 26.5621(14),
b = 15.7462(8),
solid, ½a 2D8
ꢁ
¼ þ4:5 (c 1.00, chloroform). The enantiomeric purity
c = 32.2129(17) Å, b = 95.062(2)°, V = 13420.6(12) Å3, T = 200(2) K,
of the sample was determined to be 99.9% ee by HPLC on a
Sumika SUMICHIRAL OA-2000 column (4.6 mm i.d. ꢂ 25 cm)
with hexane–chloroform (9:1, 1.0 mL minꢀ1) as the eluent. The
retention times for (+)- and (ꢀ)-4 enantiomers were 19.0 and
23.8 min, respectively. The spectroscopic data of the sample
were identical with those of the racemate.14b
space group C2, Z = 4,
measured, 23543 unique (Rint = 0.061). Final R1 = 0.059 for 14318
data [I > 2 (I)] and wR2 = 0.145 for all data, GOF = 0.883. The details
l(MoKa
) = 0.311 mmꢀ1, 57219 reflections
r
of the crystal data have been deposited with Cambridge Crystallo-
graphic Data Centre as supplementary Publication No. CCDC
685855.23 The absolute stereochemistry of ester 8a, as well as that

F. Narumi et al. / Tetrahedron: Asymmetry 19 (2008) 1470–1475
1475
8. (a) Dieleman, C.; Steyer, S.; Jeunesse, C.; Matt, D. J. Chem. Soc., Dalton Trans.
2001, 17, 2508–2517; (b) Luo, J.; Zheng, Q.-Y.; Chen, C.-F.; Huang, Z.-T.
Tetrahedron 2005, 61, 8517–8528; (c) Shirakawa, S.; Moriyama, A.; Shimizu, S.
Org. Lett. 2007, 9, 3117–3119.
of dibenzyl ether (+)-4, was assigned to be (Sa) by using the (S)-
MNPA moiety as an internal reference.
9. (a) Iwamoto, K.; Shimizu, H.; Araki, K.; Shinkai, S. J. Am. Chem. Soc. 1993, 115,
3997–4006; (b) Ferguson, G.; Gallagher, J. F.; Giunta, L.; Neri, P.; Pappalardo, S.;
Parisi, M. J. Org. Chem. 1994, 59, 42–53; (c) Arnaud-Neu, F.; Caccamese, S.;
Fuangswasdi, S.; Pappalardo, S.; Parisi, M. F.; Petringa, A.; Principato, G. J. Org.
Chem. 1997, 62, 8041–8048; (d) Jin, T. Chem. Commun. 1998, 13, 1357–1358; (e)
Caccamese, S.; Bottino, A.; Cunsolo, F.; Parlato, S.; Neri, P. Tetrahedron:
Asymmetry 2000, 11, 3103–3112; (f) Hesek, D.; Inoue, Y.; Drew, M. G. B.;
Beer, P. D.; Hembury, G. A.; Ishida, H.; Aoki, F. Org. Lett. 2000, 2, 2237–2240; (g)
Tairov, M. A.; Vysotsky, M. O.; Kalchenko, O. I.; Pirozhenko, V. V.; Kalchenko, V.
I. J. Chem. Soc., Perkin Trans. 1 2002, 11, 1405–1411; (h) Csokai, V.; Simon, A.;
Balázs, B.; Tóth, G.; Bitter, I. Tetrahedron 2006, 62, 2850–2856.
10. (a) Narumi, F.; Yamabuki, W.; Hattori, T.; Kameyama, H.; Miyano, S. Chem. Lett.
2003, 32, 320–321; (b) Cao, Y.-D.; Luo, J.; Zheng, Q.-Y.; Chen, C.-F.; Wang, M.-
X.; Huang, Z.-T. J. Org. Chem. 2004, 69, 206–208; (c) Miao, R.; Zheng, Q.-Y.;
Chen, C.-F.; Huang, Z.-T. J. Org. Chem. 2005, 70, 7662–7671; (d) Luo, J.; Zheng,
Q.-Y.; Chen, C.-F.; Huang, Z.-T. Chem. Eur. J. 2005, 11, 5917–5928; (e)
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Y.; Chen, C.-F.; Huang, Z.-T. Org. Lett. 2007, 9, 4447–4450.
11. Reviews: Morohashi, N.; Narumi, F.; Iki, N.; Hattori, T.; Miyano, S. Chem. Rev.
2006, 106, 5291–5316.
12. Morohashi, N.; Iki, N.; Sugawara, A.; Miyano, S. Tetrahedron 2001, 57, 5557–
5563.
13. Morohashi, N.; Yokomakura, K.; Hattori, T.; Miyano, S. Tetrahedron Lett. 2006,
47, 1157–1161.
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Matsumura, N.; Yamabuki, W.; Kameyama, H.; Miyano, S. Org. Biomol. Chem.
2004, 2, 890–898.
4.8. X-ray analysis of ester 9a
The single crystals were obtained by slow diffusion of acetoni-
trile into a diethylketone solution of ester 9a. Data were collected
on a Rigaku/MSC Mercury CCD diffractometer using MoK
tion (k = 0.71073Å). The calculation was performed using the soft-
ware package TEXSAN (v. 1.11).24 The structure was solved by the
direct methods with SIR200225 and refined by full-matrix least
squares methods with SHELXL-97.22 Crystal data and refinement sta-
a radia-
tistics are as follows:
C
130H161N3O12S8, M = 2214.19, triclinic,
= 104.985(9)°,
= 90.097(8)°, V = 3546(2) Å3, T = 200.2 K, space
(MoK
) = 0.177 mmꢀ1, 44185 reflections mea-
a = 14.719(5), b = 15.420(6), c = 17.010(7) Å,
a
b = 107.366(7)°,
group P1, Z = 1,
c
l
a
sured, 24474 unique (Rint = 0.046). Final R1 = 0.082 for 20363 data
[I > 2 (I)] and wR2 = 0.278 for all data, GOF = 1.113. The details of
r
the crystal data have been deposited with Cambridge Crystallo-
graphic Data Centre as supplementary publication No. CCDC
685856.23 The absolute stereochemistry of ester 9a, as well as that
of (+)-6, was assigned to be (Sa) by using the (S)-MNPA moiety as
an internal reference.
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