Synthesis of 1,7-dioxaspiro[5.5]undecanes and 1 -oxa-7-thiaspiro[5.5] undecanes from exo-glycal

Article abstract of DOI:10.1016/j.tet.2010.04.075

A new spirocyclization was developed for the synthesis of 1,7-dioxaspiro[55]undecanes and 1-oxa-7-thiaspiro[55]undecanes by reaction of exo-glycal with awl alcohols or thiophenols in the presence of Lewis acid BF₃·OEt₂. The reaction proceeded through tandem Ferrier rearrangement, glycosylation, and FriedelCrafts alkylation to provide the corresponding products in good to excellent yields.

Full text of DOI:10.1016/j.tet.2010.04.075

Tetrahedron 66 (2010) 5229e5234
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 1,7-dioxaspiro[5.5]undecanes and 1-oxa-7-thiaspiro[5.5]undecanes
from exo-glycal
,
a
a
a
b
c
Hui-Chang Lin a , Yen-Bo Chen , Zi-Ping Lin , Fung Fuh Wong , Chun-Hung Lin , Shao-Kai Lin
*
a Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan, ROC
b Institute of Biological Chemistry, Academia Sinica, No. 128, Academia Road, Section 2, Nan-Kang, Taipei 11529, Taiwan, ROC
c Sustainable Environment Research Center, National Cheng Kung University, No. 500, Sec. 3, An-ming Rd., Tainan City 709, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
A new spirocyclization was developed for the synthesis of 1,7-dioxaspiro[5.5]undecanes and 1-oxa-7-
thiaspiro[5.5]undecanes by reaction of exo-glycal with aryl alcohols or thiophenols in the presence of
Lewis acid BF3$OEt2. The reaction proceeded through tandem Ferrier rearrangement, glycosylation, and
FriedeleCrafts alkylation to provide the corresponding products in good to excellent yields.
Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
Received 26 January 2010
Received in revised form 14 April 2010
Accepted 20 April 2010
Available online 24 April 2010
Keywords:
Spiroacetals
Spirocyclization
Ferrier rearrangement
FriedeleCrafts alkylation
1. Introduction
2. Result and discussion
Spiroacetals attract large attention because they are the struc-
tural feature of many important natural products,1 among, which
1,7-dioxaspiro[5.5]undecane is the major component of the pher-
omone of olive fruit fly (Dacus oleae).2 Their metabolites were also
found as the complex antiparasitic agents3 or polyether antibiotics
of the monensin4,5 and lonomycin type.6
exo-Glycal 1 was prepared as the starting material by following
the previous publication procedure via reduction and acetylation of
exo-glycocosyl ester.14,15 To search for the optimum conditions, we
carried out the reaction by varying the anhydrous solvent and
temperature by selecting CH2Cl2, THF, and acetonirile (MeCN) as
the solvents and setting the reaction temperatures between ꢀ25
and 25 ꢁC. Treatment of exo-glycal 1 and 4-methoxyphenol (2e)
with 1.0 equiv of boron trifluoride diethyl etherate (BF3$OEt2) in
CH2Cl2 solution at 0 ꢁC for 30 min provided the best result (see
Scheme 1 and entries 1e5 of Table 1).
To investigate the catalytic activity of Lewis acids, we chose exo-
glycal 1 and 4-methoxyphenol 2e as the model to build up the best
reaction condition and search for the best catalyst. We treated
a anhydrous CH2Cl2 solution of exo-glycal 1 and 4-methoxyphenol
2e with 1.0 equiv of various Lewis acids, including aluminum
chloride (AlCl3), boron trifluoride diethyl etherate (BF3$OEt2), iron
For the reason that 1,7-dioxaspiro[5.5]undecanes were impor-
tant skeletons of the natural products, many methods were
developed to synthesize the [5.5]spiroacetals. For instance, typical
methods for the preparation of racemic spiroacetals are the use of
radical methodology.7,8 On the other hand, several literatures
report the synthesis chiral pyranose spiroacetals by means of the
acid catalyzed cyclization,9 intramolecular hydrogen abstraction
reaction,10,11 ring-closing metathesis,12 and NBS oxidatively rear-
ranges.13 However, most of those methods could not provide
straightforward and satisfactory process due to the expersive, toxic,
and moisture-sensitive starting materials,12 the multiple steps,9c
the low yields,10,11 and the harsh reaction conditions.12 In this
paper, we developed a convenience method for synthesis of pyra-
nose spiroacetal derivatives from exo-glycal with aryl alcohols or
thiophenols by using BF3$OEt2 as the catalyst via the tandem Fer-
rier rearrangement, glycosylation, and FriedeleCrafts alkylation.
OBn
O
OH
BnO
BnO
OBn
O
BnO
BnO
BF3.OEt2
+
OAc
CH2Cl2, 0 oC, 30 mins
BnO
O
OBn
OMe
OMe
1
2e
3e
* Corresponding author. Tel.: þ886 4 2205 3366x5612; fax: þ886 4 2207 8083;
Scheme 1.
e-mail addresses: lhc550005@yahoo.com.tw, huichang@mail.cmu.edu.tw (H.-C. Lin).
0040-4020/$ e see front matter Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.075

5230
H.-C. Lin et al. / Tetrahedron 66 (2010) 5229e5234
chloride (FeCl3), trifluoroacetic acid (TFA), and triphenylphospho-
nium bromide (PPh3$HBr) at 0 ꢁC for 30 min. We found the use of
BF3$OEt2 as the Lewis catalyst provided the product 3e in the best
isolated yield (81%, Table 1).
Furthermore, we applied the same synthetic strategy to various
aryl alcohols 2aei bearing an alkyl, alkoxy, 4-(n-pentylthio)phenol,
bromo, and cholro groups at the para-position. The reactions
We also applied the same method to use thiophenols 4aee
equipped with various para-substitutents, including Me, t-Bu, OMe,
Cl, and Br groups. The reaction provided the corresponding 1-oxa-
7-thiaspiro[5.5]undecanes 5aee in 74e89% yields after normal
workup and purification (see Scheme 3 and Table 3).
We proposed a plausible mechanism for the formation of 1,7-
dioxaspiro[5.5]undecane 3e through tandem Ferrier rearrange-
gave the high stereoselective a-glycosidation spiro products 3aei
OBn
O
SH
BnO
BnO
OBn
O
BnO
BnO
Table 1
BF3.OEt2
+
Application of different Lewis acids for synthesis of 1,7-dioxaspiro[5.5]undecane 3e
OAc
CH2Cl2, 0 oC, 30 mins
BnO
S
OBn
Entry Lewis
acid
Reaction
Reaction 1,7-Dioxaspiro[5.5]undecanes 3e
R
R
temperature (ꢁC) solvent
Yieldsa,b (%)
1
4a-4e
5a-5e
1
2
3
4
5
6
7
8
9
BF3$OEt2
0
0
0
CH2Cl2 81
Scheme 3.
BF3$OEt2
BF3$OEt2
BF3$OEt2
THF
MeCN
72
0
25
CH2Cl2 53
Table 3
The results for synthesis of 1-oxa-7-thiaspiro[5.5]undecanes 5aee
BF3$OEt2 ꢀ25
CH2Cl2
CH2Cl2
CH2Cl2
0
0
0
TFA
0
0
0
0
AlCl3
FeCl3
PPh3$HBr
Entry
Thiophenols s 4aee
R (para-position)
1-Oxa-7-thiaspiro[5.5]undecanes 5aee
CH2Cl2 21
CH2Cl2 74
Products
Yieldsa,b (%)
1
2
3
4
5
4a
4b
4c
4d
4e
Me
t-Bu
OMe
Cl
5a
5b
5c
5d
5e
80
89
74
78
79
a
The yield was determined by the column separation.
All of the isolated products are the a-glycosidation spiro products.
b
in71e89% yields(see Scheme 2 and Table 2)and theirstructures were
identified and determined by DEPT, NOESY, and other spectroscopic
methods. For example, compound 3e possessed pyranose spiroacetal
characteristic peaks: a multiple resonance at
H2b0 proton, a multiple resonance at 2.14e2.05 ppm for the H2a0
proton, a multiple resonance at
2.90e2.81 ppm for the H1a0
proton, and a doubletedoublet resonanceat
2.45(J¼16.0, 5.6 Hz) for
the H1b0 proton. The 13C characteristic peak of the anomeric center
represented at 98.76 ppm.
Br
a
The yield was determined by the column separation.
All of isolated products are the a-glycosidation spiro products.
b
d 1.57e1.62 ppm for the
d
d
ment, glycosylation, and FriedeleCrafts alkylation (see Scheme 4),
which accounted for our approach and design. BF3$OEt2 catalyzed
exo-glycal 1 to undergo the Ferrier rearrangement (allylic rear-
rangement) to give the
quently, the -conjugated oxonium ion 6 would glycosylate
d
a,b
-conjugated oxonium ion 6.16 Conse-
d
However, when we applied this method to o-cresol, m-anisole,
and m-chlorophenol, the corresponding spiro product cannot be
obtained in quantitative yields and the poor stereoselectivity was
a,b
methoxyphenol 2e to give adduct 7.14 Upon further reaction with
Lewis acid, intermediate 7 would undergo FriedeleCrafts alkylation
to generate the final 1,7-dioxaspiro[5.5]undecane product 3e.
In conclusion, exo-glycal 1 was successfully converted to 1,7-
dioxaspiro[5.5]undecanes by reacting aryl alcohols with BF3$OEt2
as the catalyst via the tandem Ferrier rearrangement, glycosylation,
and FriedeleCrafts alkylation. This new method was also applicable
to thiophenol as the reactants to give the corresponding 1-oxa-7-
thiaspiro[5.5]undecanes in good yields.
OBn
OH
BnO
4
BnO
OBn
O
BnO
BnO
1'
5
2'
2a
O 1
BF3.OEt2
2
+
3 BnO
OAc
3'
CH2Cl2, 0 oC, 30 mins
O
4'R
6a
OBn
R
6'
5'
1
2a-2i
3a-3i
Scheme 2.
3. Experimental section
3.1. General procedure
Table 2
The results for the synthesis of 1,7-dioxaspiro[5.5]undecanes 3aei
Entry
Aryl alcohols 2aei
R (para-position)
1,7-Dioxaspiro[5.5]undecanes 3aei
All chemicals were reagent grade and used as purchased. All
reactions were carried out under nitrogen atmosphere and moni-
tored by TLC analysis. Flash column chromatography was carried
out on silica gel (230e400 mesh). Commercially available reagents
were used without further purification unless otherwise noted.
Dichloromethane, ethyl acetate, hexanes, and methanol were pur-
chased from Mallinckrodt Chemical Co. The following compounds
were purchased from Acoros Chemical Co: boron trifluoride diethyl
Products
Yieldsa,b (%)
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
Me
Et
3a
3b
3c
3d
3e
3f
3g
3h
3i
81
87
76
71
81
89
71
78
74
CH2O-n-Bu
CH2O-n-Oct
OMe
O-n-Bu
S-n-Pent
Cl
etherate,
butoxyphenol, 4-tert-butylthiophenol, 4-chlorothiophenol, p-cresol,
4-ethylphenol, 4-hydroxy- -octoxytoluene, 4-methoxyphenol,
a-butoxy-4-hydroxytoluene, 4-bromothiophenol, 4-n-
Br
a
a
The yield was determined by the column separation.
All of isolated products are the a-glycosidation spiro products.
b
4-methoxybenzenethiol, 4-(n-pentylthio)phenol, p-toluenethiol.
Purification by gravity column chromatography was carried out by
use of Merck Reagents Silica Gel 60 (particle size 0.063e0.200 mm,
70e230 mesh ASTM). Infrared (IR) spectra were measured on
a Bomem Michelson Series FT-IR spectrometer. The wavenumbers
reported are referenced to the polystyrene 1601 cmꢀ1 absorption.
Absorption intensities are recordedbythefollowingabbreviations:s,
found for the o-Me, m-Cl, and m-OMe group made the conversion
unfeasible. The synthetic strategy was also applicable to exo-glucal
with p-chlorophenol. Unfortunately, the racemic glycosidation
spiro products were provided.

H.-C. Lin et al. / Tetrahedron 66 (2010) 5229e5234
5231
OBn
O
OMe
BnO
BnO
OBn
O
BnO
BnO
BF3.OEt2
+
OAc
CH2Cl2, 0 oC, 30 min
BnO
O
OBn
OMe
OH
1
2e
3e
BF3.OEt2
BF3 OEt2
OBn
O
OBn
BnO
BnO
BnO
BnO
O
O
H
O
BnO
O
OBn
OMe
1a
8
+
H
OBn
O
OMe
BnO
BnO
OBn
O
BnO
BnO
+
BnO
O
BnO
OH
2e
OMe
6
7
Scheme 4.
strong; m, medium; w, weak. Proton NMR spectra were obtained on
a Bruker (200 or 400 MHz) spectrometer by use of CDCl3 and DMSO-
d6 as solvent. Carbon-13 NMR spectra were obtained on a Bruker (50
or 100 MHz) spectrometer by used of CDCl3 as solvent. Carbon-13
128.59,128.58,128.41,128.40,128.28,128.27,128.26,128.25,128.24,
128.23, 128.22, 128.21, 128.20, 127.87, 127.86, 127.69, 127.60, 127.59,
127.55, 127.52, 127.51, 122.35, 117.27, 98.88, 80.47, 79.06, 75.71,
74.92, 74.76, 73.15, 72.82, 70.84, 68.80, 27.20, 20.65, 20.51; ESIMS
m/z (rel intens) 656 (Mþ,1), 240 (5), 181 (6), 121 (3), 91 (100); HRMS
(EI) m/z calcd for C43H44O6 656.3138, found 656.3132. Anal. Calcd
for C43H44O6; C: 78.63; H: 6.75. Found: C: 78.60; H: 6.72.
chemical shifts are referenced to the center of the CDCl3 triplet (
d
77.0 ppm). Multiplicities are recorded by the following abbrevia-
tions: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; J,
coupling constant (Hz). Elemental analyses were carried out on
a Heraeus CHNeO RAPID element analyzer.
3.2.2. 1,7-Dioxaspiro[5.5]undecane derivative 3b. Pale yellow oil;
25
[
a
]
þ64.00 (c 0.65, CHCl3); IR (CHCl3) 2924, 1645, 1550,
D
3.2. Standard procedure for preparation of 1,7-dioxaspiro
[5.5]undecanes 3aei and 1-Oxa-7-thiaspiro[5.5]undecanes
5aee
1100 cmꢀ1
;
1H NMR (CDCl3, 400 MHz)
d
7.35e7.15 (18H, m, ArH),
7.02e7.00 (2H, m, ArH), 6.86e6.83 (1H, m, ArH), 6.77e6.74 (2H, m,
ArH), 4.90 (2H, d, J¼11.2 Hz, CH2Ph), 4.75 (2H, br s, CH2Ph), 4.66 (1H,
d, J¼11.2 Hz, CH2Ph), 4.56 (1H, d, J¼11.2 Hz, CH2Ph), 4.23 (1H, dd,
J3,4¼2.8 Hz, J3,2¼10.0 Hz, H3), 4.19 (1H, d, J¼11.2 Hz, CH2Ph), 4.16
(1H, d, J¼11.2 Hz, CH2Ph), 4.02 (1H, dd, J4,5¼1.2 Hz, J4,3¼2.8 Hz, H4),
3.96e3.90 (2H, m, H2, H5), 3.52 (1H, dd, J6a,5¼7.2 Hz, J6a,6b¼9.6 Hz,
H6a), 3.34 (1H, dd, J6b,5¼5.6 Hz, J6b,6a¼9.6 Hz, H6b), 2.90e2.82 (1H,
m, H10a), 2.50e2.42 (3H, m, CH2, H10b), 2.15e2.03 (1H, m, H20a),
1.65e1.61 (1H, m, H20b), 1.12 (3H, t, J¼7.6 Hz, CH3); 13C NMR (CDCl3,
To a solution of exo-glycal 1 (1.0 equiv) in CH2Cl2 were added
with catalyst BF3$OEt2 (1.0 equiv) and aryl alcohol (3.0 equiv) or
thiophenol (3.0 equiv). The reaction mixture was stirred at 0 ꢁC for
30 min. When the reaction was completed, the resulting solution
was added to CH2Cl2 (50 mL), washed with H2O (20 mLꢂ2), and
brine (20 mLꢂ2). The organic layer was concentrated under re-
duced pressure and purified by column chromatography on silica
gel (15% EtOAc in hexanes as eluant) to give 1,7-dioxaspiro[5.5]
undecanes 3aei in 71e89% yields or 1-oxa-7-thiaspiro[5.5]unde-
canes 5aee in 74e89% yields.
100 MHz):
d 149.91, 138.76, 138.63, 138.16, 137.97, 136.54, 128.58,
128.57, 128.41, 128.40, 128.28, 128.27, 128.26, 128.25, 128.24, 128.23,
128.22, 128.21, 128.13, 127.89, 127.88, 127.68, 127.60, 127.59, 127.52,
127.51, 127.50, 126.40, 122.30, 117.27, 98.91, 80.48, 79.10, 75.71,
74.93, 74.76, 73.15, 72.82, 70.83, 68.80, 27.99, 27.23, 20.72, 1565.
ESIMS m/z (rel intens) 670 (Mþ, 1), 181 (18), 105 (3), 91 (100); HRMS
(EI) m/z calcd for C44H46O6 670.3294, found 670.3304. Anal. Calcd
for C44H46O6; C: 78.78; H: 6.91. Found: C: 78.74; H: 6.89.
3.2.1. 1,7-Dioxaspiro[5.5]undecane derivative 3a. Pale yellow oil;
[
a]
25 þ16.97 (c 2.05, CHCl3); IR (CHCl3) 2923,1644,1552,1101 cmꢀ1
;
D
1H NMR (CDCl3, 400 MHz)
d
7.34e7.13 (18H, m, ArH), 7.01e6.99 (2H,
m, ArH), 6.83e6.80 (1H, m, ArH), 6.74e6.71 (2H, m, ArH), 4.90 (2H,
d, J¼11.2 Hz, CH2Ph), 4.74 (2H, br s, CH2Ph), 4.66 (1H, d, J¼11.2 Hz,
CH2Ph), 4.56 (1H, d, J¼11.2 Hz, CH2Ph), 4.23 (1H, dd, J3,4¼2.8 Hz,
J3,2¼10 Hz, H3), 4.19 (1H, d, J¼11.2 Hz, CH2Ph), 4.15 (1H, d, J¼11.2 Hz,
CH2Ph), 4.01 (1H, dd, J4,5¼1.2 Hz, J4,3¼2.8 Hz, H4), 3.95e3.89 (2H, m,
H2, H5), 3.51 (1H, dd, J6a,5¼7.2 Hz, J6a,6b¼9.6 Hz, H6a), 3.34 (1H, dd,
J6b,5¼5.6 Hz, J6b,6a¼9.6 Hz, H6b), 2.89e2.80 (1H, m, H10a), 2.43 (1H,
3.2.3. 1,7-Dioxaspiro[5.5]undecane derivative 3c. Pale yellow oil;
[a]
25 þ19.50 (c 2.62, CHCl3); IR (CHCl3) 2923, 1646, 1548, 1105 cmꢀ1
;
D
1H NMR (CDCl3, 400 MHz)
d
7.35e7.16 (18H, m, ArH), 7.05e7.02 (2H,
m, ArH), 6.99 (1H, dd, J¼2.0 Hz, J¼8.4 Hz, ArH), 6.92 (1H, br s, ArH),
6.80 (1H, d, J¼8.4 Hz, ArH), 4.91 (1H, d, J¼11.2 Hz, CH2Ph), 4.90 (1H, d,
J¼11.6 Hz, CH2Ph), 4.74 (2H, br s, CH2Ph), 4.67 (1H, d, J¼11.2 Hz,
CH2Ph),4.56(1H, d,J¼11.2 Hz,CH2Ph), 4.30(2H,brs,H60),4.22(1H, dd,
J3,4¼2.8 Hz, J3,2¼10.0 Hz, H3), 4.21 (1H, d, J¼11.6 Hz, CH2Ph), 4.18 (1H,
d, J¼11.6 Hz, CH2Ph), 4.04 (1H, br s, H4), 3.94e3.90 (2H, m, H2, H5),
dd, J1 b,2 a¼5.6 Hz, J1 b,1 a¼16.0 Hz, H10b), 2.21e2.06 (1H, m, H20a),
0
0
0
0
2.16 (3H, s, CH3), 1.65e1.60 (1H, m, H20b); 13C NMR (CDCl3,
100 MHz):
d 149.71, 138.74, 138.61, 138.13, 137.95, 130.06, 129.37,

5232
H.-C. Lin et al. / Tetrahedron 66 (2010) 5229e5234
3.51 (1H, dd, J6a,5¼8.0 Hz, J6a,6b¼9.6 Hz, H6a), 3.38 (2H, t, J¼6.8 Hz,
H70), 3.30 (1H, dd, J6b,5¼5.2 Hz, J6b,6a¼9.6 Hz, H6b), 2.90e2.82 (1H, m,
CH2Ph), 4.21 (1H, dd, J3,4¼2.8 Hz, J3,2¼10.4 Hz, H3), 4.19 (1H, d,
J¼11.6 Hz, CH2Ph), 4.15 (1H, d, J¼11.6 Hz, CH2Ph), 4.01 (1H, br s, H4),
3.93e3.87 (2H, m, H2, H5), 3.77 (2H, t, J¼6.4 Hz, H60), 3.49 (1H, dd,
J6a,5¼7.2 Hz, J6a,6b¼9.6 Hz, H6a), 3.33 (1H, dd, J6b,5¼5.6 Hz,
J6b,6a¼9.6 Hz, H6b), 2.90e2.81 (1H, m, H10a), 2.44 (1H, dd,
H10a), 2.47 (1H, dd, J1 b,2 a¼5.2 Hz, J1 b,1 a¼16.0 Hz, H10b), 2.13e2.05
(1H, m, H20a), 1.65e1.60 (1H, m, H20b), 1.57e1.47 (1H, m, H80),
1.35e1.23 (1H, m, H90), 0.83 (3H, t, J¼7.2 Hz, CH3); 13C NMR (CDCl3,
0
0
0
0
J1 b,2 a¼5.6 Hz, J1 b,1 a¼16.4 Hz, H10b), 2.13e2.05 (1H, m, H20a),
1.67e1.57 (3H, m, H20b, H70), 1.43e1.34 (2H, m, H80), 0.88 (3H, t,
0
0
0
0
100 MHz):
d 151.45, 138.75, 138.59, 138.10, 137.90, 131.08, 128.64,
128.57, 128.56, 128.40, 128.39, 128.30, 128.29, 128.26, 128.25, 128.22,
128.21, 128.20, 128.19, 127.86, 127.85, 127.70, 127.61, 1277.56, 127.54,
127.51, 127.50,126.76, 122.54, 117.39, 99.01, 80.41, 78.98, 75.70, 74.80,
74.79, 73.20, 72.79, 72.69, 70.74, 70.17, 68.55, 31.82, 27.11, 20.66,19.36,
13.89; ESIMS m/z (rel intens) 728 (Mþ,0.7), 240 (7), 181 (8), 91 (100);
HRMS (EI) m/z calcd for C47H52O7 728.3713, found 728.3722. Anal.
Calcd for C47H52O7; C: 77.44; H: 7.32. Found: C: 77.49; H: 7.28.
J¼7.2 Hz, CH3); 13C NMR (CDCl3, 100 MHz):
d 153.30, 145.54, 138.62,
138.52, 138.00, 137.84, 128.67, 128.66, 128.41, 128.40, 128.28, 128.27,
128.26, 128.25, 128.24, 128.23, 128.22, 128.21, 127.85, 127.84, 127.72,
127.61, 127.62, 127.55, 127.49, 127.48, 123.22, 118.03, 114.10, 113.42,
98.73, 80.45, 78.85, 75.70, 74.70, 74.69, 73.11, 72.76, 70.74, 68.75,
67.94, 31.44, 27.00, 21.00, 19.24, 13.87; ESIMS m/z (rel intens) 714
(Mþ, 2), 457 (8), 91 (100); HRMS (EI) m/z calcd for C46H50O7
714.3557, found 714.3551. Anal. Calcd for C46H50O7; C: 77.28; H:
7.05. Found: C: 77.34; H: 7.08.
3.2.4. 1,7-Dioxaspiro[5.5]undecane derivative 3d. Pale yellow oil;
[
a]
25 þ20.67 (c 1.19, CHCl3); IR (CHCl3) 2936, 1643, 1468, 1101 cmꢀ1
;
D
1H NMR (CDCl3, 400 MHz)
d
7.34e7.13 (18H, m, ArH), 7.04e7.02 (2H,
m, ArH), 6.98 (1H, dd, J¼2.0, 8.0 Hz, ArH), 6.93 (1H, br s, ArH), 6.79
(1H, d, J¼8.0 Hz, ArH), 4.89 (1H, d, J¼11.2 Hz, CH2Ph), 4.74 (2H, br s,
CH2Ph), 4.66 (1H, d, J¼11.6 Hz, CH2Ph), 4.55 (1H, d, J¼11.2 Hz,
CH2Ph), 4.29 (2H, br s, H60), 4.24e4.18 (3H, m, H3, CH2Ph), 4.03 (1H,
br s, H4), 3.94e3.90 (2H, m, H2, H5), 3.52 (1H, dd, J6a,5¼8.0 Hz,
J6a,6b¼9.6 Hz, H6a), 3.36 (2H, t, J¼6.4 Hz, H70), 3.30 (1H, dd,
J6b,5¼5.6 Hz, J6b,6a¼9.6 Hz, H6b), 2.90e2.82 (1H, m, H10a), 2.47 (1H,
3.2.7. 1,7-Dioxaspiro[5.5]undecane derivative 3g. Pale yellow oil;
25
[a
]
þ42.24 (c 0.98, CHCl3); IR (CHCl3) 2929, 1643, 1469,
D
1101 cmꢀ1
;
1H NMR (CDCl3, 400 MHz)
d
7.34e7.13 (19H, m, ArH),
7.05e6.98 (3H, m, ArH), 6.75 (1H, d, J¼8.4 Hz, ArH), 4.90 (2H, d,
J¼11.6 Hz, CH2Ph), 4.74 (2H, br s, CH2Ph), 4.66 (1H, d, J¼11.6 Hz,
CH2Ph), 4.55 (1H, d, J¼11.6 Hz, CH2Ph), 4.23e4.17 (3H, m, H3,
CH2Ph), 4.01 (1H, br s, H4), 3.92e3.90 (2H, m, H2, H5), 3.51 (1H, dd,
J6a,5¼7.6 Hz, J6a,6b¼9.6 Hz, H6a), 3.32 (1H, dd, J6b,5¼5.6 Hz,
J6b,6a¼9.6 Hz, H6b), 2.89e2.80 (1H, m, H10a), 2.72 (2H, t, J¼7.6 Hz,
dd, J1 b,2 a¼5.6 Hz, J1 b,1 a¼16.4 Hz, H10b), 2.14e2.05 (1H, m, H20a),
1.65e1.60 (1H, m, H20b), 1.55e1.48 (1H, m, H80), 1.28e1.13 (10H, m,
H90-H130), 0.80 (3H, t, J¼6.8 Hz, CH3); 13C NMR (CDCl3, 100 MHz):
0
0
0
0
H70), 2.44 (1H, dd, J1 b,2 a¼5.6 Hz, J1 b,1 a¼16.4 Hz, H10b), 2.13e2.03
(1H, m, H20a), 1.64e1.60 (1H, m, H20b), 1.55e1.48 (2H, m, H80),
1.33e1.13 (4H, m, H90, H100), 0.78 (3H, t, J¼7.2 Hz, CH3); 13C NMR
0
0
0
0
d
151.46, 138.77, 138.60, 138.11, 137.91, 131.09, 128.65 128.58, 128.57,
128.41, 128.40, 128.31, 128.30, 128.27, 128.26, 128.22, 128.21, 128.20,
127.87, 127.86, 127.71, 127.70, 127.62, 127.56, 127.55, 127.52, 127.51,
126.77, 122.55, 117.40, 99.02, 80.42, 78.99, 75.71, 74.81, 74.80, 73.21,
72.80, 72.69, 70.75, 7.054, 68.56, 31.82, 29.75, 29.45, 29.25, 27.12,
26.20, 22.64, 20.67, 14.07; FAB-MS m/z (rel intens) 785 (MþHþ, 1),
181 (45), 91 (100), 55 (68); HRMS (FAB) m/z calcd for C51H61O7
(MþHþ) 785.4417, found 785.4425. Anal. Calcd for C51H60O7; C:
78.03; H: 7.70. Found: C: 78.06; H: 6.72.
(CDCl3, 100 MHz):
d 151.00, 138.70, 138.54, 138.04, 137.86, 131.61,
129.83, 128.62, 128.61, 128.41, 128.40, 128.34, 128.33, 128.28, 128.27,
128.24, 128.23, 128.22, 128.21, 128.20, 127.82, 127.81, 127.75, 127.65,
127.60, 127.58, 127.52, 127.51, 127.50, 123.40, 118.10, 99.10, 80.38,
78.83, 75.72, 74.83, 74.79, 73.21, 72.81, 70.91, 68.67, 35.41, 30.91,
29.00, 27.01, 22.21, 20.61, 13.92; FAB-MS m/z (rel intens) 745
(MþHþ, 3), 653 (2), 209 (5), 181 (12), 90 (75); HRMS (FAB) m/z calcd
for C47H53O6S (MþHþ) 745.3563, found 745.3553. Anal. Calcd for
C47H52O6S; C: 75.77; H: 7.04. Found: C: 75.83; H: 7.07.
3.2.5. 1,7-Dioxaspiro[5.5]undecane derivative 3e. Pale yellow oil;
[
a
]
25 þ7.79 (c 1.77, CHCl3); IR (CHCl3) 2923,1640,1493,1106 cmꢀ1; 1H
D
NMR (CDCl3, 400 MHz)
d
7.38e7.13 (18H, m, ArH), 7.01e6.98 (2H, m,
3.2.8. 1,7-Dioxaspiro[5.5]undecane derivative 3h. Pale yellow oil;
ArH), 6.75(1H, d, J¼8.8 Hz, ArH), 6.58(1H, dd, J¼2.8,8.8 Hz, ArH), 6.48
(1H, d, J¼2.8 Hz, ArH), 4.91 (1H, d, J¼11.2 Hz, CH2Ph), 4.90 (1H, d,
J¼11.6 Hz, CH2Ph), 4.74 (2H, br s, CH2Ph), 4.67 (1H, d, J¼11.2 Hz,
CH2Ph), 4.56 (1H, d, J¼11.6 Hz, CH2Ph), 4.21 (1H, dd, J3,4¼2.8 Hz,
J3,2¼10.0 Hz, H3), 4.19 (1H, d, J¼11.6 Hz, CH2Ph), 4.16 (1H, d, J¼11.2 Hz,
CH2Ph), 4.01 (1H, dd, J4,5¼1.2 Hz, J4,3¼2.8 Hz, H4), 3.93e3.87 (2H, m,
H2, H5), 3.64 (3H, s, OCH3), 3.49 (1H, dd, J6a,5¼7.2 Hz, J6a,6b¼9.6 Hz,
H6a), 3.34 (1H, dd, J6b,5¼5.6 Hz, J6b,6a¼9.6 Hz, H6b), 2.90e2.81(1H, m,
[a
]
25 þ37.31 (c 0.67, CHCl3); IR (CHCl3) 2966, 1640, 1490, 1102 cmꢀ1
;
D
1H NMR (CDCl3, 400 MHz)
d 7.28e6.74 (23H, m, ArH), 4.89 (2H, d,
J¼11.6 Hz, CH2Ph), 4.73 (2H, br s, CH2Ph), 4.65 (1H, d, J¼11.6 Hz,
CH2Ph), 4.54 (1H, d, J¼11.6 Hz, CH2Ph), 4.23e4.17 (3H, m, H3,
CH2Ph), 4.00 (1H, dd, J4,5¼0.8 Hz, J4,3¼2.8 Hz, H4), 3.92e3.86 (2H,
m, H2, H5), 3.49 (1H, dd, J6a,5¼7.2 Hz, J6a,6b¼9.6 Hz, H6a), 3.32 (1H,
dd, J6b,5¼5.6 Hz, J6b,6a¼9.6 Hz, H6b), 2.86e2.79 (1H, m, H10a), 2.43
(1H, dd, J1 b,2 a¼5.6 Hz, J1 b,1 a¼16.4 Hz, H10b), 2.10e2.02 (2H, m,
0
0
0
0
H10a), 2.45 (1H, dd, J1 b,2 a¼5.6 Hz, J1 b,1 a¼16.0 Hz, H10b), 2.14e2.05
H10b, H20a), 1.63e1.58 (1H, m, H20b); 13C NMR (CDCl3, 100 MHz):
0
0
0
0
(1H, m, H20a), 1.62e1.57 (1H, m, H20b); 13C NMR (CDCl3, 100 MHz):
d
150.48, 138.55, 138.41, 137.85, 137.73, 128.70, 128.69, 128.68,
d
153.72,145.70,138.62,138.52,138.00,137.84,128.67, 128.66, 128.41,
128.45,128.44,128.33,128.32,128.31,128.30,128.28,128.27,128.26,
128.25, 127.80, 127.79, 127.78, 127.69, 127.68, 127.67, 127.52, 127.51,
126.97, 125.71, 124.41, 118.85, 99.05, 80.34, 78.56, 75.79, 74.75,
74.59, 73.24, 72.80, 70.99, 68.65, 26.69, 20.60; ESIMS m/z (rel
intens) 676 (Mþ, 1), 181 (9), 91 (100); HRMS (EI) m/z calcd for
C42H41ClO6 676.2592, found 676.2595. Anal. Calcd for C42H41ClO6;
C: 74.49; H: 6.10. Found: C: 74.50; H: 6.16.
128.40, 128.30, 128.29, 128.28, 128.27, 128.26, 128.25, 128.24, 128.23,
127.84, 127.83, 127.73, 127.62, 127.61, 127.60, 127.50, 127.49, 123.30,
118.10, 113.43, 112.85, 98.76, 80.45, 78.84, 75.71, 74.72, 74.71, 73.12,
72.77, 70.76, 68.74, 55.50, 27.00, 21.03; ESIMS m/z (rel intens) 672
(Mþ,1), 181 (7), 91 (100); HRMS (EI) m/z calcd for C43H44O7 672.3087,
found 672.3091. Anal. Calcd for C43H44O7; C: 76.65; H: 6.73. Found: C:
76.69; H: 6.78.
3.2.9. 1,7-Dioxaspiro[5.5]undecane derivative 3i. Pale yellow oil;
3.2.6. 1,7-Dioxaspiro[5.5]undecane derivative 3f. Pale yellow oil;
[
a
]
25 þ25.82 (c 1.51, CHCl3); IR (CHCl3) 2950, 1634, 1489, 1107 cmꢀ1
;
D
25
[
a]
þ32.40 (c 1.50, CHCl3); IR (CHCl3) 2930, 1642, 1494,
1H NMR (CDCl3, 400 MHz)
d
7.34e7.17 (20H, m, ArH), 7.02e6.99
D
1105 cmꢀ1
;
1H NMR (CDCl3, 400 MHz)
d
7.35e7.15 (18H, m, ArH),
(2H, m, ArH), 6.70 (1H, d, J¼8.4 Hz, ArH), 4.90 (2H, d, J¼11.2 Hz,
CH2Ph), 4.74 (2H, br s, CH2Ph), 4.66 (1H, d, J¼11.2 Hz, CH2Ph), 4.55
(1H, d, J¼11.2 Hz, CH2Ph), 4.24e4.18 (3H, m, H3, CH2Ph), 4.00 (1H,
dd, J4,5¼1.2 Hz, J4,3¼2.8 Hz, H4), 3.92e3.86 (2H, m, H2, H5), 3.50
(1H, dd, J6a,5¼7.2 Hz, J6a,6b¼9.6 Hz, H6a), 3.32 (1H, dd, J6b,5¼5.6 Hz,
7.01e6.98 (2H, m, ArH), 6.74 (1H, d, J¼8.8 Hz, ArH), 6.58 (1H, dd,
J¼2.8 Hz, J¼8.8 Hz, ArH), 6.48 (1H, d, J¼2.8 Hz, ArH), 4.90 (1H, d,
J¼11.2 Hz, CH2Ph), 4.89 (1H, d, J¼11.2 Hz, CH2Ph), 4.74 (2H, br s,
CH2Ph), 4.67 (1H, d, J¼11.2 Hz, CH2Ph), 4.56 (1H, d, J¼11.2 Hz,

H.-C. Lin et al. / Tetrahedron 66 (2010) 5229e5234
5233
J6b,6a¼9.6 Hz, H6b), 2.89e2.80 (1H, m, H10a), 2.45 (1H, dd,
127.33,127.32,126.22,120.95,114.30, 94.24, 81.62, 76.34, 75.03, 74.76,
74.30, 73.46, 72.55, 71.85, 68.98, 55.15, 29.69, 26.50; FAB-MS m/z (rel
intens)689(MþHþ,15), 581(40), 243(35),181(65),149(80), 91(100),
55 (82); HRMS (FAB) m/z calcd for C43H45O6S (MþHþ) 689.2937,
found 689.2940. Anal. Calcd for C43H44O6S; C: 74.97; H: 6.44. Found:
C: 74.94; H: 6.41.
J1 b,2 a¼4.8 Hz, J1 b,1 a¼16.0 Hz, H10b), 2.11e2.02 (2H, m, H10b, H20a),
0
0
0
0
1.63e1.59 (1H, m, H20b); 13C NMR (CDCl3, 100 MHz):
d 151.09,
138.61, 138.46, 137.91, 137.79, 131.58, 129.91, 128.67, 128.66, 128.36,
128.35,128.34,128.33,128.32,128.31,128.30,128.29,128.27,128.26,
128.25, 128.24, 127.82, 127.81, 127.80, 127.69, 127.68, 127.54, 127.53,
125.04, 119.34, 113.18, 99.10, 80.36, 78.65, 75.80, 74.79, 74.78, 73.28,
72.85, 71.06, 68.70, 26.75, 20.60; ESIMS m/z (rel intens) 720 (Mþ, 1),
181 (11), 91 (100); HRMS (EI) m/z calcd for C42H41BrO6 720.2087,
found 720.2084. Anal. Calcd for C42H41BrO6; C: 69.90; H: 5.73.
Found: C: 69.95; H: 5.77.
3.2.13. 1-Oxa-7-thiaspiro[5.5]undecane derivative 5d. Pale yellow
25
oil; [
a
;
]
þ56.62 (c 4.35, CHCl3); IR (CHCl3) 2964, 1642, 1480, 1097
D
cmꢀ1
1H NMR (CDCl3, 400 MHz)
d 7.29e7.20 (17H, m, ArH),
6.95e6.88 (4H, m, ArH), 6.84e6.80 (2H, m, ArH), 4.90 (1H, d,
J¼11.6 Hz, CH2Ph), 4.88 (1H, d, J¼11.6 Hz, CH2Ph), 4.68 (1H, d,
J¼11.6 Hz, CH2Ph), 4.64 (1H, d, J¼11.6 Hz, CH2Ph), 4.62 (1H, d,
J¼11.6 Hz, CH2Ph), 4.49 (1H, d, J¼11.6 Hz, CH2Ph), 4.36e4.33 (3H, m,
H5, CH2Ph), 4.07 (1H, d, J¼9.6 Hz, H2), 3.99 (1H, dd, J3,4¼2.8 Hz,
J3,2¼9.6 Hz, H3), 3.93 (1H, br s, H4), 3.49e3.72 (2H, m, H6),
2.73e2.66 (1H, m, H10a), 2.15e2.01 (2H, m, H10b, H20a), 1.80e1.72
3.2.10. 1-Oxa-7-thiaspiro[5.5]undecane derivative 5a. Pale yellow
25
oil; [
a
]
þ1.21 (c 1.98, CHCl3); IR (CHCl3) 2950, 1644, 1492,
D
1100 cmꢀ1
;
1H NMR (CDCl3, 400 MHz)
d
7.28e6.99 (23H, m, ArH),
4.85 (1H, d, J¼11.6 Hz, CH2Ph), 4.82 (1H, d, J¼10.8 Hz, CH2Ph), 4.59
(2H, br s, CH2Ph), 4.53 (1H, d, J¼11.6 Hz, CH2Ph), 4.49 (1H, d,
J¼10.8 Hz, CH2Ph), 4.39 (1H, d, J¼11.6 Hz, CH2Ph), 4.35 (1H, d,
J¼11.6 Hz, CH2Ph), 4.06e4.02 (1H, m, H5), 3.93 (1H, br s, H4), 3.84
(1H, dd, J3,4¼2.8 Hz, J3,2¼9.6 Hz, H3), 3.69 (1H, d, J¼9.6 Hz, H2),
3.52e3.43 (2H, m, H6), 3.04e2.97 (1H, m, H10a), 2.79e2.73 (1H, m,
H10b), 2.23 (3H, s, CH3), 2.03e1.92 (1H, m, H20a), 1.81e1.74 (1H, m,
(1H, m, H20b); 13C NMR (CDCl3, 100 MHz):
d 138.78, 138.06, 137.85,
137.68, 134.69, 134.45, 131.46, 128.68, 128.67, 128.59, 128.58, 128.47,
128.46,128.45,128.44,128.41,128.40,128.31,128.30,128.23,128.22,
127.85, 127.78, 127.77, 127.71, 127.55, 127.54, 127.45, 127.37, 127.36,
94.59, 81.62, 75.77, 74.96, 74.66, 74.35, 73.53, 72.52, 72.18, 69.17,
37.36, 27.41; FAB-MS m/z (rel intens) 693 (MþHþ, 3), 585 (4), 243
(8), 181 (39), 91 (100), 55 (80); HRMS (FAB) m/z calcd for
C42H42ClO5S (MþHþ) 693.2441, found 693.2451. Anal. Calcd for
C42H41ClO5S; C: 72.76; H: 5.96. Found: C: 72.72; H: 5.93.
H20b); 13C NMR (CDCl3, 100 MHz):
d 140.86, 138.85, 138.36, 138.02,
137.91, 136.22, 131.92, 138.36, 138.35, 129.66, 129.65, 128.53, 128.52,
128.39, 128.38, 128.37, 128.28, 128.27, 128.19, 128.18, 127.85, 127.84,
127.82, 127.81, 127.60, 127.59, 127.51, 127.50, 126.95, 126.94, 98.50,
80.94, 78.72, 75.54, 74.38, 74.13, 73.41, 72.36, 70.17, 68.75, 37.26,
27.74, 20.97 ESIMS m/z (rel intens) 672 (Mþ, 1), 377 (6), 181 (7), 91
(100); HRMS (EI) m/z calcd for C43H44O5S 672.2909, found 672.2902.
Anal. Calcd for C43H44O5S; C: 76.75; H: 6.59. Found: C: 76.71; H: 6.54.
3.2.14. 1-Oxa-7-thiaspiro[5.5]undecane derivative 5e. Pale yellow
25
oil; [
a
]
D
þ131.58 (c 1.16, CHCl3); IR (CHCl3) 2950, 1643, 1466,
1094 cmꢀ1 1H NMR (CDCl3, 400 MHz)
; d 7.31e7.17 (17H, m, ArH),
7.12e7.06 (4H, m, ArH), 6.78e6.76 (2H, m, ArH), 4.91 (1H, d,
J¼11.6 Hz, CH2Ph), 4.90 (1H, d, J¼11.6 Hz, CH2Ph), 4.70 (1H, d,
J¼11.6 Hz, CH2Ph), 4.67 (1H, d, J¼11.6 Hz, CH2Ph), 4.64 (1H, d,
J¼11.6 Hz, CH2Ph), 4.51 (1H, d, J¼11.6 Hz, CH2Ph), 4.41e4.35 (3H, m,
H5, CH2Ph), 4.08 (1H, d, J¼9.6 Hz, H2), 4.00 (1H, dd, J3,4¼2.4 Hz,
J3,2¼9.6 Hz, H3), 3.95 (1H, br s, H4), 3.50e3.48 (2H, m, H6),
2.74e2.67 (1H, m, H10a), 2.15e2.02 (2H, m, H10b, H20a), 1.82e1.74
3.2.11. 1-Oxa-7-thiaspiro[5.5]undecane derivative 5b. Pale yellow
25
oil; [
a
]
þ5.54 (c 1.64, CHCl3); IR (CHCl3) 2960, 1642, 1493,
D
1094 cmꢀ1
;
1H NMR (CDCl3, 400 MHz)
d
7.26e7.17 (23H, m, ArH),
4.85 (1H, d, J¼11.6 Hz, CH2Ph), 4.83 (1H, d, J¼11.6 Hz, CH2Ph), 4.66
(1H, d, J¼11.6 Hz, CH2Ph), 4.58 (1H, d, J¼11.6 Hz, CH2Ph), 4.55 (1H, d,
J¼11.6 Hz, CH2Ph), 4.52 (1H, d, J¼11.6 Hz, CH2Ph), 4.40 (1H, d,
J¼11.6 Hz, CH2Ph), 4.36 (1H, d, J¼11.6 Hz, CH2Ph), 4.06e4.03 (1H, m,
H5), 3.94 (1H, br s, H4), 3.84 (1H, dd, J3,4¼2.4 Hz, J3,2¼9.6 Hz, H3),
3.72 (1H, d, J¼9.6 Hz, H2), 3.55e3.44 (2H, m, H6), 3.05e2.98 (1H, m,
H10a), 2.82e2.75 (1H, m, H10b), 2.04e1.96 (1H, m, H20a), 1.84e1.80
(1H, m, H20b), 1.20 (9H, br s, 3CH3); 13C NMR (CDCl3, 100 MHz):
(1H, m, H20b); 13C NMR (CDCl3, 100 MHz):
d 138.81, 138.09, 137.87,
137.70, 135.47, 128.53, 128.52, 128.51, 128.50, 128.49, 128.48, 128.47,
128.46, 128.45, 128.38, 128.37, 128.27, 128.26, 127.92, 127.85, 127.84,
127.83, 127.76, 127.61, 127.60, 127.51, 127.42, 127.41, 122.72, 119.30,
94.62, 81.67, 75.78, 75.01, 74.70, 74.40, 73.60, 72.60, 72.24, 69.23,
37.37, 27.24; FAB-MS m/z (rel intens) 737 (MþHþ, 6), 631 (10), 629
(9), 181 (63), 90 (100); HRMS (FAB) m/z calcd for C42H42BrO5S
(MþHþ) 737.1936, found 737.1941. Anal. Calcd for C42H41BrO5S; C:
68.38; H: 5.60. Found: C: 68.31; H: 5.57.
d
149.35,138.85,138.35,138.03,137.90,132.15,129.64,129.63,128.42,
128.41, 128.39, 128.38, 128.37, 128.31, 128.30, 128.20, 128.19, 127.85,
127.84, 127.81, 127.80, 127.68, 127.58, 127.51, 127.50, 127.44, 125.91,
125.90, 98.51, 80.97, 78.59, 75.50, 74.38, 74.10, 73.41, 72.35, 70.19,
68.72, 37.32, 34.39, 31.25, 31.24, 31.23, 27.40; FAB-MS m/z (rel intens)
715 (MþHþ, 1), 253 (6), 181 (22), 105 (22), 91 (100), 57 (73); HRMS
(FAB) m/z calcd for C46H51O5S (MþHþ) 715.3457, found 715.3449.
Anal. Calcd for C46H50O5S; C: 77.28; H: 7.05. Found: C: 77.32; H: 7.01.
Acknowledgements
The authors thank the National Science Council of Taiwan
(NSC97-2113-M-039-001) and China Medical University, Taiwan
(CMU95-194 and CMU97-226) for their financial support.
3.2.12. 1-Oxa-7-thiaspiro[5.5]undecane derivative 5c. Pale yellow
25
oil; [
a
;
]
þ24.40 (c 0.79, CHCl3); IR (CHCl3) 2955, 1645, 1496, 1095
D
cmꢀ1
1H NMR (CDCl3, 400 MHz)
d 7.26e7.17 (18H, m, ArH),
Supplementary data
7.02e7.00(2H, m, ArH), 6.57e6.53(3H, m, ArH), 4.90(1H, d,J¼11.6 Hz,
CH2Ph), 4.80 (1H, d, J¼11.6 Hz, CH2Ph), 4.68 (1H, d, J¼11.6 Hz, CH2Ph),
4.64 (1H, d, J¼11.6 Hz, CH2Ph), 4.51 (1H, d, J¼11.6 Hz, CH2Ph),
4.45e4.42 (1H, m, H5), 4.37 (2H, br s, CH2Ph), 4.05 (1H, d, J¼9.6 Hz,
H2), 4.00 (1H, dd, J3,4¼2.4 Hz, J3,2¼9.6 Hz, H3), 3.93 (1H, dd,
J4,5¼1.2 Hz, J4,3¼2.4 Hz, H4), 3.65 (3H, s, OCH3), 3.51 (1H, dd,
J6a,5¼6.8 Hz, J6a,6b¼9.6 Hz, H6a), 3.44 (1H, dd, J6b,5¼4.8 Hz,
J6b,6a¼9.6 Hz, H6b), 2.69e2.61 (1H, m, H10a), 2.35e2.27 (1H, m, H10b),
2.10e2.03 (1H, m, H20a), 1.87e1.78 (1H, m, H20b); 13C NMR (CDCl3,
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2010.04.075.
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