Highly diastereoselective Diels-Alder reactions of acrylic esters incorporated into a variety of hexopyranosides

Article abstract of DOI:10.1081/CAR-100108271

The Diels-Alder reactions of a variety of hexopyranosides carrying an acrylic ester with cyclopentadiene were examined. Some acrylic esters provided the cycloaddition products carrying a norbornene carboxylate with a high level of diastereoselectivity. Plausible mechanisms are presented for the cases of a 4-O-acryloyl-6-deoxy-α-D-glucopyranosidic and 2-O-acryloyl-α-D-glucopyranosidic substrates. By reductive removal of the carbohydrate templates from the adducts, either 2S or 2R-enriched 5-norbornene-2-methanol were obtained.

Full text of DOI:10.1081/CAR-100108271

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HIGHLY DIASTEREOSELECTIVE DIELS-ALDER
REACTIONS OF ACRYLIC ESTERS INCORPORATED INTO
A VARIETY OF HEXOPYRANOSIDES
Takayuki Nagatsuka a , Shuhei Yamaguchi a , Kiichiro Totani a , Ken-ichi Takao a & Kin-ichi
Tadano b
a Department of Applied Chemistry , Keio University , Hiyoshi, Kohoku-ku, Yokohama,
223-8522, Japan
b Department of Applied Chemistry , Keio University , Hiyoshi, Kohoku-ku, Yokohama,
223-8522, Japan
Published online: 16 Aug 2006.
To cite this article: Takayuki Nagatsuka , Shuhei Yamaguchi , Kiichiro Totani , Ken-ichi Takao & Kin-ichi Tadano
(2001) HIGHLY DIASTEREOSELECTIVE DIELS-ALDER REACTIONS OF ACRYLIC ESTERS INCORPORATED INTO A VARIETY OF
HEXOPYRANOSIDES, Journal of Carbohydrate Chemistry, 20:7-8, 519-535
To link to this article: http://dx.doi.org/10.1081/CAR-100108271
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J. CARBOHYDRATE CHEMISTRY, 20(7&8), 519–535 (2001)
HIGHLY DIASTEREOSELECTIVE DIELS-ALDER
REACTIONS OF ACRYLIC ESTERS
INCORPORATED INTO A VARIETY OF
HEXOPYRANOSIDES
Takayuki Nagatsuka, Shuhei Yamaguchi, Kiichiro Totani,
Ken-ichi Takao, and Kin-ichi Tadano*
Department of Applied Chemistry, Keio University, Hiyoshi,
Kohoku-ku, Yokohama 223-8522, Japan
This paper is dedicated to Professor Joachim Thiem with respect and ad-
miration on the occasion of his 60th birthday.
ABSTRACT
The Diels-Alder reactions of a variety of hexopyranosides carrying an acrylic
ester with cyclopentadiene were examined. Some acrylic esters provided the
cycloaddition products carrying a norbornene carboxylate with a high level of
diastereoselectivity. Plausible mechanisms are presented for the cases of a 4-
O-acryloyl-6-deoxy-ꢀ-D-glucopyranosidic and 2-O-acryloyl-ꢀ-D-glucopyra-
nosidic substrates. By reductive removal of the carbohydrate templates from
the adducts, either 2S or 2R-enriched 5-norbornene-2-methanol were obtained.
INTRODUCTION
The use of chiral auxiliaries prepared from readily available natural products,
such as carbohydrates, is one of the promising approaches for asymmetric synthe-
sis of chiral compounds.1,2 Several carbohydrate derivatives are sources of chiral
nonracemic materials, from which synthetically useful auxiliaries have been de-
signed and prepared.3–6 We have studied extensively the utility of hexopyranose
derivatives as chiral templates for stereoselective carbon-carbon bond forming re-
*Corresponding author.
519
Copyright © 2001 by Marcel Dekker, Inc.
www.dekker.com

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NAGATSUKA ET AL.
Scheme 1.
actions, and reported the highly stereoselective 1,4-conjugate additions of
organocopper reagents7 or alkyl radicals8 to a variety of hexopyranose-derived chi-
ral crotonyl esters. In this paper, we report in detail the results on the intermolecu-
lar Diels-Alder reactions conducted using chiral acrylic esters incorporated into
methyl ꢀ-D-gluco- and mannopyranosidic templates.9,10
RESULTS AND DISCUSSION
4-O-Acrylic ester derivatives of methyl 6-deoxy-ꢀ-D-glucopyranoside 2, 4,
and 6 (Scheme 1) as substrates for the attempted Diels-Alder reaction, were pre-
pared from known 2,3-O-alkylated 1,7 2,3-O-acylated 3,7 or 2,3-O-silylated 58
methyl 6-deoxy-ꢀ-D-glucopyranosides, respectively, by acryloylation at 4-OH.
Acrylic esters incorporated at C-2 of methyl ꢀ-D-mannopyranoside 9, 11, and 12
(Scheme 1) were prepared from the known 4,6-O-benzyl derivative of methyl ꢀ-D-
mannopyranoside 711 via regioselective benzylation of 3-OH (for 8) or regioselec-
tive acryloylation of 2-OH (for 10) followed by acryloylation (for 9) or acylation
(for 11 and 12), respectively. On the other hand, 2-acrylic ester 15 (Scheme 1) was
prepared from methyl 4,6-O-benzyl-ꢀ-D-glucopyranoside 13,12 which was in turn
prepared from methyl 4,6-O-benzylidene-ꢀ-D-glucopyranoside in an overall yield
Scheme 2.

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521
Table 1. Diels-Alder Reaction of the Substrates 2, 4 and 6 Under Thermal Condi-
tionsa
Entry
Substrate
Yieldb
Endo:Exoc
Endo-S:Rc
1
2
3
2
4
6
96
96
97
79:21
89:11
80:20
71:29
87:13
ꢄ95:5
a Cyclopentadiene, CH2Cl2, rt, 2–5 days. bCombined yield of diastereomeric
adducts (%). cDetermined by 1H NMR analysis.
of 62% (four steps), via regioselective acryloylation of 2-OH followed by silyla-
tion of 3-OH.
We investigated first the Diels-Alder reactions of the methyl 6-deoxy-ꢀ-D-
glucopyranosidic substrates 2, 4, and 6 with cyclopentadiene (Scheme 2). The re-
sults under thermal conditions (conducted at room temperature) are shown in Table
1. In every case, the Diels-Alder reaction proceeded efficiently to provide the
adduct as a mixture of diastereomers (endo-S, endo-R, and exo isomers). The ratio
of the endo/exo isomers and the diastereomeric ratio of the two endo adducts
(16S:16R, 17S:17R, or 18S:18R) were determined by 1H NMR analysis on the ba-
sis of the integration ratio of ring protons on each norbornene part in the diastere-
omeric mixture. In the case of 2,3-O-benzyl derivative 2, moderate endo/exo se-
lectivity and moderate diastereoselectivity in the ꢁ-facial attack leading to the two
endo-adducts were observed (entry 1). The reaction of 4 or 6, which possesses a
bulkier substituent (R ꢂ Piv or TBS) at C-3, afforded the endo-S adduct 17S or 18S
with improved diastereoselectivity (entries 2 and 3). However, the endo/exo selec-
tivity was not satisfactorily high in each case. The absolute configuration for the
newly formed norbornene ring was determined by comparison with the reported
optical signs for both enantiomers of 5-norbornene-2-carboxylic acid and/or 2-
methanol,13–15 prepared by hydrolytic or reductive removal of the carbohydrate
templates. In the case of the substrate 6, the mixture of the endo adducts 18S/18R
was obtained after separating the minor exo adducts by chromatographic purifica-
tion on silica gel (Scheme 3). Removal of the carbohydrate templates from this
mixture was conducted by reductive cleavage using DIBALH to provide (2S) en-
riched 5-norbornene-2-methanol 19S. The carbohydrate template 5 was recovered
efficiently. The optical rotation of (2S)-enriched 19S was [ꢀ]22D ꢃ69° (c 0.195,
Scheme 3.

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NAGATSUKA ET AL.
Table 2. Diels-Alder Reaction of the Substrates 2, and 4 in the Presence of
EtAlCl2a
Entry
Substrate
Yieldb
Endo:Exoc
Endo-S:Rc
1
2
3
2
4
6
63
79
ꢄ95:5
ꢄ95:5
—
ca. 1:1
10:90
—
NRd
b
a EtAlCl2 (2 eq), cyclopentadiene, CH2Cl2, ꢃ78ꢆC, 15 min. Combined yield of
c
1
d
diastereomeric adducts (%). Determined by H NMR analysis. Reaction did not
take place.
EtOH), and that of enantiopure (2S)-endo-5-norbornene-2-methanol is [ꢀ]D
ꢃ76.6° (95% EtOH). Therefore, the absolute stereochemistry of 19S was estab-
lished. Benzoylation of the (2S) enriched 19S and HPLC analysis (serial connec-
tion of Chiralcel ODꢅODMH; hexane:EtOH ꢂ 300:1) of the resulting benzoate
verified that the enantiomeric ratio (2S :2R) of 19 was 97:3.
The results of the Diels-Alder reactions of 2 and 4 conducted in the presence
of EtAlCl2 (2 molar equivalents) as Lewis acid are summarized in Table 2. The
Diels-Alder reactions proceeded at ꢃ78 °C efficiently to provide a mixture of the
endo adducts 16S/16R or 17S/17R predominantly although the combined yield of
two endo adducts was moderate in each case (entries 1 and 2). In the case of 4,
highly diastereoselective formation of the endo adduct 17R was observed. Inter-
estingly, the p-facial selectivity in the Lewis acid mediated endo mode Diels-Alder
Figure 1. Plausible transition states of Diels-Alder reactions for substrate 4.

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523
Scheme 4.
reaction of 4 was opposite to that observed under the thermal conditions (entry 2
in Table 1 vs. entry 2 in Table 2). We propose a plausible transition state mecha-
nism to interpret this reverse p-facial selectivity observed using the substrate 4 un-
der the thermal or the Lewis acid mediated conditions (Figure 1). In the case of the
thermal conditions, the dienophile part is apt to exist in an s-cis, syn conformation
(TS-1). Then cyclopentadiene approaches from the less hindered side by reason of
avoiding the steric hindrance expected by the presence of a substituent at C-3 such
as a pivaloyloxy group in the case of 4. Consequently, the endo-S adduct 17S was
obtained predominantly. By comparison, in the presence of EtAlCl2, the dienophile
part is likely to change to s-trans, syn conformation as a result of Lewis acid coor-
dination to the acryloyl carbonyl.16,17 Cyclopentadiene can then favorably ap-
proach the dienophile part from the less hindered side (TS-2). As a result, the endo-
R adduct 17R was obtained predominantly under the latter conditions.
Next we investigated the Diels-Alder reactions of the ꢀ-D-mannopyranosidic
substrates 9, 11, and 12 with cyclopentadiene (Scheme 4). The Diels-Alder reac-
tions of these substrates under thermal conditions proceeded with no significant ꢁ-
facial selectivities (d.r. of two endo adducts was ca. 1 : 1 in every case). In contrast,
the Diels-Alder reactions in the presence of Lewis acid proceeded stereoselec-
tively, especially in the cases of 11 and 12. The results are summarized in Table 3.
Table 3. Diels-Alder Reaction of the Substrates 9, 11, and 12 in the Presence of
EtAlCla2
Entry
Substrate
Yieldb
Endo:Exoc
Endo-S:Rc
1
2
3
9
11
12
83
84
98
ꢄ95:5
ꢄ95:5
ꢄ95:5
33:67
9:91
11:89
b
a EtAlCl2 (2 eq), cyclopentadiene, CH2Cl2, ꢃ78ꢆC, 15 min. Combined yield of
diastereomeric adducts (%). cDetermined by 1H NMR analysis.

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NAGATSUKA ET AL.
Scheme 5.
The Diels-Alder reaction proceeded at ꢃ78 °C to provide a mixture of two endo
adducts 20S/20R-22S/22R with high endo/exo selectivity. Also, the substrates 11
and 12 possessing an acyloxy substituent at C-3 provided the respective endo-R
adducts 21R and 22R with remarkably high diastereoselectivity (entry 1 vs. entries
2 and 3). As shown in Scheme 5, the diastereomerically homogeneous endo-R
adduct 22R was separated from other adducts by chromatographic separation on
silica gel. After reductive cleavage of the carbohydrate template, enantiomerically
pure (2R)-endo-5-norbornene-2-methanol 19R was obtained. The carbohydrate
template 7 was recovered quantitatively.
We investigated the influence of the stoichiometry of Lewis acid on the
Diels-Alder reaction using 4 or 11 as the substrate. The results are summarized in
Table 4. Independent of the amount of EtAlCl2, high endo/exo selectivities were
observed in every case. Despite the low yield of the reaction, the substrate 4 pro-
vided 17R with high ꢁ-facial selectivity using 1 equiv of EtAlCl2.
Finally, we conducted the Diels-Alder reaction of another glucopyranose
derivative 15, which was more accessible than the 6-deoxyglucopyranosidic sub-
strates 2, 4, and 6 (Scheme 6). As shown in Table 5, the Diels-Alder reaction un-
der thermal conditions provided the endo-R adduct 23R preferentially although the
endo/exo selectivity was moderate. On the other hand, the Lewis acid promoted
Diels-Alder reaction proceeded smoothly at ꢃ78 °C to provide the endo-S adduct
23S with high endo/exo and ꢁ-facial selectivities. As shown in Figure 2, this stere-
ochemical reversal of the ꢁ-facial selectivity can be interpreted using the analo-
gous transition state argument described for the case of 4. The conformational
Table 4. Influence of EtAlCl2 Stoichiometrya
Entry
Substrate
EtAlCl2 (eq.)
Yieldb (%)
Endo:exoc
Endo-S:Rc
1
2
3
4
5
6
4
4
4
11
11
11
1
2
4
1
2
4
ca. 30
79
ꢄ95:5
ꢄ95:5
ꢄ95:5
ꢄ95:5
ꢄ95:5
ꢄ95:5
12:88
10:90
8:92
17:83
9:91
85
83
85
84
10:90
a EtAlCl2, cyclopentadiene, CH2Cl2, ꢃ78ꢆC, 15 min. b Combined yield of diastereomeric adducts
(%). c Determined by 1H NMR analysis.

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525
Scheme 6.
Table 5. Diels-Alder Reaction of the Gluco-Type Substrate 15
Entry
EtAlCl2 (eq.)
Time/temp.
Yielda
Endo:exob
Endo-S:Rb
1
2
—
2
2 days/rt
1 h/ꢃ78ꢆC
96
97
74:26
94:6
9:91
92:8
a Combined yield of diastereomeric adducts (%). b Determined by 1H NMR analysis.
Figure 2. Plausible transition states of Diels-Alder reactions for substrate 15.

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NAGATSUKA ET AL.
Scheme 7.
change of the acryloyl ester part in the presence of EtAlCl2 is responsible for the
reversal of the ꢁ-facial selectivity (TS-3 vs TS-4). As shown in Scheme 7, the mix-
ture of the endo-adducts 24S/24R was readily obtained by separation of the exo-
isomers from the mixture of the adducts 23 after desilylation of the 2-O-TBS
group.
In summary, we have found a novel diastereoselective Diels-Alder reaction
realized on the carbohydrate templates. The present work provides a practical
method to prepare optically active chiral norbornene derivatives. In some cases, the
predominant endo adducts can be readily separated from the other diastereomers.
Removal of the carbohydrate templates from the endo-adducts provides enan-
tiomerically enriched or pure (2S) or (2R)-endo-5-norbornene-2-methanol.
EXPERIMENTAL
General Methods. Specific rotations were measured in a 10 mm cell by a
JASCO DIP-370 instrument. IR spectra were recorded by a JASCO FT-IR-200
spectrometer. 1H (300 MHz) and 13C NMR (75 MHz) spectra were recorded by a
JEOL JNM-LA 300FT NMR spectrometer in CDCl3 solution with tetramethylsi-
lane as an internal standard. High-resolution mass spectra (HRMS) were measured
by a JEOL JMS-GC MATE spectrometer (EI, 70 eV). Thin-layer chromatography
(TLC) was performed on Merck Kieselgel 60 F254 plates. Crude reaction mixtures
and extractive materials were purified by chromatography on silica gel 60K070
(Katayama Chemical) or Wakogel C-300 (Wako Chemicals). Unless otherwise de-
scribed, reactions were carried out at room temperature. Combined organic ex-
tracts were dried over anhydrous Na2SO4. Solvents were removed from the reac-
tion mixture or combined organic extracts by concentration under reduced pressure
using an evaporator at a bath temperature of 30–40 °C.
The Preparation of the Substrates 2, 4, 6 and 9. To a cooled (ꢃ18 °C)
stirred solution of 17 (644 mg, 1.56 mmol) in CH2Cl2 (15 mL) were added acryloyl
chloride (0.26 mL, 3.2 mmol) and triethylamine (0.88 mL, 6.3 mmol). The mixture

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527
was stirred for 20 min and quenched with saturated aqueous NaHCO3, diluted with
CHCl3 (100 mL) and then washed with saturated aqueous NaHCO3 (50 mL ꢇ 3).
The organic layer was dried and concentrated in vacuo. The residue was purified
by column chromatography on silica gel (EtOAc:hexane, 1:7) to give 566 mg
(76%) of 2. Analogously, the substrates 4, 6, and 9 were prepared from 37 (75%),
58 (98%), and 811 (53%), respectively.
Methyl 4-O-acryloyl-2,3-di-O-benzyl-6-deoxy-ꢀ-D-glucopyranoside (2).
Compound 2 was obtained as a colorless oil : TLC, Rf 0.37 (EtOAc:hexane, 1:3);
[ꢀ]2D8.0 ꢅ28.7° (c 0.66, CHCl3); IR (neat) 3100ꢃ2800, 1735, 1635 cmꢃ1; 1H NMR
ꢈ 1.13 (d, J ꢂ 6.1 Hz, 3H, 6-CH3), 3.39 (s, 3H, OMe), 3.58 (dd, J ꢂ 3.7, 9.5 Hz,
1H, H-2), 3.79 (dq, J ꢂ 9.6, 6.1 Hz, 1H, H-5), 3.91 (t, J ꢂ 9.4 Hz, 1H, H-3), 4.54
(d, J ꢂ 3.6 Hz, 1H, H-1), 4.63, 4.84 (ABq, J ꢂ 11.2 Hz, 2H, CH2MPh), 4.65, 4.80
(ABq, J ꢂ 12.0 Hz, 2H, CH2MPh), 4.83 (t, J ꢂ 9.6 Hz, 1H, H-4), 5.84 (dd, J
ꢂ 1.5, 10.4 Hz, 1H, COCHBCHH), 6.05 (dd, J ꢂ 10.4, 17.3 Hz, 1H,
COCHBCHH), 6.40 (dd, J ꢂ 1.5, 17.3 Hz, 1H, COCHBCHH), 7.24–7.35 (m,
10H, Ph ꢇ 2); 13C NMR ꢈ 17.32, 55.29, 65.34, 73.46, 75.27, 75.39, 78.94, 79.86,
98.17, 127.48, 127.93 ꢇ 4, 128.11, 128.14, 128.27 ꢇ 2, 128.45 ꢇ 2, 131.28,
138.06, 138.47, 165.15. HRMS: Calcd for C24H28O6 (M)ꢅm/z: 412.1886. Found:
412.1883.
Methyl 4-O-acryloyl-6-deoxy-2,3-di-O-pivaloyl-ꢀ-D-glucopyranoside (4).
Compound 4 was obtained as colorless crystals: mp 71.0–73.0 °C; TLC, Rf 0.75
(EtOAc:hexane, 1:4); [ꢀ]2D5.0 ꢅ124° (c 1.59, CHCl3); IR (neat) 3100ꢃ2800, 1740,
1635 cmꢃ1; 1H NMR ꢈ 1.08, 1.17 (2s, 18H, OPiv ꢇ 2), 1.20 (d, J ꢂ 6.3 Hz, 3H,
6-CH3), 3.39 (s, 3H, OMe), 3.93 (dq, J ꢂ 10.0, 6.3 Hz, 1H, H-5), 4.82 (dd, J ꢂ 3.8,
10.0 Hz, 1H, H-2), 4.90 (d, J ꢂ 3.8 Hz, 1H, H-1), 4.94 (t, J ꢂ 10.0 Hz, 1H, H-3),
5.56 (t, J ꢂ 10.0 Hz, 1H, H-4), 5.87 (dd, J ꢂ 1.2, 10.5 Hz, 1H, COCHBCHH),
6.05 (dd, J ꢂ 10.2, 17.2 Hz, 1H, COCHBCHH), 6.40 (dd, J ꢂ 1.2 Hz, 17.2 Hz,
1H, COCHBCHH); 13C NMR ꢈ 17.11, 26.88 ꢇ 3, 26.91 ꢇ 3, 38.57, 38.62, 55.40,
65.04, 69.17, 71.24, 73.56, 96.62, 127.58, 132.01, 164.79, 177.01, 177.61. HRMS:
Calcd for C19H29O7 (MMOCH3)ꢅm/z: 369.1913. Found: 369.1903.
Methyl 4-O-acryloyl-2,3-di-O-t-butyldimethylsilyl-6-deoxy-ꢀ-D-glucopy-
ranoside (6). Compound 6 was obtained as colorless crystals: mp 88.0–90.0 °C:
TLC, Rf 0.64 (EtOAc:hexane, 1:8); [ꢀ]2D6.0 ꢅ70.0° (c 1.82, CHCl3); IR (neat)
1
3100ꢃ2800, 1730, 1635 cmꢃ1; H NMR ꢈ 0.00, 0.07, 0.10, 0.10 (4s, 12H,
(t-Bu)(CH3)2Si ꢇ 2), 0.80, 0.92 (2s, 18H, (t-Bu)(CH3)2Si ꢇ 2), 1.11 (d, J ꢂ 6.6
Hz, 3H, 6-CH3), 3.37 (s, 3H, OMe), 3.67 (dd, J ꢂ 3.7, 9.1 Hz, 1H, H-2), 3.73–3.79
(m, 1H, H-5), 3.94 (t, J ꢂ 9.1 Hz, 1H, H-3), 4.62 (d, J ꢂ 3.7 Hz, 1H, H-1), 4.75 (t,
J ꢂ 9.1 Hz, 1H, H-4), 5.86 (dd, J ꢂ 1.7, 10.4 Hz, 1H, COCHBCHH), 6.13 (dd, J
ꢂ 10.4, 17.4 Hz, 1H, COCHBCHH), 6.43 (dd, J ꢂ 1.7, 17.4 Hz, 1H,
COCHBCHH); 13C NMR ꢈ ꢃ4.56, ꢃ4.43, ꢃ3.44, ꢃ3.03, 17.53, 17.76, 18.37,
25.79 ꢇ 3, 26.12 ꢇ 3, 55.02, 65.44, 71.80, 74.37, 76.52, 100.19, 128.49, 131.45,
165.30. HRMS: Calcd for C21H41O5Si2 (MMOCH3)ꢅm/z: 429.2493. Found:
429.2483.

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NAGATSUKA ET AL.
Methyl 2-O-acryloyl-3,4,6-tri-O-benzyl-ꢀ-D-mannopyranoside (9).
Compound 9 was obtained as a colorless oil: TLC, Rf 0.58 (EtOAc:hexane, 1:2);
1
[ꢀ]2D5.0ꢅ 15.2° (c 0.525, CHCl3); IR (neat) 3100ꢃ2800, 1730 cmꢃ1; H NMR ꢈ
3.37 (s, 3H, OMe), 3.71–3.84 (m, 3H, H-5, 6, 6ꢉ), 3.91 (t, J ꢂ 9.3 Hz, 1H, H-4),
4.01 (dd, J ꢂ 3.4, 9.3 Hz, 1H, H-3), 4.48, 4.68 (ABq, J ꢂ 11.0 Hz, 2H, CH2-Ph),
4.52, 4.72 (ABq, J ꢂ 12.5 Hz, 2H, CH2-Ph), 4.52, 4.85 (ABq, J ꢂ 10.7 Hz, 2H,
CH2-Ph), 4.77 (d, J ꢂ 1.9 Hz, 1H, H-1), 5.45 (dd, J ꢂ 1.9 Hz, 3.4 Hz, 1H, H-2),
5.86 (dd, J ꢂ 1.5, 10.4 Hz, 1H, COCHBCHH), 6.21 (dd, J ꢂ 10.4, 17.3 Hz, 1H,
COCHBCHH), 6.47 (dd, J ꢂ 1.5, 17.3 Hz, 1H, COCHBCHH), 7.14–7.37 (m,
15H, Ph ꢇ 3); 13C NMR ꢈ 54.96, 68.63, 68.91, 71.26, 71.62, 73.41, 74.27, 75.14,
78.14, 98.73, 127.55, 127.60, 127.67, 127.71 ꢇ 2, 127.86 ꢇ 2, 128.03 ꢇ 2, 128.18,
128.29 ꢇ 4, 128.34 ꢇ 2, 131.63, 137.93, 138.24, 138.37, 165.45. HRMS: Calcd
for C30H31O6 (MMOCH3)ꢅm/z: 487.2121. Found: 487.2119.
Methyl 2-O-acryloyl-4,6-di-O-benzyl-ꢀ-D-mannopyranoside (10). To a
cooled (0 °C) stirred solution of 711 (1.48 g, 3.96 mmol) in THF (30 mL) was added
NaH (60% in mineral oil, 361 mg, 9.03 mmol). After the mixture was stirred for 1
h at 0 °C, HgCl2 (1.08 g, 3.96 mmol) was added. The mixture was stirred at 0 °C
for 1 h and acryloyl chloride (0.66 mL, 7.90 mmol) was added. After being stirred
at 0 °C for 1.5 h, the mixture was quenched with water and several drops of AcOH,
diluted with EtOAc (200 mL), and washed with saturated aqueous NaHCO3 (100
mL ꢇ 2). The organic layer was dried and concentrated in vacuo. The residue was
purified by column chromatography on silica gel (EtOAc:hexane, 1:5 to 1:1) to
give 1.47 g (87%) of 10 as a colorless oil and 0.147 g (9%) of the 3-O-acryloyl
derivative. Compound 10 as a colorless oil: TLC, Rf 0.74 (EtOAc:toluene, 1:1);
[ꢀ]2D5.0 ꢅ31.1° (c 0.90, CHCl3); IR (neat) 3460, 3100ꢃ2800, 1725 cmꢃ1; 1H NMR
ꢈ 1.95 (b, 1H, OH), 3.37 (s, 3H, OMe), 3.72–3.85 (m, 4H, H-4, 5, 6, 6ꢉ), 4.16 (dd,
J ꢂ 3.6, 8.6 Hz, 1H, H-3), 4.54, 4.71(ABq, J ꢂ 12.0 Hz, 2H, CH2-Ph), 4.57, 4.77
(ABq, J ꢂ 10.5 Hz, 2H, CH2-Ph), 4.77 (d, J ꢂ 1.7 Hz, 1H, H-1), 5.17 (dd, J ꢂ 1.7,
3.6 Hz, 1H, H-2), 5.88 (dd, J ꢂ 1.5, 10.5 Hz, 1H, COCHBCHH), 6.19 (dd, J
ꢂ 10.5, 17.3 Hz, 1H, COCHBCHH), 6.45 (dd, J ꢂ 1.5, 17.3 Hz, 1H,
COCHBCHH), 7.22–7.36 (m, 10H, Ph ꢇ 2); 13C NMR ꢈ 55.04, 68.87, 70.44,
71.01, 72.54, 73.51, 74.83, 75.86, 98.47, 127.62, 127.76 ꢇ 2, 127.81, 127.85 ꢇ 2,
127.94, 128.32 ꢇ 2, 128.44 ꢇ 2, 131.84, 138.16, 138.21, 165.85. HRMS: Calcd
for C24H28O7 (M)ꢅm/z: 428.1815. Found: 428.1839.
Methyl 2-O-acryloyl-3-O-benzoyl-4,6-di-O-benzyl-ꢀ-D-mannopyra-
noside (11). To a cooled (0 °C) stirred solution of 10 (70.2 mg, 0.164 mmol) in
pyridine (2 mL) was added benzoyl chloride (0.05 mL, 0.4 mmol). The mixture
was stirred for 13 h, diluted with EtOAc (20 mL), and washed with saturated aque-
ous NaHCO3 (10 mL ꢇ 5). The organic layer was dried and concentrated in vacuo.
The residue was purified by column chromatography on silica gel (EtOAc:hexane,
1:5) to provide 72.5 mg (83%) of 11 as a colorless oil: TLC, Rf 0.51 (EtOAc:hex-
ane, 1:2); [ꢀ]2D5.0 ꢃ8.0° (c 2.01, CHCl3); IR (neat) 3200ꢃ2800, 1730, 1640, 1620,
1600 cmꢃ1; 1H NMR ꢈ 3.42 (s, 3H, OMe), 3.75 (dd, J ꢂ 1.7, 10.7 Hz, 1H, H-6),

ORDER
REPRINTS
DIELS-ALDER REACTIONS
529
3.85–3.96 (m, 2H, H-5, 6ꢉ), 4.19 (t, J ꢂ 9.8 Hz, 1H, H-4), 4.50, 4.63 (ABq, J
ꢂ 10.7 Hz, 2H, CH2-Ph), 4.55, 4.74 (ABq, J ꢂ 11.9 Hz, 2H, CH2-Ph), 4.82 (d, J
ꢂ 2.0 Hz, 1H, H-1), 5.45 (dd, J ꢂ 2.0, 3.4 Hz, 1H, H-2), 5.66 (dd, J ꢂ 3.4, 9.8 Hz
1H, H-3), 5.87 (dd, J ꢂ 1.5, 10.4 Hz, 1H, COCHBCHH), 6.20 (dd, J ꢂ 10.4, 17.3
Hz, 1H, COCHBCHH), 6.42 (dd, J ꢂ 1.5, 17.3 Hz, 1H, COCHBCHH),
7.03–7.60 (m, 15H, Ph ꢇ 3); 13C NMR ꢈ 55.12, 68.61, 70.37, 71.23, 72.36, 73.12,
73.55, 74.85, 98.53, 127.65 ꢇ 2, 127.80 ꢇ 2, 127.83 ꢇ 2, 127.86, 128.22 ꢇ 4,
128.32 ꢇ 3, 129.61 ꢇ 2, 131.83, 133.06, 137.67, 138.11, 165.02, 165.30. HRMS:
Calcd for C31H32O8 (M)ꢅm/z: 532.2097. Found: 532.2082.
Methyl 3-O-acetyl-2-O-acryloyl-4,6-di-O-benzyl-ꢀ-D-mannopyranoside
(12). To a solution of 10 (117 mg, 0.27 mmol) in pyridine (2 mL) was added
acetic anhydride (1 mL). The mixture was stirred for 11 h and the solvent was re-
moved by concentration in vacuo. The residue was purified by column chro-
matography on silica gel (EtOAc:hexane, 1:5) to provide 114 mg (89%) of 12 as a
colorless oil : TLC, Rf 0.53 (EtOAc:hexane, 1:2); [ꢀ]2D6.0 ꢅ31.8° (c 1.46, CHCl3);
1
IR (neat) 3100ꢃ2800, 1740 cmꢃ1; H NMR ꢈ 1.95 (s, 3H, OAc), 3.39 (s, 3H,
OMe), 3.70–3.76 (m, 1H, H-6), 3.81–3.87 (m, 2H, H-5, 6ꢉ), 4.02 (t, J ꢂ 9.5 Hz,
1H, H-4), 4.50, 4.63 (ABq, J ꢂ 11.2 Hz, 2H, CH2-Ph), 4.53, 4.73 (ABq, J ꢂ 12.0
Hz, 2H, CH2-Ph), 4.75 (d, J ꢂ 1.7 Hz, 1H, H-1), 5.33 (dd, J ꢂ 1.7, 3.4 Hz, 1H, H-
2), 5.37 (dd, J ꢂ 3.4, 9.5 Hz, 1H, H-3), 5.89 (dd, J ꢂ 1.0, 10.4 Hz, 1H,
COCHBCHH), 6.19 (dd, J ꢂ 10.4, 17.3 Hz, 1H, COCHBCHH), 6.46 (dd, J
ꢂ 1.0, 17.3 Hz, 1H, COCHBCHH), 7.15–7.39 (m, 10H, ꢃPh ꢇ 2); 13C NMR ꢈ
20.81, 55.02, 68.53, 70.04, 71.19, 71.88, 72.92, 73.45, 74.71, 98.48, 127.48 ꢇ 2,
127.60, 127.63, 127.75 ꢇ 2, 127.86, 128.29 ꢇ 4, 131.76, 138.00, 138.09, 165.09,
169.84. HRMS: Calcd for C26H30O8 (M)ꢅm/z: 470.1941. Found: 470.1944.
Methyl 2-O-acryloyl-4,6-di-O-benzyl-ꢀ-D-glucopyranoside (14). As de-
scribed for the preparation of 10, 802 mg (2.14 mmol) of 1312 was treated with
NaH (60% in mineral oil, 202 mg, 5.06 mmol), HgCl2 (581 mg, 2.14 mmol), and
acryloyl chloride (0.36 mL, 4.3 mmol) to give 810 mg (88%) of 14 after chro-
matographic purification on silica gel. Compound 14 as a colorless oil: TLC, Rf
0.32 (EtOAc:hexane, 1:2); [ꢀ]2D6.0 ꢅ100.8° (c 1.70, CHCl3); IR (neat) 3100ꢃ2800,
1725 cmꢃ1; 1H NMR ꢈ 2.28 (br, 1H, OH), 3.36 (s, 3H, OMe), 3.60–3.81 (m, 4H,
H-4, 5, 6, 6ꢉ), 4.13 (t. J ꢂ 10.0 Hz, 1H, H-3), 4.54, 4.67 (ABq, J ꢂ 11.9 Hz, 2H,
CH2-Ph), 4.57, 4.77 (ABq, J ꢂ 11.2 Hz, 2H, CH2-Ph), 4.82 (dd, J ꢂ 3.8, 10.0 Hz,
1H, H-2), 4.97 (d, J ꢂ 3.8 Hz, 1H, H-1), 5.88 (dd, J ꢂ 1.5, 10.4 Hz, 1H,
COCHBCHH), 6.20 (dd, J ꢂ 10.4, 17.3 Hz, 1H, COCHBCHH), 6.28 (dd, J
ꢂ 1.5, 17.3 Hz, 1H, COCHBCHH), 7.21–7.36 (m, 10H, ꢃPh ꢇ 2); 13C NMR ꢈ
55.15, 68.35, 69.81, 71.98, 73.51, 73.63, 74.73, 77.90, 96.87, 127.71 ꢇ 2, 127.91
ꢇ 5, 128.37 ꢇ 2, 128.47 ꢇ 2, 132.02, 137.83, 138.11, 165.89. HRMS: Calcd for
C23H25O6 (MMOCH3)ꢅm/z: 397.1651. Found: 397.1655.
Methyl 2-O-acryloyl-4,6-di-O-benzyl-3-O-t-butyldimethylsilyl-ꢀ-D-glu-
copyranoside (15). To a cooled (0 °C) stirred solution of 14 (113 mg, 0.26

ORDER
REPRINTS
530
NAGATSUKA ET AL.
mmol) in pyridine (3 mL) was added TBSOTf (0.07 mL, 0.30 mmol). The mixture
was stirred for 2 h, diluted with EtOAc (20 mL), and washed with saturated aque-
ous NaHCO3 (10 mL ꢇ 3). The organic layer was dried and concentrated in vacuo.
The residue was purified by column chromatography on silica gel (EtOAc:hexane,
1:10) to give 129 mg (90%) of 15 as a colorless oil : TLC, Rf 0.63 (EtOAc:hexane,
1:3); [ꢀ]2D0.5 ꢅ107° (c 3.41, CHCl3); IR (neat) 3100ꢃ2800, 1730, 1635 cmꢃ1; 1H
NMR ꢈ 0.04, 0.07 (2s, 6H, (t-Bu)Me2Si), 0.85 (s, 9H, (t-Bu)Me2Si), 3.34 (s, 3H,
OMe), 3.45–3.81 (m, 4H, H-4, 5, 6, 6ꢉ), 4.14 (t, J ꢂ 9.2 Hz, 1H, H-3), 4.50, 4.82
(ABq, J ꢂ 11.2 Hz, 2H, CH2-Ph), 4.54, 4.60 (ABq, J ꢂ 12.2 Hz, 2H, CH2-Ph), 4.84
(dd, J ꢂ 3.7, 9.2 Hz, 1H, H-2), 4.91 (d, J ꢂ 3.7 Hz, 1H, H-1), 5.86 (dd, J ꢂ 1.5,
10.2 Hz, 1H, COCHBCHH), 6.20 (dd, J ꢂ 10.2, 17.3 Hz, 1H, COCHBCHH),
6.48 (dd, J ꢂ 1.5, 17.3 Hz, 1H, COCHBCHH), 7.18–7.34 (m, 10H, Ph ꢇ 2); 13
C
NMR ꢈ ꢃ4.21, ꢃ4.13, 17.88, 25.74 ꢇ 3, 54.99, 68.58, 70.12, 72.03, 73.45, 74.10,
74.80, 78.92, 97.02, 127.29 ꢇ 2, 127.39, 127.60, 127.75 ꢇ 2, 128.06, 128.21 ꢇ 2,
128.31 ꢇ 2, 131.65, 137.86, 138.18, 165.60. HRMS: Calcd for C29H39O6Si
(MMOCH3)ꢅm/z: 511.2516. Found: 511.2515.
Typical Experimental Procedures for the Diels-Alder Reaction. Ther-
mal conditions (entry 1 in Table 1). To a stirred solution of 2 (80.3 mg, 0.195
mmol) in CH2Cl2 (2 mL) was added cyclopentadiene (0.2 mL) at ꢃ18 °C. The
mixture was stirred for 2 days and the solvent was removed by concentration in
vacuo. The residue was purified by column chromatography (EtOAc:hexane, 1:9)
to give 90.7 mg (96%) of 16 as a diastereomeric mixture. The ratio of the mixture
was determined by 1H NMR (300 MHz) analysis. Analogously, compounds 4, 6,
and 15 were subjected to the Diels-Alder reaction with cyclopentadiene to give the
adducts 17 (2 days, 96%; entry 2 in Table 1), 18 (5 days, 97%; entry 3 in Table 1),
and 23 (2 days, 96%; entry 1 in Table 5), respectively, after chromatographic pu-
rification on silica gel.
Lewis Acid Promoted Conditions (entry 1 in Table 2). The following re-
action was carried out under an argon atmosphere. To a cooled (ꢃ78 °C) stirred so-
lution of 2 (60.6 mg, 0.147 mmol) in CH2Cl2 (1 mL) was added 1.0 M solution of
EtAlCl2 in hexane (0.31 mL, 0.31 mmol). The mixture was stirred at ꢃ78 °C for
30 min and cyclopentadiene (0.10 mL) was added. After being stirred at ꢃ78 °C
for 15 min, the mixture was quenched with 1 M aqueous HCl and allowed to warm
to room temperature. The mixture was diluted with EtOAc (20 mL) and washed
with 1 M aqueous HCl (10 mL ꢇ 2). The organic layer was dried and concentrated
in vacuo. The residue was purified by column chromatography on silica gel
(EtOAc:hexane, 1:9) to give 33.9 mg (63%) of 16 as a diastereomeric mixture. The
ratio of the mixture was determined by 1H NMR (300 MHz) analysis. Analogously,
compounds 4, 9, 11, 12, and 15 were subjected to the Diels-Alder reaction with cy-
clopentadiene in the presence of EtAlCl2 to give the adducts 17 (at ꢃ78 °C for 10
min, 79%; entry 2 in Table 2), 20 (at ꢃ78 °C for 15 min, 83%; entry 1 in Table 3),
21 (at ꢃ78 °C for 10 min, 84%; entry 2 in Table 3), 22 (at ꢃ78 °C for 15 min, 98%;
entry 3 in Table 3), and 23 (at ꢃ78 °C for 1 hr, 97%; entry 2 in Table 5), respec-
tively, after chromatographic purification on silica gel.

ORDER
REPRINTS
DIELS-ALDER REACTIONS
531
Methyl 2,3-di-O-benzyl-4-O-(bicyclo[2.2.1]hept-5-ene-2-carbonyl)-6-de-
oxy-ꢀ-D-glucopyranoside (16) obtained under thermal conditions (entry 1 in
Table 1). Compound 16 (endo :exo ꢂ 79:21, endo-S:R ꢂ 71:29) was obtained as
a colorless oil : TLC, Rf 0.57 (EtOAc:hexane, 1: 3); IR (neat) 3100ꢃ2800, 1740
cmꢃ1; 1H NMR ꢈ 1.04–1.14 (m, 3H, CH3-6), 1.21–1.47 (m, 3H, H-3, 7, 7ꢉ of the
norbornene), 1.81–1.90 (m, 1H, H-3ꢉ of the norbornene), 2.06–2.10 (m, 1H ꢇ 2/9,
H-2 of the exo norbornene), 2.70 (dt, J ꢂ 3.9, 9.3 Hz, 1H ꢇ 5/9, H-2 of the endo
2S norbornene), 2.80–2.87 (m, 1H ꢇ 2/9, H-2 of the endo 2R norbornene, and 1H
ꢇ 7/9, H-4 of the endo norbornenes and 1H ꢇ 2/9, H-1 of the exo norbornene),
2.95 (br, 1H ꢇ 2/9, H-4 of the exo norbornene), 3.11 (br, 1H ꢇ 5/9, H-1 of the endo
2S norbornene), 3.15 (br, 1H ꢇ 2/9, H-1 of the endo 2R norbornene), 3.38–3.39 (m,
3H, OMe), 3.53–3.61 (m, 1H, H-2), 3.70–3.81 (m, 1H, H-5), 3.84–3.94 (m, 1H,
H-3), 4.52–4.55 (m, 1H, H-1), 4.59–4.94 (m, 5H, H-4, CH2MPh ꢇ 2), 5.83–5.88
(m, 1H ꢇ 7/9, H-6 of the endo norbornene), 6.06–6.16 (m, 1H, H-5 of the nor-
bornene, and 1H ꢇ 2/9, H-6 of the exo norbornene), 7.25–7.35 (m, 10H, Ph ꢇ 2);
13C NMR for the 16S ꢈ17.44, 29.20, 42.41, 43.33, 45.53, 49.45, 49.71, 55.29,
65.39, 73.41, 74.78, 75.21, 79.22, 79.78, 98.12, 127.42 ꢇ 2, 127.70, 127.91,
128.11 ꢇ 2, 128.24 ꢇ 2, 128.42 ꢇ 2, 132.07, 138.00 ꢇ 2, 173.64. HRMS: Calcd
for C28H31O5 (MMOCH3)ꢅm/z: 447.2172. Found: 447.2176.
Methyl 4-O-(bicyclo[2.2.1]hept-5-ene-2-carbonyl)-6-deoxy-2,3-di-O-pi-
valoyl-ꢀ-D-glucopyranoside (17) obtained under Lewis acid promoted condi-
tions (entry 2 in Table 2). Compound 17 (endo:exo ꢂꢄ95:5, endo-S:R ꢂ
10:90) was obtained as a colorless oil : TLC, Rf 0.65 (EtOAc:hexane, 1:4); IR
1
(neat) 3100ꢃ2800, 1740 cmꢃ1; H NMR ꢈ 1.12, 1.16 (2s, 18H, OPiv ꢇ 2),
1.10–1.45 (m, 6H, H-3, 7, 7ꢉ of the norbornene, and CH3-6 of the endo adducts),
1.85 (ddd, J ꢂ 4.1, 8.3, 16.1 Hz, 1H ꢇ 1/10, H-3ꢉ of the endo 2S norbornene), 1.97
(ddd, J ꢂ 3.7, 9.8, 12.0 Hz, 1H ꢇ 9/10, H-3ꢉ of the endo 2R norbornene),
2.86–2.92 (m, 2H, H-2, 4 of the norbornene), 3.15 (br, 1H, H-1 of the norbornene),
3.37 (s, 3H ꢇ 9/10, OMe of the endo 2R adduct), 3.39 (s, 3H ꢇ 1/10, OMe of the
endo 2S adduct), 3.86 (dq, J ꢂ 12.4, 6.1 Hz, 1H, H-5), 4.77 (dd, J ꢂ 3.7, 9.8 Hz,
1H, H-2), 4.81 (t, J ꢂ 9.8 Hz, 1H, H-3), 4.87 (d, J ꢂ 3.7 Hz, 1H, H-1), 5.49 (t, J
ꢂ 9.8 Hz, 1H, H-4), 5.87 (dd, J ꢂ 2.7, 5.7 Hz, 1H ꢇ 1/10, H-6 of the endo 2S nor-
bornene), 5.97 (dd, J ꢂ 2.9, 5.6 Hz, 1H ꢇ 9/10, H-6 of the endo 2R norbornene),
6.14 (dd, J ꢂ 2.9, 5.6 Hz, 1H ꢇ 9/10, H-5 of the endo 2R norbornene), 6.20 (dd, J
ꢂ 2.5, 5.7 Hz, 1H ꢇ 1/10, H-5 of the endo 2S norbornene); 13C NMR for 17R ꢈ
17.25, 26.94 ꢇ 3, 27.08 ꢇ 3, 29.07, 38.69 ꢇ 2, 42.46, 43.08, 45.66, 49.84, 55.47,
65.02, 69.55, 71.32, 73.27, 96.61, 131.83, 138.18, 173.48, 177.18, 177.74. HRMS:
Calcd for C25H38O8 (M)ꢅm/z: 466.2566. Found: 466.2573.
Methyl 4-O-(bicyclo[2.2.1]hept-5-ene-2-carbonyl)-2,3-di-O-t-butyldi-
methylsilyl-6-deoxy-ꢀ-D-glucopyranoside (18) obtained under thermal condi-
tions (entry 3 in Table 1). Compound 18 (18S:18R ꢂꢄ95:5) was obtained as
white solids:TLC, Rf 0.69 for endo-isomers (EtOAc:hexane, 1:8); IR (neat)
1
3000ꢃ2800, 1750 cmꢃ1; H NMR for the endo 2S adduct ꢈ 0.09 (s, 6H,
(t-Bu)Me2Si), 0.10 (s, 6H, (t-Bu)Me2Si), 0.82, 0.92 (2s, 18H, (t-Bu)Me2Si), 1.09

ORDER
REPRINTS
532
NAGATSUKA ET AL.
(d, J ꢂ 6.3 Hz, 3H, 6-CH3), 1.29–1.32 (m, 1H, H-7 of the norbornene), 1.39–1.45
(m, 2H, H-3, 7ꢉ of the norbornene), 1.89 (ddd, J ꢂ 4.1, 9.6, 12.9 Hz, 1H, H-3ꢉ of
the norbornene), 2.92 (br, 1H, H-1 of the norbornene), 2.96 (dt, J ꢂ 3.9, 9.6 Hz,
1H, H-2 of the norbornene), 3.19 (br, 1H, H-4 of the norbornene), 3.38 (s, 3H,
OMe), 3.65 (dd, J ꢂ 3.7, 9.1 Hz, 1H, H-2), 3.37–3.75 (m, 1H, H-5), 3.91 (t, J
ꢂ 9.1 Hz, 1H, H-3), 4.61 (d, J ꢂ 3.7 Hz, 1H, H-1), 4.62 (t, J ꢂ 9.1 Hz, 1H, H-4),
5.85 (dd, J ꢂ 2.7, 5.6 Hz, 1H, H-6 of the norbornene), 6.25 (dd, J ꢂ 3.2, 5.6 Hz,
1H, H-5 of the norbornene); 13C NMR for 18S ꢈꢃ4.52, ꢃ4.43, ꢃ3.41, ꢃ2.88,
17.73, 17.81, 18.27, 25.84 ꢇ 3, 26.12 ꢇ 3, 29.49, 42.52, 43.51, 46.01, 50.17,
55.01, 65.50, 71.87, 74.35, 76.24, 100.13, 131.60, 138.21, 173.82. HRMS: Calcd
for C26H47O5Si2 (MMOCH3)ꢅm/z: 495.2962. Found: 495.2962.
Methyl 3,4,6-tri-O-benzyl-2-O-(bicyclo[2.2.1]hept-5-ene-2-carbonyl)-ꢀ-
D-manno-pyranoside (20) obtained under Lewis acid promoted conditions
(entry 1 in Table 3). Compound 20 (endo:exo ꢂꢄ95:5, endo-S:R ꢂ 33:67) was
obtained as a colorless oil: TLC, Rf 0.57 (EtOAc:hexane, 1:2); IR (neat)
1
3100ꢃ2800, 1740 cmꢃ1; H NMR ꢈ 1.25 (m, 1H, H-7 of the norbornene),
1.37–1.49 (m, 2H, H-3, 7ꢉ of the norbornene), 1.84–1.96 (m, 1H, H-3ꢉ of the nor-
bornene), 2.88 (br, 1H, H-4 of the norbornene), 3.00–3.09 (m, 1H, H-2 of the nor-
bornene), 3.22 (br, 1H ꢇ 1/3, H-1 of the endo 2S norbornene), 3.25 (br, 1H ꢇ 2/3,
H-1 of the endo 2R norbornene), 3.35 (s, 3H, OMe), 3.70–3.98 (m, 5H, H-3, 4, 5,
6, 6ꢉ), 4.45–4.90 (m, 7H, H-1, CH2-Ph ꢇ 3), 5.27 (dd, J ꢂ 2.0, 2.9 Hz, 1H ꢇ 1/3,
H-2 of the endo 2S adduct), 5.35 (dd, J ꢂ 2.0, 2.9 Hz, 1H ꢇ 2/3, H-2 of the endo
2R adduct), 5.90 (dd, J ꢂ 2.7, 5.6 Hz, 1H ꢇ 2/3, H-6 of the endo 2R norbornene),
6.00 (dd, J ꢂ 2.9, 5.5 Hz, 1H ꢇ 1/3, H-6 of the endo 2S norbornene), 6.04 (dd, J
ꢂ 2.9, 5.6 Hz, 1H ꢇ 2/3, H-5 of the endo 2R norbornene), 6.12 (dd, J ꢂ 2.9, 5.5
Hz, 1H ꢇ 1/3, H-5 of the endo 2S norbornene), 7.16–7.39 (m, 15H, Ph ꢇ 3); 13
C
NMR for 20R ꢈ28.95, 42.46, 43.26, 46.03, 49.50, 54.89, 67.94, 68.96, 71.36,
71.44, 73.36, 74.20, 75.16, 78.30, 98.93, 127.52 ꢇ 2, 127.63 ꢇ 3, 127.99 ꢇ 2,
128.13 ꢇ 2, 128.21 ꢇ 2, 128.29 ꢇ 4, 132.93, 137.26, 138.00, 138.31, 138.41,
173.91. HRMS: Calcd for C35H37O6 (MMOCH3)ꢅm/z: 553.2590. Found:
553.2579.
Methyl 3-O-benzoyl-4,6-di-O-benzyl-2-O-(bicyclo[2.2.1]hept-5-ene-2-
carbonyl)-ꢀ-D-mannopyranoside (21) obtained under Lewis acid promoted
conditions (entry 2 in Table 3). Compound 21 (endo:exo ꢂꢄ95:5, endo-S:R ꢂ
9:91) was obtained as a colorless oil: TLC, Rf 0.66 (EtOAc:hexane, 1:2); IR (neat)
3100ꢃ2800, 1730, 1600 cmꢃ1; 1H NMR for 21R ꢈ1.26–1.44 (m, 3H, H-3, 7, 7ꢉ of
the norbornene), 1.88 (ddd, J ꢂ 3.7, 9.3, 11.9 Hz, 1H, H-3 of the norbornene), 2.87
(br, 1H, H-4 of the norbornene), 3.01 (dt, J ꢂ 3.9, 9.3 Hz, 1H, H-2 of the nor-
bornene), 3.26 (br, 1H, H-1 of the norbornene), 3.41 (s, 3H, OMe), 3.77 (dd, J
ꢂ 2.0, 13.9 Hz, 1H, H-6), 3.85–3.94 (m, 2H, H-5, 6ꢉ), 4.23 (t, J ꢂ 9.8 Hz, 1H, H-
4), 4.54, 4.66 (ABq, J ꢂ 10.7 Hz, 2H, CH2-Ph), 4.56, 4.76 (ABq, J ꢂ 11.9 Hz, 2H,
CH2-Ph), 4.74 (d, J ꢂ 2.0 Hz, 1H, H-1), 5.30 (dd, J ꢂ 2.0, 3.3 Hz, 1H, H-2), 5.62
(dd, J ꢂ 3.3, 9.8 Hz 1H, H-3), 5.82 (dd, J ꢂ 2.7, 5.8 Hz, 1H, H-6 of the nor-

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533
bornene), 6.07 (dd, J ꢂ 3.2, 5.8 Hz, 1H, H-5 of the norbornene), 7.06–7.58 (m,
15H, Ph ꢇ 3); 13C NMR for 21R ꢈ29.03, 42.41, 43.31, 45.71, 49.66, 55.07, 68.63,
70.04, 71.36, 72.56, 73.07, 73.40, 74.85, 76.59, 98.58, 127.53, 127.68 ꢇ 3, 127.88
ꢇ 2, 128.26 ꢇ 2, 128.29 ꢇ 4, 129.64 ꢇ 2, 132.35, 133.06, 137.63, 137.77, 138.18,
165.38, 173.51. HRMS: Calcd for C36H38O8 (Mꢅ) m/z: 598.2567. Found:
598.2573.
Methyl 3-O-acetyl-4,6-di-O-benzyl-2-O-(bicyclo[2.2.1]hept-5-ene-2-car-
bonyl)-ꢀ-D-mannopyranoside (22) obtained under Lewis acid promoted con-
ditions (entry 3 in Table 3). Diastereomerically homogenous 22R was obtained
as a colorless oil by chromatographic separation of the Diels-Alder adducts on sil-
ica gel: TLC, Rf 0.58 (EtOAc:hexane, 1:2); [ꢀ]2D1.5 ꢅ68.1° (c 1.96, CHCl3); IR
(neat) 3100ꢃ2800, 1750 cmꢃ1; 1H NMR ꢈ 1.24–1.46 (m, 3H, H-3, 7, 7ꢉ of the nor-
bornene), 1.84–1.93 (m, 1H, H-3ꢉ of the norbornene), 1.91 (s, 3H, OAc), 2.92 (br,
1H, H-4 of the norbornene), 3.02 (dt, J ꢂ 3.8, 9.0 Hz, 1H, H-2 of the norbornene),
3.27 (br, 1H, H-1 of the norbornene), 3.38 (s, 3H, OMe), 3.72–3.89 (m, 3H, H-5,
6, 6ꢉ), 4.06 (t, J ꢂ 9.8 Hz, 1H, H-4), 4.53, 4.61 (ABq, J ꢂ 11.2 Hz, 2H, CH2-Ph),
4.54, 4.76 (ABq, J ꢂ 11.9 Hz, 2H, CH2-Ph), 4.67 (d, J ꢂ 1.9 Hz, 1H, H-1), 5.21
(dd, J ꢂ 1.9, 3.3 Hz, 1H, H-2), 5.30 (dd, J ꢂ 3.3, 9.8 Hz, 1H, H-3), 5.97 (dd, J
ꢂ 2.7, 5.6 Hz, 1H, H-6 of the norbornene), 6.18 (dd, J ꢂ 2.9, 5.6 Hz, 1H, H-5 of
the norbornene), 7.16–7.42 (m, 10H, Ph ꢇ 2); 13C NMR ꢈ 20.91, 28.69, 42.44,
43.20, 45.93, 49.64, 55.02, 68.56, 69.48, 71.32, 72.02, 72.81, 73.43, 74.68, 98.68,
127.58 ꢇ 2, 127.67 ꢇ 2, 127.71 ꢇ 2, 128.27 ꢇ 2, 128.34 ꢇ 2, 132.30, 137.68,
137.98, 138.18, 169.74, 173.49. HRMS: Calcd for C31H36O8 (M)ꢅm/z: 536.2410.
Found: 536.2412.
Methyl 4,6-O-benzyl-2-O-(bicyclo[2.2.1]hept-5-ene-2-carbonyl)-3-O-t-
butyldimethylsilyl-ꢀ-D-glucopyranoside (23) obtained under Lewis acid pro-
moted conditions (entry 2 in Table 5). Compound 23 (endo:exo ꢂ 94:6,
endo-S:R ꢂ 92:8) was obtained as a colorless oil: TLC, Rf 0.66 (EtOAc:hexane,
1
1:3); IR (neat) 3100ꢃ2800, 1730 cmꢃ1; H NMR for 23S ꢈ0.04, 0.11 (2s, 6H,
(t-Bu)Me2Si), 0.89 (s, 9H, (t-Bu)Me2Si), 1.25–1.29 (m, 1H, H-7 of the nor-
bornene), 1.36–1.51 (m, 2H, H-3, 7ꢉ of the norbornene), 2.01 (ddd, J ꢂ 3.7, 9.7,
11.5 Hz, 1H, H-3ꢉ of the norbornene), 2.90 (br, 1H, H-4 of the norbornene), 3.00
(dt, J ꢂ 3.9, 9.7 Hz, 1H, H-2 of the norbornene), 3.23 (br, 1H, H-1 of the nor-
bornene), 3.28 (s, 3H, OMe), 3.52 (t, J ꢂ 9.4 Hz, 1H, H-4), 3.60–3.74 (m, 3H,
H-5, 6, 6ꢉ), 4.06 (t, J ꢂ 9.4 Hz, 1H, H-3), 4.49, 4.59 (ABq, J ꢂ 12.0 Hz, 2H,
CH2-Ph), 4.53, 4.80 (ABq, J ꢂ 11.2 Hz, 2H, CH2-Ph), 4.60 (dd, J ꢂ 3.7, 9.4 Hz,
1H, H-2), 4.81 (d, J ꢂ 3.7 Hz, 1H, H-1), 6.03 (dd, J ꢂ 2.7, 5.5 Hz, 1H, H-6 of
the norbornene), 6.18 (dd, J ꢂ 2.9, 5.5 Hz, 1H, H-5 of the norbornene),
7.17–7.31 (m, 10H, Ph ꢇ 2); 13C NMR 23S ꢈ ꢃ4.20, ꢃ4.05, 17.98, 25.86 ꢇ 3,
30.53, 42.44, 43.72, 45.22, 49.25, 55.25, 68.66, 70.11, 71.98, 73.45, 74.34,
74.73, 78.91, 96.94, 127.25 ꢇ 2, 127.35, 127.60, 127.75 ꢇ 2, 128.21 ꢇ 2,
128.32 ꢇ 2, 133.32, 137.22, 137.95, 138.29, 174.45. HRMS: Calcd for
C34H45O6Si (MBOCH3)ꢅm/z: 577.2985. Found: 577.2962.

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NAGATSUKA ET AL.
Methyl 4,6-di-O-benzyl-2-O-(bicyclo[2.2.1]hept-5-ene-2-carbonyl)-ꢀ-D-
glucopyranoside (24). Compound 23 obtained under thermal conditions
(23R:23S:the exo-isomers ꢂ 10 : 1 : 4 by 1H NMR analysis, 54.6 mg, 0.090 mmol)
was dissolved in 47% aqueous HFMCH3CN (1:9, 2.0 mL). The solution was
stirred for 4 days and neutralized with saturated aqueous NaHCO3. The mixture
was diluted with EtOAc (20 mL) and washed with saturated aqueous NaHCO3 (10
mL ꢇ 4). The organic layer was dried and concentrated in vacuo. The residue was
purified by column chromatography on silica gel (EtOAc:hexane, 1:4) to give 35.6
mg (80%) of the mixture of adducts 24R and 24S and 9.7 mg (20%) of the exo
adducts. The mixture of 24R and 24S (10 : 1) was obtained as a colorless oil: TLC,
1
Rf 0.35 (EtOAc:hexane, 1 : 2); IR (neat) 3500 (br), 3100ꢃ2800, 1730 cmꢃ1; H
NMR for 24R ꢈ1.26–1.28 (m, 1H, H-7 of the norbornene), 1.41–1.47 (m, 2H,
H-3, 7ꢉ of the norbornene), 1.86–1.94 (m, 1H, H-3ꢉ of the norbornene), 2.91 (br,
1H, H-4 of the norbornene), 3.00–3.07 (m, 1H, H-2 of the norbornene), 3.25 (br,
1H, H-1 of the norbornene), 3.36 (s, 3H, OMe), 3.59 (t, J ꢂ 9.5 Hz, 1H, H-4),
3.66–3.77 (m, 3H, H-5, 6, 6ꢉ), 4.09 (t, J ꢂ 9.5 Hz, 1H, H-3), 4.52, 4.66 (ABq, J
ꢂ 12.2 Hz, 2H, CH2-Ph), 4.57, 4.77 (ABq, J ꢂ 11.3 Hz, 2H, CH2-Ph), 4.68 (dd, J
ꢂ 3.7, 9.5 Hz, 1H, H-2), 4.88 (d, J ꢂ 3.7 Hz, 1H, H-1), 5.91 (dd, J ꢂ 2.7, 5.8 Hz,
1H, H-6 of the norbornene), 6.20 (dd, J ꢂ 2.9, 5.8 Hz, 1H, H-5 of the norbornene),
7.21–7.37 (m, 10H, Ph ꢇ 2); 13C NMR for 24R ꢈ29.11, 42.57, 43.13, 45.93, 49.58,
55.11, 68.41, 69.78, 72.02, 73.53 ꢇ 2, 74.65, 77.82, 96.84, 127.71, 127.83, 127.90
ꢇ 4, 128.37 ꢇ 2, 128.47 ꢇ 2, 132.14, 137.90 ꢇ 2, 138.23, 174.42. HRMS: Calcd
for C29H34O7(M)ꢅm/z: 494.2305. Found: 494.2302.
A Typical Procedure for Removal of the Carbohydrate Templates. The
following reaction was carried out under an argon atmosphere. To a cooled
(ꢃ78 °C) stirred solution of the mixture of 18S and 18R (ꢄ95:5, 170 mg, 0.323
mmol) in CH2Cl2 (4 mL) was added DIBALH (1.0 M solution in toluene, 1.0 mL,
1.0 mmol). The mixture was stirred at ꢃ78 °C for 1 h and quenched with 1 M aque-
ous HCl. This was diluted with 1 M aqueous HCl (20 mL) and extracted with
CH2Cl2 (20 mL ꢇ 3). The combined organic layers were dried and concentrated in
vacuo. The residue was purified by column chromatography on silica gel
(EtOAc:hexane, 1:8, 1:5 then 1:2) to give 36.3 mg (91%) of enantioenriched 19S
and 99.1 mg (76%) of 5. For HPLC analysis, thus obtained enantioenriched 19S
was benzoylated as follows. To a solution of 19S (2.7 mg, 0.02 mmol) in pyridine
(1 mL) was added benzoyl chloride (6 ꢊL, 0.05 mmol). The solution was stirred
for 7 h and diluted with EtOAc (10 mL), washed with saturated aqueous NaHCO3
(5 mL ꢇ 3). The organic layer was dried and concentrated in vacuo. The residue
was purified by column chromatography on silica gel (EtOAc:hexane, 1:5) to give
4.5 mg (98%) of bicyclo[2.2.1]hept-5-ene-2-methyl benzoate as a colorless oil.
ACKNOWLEDGMENT
This work was supported in part by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Science, Sports and Culture, Japan.

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Received March 26, 2001
Accepted June 19, 2001

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