Nucleophilic addition reaction of aromatic compounds with α-chloroglycidates in the presence of Lewis acid

Article abstract of DOI:10.1016/S0040-4020(03)00117-0

The epoxide 1 obtained by the Darzens condensation reaction of aldehydes with methyl dichloroacetate, reacted with aromatic compounds in the presence of aluminium chloride to afford α-aryl-β-chloro-α-hydroxyalkanoate 3. The intra-molecular nucleophilic addition of epoxide 1′ gave cyclisation compound 4. The scope and limitation of these reaction were studied for various aldehydes and aromatic compounds. The reaction was also studied in the presence of aluminium chloride supported on alumina or silica gel, which is thought to be a mild Lewis acid and harmless for environment.

Full text of DOI:10.1016/S0040-4020(03)00117-0

Tetrahedron 59 (2003) 1781–1790
Nucleophilic addition reaction of aromatic compounds
with a-chloroglycidates in the presence of Lewis acid
Jing-Rong Lin,a Aidar T. Gubaidullin,b Vakhid A. Mamedovb and Sadao Tsuboia
,
*
aDepartment of Environmental Chemistry and Materials, Faculty of Environmental Science and Technology, Okayama University,
Tsushima, Okayama 700-8530, Japan
bA. E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Science, Arbuzov str. 8, Kazan 420088, Russian Federation
Received 19 November 2002; accepted 14 January 2003
Abstract—The epoxide 1 obtained by the Darzens condensation reaction of aldehydes with methyl dichloroacetate, reacted with aromatic
compounds in the presence of aluminium chloride to afford a-aryl-b-chloro-a-hydroxyalkanoate 3. The intra-molecular nucleophilic
addition of epoxide 10 gave cyclisation compound 4. The scope and limitation of these reaction were studied for various aldehydes and
aromatic compounds. The reaction was also studied in the presence of aluminium chloride supported on alumina or silica gel, which is
thought to be a mild Lewis acid and harmless for environment. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
benzene or alkylbenzene in the presence of some Lewis
acids.2 Nakamoto et al. studied Friedel–Crafts alkylation of
benzene with some oxiranes and oxetanes.3 In 1970s,
Nakajima et al. reported asymmetric induction in the
Friedel–Crafts reaction of benzene with (þ)-1,2-epoxy-
butane.4 Inoue et al. examined the reaction of toluene
and anisole with 2-methyloxirane and 2,3-dimethyloxirane.5
Friedel–Crafts reaction is one of the most typical chemical
reaction.1 However, concerning the reaction of epoxides
with aromatic compounds in the presence of Lewis acid,
some reactions using only simple epoxides are reported. In
1960s, Hata et al. reported the reaction of epoxides with
Scheme 1.
Keywords: Darzens reactions; addition reactions; epoxides; cyclisation.
*
Corresponding author. Tel./fax: þ81-86-251-8898; e-mail: stsuboi6@cc.okayama-u.ac.jp
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00117-0

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Table 1. Reaction of 2-chloro-2,3-epoxyalkanoates with aromatic compounds in the presence of Lewis acid
Entry
R1
R2
Lewis acid
Conditions
Yield
3a, 58.8%
3b, 76.8%
3c, 55.9%
3d, 65.4%
3e, 71.4%
3f, 80.7%
3g, 60.1%
3h, 63.6%
3i, 74.2%
3j, 81.3%
3k, 62.3%
3l, 68.0%
3m, 76.3%
3n, 87.4%
3c, 13.8%;2c, 56.5%
3c, 14.4%;2c, 52.3%
syn/anti
1
2
3
4
5
6
7
8
CH3(CH2)4–
CH3(CH2)8–
(CH3)2CH–
CH3(CH2)4–
CH3(CH2)6–
CH3(CH2)8–
CH3(CH2)2–
CH3(CH2)4–
CH3(CH2)6–
CH3(CH2)8–
CH3(CH2)2–
CH3(CH2)4–
CH3(CH2)6–
CH3(CH2)8–
(CH3)2CH–
(CH3)2CH–
H
H
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
TiCl4
FeCl3
rt, 1 h
rt, 1 h
82/18
81/19
79/21
77/23
78/22
79/21
77/23
81/19
77/23
79/21
81/19
79/21
78/22
77/23
79/21
79/21
CH3–
CH3–
CH3–
CH3–
CH3CH2–
CH3CH2–
CH3CH2–
CH3CH2–
CH3(CH2)3–
CH3(CH2)3–
CH3(CH2)3–
CH3(CH2)3–
CH3–
rt, 50 min
rt, 40 min
rt, 40 min
rt, 40 min
rt, 1 h
rt, 50 min
rt, 50 min
rt, 50 min
rt, 50 min
rt, 50 min
rt, 50 min
rt, 50 min
508C, 2 h
rt, 2 h
9
10
11
12
13
14
15
16
CH3–
In 1980s, Taylor et al. studied highly stereoselective
Friedel–Crafts alkylations via epoxide transannular reac-
tions, and Friedel–Crafts cycloalkylations of some epox-
ides.6 In our laboratory, we have been studied Darzens
condensation for more than 20 years.7
2. Results and discussion
By Darzens condensation, aldehydes react with methyl
dichloroacetate in the presence of potassium tert-butoxide at
2788C to give a-chloro-a,b-epoxyalkanoates (1 or 10) in
good yields, which can be rearranged to afford isomeriza-
tion products (2). Then, the reaction of a-chloro-a,b-epoxy-
alkanoates (1) with aromatic compounds was carried out in
the presence of AlCl3. The results are shown in Table 1.
a-Aryl-b-chloro-a-hydroxyalkanoates (3) were obtained in
55.9–87.4% yield and major product was syn isomer. The
structure of syn-3 was confirmed by single-crystal X-ray
analysis of syn-3c (R1¼i-Pr, R2¼CH3).8 When the substrate
R1 became long, the reaction was more active, and the yield
became high (entries 3–6, 7–10, 11–14). The reactivity of
aromatic compounds was found as the following order;
benzene,toluene,ethylbenzene,n-butylbenzene (entries
1, 4, 8 and 12 for R1¼CH3(CH2)4–; entries 2, 6, 10 and
14 for R1¼CH3(CH2)8–). Moreover, we tried with other
aromatic compounds, and in the case of naphthalene, the
addition products were obtained in good yields of (47–84%)
(Scheme 2). But, in the case of anthracene or N,N-
dimethylaniline, the addition product was obtained in low
yields (31–35%). On the other hand, the reaction of aniline
Using the product obtained by Darzens condensation, we
have carried out various reactions. As a link of this study,
we examined the reaction of a-chloro-a,b-epoxyalkanoates
(1) with aromatic compounds in the presence of Lewis acid
(Scheme 1). Interestingly, this reaction did not give
Friedel–Crafts reaction product, but a nucleophilic addition
product of aromatic compounds to 1, a-aryl-b-chloro-a-
hydroxyalkanoate (3). Lewis acid-promoted addition
reaction of aromatic compounds to a-chloroglycidates 1 to
give alcohol 3 has never been reported, and we reported it as
a communication previously.8 On the other hand, the intra-
molecular nucleohpilic addition of the epoxide 10 in the
presence of aluminium chloride furnished a cyclisation
product 4 as our expectations (Scheme 1). Here, we report
the results about this intra-molecular cycloaddition reaction
and the detail experimental data of alcohol 3. In 1974,
Coutrot et al. has obtained compound 3 by the addition of
organomagnesium compounds to b-chloro-a-ketoesters.9
Scheme 2. Reaction of 2-chloro-2,3-epoxyalkanoates with naphthalene in the presence of AlCl3.

J.-R. Lin et al. / Tetrahedron 59 (2003) 1781–1790
1783
Table 2. Reaction of 2-chloro-2,3-epoxyalkanoates with aromatic compounds in the presence of AlCl3 supported on Al2O3 or SiO2
Entry
R1
R2
Conditions
Yield
syn/anti
1
2
3
4
5
6
7
8
9
10
(CH3)2CH–
(CH3)2CH–
(CH3)2CH–
CH3(CH2)4–
CH3(CH2)8–
(CH3)2CH–
(CH3)2CH–
(CH3)2CH–
CH3(CH2)4–
CH3(CH2)8–
CH3–
CH3–
CH3–
H
AlCl3/Al2O3¼1:2; rt, 40 min
AlCl3/Al2O3¼1:5; rt, 40 min
AlCl3/Al2O3¼1:10; rt, 40 min
AlCl3/Al2O3¼1:2; rt, 1 h
AlCl3/Al2O3¼1:2; rt, 50 min
AlCl3/SiO2¼1:2; rt, 1 h
3c, 66.5%
3c, 56.7%
3c, 49.5%
3a, 64.8%
3b, 92.2%
3c, 61.1%
3c, 53.7%
3c, 47.3%
3a, 55.1%
3b, 67.1%
82/18
80/20
76/24
83/17
84/16
81/21
78/22
78/22
81/19
75/25
H
CH3–
CH3–z
CH3–
H
AlCl3/SiO2¼1:5; rt, 1 h
AlCl3/SiO2¼1:10; rt, 1 h
AlCl3/SiO2¼1:2; rt, 1 h
H
AlCl3/SiO2¼1:2; rt, 1 h
or phenol gave the addition product only in poor yields (15–
18%). In the case of bromobenzene or nitrobenzene, the
reaction gave no product. The influence of the quantity of
AlCl3 added was also studied, and it was found that its
3 equiv. was the optimum quantity. With increasing the
quantities (5, 10 equiv.), the yield became lower and there
was no influence on the stereochemistry.8
somewhat, although the yield of addition products 3 became
higher than that of only in the presence of AlCl3 (entries 4
and 5). In the case of reactions in the presence of AlCl3
supported on SiO2, the yield of addition products 3 depends
on the nature of substrate (entries 6, 9 and 10). In all cases
the stereoselectivities were not changed so much. Then, we
examined the effects of the ratio of AlCl3/Al2O3 or SiO2,
and among the ratio of 1:2, 1:5 and 1:10, 1:2 ratio of AlCl3
supported on Al2O3 or SiO2 afforded the highest yield
(entries 1, 6).
To search the better Lewis acid, the reaction was studied in
the presence of TiCl4 or FeCl3 besides AlCl3. But
unsatisfied results were obtained, and the addition product
was obtained in very poor yield. The isomerization
prevailed in such case to give b-chloro-a-oxoalkanoates
(2) in good yields (entries 15, 16). Furthermore, we also
investigated this reaction in the presence of aluminium
chloride supported on alumina or silica gel, which is thought
to be a mild Lewis acid and harmless for environment
(Table 2). In the case of reactions in the presence of AlCl3
supported on Al2O3, the stereoselectivities changed well
Considering the generality of this reaction, we carried out
the reaction of epoxide 10 in the presence of AlCl3. As we
expected, cyclisation products 4 were furnished in good
yields of 63.5–93.2% (Table 3). In the case of 5-membered
ring, the solvent CH2Cl2 was better than (CH2Cl)2 (entries 1,
3). The stereoselectivity depends on the reaction tempera-
ture (entries 2, 3). In the case of 6-membered ring, the
solvent (CH2Cl)2 was found better (entries 4, 5). In the case
Table 3. The intra-molecular cycloaddition reaction of 2-chloro-2,3-epoxyalkanoates 10 in the presence of AlCl3
Entry
R3
n
AlCl3 (equiv.)
Solvent
Conditions
Yield
anti/syn
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
1
1
1
2
2
3
3
1
1
1
2
1
1
2
1
1
3
3
1
3
3
3
(CH2Cl)2
CH2Cl2
CH2Cl2
(CH2Cl)2
CH2Cl2
(CH2Cl)2
CH2Cl2
(CH2Cl)2
CH2Cl2
CH2Cl2
(CH2Cl)2
08C, 40 min
rt, 35 min
08C., 1 h
08C, 2 h
08C, 2 h
08C, 2 h
08C, 2 h
08C, 3 h; rt, 3 h
08C, 3 h
rt, 2 h
4a, 59.7%
4a, 38.5%b
4a, 63.5%
4b, 80.9%
4b, 62.7%
4c, 64.1%
4c, 63.0%
4d, 63.1%c
4d, 85.4%
4d, 86.7%
4e, 93.2%
79/21a
100/0
0/100
40/60
35/65
100/0
100/0
43/57a
60/40
75/25
39/61
CH3O–
CH3O–
CH3O–
CH3O–
9
10
11
r.t, 1 h
a
Stereoslectivity was determined by GC-Mass.
Yield of isomerized product was 28.6%.
Recovery was 20.6%.
b
c

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J.-R. Lin et al. / Tetrahedron 59 (2003) 1781–1790
aspect of the molecule and explain the chemical structure
reasonably. Configuration of anti-4 was also confirmed by
NOESY.
We think that the chlorine in epoxide 1 or 10 plays an
important role in these nucleophilic reactions. So, the
reaction of epoxide 5 in the presence of AlCl3 was carried
out, which epoxide 5 was obtained by Darzens reaction of
3-phenylpropionaldehyde with methyl chloroacetate. This
reaction did not give cycloaddition product 4, but a ring-
opened product of diol 6 in good yield (98%) as anticipated
(Scheme 3). To study the mechanism of this intra-molecular
cycloaddition reaction, the reaction of a-chloro-b-oxo-
alkanoate 2 obtained by the isomerization of epoxide 10 in
the presence of AlCl3 was carried out. This reaction gave
cycloaddition product 4d in 84% yield (Scheme 4).
Thus, a cnsiderable mechanism of the cycloaddition
reaction is shown in Scheme 4.
Figure 1. Geometry of molecule syn-4e in crystal.
In summary, it is found that the reaction of a-chloro-a,b-
epoxyalkanoates with aromatic compounds in the presence
of Lewis acid gives a-aryl-b-chloro-a-hydroxyalkanoates
in stead of Friedel–Crafts reaction products, and the major
product is syn isomer. The intra-molecular cycloaddition
reaction gives cyclisation product in good yield. This
nucleophilic addition reaction can be utilized in the
synthesis of donaxaridine.10 Utilizing of this cycloaddition
reaction, the total synthesis of a natural product, (2)-Galan-
thamine11 is currently under investigation.
3. Experimental
3.1. General procedure
All reactions were carried out under nitrogen atmosphere
with dry, freshly distilled solvents and under anhydrous
condition. Tetrahydrofuran (THF) was distilled from
sodium benzophenone before use. Methylene chloride
(CH2Cl2), benzene, and toluene were distilled from calcium
hydride.
Figure 2. Geometry of molecule anti-4e in crystal.
of 7-membered ring, only anti product was obtained (entries
6, 7). When phenyl ring is substituted with electron donating
group like OMe, the cycloaddition reaction became
predominant, and the yield of product 4 became higher
(entries 8–11). The structure of syn-4 was confirmed by
single-crystal X-ray analysis of syn-4e and anti-4e
(R3¼OMe, n¼2). Figures 1 and 2 illustrate the geometrical
Reagents of the highest commercial quality were purchased
and used without further purification. Reactions were
monitored by thin-layer chromatography (TLC) on
0.25 mm E. Merck silica gel plates (60F-254) using UV
light and/or 5% ethanonic phosphomolybdic acid. E. Merck
silic gel (60, particle size 0.040–0.050 mm) was used for
flash column chromatography.
Scheme 3. Study of the role of chlorine in epoxide 1.

J.-R. Lin et al. / Tetrahedron 59 (2003) 1781–1790
1785
Scheme 4. Proposed mechanism of the intra-molecular cycloaddtion reaction.
NMR spectra were recorded on Varian Gemini 200 or
JEOL 300 MHz instruments and calibrated using residual
undeuterated solvent as an internal reference. IR spectra
were recorded on a JASCO FT-IR 5000 spectrometer or
Avatar 360T2 FT-IR spectrometer (Thermo Nicolet model).
Elementary analysis was carried out on a Perkin–Elmer
2400 Series II CHNS/O Analyzer.
H, 7.78. (S,R)-(^)-3a; colorless liquid, Rf¼0.25 (hexane/
ether¼2/1); 1H NMR (200 MHz, CDCl3) d 0.91 (t, J¼
6.4 Hz, 3H), 1.29–2.10 (m, 8H), 3.76 (s, 1H),3.82 (s, 3H),
4.61 (dd, J¼1.6, 10.8 Hz, 1H), 7.36–7.66 (m, 5H); 13C
NMR (50 MHz, CDCl3) d 13.97, 22.43, 26.57, 31.06, 33.14,
53.66, 67.57, 81.34, 125.79, 128.33, 133.35, 139.39, 172.99;
IR (neat): 3512, 2959, 2928, 2854, 1737, 1458, 1247, 1135,
757 cm21. Anal. calcd for C15H21ClO3: C, 63.26; H, 7.43.
Found: C, 63.31; H, 7.78.
3.2. Preparation of starting materials
All 2-chloro-2,3-epoxyalkanoates were prepared by Darzen
condensation of aldehydes and methyl dichloroacetate.7
3.3.2. Methyl (6)-2-hydroxy-2-phenyl-3-chlorododec-
anoate (3b). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 212 mg
(62.2%) of (S,S)-(^)-3b and 50 mg (14.6%) of (S,R)-(^)-
3b. (S,S)-(^)-3b; colorless liquid, Rf¼0.40 (hexane/
3.3. General procedure for the preparation of
compounds 3
1
EtOAc¼2/1); H NMR (200 MHz, CDCl3) d 0.88 (t, J¼
To a stirring solution of aluminium chloride (400 mg,
3 mmol) in CH2Cl2 (4 mL) was added the solution of methyl
2-chloro-2,3-epoxyalkanoate 1(1 mmol) and aromatic com-
pound (1 mmol) in CH2Cl2 (2 mL) at room temperature.
The mixture was stirred for 1 h, then stopped by pouring the
ice (10 mL), the aqueous layer was extracted with EtOAc,
and the combined extracts were washed with saturated
NaHCO3 solution and brine, then dried over MgSO4.
Evaporation of the solvent gave a clean oil, which was
further purified by column chromatography as indicated
below.
6.4 Hz, 3H), 1.23–1.75 (m, 16H), 3.83 (s, 3H), 4.00 (s, 1H),
4.71 (dd, J¼1.6, 11.2 Hz, 1H), 7.33–7.73 (m, 5H); 13C
NMR (50 MHz, CDCl3) d 14.00, 22.56, 26.43, 28.56, 29.16,
29.22, 29.34, 30.46, 31.75, 53.49, 68.17, 81.23, 125.86,
128.29, 128.42, 137.72, 173.34; IR (neat): 3517, 2925,
2855, 1737, 1449, 1252, 1143, 731 cm21. Anal. calcd for
C19H29ClO3: C, 66.94; H, 8.57. Found: C, 66.98; H, 8.61.
(S,R)-(^)-3b; white solid, mp: 50–518C (from hexane),
Rf¼0.25 (hexane/EtOAc¼2/1); 1H NMR (200 MHz,
CDCl3) d 0.89 (t, J¼6.4 Hz, 3H), 1.28–2.05 (m, 16H),
3.78 (s, 1H), 3.82 (s, 3H), 4.61 (dd, J¼1.6, 10.8 Hz, 1H),
7.36–7.66 (m, 5H); 13C NMR (50 MHz, CDCl3) d 14.09,
22.65, 26.85, 28.86, 29.28, 29.36, 29.48, 31.85, 33.13,
53.64, 67.54, 81.31, 125.77, 128.17, 128.31, 139.37, 172.98;
IR (neat): 3553, 2954, 2925, 2850, 1739, 1449, 1257, 1135,
727 cm21. Anal. calcd for C19H29ClO3: C, 66.94; H, 8.57.
Found: C, 66.98; H, 8.61.
3.3.1. Methyl (6)-2-hydroxy-2-phenyl-3-chlorooctanoate
(3a). The crude product was purified by column chroma-
tography (hexane/ether¼160/1) to give 137 mg (48.2%) of
(S,S)-(^)-3a and 30 mg (10.6%) of (S,R)-(^)-3a. (S,S)-(^)-
3a; colorless liquid, Rf¼0.40 (hexane/ether¼2/1); 1H NMR
(200 MHz, CDCl3) d 0.82 (t, J¼6.8 Hz, 3H), 1.16–1.75 (m,
8H), 3.83 (s, 3H), 3.93 (s, 1H), 4.68 (dd, J¼2.2, 11.0 Hz,
1H), 7.32–7.69 (m, 5H); 13C NMR (50 MHz, CDCl3) d
13.89, 22.36, 26.22, 30.53, 30.85, 53.63, 68.26, 81.28,
125.91, 128.38, 128.51, 137.73, 173.44; IR (neat): 3514,
2958, 2932, 2864, 1742, 1450, 1257, 1075, 731 cm21. Anal.
calcd for C15H21ClO3: C, 63.26; H, 7.43. Found: C, 63.31;
3.3.3. Methyl (6)-2-hydroxy-2-(p-methylphenyl)-3-
chloro-4-methylpentanoate (3c). The crude product was
purified by column chromatography (hexane/ether¼160/1)
to give 120 mg (44.2%) of (S,S)-(^)-3c and 31 mg (11.7%)
of (S,R)-(^)-3c. (S,S)-(^)-3c; white solid, mp: 110–1118C,
Rf¼0.55 (hexane/EtOAc¼2/1); 1H NMR (200 MHz,

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J.-R. Lin et al. / Tetrahedron 59 (2003) 1781–1790
CDCl3) d 0.90 (d, J¼6.4 Hz, 3H), 0.96 (d, J¼6.4 Hz, 3H),
1.81 (m, 1H), 2.35 (s, 3H), 3.82 (s, 3H), 3.86 (s, 1H), 4.75 (d,
J¼2.0 Hz, 1H), 7.19 (d, J¼8.0 Hz, 2H); 7.57(d, J¼8.0 Hz,
2H); 13C NMR (50 MHz, CDCl3) d 16.80, 21.03, 22.53,
28.95, 53.67, 73.38, 82.10, 125.73, 129.23, 135.12, 138.15,
173.82; IR (KBr): 3504, 2960, 1740, 1512, 1437, 1257,
1154, 824, 762 cm21. Anal. calcd for C14H19ClO3: C,
62.10; H, 7.07. Found: C, 61.91; H, 7.07. (S,R)-(^)-3c;
yellow liquid, Rf¼0.50 (hexane/EtOAc¼2/1); 1H NMR
(200 MHz, CDCl3) d 1.09 (d, J¼6.4 Hz, 3H), 1.18 (d, J¼
6.4 Hz, 3H), 2.14 (m, 1H), 2.35 (s, 3H), 3.78 (s, 1H), 3.80 (s,
3H), 4.64 (d, J¼3.0 Hz, 1H), 7.19 (d, J¼8.0 Hz, 2H); 7.53
(d, J¼8.0 Hz, 2H); 13C NMR (50 MHz, CDCl3) d 18.44,
20.99, 22.33, 32.14, 53.53, 72.78, 81.60, 125.49, 128.98,
137.39, 137.93, 173.41; IR (neat): 3504, 2940, 1734, 1512,
1437, 1251, 1147, 824, 762 cm21. Anal. calcd for
C14H19ClO3: C, 62.10; H, 7.07. Found: C, 61.91; H, 7.07.
3514, 2958, 2930, 2860, 1734, 1514, 1437, 1249, 1143,
756 cm21. Anal. calcd for C18H27ClO3: C, 66.14; H, 8.33.
Found: C, 66.20; H, 8.53.
3.3.6. Methyl (6)-2-hydroxy-2-(p-methylphenyl)-3-
chlorododecanoate (3f). The crude product was purified
by column chromatography (hexane/ether¼160/1) to give
226 mg (63.8%) of (S,S)-(^)-3f and 60 mg (16.9%) of
(S,R)-(^)-3f. (S,S)-(^)-3f; colorless liquid, Rf¼0.45 (hexane/
ether¼2/1); 1H NMR (200 MHz, CDCl3) d 0.87 (t, J¼
6.4 Hz, 3H), 1.20–1.72 (m, 16H), 2.35 (s, 3H), 3.82 (s, 3H),
3.89 (s, 1H), 4.66 (dd, J¼1.8, 11.0 Hz, 1H), 7.18 (d, J¼
8.2 Hz, 2H), 7.54 (d, J¼8.2 Hz, 2H); 13C NMR (50 MHz,
CDCl3) d 14.06, 21.01, 22.62, 26.52, 28.66, 29.23, 29.31,
29.42, 30.50, 31.81, 53.54, 68.25, 81.22, 125.81, 129.22,
134.81, 138.19, 173.59; IR (neat): 3514, 2928, 1742, 1512,
1458, 1255, 1147, 756 cm21. Anal. calcd for C20H31ClO3:
C, 67.68; H, 8.80. Found: C, 67.66; H, 9.11. (S,R)-(^)-3f;
yellow liquid, Rf¼0.30 (hexane/ether¼2/1); 1H NMR
(200 MHz, CDCl3) d 0.89 (t, J¼6.4 Hz, 3H), 1.28–2.03
(m, 16H), 2.35 (s, 3H), 3.74 (s, 1H), 3.81 (s, 3H), 4.60 (dd,
J¼1.6, 10.8 Hz, 1H), 7.19 (d, J¼8.4 Hz, 2H), 7.52 (d,
J¼8.4 Hz, 2H); 13C NMR (50 MHz, CDCl3) d 14.08, 21.04,
22.65, 26.87, 28.86, 29.28, 29.36, 29.47, 31.85, 33.11,
53.57, 67.60, 81.22, 125.65, 129.05, 136.47, 138.09, 173.09;
IR (neat): 3514, 2928, 1734, 1514, 1458, 1251, 1147,
756 cm21. Anal. calcd for C20H31ClO3: C, 67.68; H, 8.80.
Found: C, 67.66; H, 9.11.
3.3.4. Methyl (6)-2-hydroxy-2-(p-methylphenyl)-3-
chlorooctanoate (3d). The crude product was purified by
column chromatography (hexane/ether¼160/1) to give
150 mg (50.4%) of (S,S)-(^)-3d and 45 mg (15.0%) of
(S,R)-(^)-3d. (S,S)-(^)-3d; yellow liquid, Rf¼0.45 (hexane/
ether¼2/1); 1H NMR (200 MHz, CDCl3) d 0.82 (t, J¼
6.8 Hz, 3H), 1.17–1.75 (m, 8H), 2.35 (s, 3H), 3.82 (s, 3H),
3.91 (s, 1H), 4.67 (dd, J¼2.0, 11.0 Hz, 1H), 7.18 (d, J¼
8.4 Hz, 2H), 7.54 (d, J¼8.4 Hz, 2H); 13C NMR (50 MHz,
CDCl3) d 13.80, 21.04, 22.39, 26.24, 30.51, 30.87, 53.54,
68.26, 81.21, 125.79, 129.20, 134.79, 138.18, 173.57; IR
(neat): 3514, 2958, 2932, 2864, 1742, 1512, 1437, 1257,
1147, 756 cm21. Anal. calcd for C16H23ClO3: C, 64.31; H,
7.76. Found: C, 64.34; H, 8.10. (S,R)-(^)-3d; yellow liquid,
3.3.7. Methyl (6)-2-hydroxy-2-(p-ethylphenyl)-3-chloro-
hexanoate (3g). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 132 mg
(46.3%) of (S,S)-(^)-3g and 39 mg (13.8%) of (S,R)-(^)-
3g. (S,S)-(^)-3g; yellow liquid, Rf¼0.30 (hexane/ether¼
2/1); 1H NMR (200 MHz, CDCl3) d 0.82 (t, J¼7.2 Hz, 3H),
1.25 (t, J¼7.6 Hz, 3H), 1.21–1.72 (m, 4H), 2.66 (q, J¼
7.6 Hz, 2H), 3.83 (s, 3H), 3.93 (s, 1H), 4.71 (dd, J¼2.0,
11.2 Hz, 1H), 7.22 (d, J¼8.4 Hz, 2H); 7.58 (d, J¼8.4 Hz,
2H); 13C NMR (50 MHz, CDCl3) d 13.18, 15.23, 19.71,
28.35, 35.23, 53.48, 67.96, 81.22, 125.84, 127.97, 134.99,
144.41, 173.56; IR (neat): 3514, 2966, 2936, 2876,1742,
1512, 1458, 1249, 1149, 754 cm21. (S,R)-(^)-3g; orange
1
Rf¼0.30 (hexane/ether¼2/1); H NMR (200 MHz, CDCl3)
d 0.91 (t, J¼6.8 Hz, 3H), 1.27–2.04 (m, 8H), 2.36 (s, 3H),
3.75 (s, 1H), 3.81 (s, 1H), 4.61 (dd, J¼2.0, 11.0 Hz, 1H),
7.20 (d, J¼8.2 Hz, 2H), 7.52 (d, J¼8.2 Hz, 2H); 13C NMR
(50 MHz, CDCl3) d 13.94, 21.02, 22.39, 26.55, 31.02,
33.08, 53.56, 67.59, 81.20, 125.64, 129.04, 136.45, 138.08,
173.07; IR (neat): 3514, 2958, 2930, 2864, 1734, 1512,
1437, 1253, 1147, 756 cm21. Anal. calcd for C16H23ClO3:
C, 64.31; H, 7.76. Found: C, 64.34; H, 8.10.
1
3.3.5. Methyl (6)-2-hydroxy-2-(p-methylphenyl)-3-
chlorodecanoate (3e). The crude product was purified by
column chromatography (hexane/ether¼160/1) to give
182 mg (55.7%) of (S,S)-(^)-3e and 51 mg (15.7%) of
(S,R)-(^)-3e. (S,S)-(^)-3e; colorless liquid, Rf¼0.28
liquid, Rf¼0.20 (hexane/ether¼2/1); H NMR (200 MHz,
CDCl3) d 0.96 (t, J¼7.0 Hz, 3H), 1.24 (t, J¼7.6 Hz, 3H),
1.45–2.12 (m, 4H), 2.66 (q, J¼7.6 Hz, 2H), 3.73 (s, 1H),
3.81 (s, 3H), 4.66 (dd, J¼2.0, 11.2 Hz, 1H), 7.21 (d, J¼
8.2 Hz, 2H); 7.54 (d, J¼8.2 Hz, 2H); 13C NMR (50 MHz,
CDCl3) d 13.38, 15.20, 20.10, 28.37, 35.22, 53.54, 67.33,
81.26, 125.71, 127.82, 136.63, 144.32, 173.07; IR (neat):
3506, 2966, 2936, 2876, 1734, 1512, 1458, 1249, 1145,
1
(hexane/ether¼2/1); H NMR (200 MHz, CDCl3) d 0.84
(t, J¼6.4 Hz, 3H), 1.18–1.60 (m, 12H), 2.35 (s, 3H), 3.82 (s,
3H), 3.89 (s, 1H), 4.66 (dd, J¼1.8, 11.0 Hz, 1H), 7.18 (d,
J¼8.2 Hz, 2H), 7.54 (d, J¼8.2 Hz, 2H); 13C NMR (50 MHz,
CDCl3) d 14.04, 21.02, 22.57, 26.54, 28.64, 28.99, 30.51,
31.68, 53.56, 68.25, 81.22, 125.82, 129.22, 134.80, 138.19,
173.59; IR (neat): 3514, 2958, 2930, 2860, 1742, 1512,
1437, 1251, 1147, 756 cm21. Anal. calcd for C18H27ClO3:
C, 66.14; H, 8.33. Found: C, 66.20; H, 8.53. (S,R)-(^)-3e;
colorless liquid, Rf¼0.16 (hexane/ether¼2/1); 1H NMR
(200 MHz, CDCl3) d 0.89 (t, J¼6.4 Hz, 3H), 1.28–2.03 (m,
12H), 2.35 (s, 3H), 3.74 (s, 1H), 3.81 (s, 3H), 4.61 (dd, J¼
1.6, 10.8 Hz, 1H), 7.20 (d, J¼8.2 Hz, 2H), 7.52 (d, J¼
8.2 Hz, 2H); 13C NMR (50 MHz, CDCl3) d 14.06, 21.04,
22.61, 26.87, 28.81, 29.01, 31.72, 33.10, 53.56, 67.60,
81.23, 125.65, 129.05, 136.47, 138.10, 173.09; IR (neat):
752 cm21
.
3.3.8. Methyl (6)-2-hydroxy-2-(p-ethylphenyl)-3-chloro-
octanoate (3h). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 161 mg
(51.5%) of (S,S)-(^)-3h and 38 mg (12.1%) of (S,R)-(^)-
3h. (S,S)-(^)-3h; yellow liquid, Rf¼0.30 (hexane/ether¼
2/1); 1H NMR (200 MHz, CDCl3) d 0.83 (t, J¼6.4 Hz, 3H),
1.24 (t, J¼7.6 Hz, 3H), 1.18–1.76 (m, 8H), 2.66 (q, J¼
7.6 Hz, 2H), 3.82 (s, 3H), 3.91 (s, 1H), 4.68 (dd, J¼1.8,
10.8 Hz, 1H), 7.21 (d, J¼8.4 Hz, 2H), 7.57 (d, J¼8.4 Hz,
2H); 13C NMR (50 MHz, CDCl3) d 13.89, 15.28, 22.38,
26.58, 28.37, 30.51, 30.87, 53.53, 68.30, 81.23, 125.85,

J.-R. Lin et al. / Tetrahedron 59 (2003) 1781–1790
1787
127.98, 134.97, 144.34, 173.58; IR (neat): 3504, 2959,
2931, 2872, 1740, 1509, 1457, 1250, 1145, 836 cm21. Anal.
calcd for C17H25ClO3: C, 65.27; H, 8.05. Found: C, 65.51;
H, 8.22. (S,R)-(^)-3h; yellow liquid, Rf¼0.23 (hexane/
ether¼2/1); 1H NMR (200 MHz, CDCl3) d 0.90 (t, J¼
6.4 Hz, 3H), 1.24 (t, J¼7.6 Hz, 3H), 1.20–2.10 (m, 8H),
2.66 (q, J¼7.6 Hz, 2H), 3.73 (s, 1H), 3.81 (s, 3H), 4.61 (dd,
J¼1.6, 10.8 Hz, 1H), 7.21 (d, J¼8.4 Hz, 2H), 7.53 (d,
J¼8.4 Hz, 2H); 13C NMR (50 MHz, CDCl3) d 13.97, 15.22,
22.42, 26.57, 28.37, 31.05, 33.11, 53.58, 67.65, 81.25,
125.70, 127.83, 136.63, 144.32, 173.10; IR (neat): 3512,
2962, 2934, 2864, 1734, 1514, 1458, 1253, 1143, 835,
665 cm21. Anal. calcd for C17H25ClO3: C, 65.27; H, 8.05.
Found: C, 65.51; H, 8.22.
81.25, 125.71, 127.83, 136.63, 144.32, 173.09; IR (neat):
3514, 2962, 2930, 2864, 1734, 1512, 1462, 1255, 1147,
746 cm21. Anal. calcd for C21H33ClO3: C, 68.37; H, 9.02.
Found: C, 68.28; H, 9.30.
3.3.11. Methyl (6)-2-hydroxy-2-(p-butylphenyl)-3-chloro-
hexanoate (3k). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 158 mg
(50.5%) of (S,S)-(^)-3k and 37 mg (11.8%) of (S,R)-(^)-
3k. (S,S)-(^)-3k; yellow liquid, Rf¼0.40 (hexane/ether¼
2/1); 1H NMR (200 MHz, CDCl3) d 0.82 (t, J¼7.2 Hz, 3H),
0.94 (t, J¼6.4 Hz, 3H), 1.27–1.71 (m, 8H), 2.62 (t, J¼
7.8 Hz, 2H), 3.83 (s, 3H), 3.92 (s, 1H), 4.70 (dd, J¼1.8,
10.8 Hz, 1H), 7.19 (d, J¼8.4 Hz, 2H); 7.57 (d, J¼8.4 Hz,
2H); 13C NMR (50 MHz, CDCl3) d 13.18, 13.87, 19.71,
22.34, 32.55, 33.37, 35.16, 53.46, 67.91, 81.22, 125.76,
128.50, 134.95, 143.13, 173.56; IR (neat): 3510, 2955,
2857, 1737, 1510, 1437, 1246, 1144, 760 cm21. Anal. calcd
for C17H25ClO3: C, 65.27; H, 8.05. Found: C, 64.86; H,
7.98. (S,R)-(^)-3k; yellow liquid, Rf¼0.15 (hexane/ether¼
2/1); 1H NMR (200 MHz, CDCl3) d 0.93 (t, J¼6.6 Hz, 3H),
0.96 (t, J¼6.4 Hz, 3H), 1.24–1.65 (m, 8H), 2.61 (t, J¼
7.6 Hz, 2H), 3.72 (s, 1H), 3.82 (s, 3H), 4.61 (dd, J¼1.8,
10.8 Hz, 1H), 7.19 (d, J¼8.2 Hz, 2H); 7.52 (d, J¼8.2 Hz,
2H); 13C NMR (50 MHz, CDCl3) d 13.38, 13.91, 20.12,
22.39, 32.45, 33.36, 35.21, 53.53, 67.38, 81.29, 125.65,
128.36, 136.60, 143.06, 178.08; IR (neat): 3514, 2962,
2874, 1736, 1512, 1460, 1249, 1145, 754 cm21. Anal. calcd
for C17H25ClO3: C, 65.27; H, 8.05. Found: C, 64.86; H,
7.98.
3.3.9. Methyl (6)-2-hydroxy-2-(p-ethylphenyl)-3-chloro-
decanoate (3i). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 195 mg
(57.1%) of (S,S)-(^)-3i and 58 mg (17.1%) of (S,R)-(^)-
3i. (S,S)-(^)-3i; colorless liquid, Rf¼0.30 (hexane/ether¼
2/1); 1H NMR (200 MHz, CDCl3) d 0.85 (t, J¼6.4 Hz, 3H),
1.24 (t, J¼7.6 Hz, 3H), 1.07–1.75 (m, 12H), 2.66 (q, J¼
7.6 Hz, 2H), 3.82 (s, 3H), 3.93 (s, 1H), 4.69 (dd, J¼1.6,
10.8 Hz, 1H), 7.21 (d, J¼8.4 Hz, 2H), 7.58 (d, J¼8.4 Hz,
2H); 13C NMR (50 MHz, CDCl3) d 14.01, 15.27, 22.56,
26.50, 28.36, 28.60, 28.95, 30.48, 31.65, 53.50, 68.25,
81.22, 125.84, 127.97, 134.98, 144.40, 173.56; IR (neat):
3513, 2955, 2928, 2857, 1733, 1511, 1457, 1245, 1140,
758 cm21. Anal. calcd for C19H29ClO3: C, 66.94; H, 8.57.
Found: C, 66.55; H, 8.86. (S,R)-(^)-3i; yellow liquid, Rf¼
1
0.13 (hexane/ether¼2/1); H NMR (200 MHz, CDCl3) d
0.89 (t, J¼6.4 Hz, 3H), 1.24 (t, J¼7.6 Hz, 3H), 1.20–2.03
(m, 12H), 2.66 (q, J¼7.6 Hz, 2H), 3.74 (s, 1H), 3.81 (s, 3H),
4.61 (dd, J¼1.6, 10.8 Hz, 1H), 7.21 (d, J¼8.4 Hz, 2H), 7.54
(d, J¼8.4 Hz, 2H); 13C NMR (50 MHz, CDCl3) d 14.07,
15.22, 22.62, 26.87, 28.36, 28.81, 29.02, 31.72, 33.10,
53.57, 67.63, 81.24, 125.69, 127.82, 136.62, 144.30, 173.09;
IR (neat): 3514, 2960, 2930, 2860, 1734, 1514, 1458, 1249,
1143, 835, 665 cm21. Anal. calcd for C19H29ClO3: C,
66.94; H, 8.57. Found: C, 66.55; H, 8.86.
3.3.12. Methyl (6)-2-hydroxy-2-(p-butylphenyl)-3-chloro-
octanoate (3l). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 183 mg
(53.7%) of (S,S)-(^)-3l and 49 mg (14.3%) of (S,R)-(^)-
3l. (S,S)-(^)-3l; colorless liquid, Rf¼0.40 (hexane/ether¼
2/1); 1H NMR (200 MHz, CDCl3) d 0.83 (t, J¼6.8 Hz, 3H),
0.93 (t, J¼7.2 Hz, 3H), 1.17–1.76 (m, 12H), 2.61 (t, J¼
7.6 Hz, 2H), 3.82 (s, 3H), 3.91 (s, 1H), 4.67 (dd, J¼1.8,
11.0 Hz, 1H), 7.18 (d, J¼8.2 Hz, 2H), 7.56 (d, J¼8.2 Hz,
2H); 13C NMR (50 MHz, CDCl3) d 13.68, 22.34, 26.22,
29.67, 30.50, 30.84, 33.39, 35.16, 53.49, 68.30, 81.24,
125.76, 128.51, 134.94, 143.15, 173.58; IR (neat): 3513,
3.3.10. Methyl (6)-2-hydroxy-2-(p-ethylphenyl)-3-chloro-
dodecanoate (3j). The crude product was purified by
column chromatography (hexane/ether¼160/1) to give
237 mg (64.2%) of (S,S)-(^)-3j and 63 mg (17.1%) of
(S,S)-(^)-3j. (S,S)-(^)-3j; colorless liquid, Rf¼0.45
2955, 2929, 2859, 1737, 1510, 1437, 1250, 1145, 761 cm21
.
Anal. calcd for C19H29ClO3: C, 66.94; H, 8.57. Found: C,
66.92; H, 8.66. (S,R)-(^)-3l; colorless liquid, Rf¼0.28
(hexane/ether¼2/1); 1H NMR (200 MHz, CDCl3) d 0.91 (t,
J¼6.8 Hz, 3H), 0.93 (t, J¼7.2 Hz, 3H), 1.26–2.17 (m,
12H), 2.61 (t, J¼7.6 Hz, 2H), 3.74 (s, 1H), 3.81 (s, 3H), 4.60
(dd, J¼1.2, 11.0 Hz, 1H), 7.19 (d, J¼8.4 Hz, 2H), 7.52 (d,
J¼8.4 Hz, 2H); 13C NMR (50 MHz, CDCl3) d 13.92, 13.95,
22.40, 26.57, 31.03, 33.10, 33.37, 35.20, 53.55, 67.67,
81.25, 125.62, 128.35, 136.56, 143.05, 173.09; IR (neat):
3506, 2960, 2932, 2864, 1734, 1512, 1458, 1251, 1147,
756 cm21. Anal. calcd for C19H29ClO3: C, 66.94; H, 8.57.
Found: C, 66.92; H, 8.66.
1
(hexane/ether¼2/1); H NMR (200 MHz, CDCl3) d 0.87
(t, J¼6.4 Hz, 3H), 1.24 (t, J¼7.6 Hz, 3H), 1.21–1.78 (m,
16H), 2.66 (q, J¼7.6 Hz, 2H), 3.82 (s, 3H), 3.92 (s, 1H),
4.68 (dd, J¼1.8, 11.2 Hz, 1H), 7.21 (d, J¼8.0 Hz, 2H), 7.57
(d, J¼8.0 Hz, 2H); 13C NMR (50 MHz, CDCl3) d 14.06,
15.28, 22.62, 26.52, 28.37, 28.66, 29.23, 29.31, 29.42,
30.50, 31.81, 53.52, 68.27, 81.24, 125.85, 127.98, 134.99,
144.42, 173.58; IR (neat): 3503, 2926, 2855, 1735, 1509,
1437, 1251, 1144, 837 cm21. Anal. calcd for C21H33ClO3:
C, 68.37; H, 9.02. Found: C, 68.28; H, 9.30. (S,S)-(^)-3j;
yellow liquid, Rf¼0.30 (hexane/ether¼2/1); 1H NMR
(200 MHz, CDCl3) d 0.89 (t, J¼6.4 Hz, 3H), 1.24 (t, J¼
7.6 Hz, 3H), 1.20–2.05 (m, 16H), 2.66 (q, J¼7.6 Hz, 2H),
3.73 (s, 1H), 3.81 (s, 3H), 4.60 (dd, J¼1.6, 10.8 Hz, 1H),
7.21 (d, J¼8.0 Hz, 2H), 7.54 (d, J¼8.0 Hz, 2H); 13C NMR
(50 MHz, CDCl3) d 14.09, 15.22, 22.66, 26.88, 28.37,
28.87, 29.29, 29.37, 29.49, 31.86, 33.12, 53.57, 67.65,
3.3.13. Methyl (6)-2-hydroxy-2-(p-butylphenyl)-3-chloro-
decanoate (3m). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 220 mg
(59.5%) of (S,S)-(^)-3m and 61 mg (16.8%) of (S,R)-(^)-
3m. (S,S)-(^)-3m; yellow liquid, Rf¼0.45 (hexane/ether¼
2/1); 1H NMR (200 MHz, CDCl3) d 0.88 (t, J¼6.6 Hz, 3H),

1788
J.-R. Lin et al. / Tetrahedron 59 (2003) 1781–1790
0.94 (t, J¼7.2 Hz, 3H), 1.22–1.72 (m, 16H), 2.61 (t, J¼
7.6 Hz, 2H), 3.83 (s, 3H), 3.91 (s, 1H), 4.68 (dd, J¼1.6,
10.8 Hz, 1H), 7.19 (d, J¼8.0 Hz, 2H), 7.57 (d, J¼8.0 Hz,
2H); 13C NMR (50 MHz, CDCl3) d 13.93, 14.08, 22.40,
22.63, 26.89, 28.82, 29.03, 31.74, 33.13, 33.38, 35.22,
53.57, 67.69, 81.28, 125.63, 128.37, 136.58, 143.07, 173.10;
IR (neat): 3510, 2955, 2928, 2857, 1737, 1510, 1437, 1246,
1144, 760 cm21. Anal. calcd for C21H33ClO3: C, 68.37; H,
9.02. Found: C, 68.40; H, 9.12. (S,R)-(^)-3m; yellow
1H), 7.45–8.16 (m, 7H); 13C NMR (50 MHz, CDCl3) d
13.23, 19.94, 31.09, 53.73, 67.35, 81.50, 123.32, 125.77,
126.34, 127.47, 128.18, 128.47, 132.92, 133.01, 136.68,
172.97; IR (neat): 3506, 2962, 1734, 1603, 1510, 1437,
1243, 1137, 756 cm21
.
3.3.16. Methyl (S,S)-(6)-2-hydroxy-2-naphtyl-3-chloro-
octanoate (3p). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 140 mg
(41.8%) of (S,S)-(^)-3p and 49 mg (14.6%) of (S,R)-(^)-
3p. (S,S)-(^)-3p; yellow liquid, Rf¼0.35 (hexane/ether¼
2/1); 1H NMR (200 MHz, CDCl3) d 0.82 (t, J¼6.6 Hz, 3H),
1.16–1.82 (m, 8H), 3.87 (s, 3H), 4.15 (s, 1H), 4.88 (dd,
J¼1.8, 11.2 Hz, 1H), 7.51–8.26 (m, 7H); 13C NMR
(50 MHz, CDCl3) d 13.83, 22.32, 26.21, 30.60, 30.81,
53.62, 68.14, 81.48, 125.65, 126.36, 126.58, 127.43, 128.24,
128.45, 132.95, 132.99, 135.05, 173.35; IR (neat): 3508,
2958, 2862, 1742, 1510, 1437, 1263, 1139, 758 cm21. (S,R)-
(^)-3p; yellow liquid, Rf¼0.20 (hexane/ether¼2/1); 1H
NMR (200 MHz, CDCl3) d 0.93 (t, J¼6.4 Hz, 3H), 1.30–
2.16 (m, 8H), 3.83 (s, 3H), 3.92 (s, 1H), 4.78 (dd, J¼1.6,
10.8 Hz, 1H), 7.48–8.17 (m, 7H); 13C NMR (50 MHz,
CDCl3) d 13.97, 22.43, 26.57, 31.05, 33.15, 53.71, 67.31,
81.50, 123.28, 125.42, 126.28, 126.48, 127.47, 128.07,
128.48, 132.92, 132.98, 172.94; IR (neat): 3512, 2954,
1
liquid, Rf¼0.30 (hexane/ether¼2/1); H NMR (200 MHz,
CDCl3) d 0.89 (t, J¼6.6 Hz, 3H), 0.92 (t, J¼7.2 Hz, 3H),
1.28–2.17 (m, 16H), 2.61 (t, J¼7.6 Hz, 2H), 3.72 (s, 1H),
3.81 (s, 3H), 4.59 (dd, J¼1.6, 10.8 Hz, 1H), 7.19 (d, J¼
8.4 Hz, 2H), 7.52 (d, J¼8.4 Hz, 2H); 13C NMR (50 MHz,
CDCl3) d 13.93, 14.08, 22.40, 22.63, 26.89, 28.82, 29.03,
31.74, 33.13, 33.38, 35.22, 53.57, 67.69, 81.28, 125.63,
128.37, 136.58, 143.07, 173.10; IR (neat): 3512, 2955,
2928, 2864, 1734, 1510, 1456, 1251, 1143, 757 cm21. Anal.
calcd for C21H33ClO3: C, 68.37; H, 9.02. Found: C, 68.40;
H, 9.12.
3.3.14. Methyl (6)-2-hydroxy-2-(p-butylphenyl)-3-chloro-
dodecanoate (3n). The crude product was purified by
column chromatography (hexane/ether¼160/1) to give
267 mg (67.3%) of (S,S)-(^)-3n and 80 mg (20.1%) of
(S,R)-(^)-3n. (S,S)-(^)-3n; yellow liquid, Rf¼0.45 (hexane/
ether¼2/1); 1H NMR (200 MHz, CDCl3) d 0.89 (t, J¼
7.2 Hz, 3H), 0.92 (t, J¼7.2 Hz, 3H), 1.27–2.10 (m, 20H),
2.61 (t, J¼7.8 Hz, 2H), 3.72 (s, 1H), 3.81 (s, 3H), 4.59 (dd,
J¼1.6, 11.0 Hz, 1H), 7.19 (d, J¼8.4 Hz, 2H), 7.52 (d,
J¼8.4 Hz, 2H); 13C NMR (50 MHz, CDCl3) d 13.93, 14.09,
22.40, 22.66, 26.89, 28.87, 29.29, 29.37, 29.49, 31.86,
33.14, 35.22, 53.55, 67.69, 81.28, 125.64, 128.36, 136.59,
143.07, 173.09; IR (neat): 3513, 2957, 2926, 2858, 1736,
1508, 1457, 1249, 1144, 837 cm21. Anal. calcd for
C23H37ClO3: C, 69.59; H, 9.39. Found: C, 69.98; H, 9.53.
(S,R)-(^)-3n; yellow liquid, Rf¼0.30 (hexane/ether¼2/1);
1H NMR (200 MHz, CDCl3) d 0.89 (t, J¼7.2 Hz, 3H), 0.92
(t, J¼7.2 Hz, 3H), 1.27–2.10 (m, 20H), 2.61 (t, J¼7.8 Hz,
2H), 3.72 (s, 1H), 3.81 (s, 3H), 4.59 (dd, J¼1.6, 11.0 Hz,
1H), 7.19 (d, J¼8.4 Hz, 2H), 7.52 (d, J¼8.4 Hz, 2H); 13C
NMR (50 MHz, CDCl3) d 13.93, 14.09, 22.40, 22.66, 26.89,
28.87, 29.29, 29.37, 29.49, 31.86, 33.14, 35.22, 53.55,
67.69, 81.28, 125.64, 128.36, 136.59, 143.07, 173.09; IR
(neat): 3514, 2958, 2928, 2860, 1736, 1512, 1460, 1249,
1141, 758 cm21. Anal. calcd for C23H37ClO3: C, 69.59; H,
9.39. Found: C, 69.98; H, 9.53.
2859, 1726, 1431, 1245, 1131, 758 cm21
.
3.3.17. Methyl (S,S)-(6)-2-hydroxy-2-naphtyl-3-chloro-
decanoate (3q). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 139 mg
(54.7%) of (S,S)-(^)-3q and 47 mg (18.5%) of (S,R)-(^)-
3q. (S,S)-(^)-3q; yellow liquid, Rf¼0.35 (hexane/ether¼
2/1); 1H NMR (200 MHz, CDCl3) d 0.84 (t, J¼6.4 Hz, 3H),
1.17–1.85 (m, 12H), 3.87 (s, 3H), 4.14 (s, 1H), 4.87 (dd,
J¼1.8, 11.2 Hz, 1H), 7.51–8.26 (m, 7H); 13C NMR
(50 MHz, CDCl3) d 13.97, 22.49, 26.51, 28.59, 28.92,
30.62, 31.61, 53.63, 68.13, 81.49, 123.26, 125.66, 126.37,
126.59, 127.43, 128.24, 128.45, 132.97, 132.99, 135.06,
173.37; IR (neat): 3512, 2956,, 2860, 1742, 1601, 1510,
1437, 1243, 1145, 731 cm21. Anal. calcd for C21H27ClO3:
C, 69.50; H, 7.50. Found: C, 69.68; H, 7.88. (S,R)-(^)-3q;
yellow liquid, Rf¼0.20 (hexane/ether¼2/1); 1H NMR
(200 MHz, CDCl3) d 0.91 (t, J¼6.4 Hz, 3H), 1.30–2.11
(m, 12H), 3.83 (s, 3H), 3.92 (s, 1H), 4.77 (dd, J¼1.6,
11.0 Hz, 1H), 7.48–8.17 (m, 7H); 13C NMR (50 MHz,
CDCl3) d 14.06, 22.62, 26.89, 28.84, 29.03, 31.72, 33.17,
53.69, 67.32, 81.51, 123.29, 125.42, 126.28, 126.48, 127.47,
128.07, 128.48, 132.93, 132.99, 136.70, 172.94; IR (neat):
3501, 2957, 2927, 2855, 1727, 1508, 1458, 1262, 1135,
757 cm21. Anal. calcd for C21H27ClO3: C, 69.50; H, 7.50.
Found: C, 69.68; H, 7.88.
3.3.15. Methyl (S,S)-(6)-2-hydroxy-2-naphtyl-3-chloro-
hexanoate (3o). The crude product was purified by column
chromatography (hexane/ether¼160/1) to give 145 mg
(47.3%) of (S,S)-(^)-3o and 15 mg (4.9%) of (S,R)-(^)-
3o. (S,S)-(^)-3o; light green liquid, Rf¼0.30 (hexane/
ether¼2/1); 1H NMR (200 MHz, CDCl3) d 0.79 (t, J¼
7.2 Hz, 3H), 1.27–1.78 (m, 4H), 3.86 (s, 3H), 4.07 (s, 1H),
4.86 (dd, J¼2.0, 11.0 Hz, 1H), 7.48–8.23 (m, 7H); 13C
NMR (50 MHz, CDCl3) d 13.19, 19.74, 32.69, 53.66, 67.85,
81.51, 123.29, 125.69, 126.41, 127.47, 128.28, 128.50,
133.01, 133.05, 133.08, 173.40; IR (neat): 3506, 2962,
2876, 1738, 1510, 1437, 1241, 1139, 758 cm21. (S,R)-(^)-
3.3.18. Methyl (S,S)-(6)-2-hydroxy-2-naphtyl-3-chloro-
dodecanoate (3r). The crude product was purified by
column chromatography (hexane/ether¼160/1) to give
256 mg (77.4%) of (S,S)-(^)-3r and 16 mg (4.8%) of
(S,R)-(^)-3r. (S,S)-(^)-3r; yellow liquid, Rf¼0.30 (hexane/
ether¼2/1); 1H NMR (200 MHz, CDCl3) d 0.87 (t, J¼
6.4 Hz, 3H), 1.18–1.85 (m, 16H), 3.87 (s, 3H), 4.12 (s, 1H),
4.86 (dd, J¼1.8, 11.0 Hz, 1H), 7.50–8.25 (m, 7H); 13C
NMR (50 MHz, CDCl3) d 14.05, 22.59, 26.52, 28.64, 29.17,
29.27, 29.38, 30.63, 31.77, 53.65, 68.13, 81.50, 123.27,
125.68, 126.38, 126.61, 127.45, 128.26, 128.47, 132.98,
1
3o; yellow liquid, Rf¼0.15 (hexane/ether¼2/1); H NMR
(200 MHz, CDCl3) d 0.98 (t, J¼7.2 Hz, 3H), 1.52–2.17 (m,
4H), 3.83 (s, 3H), 3.88 (s, 1H), 4.77 (dd, J¼2.0, 11.0 Hz,

J.-R. Lin et al. / Tetrahedron 59 (2003) 1781–1790
1789
1
133.01, 135.05, 173.38; IR (neat): 3512, 2928, 2858, 1742,
1510, 1437, 1243, 1139, 758 cm21. Anal. calcd for
C23H31ClO3: C, 70.66; H, 7.99. Found: C, 70.96; H, 8.02.
(S,R)-(^)-3r; yellow liquid, Rf¼0.15 (hexane/ether¼2/1);
1H NMR (200 MHz, CDCl3) d 0.91 (t, J¼6.4 Hz, 3H),
1.30–2.11 (m, 16H), 3.83 (s, 3H), 3.93 (s, 1H), 4.76 (dd,
J¼1.6, 10.8 Hz, 1H), 7.48–8.17 (m, 7H); 13C NMR
(50 MHz, CDCl3) d 14.09, 22.65, 26.89, 28.89, 29.28,
29.38, 29.48, 31.85, 33.18, 53.70, 67.32, 81.51, 123.29,
125.43, 126.28, 126.48, 127.47, 128.07, 128.48, 132.93,
132.99, 136.71, 172.94; IR (neat): 3512, 2954, 2859, 1727,
1432, 1245, 1132, 758 cm21. Anal. calcd for C23H31ClO3:
C, 70.66; H, 7.99. Found: C, 70.96; H, 8.02.
64–658C (from Et2O), Rf¼0.45 (hexane/EtOAc¼2/1); H
NMR (300 MHz, CDCl3) d 2.20–2.26 (m, 1H), 2.41–2.49
(m, 1H), 2.99–3.04 (m, 2H), 3.84 (s, 3H), 3.88 (s, 1H), 4.66
(dd, J¼3.6, 12.6 Hz, 1H), 7.05–7.30 (m, 4H); 13C NMR
(75 MHz, CDCl3) d 27.84, 29.41, 53.45, 63.14, 96.81,
126.88, 127.87, 128.92, 129.11, 134.87, 174.21; IR (neat):
3501, 2953, 1735, 1451, 1271, 1175, 778 cm21. Anal. calcd
for C12H13ClO3: C, 59.88; H, 5.44. Found: C, 60.21; H,
5.40.
3.4.3. 6-Chloro-5-hydroxy-6,7,8,9-tetrahydro-5H-benzo-
cycloheptene-1-carboxylic acid methyl ester (4c). The
crude product was purified by column chromatography
(hexane/ether¼100/1) to give 82 mg (64.1%) of (1S,2S)-
(^)-4c. (1S,2S)-(^)-4c; white solid, mp: 95–968C (from
Et2O), Rf¼0.45 (hexane/EtOAc¼2/1); 1H NMR (300 MHz,
CDCl3) d 1.61–1.73 (m, 1H), 1.91–2.04 (m, 1H), 2.30–
2.39 (m, 1H), 2.49–2.62 (m, 1H), 2.72 (dd, J¼8.4, 14.4 Hz,
1H), 3.19 (dd, J¼11.4, 13.2 Hz, 1H), 3.85 (s, 1H), 3.92 (s,
3H), 4.62 (dd, J¼4.2, 11.4 Hz, 1H), 7.06–7.21(m, 4H); 13C
NMR (75 MHz, CDCl3) d 26.63, 34.93, 36.14, 53.08, 65.26,
84.30, 126.19, 127.98, 128.79, 131.13, 136.88, 142.89,
173.83; IR (neat): 3510, 2953, 1736, 1449, 1266, 1122, 749
cm. Anal. calcd for C13H15ClO3: C, 61.30; H, 5.94. Found:
C, 60.98; H, 5.98.
3.4. General procedure for the preparation of
compounds 4
To a stirring solution of a-chloroglycidate 10 (0.5 mmol) in
CH2Cl2 (5 mL) was added aluminium chloride (133 mg,
1 mmol) at 08C. The mixture was stirred for 1 h at the same
temperature, then stopped by pouring water (10 mL), the
aqueous layer was extracted with EtOAc, and the combined
extracts were washed with saturated NaHCO3 solution and
brine, then dried over MgSO4. Evaporation of the solvent
gave a clean oil, which was further purified by column
chromatography as indicated below.
3.4.4. 2-Chloro-1-hydroxy-6-methoxy-indan-1-carb-
oxylic acid methyl ester (4d). The crude product was
purified by column chromatography (hexane/ether¼100/1)
to give 100 mg (66.2%) of (1S,2R)-(^)-4d and 31 mg
(20.5%) of (1S,2S)-(^)-4d. (1S,2R)-(^)-4d; white solid,
mp: 77–788C (from Et2O), Rf¼0.40 (hexane/EtOAc¼2/1);
1H NMR (300 MHz, CDCl3) d 3.19 (dd, J¼9.6, 15.0 Hz,
1H), 3.30 (dd, J¼8.1, 15.0 Hz, 1H), 3.69 (s, 3H), 3.71 (s,
3H), 4.38 (s, 1H), 4.43 (dd, J¼8.1, 9.6 Hz, 1H), 6.72 (d, J¼
2.7 Hz, 1H), 6.81 (dd, J¼2.7, 8.4 Hz, 1H), 7.06 (d, J¼
8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 38.86, 53.42,
55.43, 65.78, 86.88, 107.70, 116.61, 125.50, 131.83, 141.81,
159.53, 172.83; IR (neat): 3462, 2970, 1725, 1612, 1491,
1235, 1173, 816 cm21. Anal. calcd for C12H13ClO4: C,
56.15; H, 5.10. Found: C, 56.36; H, 5.34. (1S,2S)-(^)-4d;
white solid, mp: 69–708C (from Et2O), Rf¼0.30 (hexane/
EtOAc¼2/1); 1H NMR (300 MHz, CDCl3) d 3.22 (dd,
J¼7.8, 15.0 Hz, 1H), 3.43 (dd, J¼6.9, 15.0 Hz, 1H), 3.61 (s,
1H), 3.79 (s, 3H), 3.85 (s, 3H), 4.88 (dd, J¼6.9, 7.8 Hz, 1H),
6.79 (d, J¼2.4 Hz, 1H), 6.91 (dd, J¼2.4, 8.4 Hz, 1H), 7.17
(d, J¼8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 39.22,
53.44, 55.52, 63.92, 83.41, 108.88, 116.76, 125.63, 132.34,
141.50, 159.55, 172.73; IR (neat): 3514, 2982, 1733, 1616,
1504, 1255, 1158, 829 cm21. Anal. calcd for C12H13ClO4:
C, 56.15; H, 5.10. Found: C, 56.36; H, 5.34.
3.4.1. 2-Chloro-1-hydroxy-indan-1-carboxylic acid
methyl ester (4a). The crude product was purified by
column chromatography (hexane/ether¼100/1) to give
66 mg (63.5%) of (1S,2R)-(^)-4a and 30 mg (28.6%) of
isomerizarion product. (1S,2R)-(^)-4a; white solid, mp:
1
90–918C (from Et2O), Rf¼0.50 (hexane/EtOAc¼2/1); H
NMR (300 MHz, CDCl3) d 3.31–3.48 (m, 2H), 3.78 (s, 3H),
4.45 (s, 1H), 4.52 (dd, J¼8.1, 9.9 Hz, 1H), 7.24–7.33 (m,
4H); 13C NMR (75 MHz, CDCl3) d 39.60, 53.36, 65.65,
86.79, 123.49, 124.65, 127.66, 129.53, 140.04, 140.76,
172.82; IR (neat): 3504, 2956, 1725, 1437, 1228, 1121,
765 cm21. Anal. calcd for C11H11ClO3: C, 58.29; H, 4.89.
Found: C, 58.06; H, 5.14. (1S,2S)-(^)-4a; light yellow
liquid, Rf¼0.20 (hexane/EtOAc¼2/1); 1H NMR (300 MHz,
CDCl3) d 3.16 (dd, J¼8.1, 14.1 Hz, 1H), 3. 45 (dd, J¼6.6,
14.1 Hz, 1H), 3.80 (s, 1H), 3.89 (s, 3H), 5.17 (dd, J¼6.6,
8.1 Hz, 1H), 7.24–7.35 (m, 4H); 13C NMR (75 MHz,
CDCl3) d 38.54, 53.40, 58.27, 94.24, 126.99, 127.38,
128.49, 128.68, 129.41, 135.47, 186.17; IR (neat): 3496,
2956, 1736, 1455, 1262, 1093, 699 cm21. Anal. calcd for
C11H11ClO3: C, 58.29; H, 4.89. Found: C, 58.06; H, 5.14.
3.4.2. 2-Chloro-1-hydroxy-1,2,3,4-tetrahydro-naphthal-
ene-1-carboxylic acid methyl ester (4b). The crude
product was purified by column chromatography
(hexane/ether¼400/1) to give 38 mg (31.7%) of (1S,2R)-
(^)-4b and 59 mg (49.2%) of (1S,2S)-(^)-4b. (1S,2R)-(^)-
4b; colorless liquid, Rf¼0.50 (hexane/EtOAc¼2/1); 1H
NMR (300 MHz, CDCl3) d 2.31–2.39 (m, 1H), 2.69–2.84
(m, 1H), 2.99–3.02 (m, 2H), 3.76 (s, 3H), 4.35 (dd, J¼4.2,
13.2 Hz, 1H), 4.58 (s, 1H), 7.11–7.38 (m, 4H); 13C NMR
(75 MHz, CDCl3) d 28.80, 30.49, 53.53, 64.42, 78.60,
126.74, 126.95, 128.47, 128.65, 135.33, 135.70, 173.25; IR
(neat): 3502, 2954, 1736, 1493, 1435, 1263, 1128,
774 cm21. Anal. calcd for C12H13ClO3: C, 59.88; H, 5.44.
Found: C, 60.21; H, 5.40. (1S,2S)-(^)-4b; white solid, mp:
3.4.5. 2-Chloro-1-hydroxy-7-methoxy-1,2,3,4-tetrahydro-
naphthalene-1-carboxylic acid methyl ester (4e). The
crude product was purified by column chromatography
(hexane/ether¼100/1) to give 68 mg (35.6%) of (1S,2R)-
(^)-4e and 110 mg (57.6%) of (1S,2S)-(^)-4e. (1S,2R)-
(^)-4e; white solid, mp: 111–1128C (from Et2O), Rf¼0.40
(hexane/EtOAc¼2/1); 1H NMR (300 MHz, CDCl3) d 2.30–
2.37 (m, 1H), 2.69–2.81 (m, 1H), 2.92–2.97 (m, 2H), 3.77
(s, 3H), 3.78 (s, 3H), 4.33 (dd, J¼4.5, 13.2 Hz, 1H), 4.57 (s,
1H), 6.91 (dd, J¼3.0, 8.4 Hz, 1H), 6.87 (d, J¼3.0 Hz, 1H),
7.03 (d, J¼8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) d

1790
J.-R. Lin et al. / Tetrahedron 59 (2003) 1781–1790
28.01, 30.60, 53.59, 55.34, 64.65, 78.67, 110.76, 115.67,
127.86, 129.76, 136.18, 158.34, 173.22; IR (neat): 3444,
2956, 1733, 1615, 1501, 1281, 1132, 889 cm21. Anal. calcd
for C13H15ClO4: C, 57.68; H, 5.59. Found: C, 58.00; H,
5.80. (1S,2S)-(^)-4e; white solid, mp: 81–828C (from
Et2O), Rf¼0.35 (hexane/EtOAc¼2/1); 1H NMR (300 MHz,
CDCl3) d 2.16–2.24 (m, 1H), 2.34–2.49 (m, 1H), 2.90–
2.95 (m, 2H), 3.74 (s, 3H), 3.83 (s, 3H), 3.92 (s, 1H), 4.64
(dd, J¼3.3, 11.8 Hz, 1H), 6.57 (d, J¼2.7 Hz, 1H), 6.84 (dd,
J¼2.7, 8.4 Hz, 1H), 7.05 (d, J¼8.4 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 27.96, 28.54, 53.40, 55.26, 63.20,
77.28, 112.02, 115.60, 126.90, 130.08, 135.61, 158.20,
174.08; IR (neat): 3444, 2956, 1736, 1614, 1506, 1243,
1132, 816 cm21. Anal. calcd for C13H15ClO4: C, 57.68; H,
5.59. Found: C, 58.00; H, 5.80.
Crystallographic data for syn-4e. C13H15O3Cl, colorless
shapeless crystal of dimension 0.6£0.6£0.3mm3, mol.
weigth 254.72, monoclinic, P21/n, a¼8.033(8), b¼
3
˚
˚
8.511(4), c¼19.13(3) A, b¼99.20(6)8, V¼1291 A , Z¼4,
r¼1.31 g cm23. Final R¼0.046, Rw¼0.061 for 1400 reflec-
tions with I.3s(I).
Crystallographic data for anti-4e. C13H15O3Cl, colorless
prismatic crystal of dimension 0.4£0.3£0.2 mm3, mol.
weigth 254.72, monoclinic, C2/c, a¼15.146(8), b¼
3
˚
˚
11.46(1), c¼15.65(1) A, b¼104.05(4)8, V¼2635 A , Z¼8,
r¼1.28 g cm23. Final R¼0.048, Rw¼0.061 for 1772 reflec-
tions with I.3s(I).
3.5. General procedure for the reaction with AlCl3
supported by Al2O3 or SiO2
Acknowledgements
We are grateful to SC-NMR laboratory of Okayama
University for the measurement of NMR spectra.
To a stirring solution of aluminium chloride (400 mg,
3 mmol) in CH2Cl2 (4 mL) was added Al2O3 or SiO2
(6 mmol) at room temperature. After stirred for 10 min, the
solution of methyl 2-chloro-2,3-epoxyalkanoate 1(1 mmol)
in CH2Cl2 (2 mL) was added.
References
The mixture was stirred for 1 h, then stopped by pouring the
ice (10 mL), the aqueous layer was extracted with EtOAc,
and the combined extracts were washed with saturated
NaHCO3 solution and brine, then dried over MgSO4.
Evaporation of the solvent gave a clean oil, which was
further purified by column chromatography.
1. Friedel–Crafts and Related Reaction; Olah, G. A., Ed.;
Interscience: New York, 1964.
2. Hata, S.; Matsuda, H.; Mastuda, S. Kogyo Kagaku Zasshi
1967, 70(12), 2291–2297.
3. Nakamoto, Y.; Nakajima, T.; Suga, S. Kogyo Kagaku Zasshi
1969, 72(12), 2594–2598.
4. Nakajima, T.; Nakamoto, Y. Suga. Si. Bull. Chem. Soc. Jpn
1975, 48(3), 960–965.
3.6. X-Ray structure determination
5. Inoue, M.; Chano, K.; Itoh, O.; Sugita, T.; Ichikawa, K. Bull.
Chem. Soc. Jpn 1980, 53, 458–463.
The X-Ray diffraction data for crystals syn-4e and anti-4e
were collected on a CAD4 Enraf-Nonius automatic
diffractometer (graphite monochromator, Cu Ka radiation
6. (a) Taylor, S. K.; Lilley, G. L.; Lilley, K. J.; McCoy, P. A.
J. Org. Chem. 1981, 46(13), 2709–2712. (b) Taylor, S. K.;
Davisson, M. E.; Hissom, B.; Rolf, J.; Brown, S. L.; Pristach,
H. A.; Schramm, S. B.; Harvey, S. M. J. Org. Chem. 1987,
52(3), 425–429.
˚
(1.54184 A), v/2u scan method, u#57.218). A total of 1774
(syn-4e) and 2931 (anti-4e) reflections were measured, of
which 1400 and 1772 were unique with I.3s respectively.
The stability of crystals and of experimental conditions was
checked every 2 h using three control reflections, while
the orientation was monitored every 200 reflections by
centering two standards. No significant decay was observed.
Corrections for Lorentz and polarization effects were
applied, but not for absorption. The structures were solved
by direct method and difference Fourier syntheses using SIR
program12 and MolEN package.13 All non-hydrogen atoms
were refined anisotropically, H-atoms were located in dF
maps and refined isotropically. All figures were made using
the program PLATON.14
7. (a) Tsuboi, S.; Furutani, H.; Takeda, A.; Kawazoe, K.; Sato, H.
Bull. Chem. Soc. Jpn 1987, 60(7), 2457–2459. (b) Mamedov,
V. A.; Nuretdinov, I. A. Izv. Akad. Nauk. Ser. Khim. 1992,
2159. Related papers are cited therein.
8. Lin, J.-r.; Kanazaki, S.; Kashino, S.; Tsuboi, S. Synlett 2002, 6,
899–902.
9. Juy, M.; Combret, J. C.; Coutrot, P. C. R. Hebd. Seances Acad.
Sci., Ser. C 1974, 279(11), 469–472.
10. (a) Ubaidullaev, K. A.; Shakairov, R.; Yunosov, S. Y. Khim.
Prir. Soedin. 1976, 12, 553. (b) Hasse, B. R.; John, K. M.
J. Nat. Prod. 1997, 60, 1152.
11. Asoeva, E. Z.; Muraveva, D. A.; Molodozhnikov, M. M.;
Rabinovich, I. M. Farmatsiya (Moscow) 1968, 17(5), 47–49.
12. Altomare, A.; Cascarano, G.; Giacovazzo, C.; Viterbo, D. Acte
Crystallogr. A. 1991, 6, 744–748.
Crystallographic data (excluding structure factors) for the
structures syn-4e and anti-4e in this paper have been
deposited with the Cambridge Crystallographic Data Centre
as supplementary publication numbers CCDC 200326 (for
syn-4e) and 200327 (for anti-4e) respectively. Copies of the
data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:
þ44(0) 1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
13. Straver, L.; Schierbeek, A. J. MolEN Structure Determination
System, Nonius B.V., 1994, V.1–2.
14. Spek, A. L. PLATON, A Multipurpose Crystallographic Tool,
Utrecht University, Utrecht, The Netherlands, 2000.