Michael reactions on conformationally flexible methyl 3-C-nitro-hex-2-enopyranoside derivatives

Article abstract of DOI:10.1016/S0008-6215(00)00075-6

Dimethyl malonate and dibenzoylmethane attacked the C-2 position of the title 3-nitro-2-enopyranosides from the side opposite the anomeric methoxyl group to afford the 3-enopyranosides (S(N)2' products). In the case of 2,4-pentanedione and ethyl acetoacet

Full text of DOI:10.1016/S0008-6215(00)00075-6

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Carbohydrate Research 327 (2000) 489–496
Note
Michael reactions on conformationally flexible methyl
3-C-nitro-hex-2-enopyranoside derivatives
Tohru Sakakibara a,*, Kiohisa Tokuda b, Tsutomu Hayakawa a, Akinori Seta a
a Faculty of Science, Yokohama City Uni6ersity, Seto, Kanazawa-ku, Yokohama 236, Japan
b Graduate School of Integrated Science, Yokohama City Uni6ersity, Seto, Kanazawa-ku, Yokohama 236, Japan
Received 20 September 1999; accepted 18 February 2000
Abstract
Dimethyl malonate and dibenzoylmethane attacked the C-2 position of the title 3-nitro-2-enopyranosides from the
side opposite the anomeric methoxyl group to afford the 3-enopyranosides (SN2% products). In the case of
2,4-pentanedione and ethyl acetoacetate, further intramolecular cyclization occurred to yield dihydropyran deriva-
tives. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Nitro sugar; The Michael reaction; Intramolecular cyclization; SN2% reaction
ible 2-enopyranosides. We have previously
reported sodium borodeuteride reductions of
methyl 4,6-di-O-acetyl-2,3-dideoxy-3-C-nitro-
1. Introduction
If a Michael acceptor is conformationally
flexible, the direction of approach by nucle-
ophiles should be determined by the con-
former from which the reaction proceeds. For
a 2-enopyranoside derivative, two half-chair
conformations, 5HO and OH5, may be in-
volved. However, only the H5 conformation
is allowed in the case of methyl 4,6-O-benzyli-
dene-2,3-dideoxy-3-C-nitro-b- (1) and -a-
hex-2-enopyranoside (2), because ring
inversion is prevented by the 4,6-O-benzyli-
dene group. After studies of nucleophilic addi-
tion reactions of these conformationally rigid
2-enopyranoside derivatives [1], we have stud-
ied similar reactions of conformationally flex-
b-D
-erythro-hex-2-enopyranoside (3), its a-
D
anomer 4, and their 4-epimers [2], as well as
their oxidation of 4 with peroxides [3]. In
these reactions, all nucleophiles added at C-2
from the side opposite the anomeric methoxyl
group, as observed in similar reactions of the
4,6-O-benzylidene derivatives 1 and 2 [4]. It is
O
D-
noteworthy that the b-
D
anomer 3 adopts the
5HO conformation, while the a-
D
anomer 4
O
has the H5 conformation [2].
Active methylene compounds also attacked
the 2-position of 4,6-O-benzylidene derivatives
1 [5] and 2 [6] with high stereoselectivity trans
manner to the anomeric methoxyl group.
For comparison with these results we have
now performed reactions of 4,6-diacetates 3
and 4 with active methylene compounds.
* Corresponding author.
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00075-6

490
T. Sakakibara et al. / Carbohydrate Research 327 (2000) 489–496
1
allo configuration having the C4 conforma-
tion was assigned to 7 by the NOE differ-
2. Results and discussion
1
ence spectrum and the JC-1,H-1 value (171
Although the reactions of 4,6-O-benzyli-
dene derivatives 1 and 2 with diethyl mal-
onate proceeded smoothly to give adducts in
good yields, similar reaction of the 4,6-di-O-
Hz). This structure is reasonable because an
intermediary SN2% product corresponding to
5 has a structure suitable for intramolecular
cyclization. It is noteworthy that the struc-
ture assigned as the most favorable heat of
formation, as calculated by the semiempirical
molecular orbital method (AM1 [8]): −243.3
(allo, 1C4), −240.4 (allo, o,3B), −239.1
acetyl-b-
D
anomer 3 with dimethyl malonate
afforded many products, partially because of
deacetylation. After attempts to improve the
yield by varying the solvents, bases, and re-
action temperature, we obtained the SN2%
product 5 when the reaction was performed
at −20 °C in oxolane in the presence of
sodium hydride. Although the reaction pro-
ceeded cleanly, the isolated yield of 5 was
moderate (44%) because of partial decompo-
sition of 5 during chromatographic separa-
tion. The structure of 5 as deduced by IR
and 1H NMR spectra was confirmed by
comparison with an authentic sample pre-
pared from methyl 4,6-O-benzylidene-2,3-
dideoxy-2-C-bis(methoxycarbonyl)methyl-3-
(gluco, C4), −239.5 (gluco, o,3B), −236.7
1
4
(ido, C1), −237.6 (ido, Bo,3), −236.6 (talo,
4C1), and −237.5 kcal/mol (talo, Bo,3) (Fig.
1).
Treatment of 3 with ethyl acetoacetate af-
forded the bicyclic compound 8 in 91% yield.
The allo configuration having the C4 confor-
1
mation for 8 was again deduced from the
NMR data.
Similar reactions of the a-
D
anomer 4 with
dimethyl malonate and dibenzoylmethane af-
forded the SN2% products 11 and 12 in 29
and 89% yields, respectively. The threo struc-
ture for 11 was confirmed by comparison
with an authentic sample prepared from the
C-nitro-b- -glucopyranoside (9) via deben-
D
zylidenation, regioselective acetylation at C-
6, and subsequent dehydration. The 1Ho
conformation for 5 could be assigned by the
J1,2 coupling (0 Hz) and confirmed by the
1JC-1,H-1 value (173 Hz) [7].
known
4,6-O-benzylidene-a- -mannopyra-
D
O
noside derivative 15 [9]. The H1 conforma-
tion for 11 and 12 was deduced by J1,2 (0
Hz), the allylic long-range coupling, J2,4 (0
Similar reaction with dibenzoylmethane
also gave the SN2% product 6, having the Ho
conformation, in 77% yield. Several attempts
to introduce another dibenzoylmethane
group into the nitroalkene moiety of 6 were
unsuccessful (Scheme 1).
1
1
Hz) [10], and JC-1,H-1 values. Cyclization
again occurred in the reactions with 2,4-pen-
tanedione and ethyl acetoacetate to give 13
and 14 in 97 and 98% yields, respectively.
4
The talo configuration having the C1 confor-
Treatment of the b-
D
anomer 3 with 2,4-
mation was assigned to these bicyclic com-
pounds by the NOE difference spectra and
pentanedione gave a complex mixture, be-
cause of intramolecular cyclization of a
initially formed SN2% product. Such a cycliza-
tion should involve attack of an enolate,
generated from the acetyl group, on the ni-
troalkene moiety, giving the dihydropyran
derivative. Attempts at suppressing the cy-
clization or isolating the SN2% product corre-
sponding to 5 were not successful. We
therefore tried to find suitable conditions for
the cyclization and isolated the bicyclic
product 7 in 77% yield. In the 13C NMR
spectrum the C-2 signal appeared at a much
higher field than that of C-4, indicating that
the oxygen atom was attached to C-4. The
1
the JC-1,H-1 values. The structure assigned to
13 is the most favorable one calculated by
the AM1 method in the following, possible
1
eight derivatives: −237.3 (allo, C4), −239.1
(allo, o,3B), −236.3 (gluco, 1C4), −239.7
(gluco, o,3B), −241.1 (ido, C1), −236.5 (ido,
4
4
Bo,3), −242.9 (talo, C1), and −239.4 kcal/
mol (talo, Bo,3) (Fig. 1).
Active methylene compounds thus at-
tacked the 2-position of 3-nitro-2-enopyra-
nosides 3 and 4 exclusively from the side
opposite the anomeric methoxyl group, as
observed in similar reactions of the 4,6-O-
benzylidene derivatives 1 and 2.

T. Sakakibara et al. / Carbohydrate Research 327 (2000) 489–496
491
difference spectra are estimated only approxi-
mately, because measurement conditions were
not completely optimized. IR spectra were
recorded for KBr pellets. Reaction mixtures
were dried over MgSO4 and evaporated under
diminished pressure. Column chromatography
was conducted on silica gel (Wakogel C-300).
Methyl 6-O-acetyl-2,3,4-trideoxy-2-C-bis-
3. Experimental
General methods.—Melting points are un-
corrected. Optical rotations were determined
with a Horiba High sensitivity Polarimeter
(SEPA-200). The H and 13C NMR spectra
1
were recorded at 270 and 67.8 MHz, respec-
tively, with a JNM-EX270 spectrometer for
solutions in CDCl3 with Me4Si as the internal
standard. The integration values in the NOE
(methoxycarbonyl)methyl-3-C-nitro-i-
D
-ery-
thro-hex-3-enopyranoside (5).—(a) From 3. A
Scheme 1.

492
T. Sakakibara et al. / Carbohydrate Research 327 (2000) 489–496
Fig. 1. Possible eight structures for 7 and 13 calculated by the AM1 method. R=OMe and R2=H or R1=H and R2=OMe.
suspension of NaH (10 mg, 0.23 mmol) in
oxolane (5 mL) was stirred under N2 and
cooled to −20 °C. To the solution were
added successively dimethyl malonate (70 mg,
0.53 mmol) in oxolane (1 mL) and 3 [2] (50
mg, 0.17 mmol) in oxolane (1 mL). After
confirming the disappearance of 3 on thin-
layer chromatography (TLC) (within 5 min),
aq NH4Cl was added and the mixture was
diluted with EtOAc. The organic layer was
washed with aq satd NaCl, dried, and evapo-
rated to a syrup that was chromatographed
with 50:1 toluene–EtOAc to give 27.5 mg
(44%) of 5 as a syrup; [h]2D5 −93° (c 1.0,
CH2Cl2); wmax broad 1730 (OAc and CO2Me),
3.82.
(b) From 10. A stirred solution of 10 (160
mg, 0.42 mmol) and MsCl (53 mg, 0.46 mmol)
in oxolane (5 mL) was cooled to −20 °C and
Et3N (100 mg, 1.0 mmol) in 2 mL of oxolane
was added. After stirring for 30 min at
−20 °C, the mixture was diluted with EtOAc
(30 mL) and the organic layer was washed
with aq M HCl (10 mL) and aq satd NaCl
(3×10 mL), and then dried and evaporated.
The residue was purified by column chro-
matography to give 91 mg (60%) of 5, identi-
1
cal with an authentic sample by IR and H
NMR spectra.
Methyl 6-O-acetyl-2,3-dideoxy-2-C-bis(me-
1
and 1530 cm−1 (NO2); H NMR: l 5.13 (s, 1
thoxycarbonyl)methyl-3-C-nitro-i- -glucopy-
D
H, H-1), 3.77 (dd, 1 H, J2,2% 5.6, J2,4 0, J2,5 1.0
Hz, H-2), 7.44 (d, 1 H, J4,5 2.6 Hz, H-4), 4.67
(br t, 1 H, J5,6 7.3, J5,6% 6.6 Hz, H-5), 4.30 (dd,
1 H, J6,6% 10.9 Hz, H-6), 4.14 (dd, 1 H, H-6%),
3.44 (s, 3 H, OMe), 2.12 (s, 3 H, OAc), 3.73 (s,
3 H, CO2Me), 3.76 (s, 3 H, CO2Me), and 3.61
ranoside (10).—A suspension of 9 (1.0 g, 2.35
mmol) in 70% aq AcOH (50 mL) was stirred
for 2 h at 80 °C. The mixture was evaporated
below 50 °C and the resulting syrup was chro-
matographed with 9:1 toluene–MeOH to give
the debenzylidenated product (650 mg, 82%).
Without further purification, the crude
product (1.93 mmol) was dissolved in pyridine
(5 mL), and AcCl (200 mg, 2.55 mmol) was
added at 0 °C and the mixture was stirred for
4 h at 0 °C. To the mixture was added MeOH
(1 mL) at a rate so that the temperature did
13
(d, 1 H, H-2%); C NMR: l 98.82 (C-1), 38.30
(C-2), 131.70 (C-4), 69.11 (C-5), 64.98 (C-6),
56.26 (OMe), 20.72 (OAc), 52.89 (Me), 53.03
1
(COMe), and 50.80 (C-2%); JC-1,H-1 173 Hz.
Anal. Calcd for C14H19NO10: C, 46.54; H,
5.30; N, 3.88. Found: C, 46.84; H, 5.46; N,

T. Sakakibara et al. / Carbohydrate Research 327 (2000) 489–496
493
C, 53.65; H, 5.45; N, 3.29. Found: C, 53.80;
H, 5.51; N, 3.09.
not exceed 5 °C. After stirring for an addi-
tional 30 min at ambient temperature, the
mixture was diluted with EtOAc (30 mL) and
the organic layer was washed with aq
NaHCO3 (20 mL), aq satd NaCl (20 mL), aq
M HCl, and aq satd NaCl (2×20 mL), and
then dried and evaporated. The resulting
syrup was purified on a column of silica gel
with 10:1 toluene–EtOAc to give 530 mg
(72%) of 10 as a syrup; [h]2D5 −64° (c 0.8,
CH2Cl2); wmax 3450 (OH), 1740 (OAc), and
Methyl
6-O-acetyl-2-C-dibenzoylmethyl-
-erythro-hex-3-
2,3,4-trideoxy-3-C-nitro-i-
D
enopyranoside (6).—A stirred suspension of
NaH (10 mg, 0.23 mmol) in oxolane (5 mL)
was cooled to −20 °C under N2, and diben-
zoylmethane (116 mg, 0.52 mmol) in oxolane
(1 mL) and 3 (50 mg, 0.17 mmol) in oxolane
(1 mL) were successively added. The mixture
was stirred for 5 min at −20 °C and treated
with aq NH4Cl and then diluted with EtOAc.
The organic layer was washed with aq satd
NaCl, dried, and evaporated. The syrup ob-
tained was chromatographed with 100:1
toluene–EtOAc to give 60 mg (77%) of 6 as a
syrup; [h]2D5 −49° (c 1.0, CH2Cl2); wmax 1740
(OAc), 1690, 1670 (COPh), and 1525 cm−1
1
1555 cm−1 (NO2); H NMR: l 5.01 (d, 1 H,
J1,2 8.6 Hz, H-1), 2.85 (ddd, 1 H, J2,2% 3.6, J2,3
11.9 Hz, H-2), 4.84 (dd, 1 H, J3,4 9.6 Hz, H-3),
4.02 (dt, 1 H, J4,5 9.9, J4,OH 5.0 Hz, H-4), 3.55
(ddd, 1 H, J5,6 3.3, J5,6% 2.3 Hz, H-5), 4.62 (dd,
1 H, J6,6% 12.2 Hz, H-6), 4.25 (dd, 1 H, H-6%),
3.46 (d, 1 H, H-2%), 3.45 (s, 3 H, OMe), 2.17
(s, 3 H, OAc), 3.79 (s, 3 H, CO2Me), and 3.71
(s, 3 H, CO2Me); 13C NMR: l 101.33 (C-1),
44.76 (C-2), 89.07 (C-3), 68.18 (C-4), 73.91
(C-5), 62.73 (C-6), 57.72, 52.76, 52.67, and
20.8. Anal. Calcd for C14H21NO11: C, 44.33;
H, 5.58; N, 3.69. Found: C, 44.52; H, 5.85; N,
3.58.
1
(CꢀCꢁNO2); H NMR (C6D6): l 5.57 (d, 1 H,
J1,2 1.7 Hz, H-1), 4.43 (td, 1 H, J2,2% 3.3, J2,5
1.7 Hz, H-2), ꢀ7.18 (overlapped with C6H5,
H-4), 3.92 (br tt, 1 H, J4.5 2.0, J5,6 6.6, J5,6% 5.1
Hz, H-5), 3.99 (dd, 1 H, J6,6% 9.5 Hz, H-6),
3.77 (dd, 1 H, H-6%), 5.80 (d, 1 H, H-2%), 3.13
(s, 3 H, OMe), 1.54 (s, 3 H, OAc), 6.9–7.2 (m,
6 H, C6H5), 7.76 (br d, 2 H, C6H5), and 7.94
(br d, 2 H, C6H5); 13C NMR: l 99.81 (C-1),
39.89 (C-2), 128.97 (C-4), 69.56 (C-5), 65.37
(C-6), 57.07 (OMe), 21.39 (OAc), and 54.50
Methyl 4,6-O-benzylidene-2,3-dideoxy-2-C-
bis(methoxycarbonyl)methyl - 3 - C - nitro - i - -
D
glucopyranoside (9).—To a cooled (−20 °C)
suspension of 1 [11] (250 mg, 0.85 mmol) and
NaH (37 mg, 0.9 mmol) in oxolane (10 mL)
was added dropwise dimethyl malonate (169
mg, 1.28 mmol) in oxolane (5 mL) and then
stirring was continued for an additional 15
min at −20 °C. After addition of aq HCl, the
mixture was extracted with EtOAc. The com-
bined extracts were washed with aq satd NaCl
(twice), dried, and evaporated. The residue
was chromatographed with 40:1 and 30:1 hex-
ane–EtOAc and 50:1 toluene–EtOAc to give
330 mg (91%) of 9; mp 141–141.5 °C (i-
PrOH), [h]2D5 −69° (c 1.0, CH2Cl2); wmax 1770,
1
(C-2’); JC-1,H-1 173 Hz. Anal. Calcd for
C24H23NO8: C, 63.57; H, 5.11; N, 3.09. Found:
C, 63.56; H, 5.14; N, 3.12.
(1S,5R,6R,8R,9S)-8-Acetoxymethyl-4-ace-
tyl-6-methoxy-3-methyl-9-nitro-2,7-dioxabi-
cyclo[3.3.1]non-3-ene (7).—A stirred suspen-
sion of NaH (20 mg, 0.5 mmol) in oxolane (4
mL) was cooled to −20 °C and 2,4-pentane-
dione (100 mg, 1.0 mmol) in oxolane (2 mL)
and 3 (50 mg, 0.17 mmol) in oxolane (2 mL)
were successively added. The starting material
3 disappeared (TLC) within 1 min. The mix-
ture was allowed to rise to 0 °C over a period
of ꢀ30 min and kept for an additional hour
at 0 °C. After addition of aq NH4Cl, the
mixture was diluted with EtOAc and the or-
ganic layer was washed with aq satd NaCl
(twice), dried, and evaporated. The resulting
syrup was chromatographed with 50:1
toluene–EtOAc to give 44 mg (77%) of 7 as a
syrup; [h]2D5 −39° (c 0.5, CH2Cl2); wmax 1750
1
1740 (OAc), and 1560 cm−1 (NO2); H NMR
(C6D6): l 5.13 (d, 1 H, J1,2 8.3 Hz, H-1), 2.93
(ddd, 1 H, J2,2% 3.6, J2,3 11.9 Hz, H-2), 5.04
(dd, 1 H, J3,4 9.6 Hz, H-3), 4.19 (t, 1 H, J4,5
9.6 Hz, H-4), 3.61 (ddd, 1 H, J5,6a 9.6, J5,6e 5.0
Hz, H-5), 3.85 (t, 1 H, J6a,6e 10.6 Hz, H-6a),
4.41 (dd, 1 H, H-6e), 3.51 (d, 1 H, H-2%), 3.47
(s, 3 H, OMe), 3.80 (s, 3 H, CO2Me), and 3.73
(s, 3 H, CO2Me). Anal. Calcd for C19H23NO10:

494
T. Sakakibara et al. / Carbohydrate Research 327 (2000) 489–496
H, 5.89; N, 3.90. Found: C, 50.40; H, 6.03; N,
4.05.
(OAc), 1680 and 1620 (CꢀCꢁAc), and 1560
1
cm−1 (NO2); H NMR (C6D6) (carbohydrate
Methyl 6-O-acetyl-2,3,4-trideoxy-2-C-bis-
numbering is used in NMR data through this
article): l 4.65 (d, 1 H, J1,2 2.0 Hz, H-1), 4.14
(td, 1 H, J2,3 3.0, J2,4 2.0 Hz, H-2), 4.62 (dd, 1
H, J3,4 2.0 Hz, H-3), 4.98 (q, 1 H, J4,5 2.0 Hz,
H-4), 4.23 (ddd, 1 H, J5,6 8.9, J5,6% 5.9 Hz,
H-5), 3.89 (dd, 1 H, J6,6% 11.6 Hz, H-6), 3.98
(dd, 1 H, H-6%), 2.96 (s, 3 H, OMe), 1.58 (s, 3
H, OAc), 1.87 (s, 3 H, CAc), and 1.84 (s, 3 H,
CꢀCꢁMe); NOE difference spectrum: H-2
(9%), H-4 (6%), and H-6 and H-6% (7%) irradi-
ated at H-3; 13C NMR: l 102.18 (C-1), 35.70
(C-2), 70.96 (C-3), 69.68 (C-4), 77.49 (C-5),
62.38 (C-6), 56.36 (OMe), 20.59 (OAc), 20.92
(methoxycarbonyl)methyl-3-C-nitro-h- -threo-
D
hex-3-enopyranoside (11).—(a) From 4. A
suspension of NaH (40 mg, 0.92 mmol) in
oxolane (5 mL) was cooled to −20 °C under
N2. To the solution dimethyl malonate (180
mg, 1.36 mmol) in oxolane (1 mL) and 4 [2]
(200 mg, 0.69 mmol) in oxolane (1 mL) were
successively added. The mixture was stirred
for 5 min and then partitioned between aq
NH4Cl and EtOAc (70 mL). The organic layer
was washed with aq satd NaCl, dried, and
evaporated to a syrup, which was chro-
matographed with 50:1 and 30:1 toluene–
EtOAc to give 72 mg (29%) of 11 as a syrup.
Compound 11 partially decomposed during
chromatographic separation; [h]2D5 +38° (c
1.0, CH2Cl2); wmax 1730 (ester), and 1530 cm−1
1
(Me), and 30.30 (COMe); JC-1,H-1 171 Hz.
Anal. Calcd for C14H19NO8: C, 51.06; H, 5.82;
N, 4.25. Found: C, 51.04; H, 5.79; N, 4.25.
By shortening the reaction time by 5 min
and quenching the reaction at −20 °C a mix-
ture of 7 and the SN2% product corresponding
1
(NO2); H NMR: l 5.10 (s, 1 H, H-1), 3.72
(dd, 1 H, J2,2% 6.3, J2,5 2.6 Hz, H-2), 7.36 (d, 1
H, J4,5 2.3 Hz, H-4), 4.55 (br tt, 1 H, J5,6 5.3,
J5,6% 5.0 Hz, H-5), 4.39 (dd, 1 H, J6,6% 11.2 Hz,
H-6), 4.20 (dd, 1 H, H-6%), 3.64 (d, 1 H, H-2%),
3.46 (s, 3 H, OMe), 2.12 (s, 3 H, OAc), 3.72 (s,
3 H, COMe), and 3.75 (s, 3 H, COMe); 13C
NMR: l 98.74 (C-1), 38.37 (C-2), 132.22 (C-
4), 66.67 (C-5), 63.30 (C-6), 55.98 (OMe),
20.60 (OCOCH3), 52.78 (COMe), and 51.79
1
to 5 was obtained, as judged by H NMR
spectroscopy {4.93 (1 H, d, J1,2 2.3 Hz, H-1),
3.76 (1 H, dt, J2,2% 5.9, J2,5 2.3 Hz, H-2), 7.40 (1
H, d, J4,5 2.6 Hz, H-4), 4.72 (1 H, m, H-5),
4.16 (1 H, dd, J5,6 6.6, J6,6% 10.9 Hz, H-6), 4.28
(1 H, dd, J5,6% 6.9 Hz, H-6%), 3.91 (1 H, d,
H-2%), 3.41 (3 H, s, OMe), 2.22, 2.20, and 2.12
(3 H, all s, 2×COMe, OAc)}.
(1S,5R,6R,8R,9S) - 8 - Acetoxymethyl - 4-
ethoxycarbonyl-6-methoxy-3-methyl-9-nitro-2,
7-dioxabicyclo[3.3.1]non-3-ene (8).—Similar
treatment of 3 (30 mg, 0.10 mmol) with ethyl
acetoacetate (68 mg, 0.52 mmol) in the pres-
ence of NaH (12 mg, 0.3 mmol) afforded 34
mg (91%) of 8 as a syrup; [h]2D5 −37° (c 1.0,
CH2Cl2); wmax 1740 (OAc), 1710, 1680, and
1625 (CꢀCꢁCO2Et), and 1550 cm−1 (NO2); 1H
NMR (C6D6): l 4.82 (d, 1 H, J1,2 2.3 Hz,
H-1), 4.22 (td, 1 H, J2,3 3.0, J2,4 2.0 Hz, H-2),
4.65 (dd, 1 H, J3,4 2.0 Hz, H-3), 5.01 (q, 1 H,
J4,5 1.7 Hz, H-4), 4.25 (ddd, 1 H, J5,6 8.9, J5,6%
5.9 Hz, H-5), 3.89 (dd, 1 H, J6,6% 11.5 Hz,
H-6), 4.01 (dd, 1 H, H-6%), 2.99 (s, 3 H, OMe),
1.59 (s, 3 H, OAc), 0.91 (s, 3 H, OCH2CH3),
3.96 (q, 2 H, OCH2CH3), and 2.25 (s, 3 H,
CꢀCꢁMe); NOE difference spectrum: H-2 and
H-5 (12%), H-4 (7.5%) and H-6 (major) and
1
(C-2%); JC-1,H-1 177 Hz. Anal. Calcd for
C14H19NO10: C, 46.54; H, 5.30; N, 3.88.
Found: C, 46.64; H, 5.45; N, 4.08.
(b) From 16. A stirred solution of 16 (70
mg, 0.18 mmol) and MsCl (60 mg, 0.52 mmol)
in oxolane (5 mL) was cooled to −20 °C and
Et3N (140 mg, 1.4 mmol) in oxolane (2 mL)
was added. After stirring for 2 h at −20 °C
and an additional 2 h at 0 °C, the mixture was
diluted with EtOAc (30 mL) and the organic
layer was washed with aq M HCl (10 mL) and
aq satd NaCl (3×10 mL), dried, and evapo-
rated. The residue was purified by column
chromatography to give 15 mg (22%) of 11,
identical with an authentic sample obtained
1
from IR and H NMR spectra.
Methyl6-O-acetyl-2,3-dideoxy-2-C-bis(meth-
oxycarbonyl)methyl - 3 - C - nitro - h -
D
- manno-
pyranoside (16).—A suspension of 15 [9] (1.0
g, 2.35 mmol) in 90% aq AcOH (30 mL) was
stirred for 4 h at 70 °C. The mixture was
1
H-6% (minor) (7%) irradiated at H-3; JC-1,H-1
173 Hz. Anal. Calcd for C15H21NO9: C, 50.14;

T. Sakakibara et al. / Carbohydrate Research 327 (2000) 489–496
495
H-6), 3.23 (dd, 1 H, H-6%), 5.64 (d, 1 H, H-2%),
3.49 (s, 3 H, OMe), and 2.02 (s, 3 H, OAc);
NOE difference spectrum: H-4 (12%) irradi-
ated at H-5 and H-2 (8%) and OMe (6%)
irradiation at H-1; 13C NMR: l 98.44 (C-1),
39.05 (C-2), 146.54 (C-3), 127.69 (overlap with
C6H5, tentative C-4), 65.34 (C-5), 63.22 (C-6),
evaporated to a syrup below 50 °C and then
chromatographed with 9:1 toluene–MeOH to
give the debenzylidenated product (550 mg,
69%). Without further purification, to the
crude product (1.63 mmol) dissolved in
pyridine (2 mL) was added AcCl (140 mg,
1.78 mmol) at −20 °C and the mixture was
stirred for 2 h at ambient temperature. To the
mixture was added MeOH (1 mL) at such a
rate that the temperature did not exceed 5 °C.
After stirring for 30 min, the mixture was
diluted with EtOAc and the organic layer was
washed with aq NaHCO3 (20 mL), aq satd
NaCl (2×20 mL), aq M HCl (20 mL), and aq
satd NaCl (2×20 mL), and then dried and
evaporated. The residue was purified by chro-
matography with 10:1 toluene–EtOAc to give
280 mg (45%) of 16; mp 86–90 °C, [h]2D5 −3°
(c 1.0, MeOH); wmax 3480 (OH), 1740 (OAc),
1
56.05 (OMe), and 54.11 (C-2%); JC-1,H-1 172
Hz. Anal. Calcd for C24H23NO8: C, 63.57; H,
5.11; N, 3.09. Found: C, 63.56; H, 5.38; N,
3.08.
(1R,5S,6S,8R,9R)-8-Acetoxymethyl-4-ace-
tyl-6-methoxy-3-methyl-9-nitro-2,7-dioxabi-
cyclo[3.3.1]non-3-ene (13).—A stirred suspen-
sion of NaH (20 mg, 0.5 mmol) in oxolane (4
mL) was cooled to −20 °C under N2. To the
solution 2,4-pentanedione (100 mg, 1.0 mmol)
in oxolane (2 mL) and 4 (50 mg, 0.17 mmol)
in oxolane (2 mL) were successively added.
The starting material 4 disappeared (TLC)
within 1 min. The mixture was allowed to rise
to 0 °C over a period of 30 min and kept for
an additional hour, and then diluted with
EtOAc (60 mL). The organic layer was
washed with aq satd NaCl, dried, and evapo-
rated. The residue was chromatographed with
50:1 toluene–EtOAc to give 55 mg (97%) of
13; mp 91.5–92.5 °C (toluene–hexane), [h]D25
−1° (c 0.9, CH2Cl2); wmax 1750 (OAc), 1680
and 1620 (CꢀCꢁAc), and 1560 cm−1 (NO2);
1H NMR: l 4.71 (d, 1 H, J1,2 2.0 Hz, H-1),
3.96 (dt, 1 H, J2,3 3.3, J2,4 2.0 Hz, H-2), 4.99
(dd, 1 H, J3,4 1.7 Hz, H-3), 5.06 (br s, 1 H,
H-4), 4.05 (t, 1 H, J5,6 6.6, J5,6% 6.3 Hz, H-5),
4.28 (dd, 1 H, J6,6% 11.3 Hz, H-6), 4.23 (dd,
1 H, H-6%), 3.42 (s, 3 H, OMe), 2.12, 2.28,
2.33 (all s, 3 H, OMe, OAc, CꢀCꢁMe); NOE
difference spectrum: H-3 (13%), H-4 (10%)
and H-6 and H-6% (4%) irradiated at H-5,
and H-2 (10%), H-4 (4.5%), H-5 (11%) irra-
diated at H-3; 13C NMR: l 100.85 (C-1),
35.67 (C-2), 73.89 (C-3), 69.27 (C-4), 71.05
(C-5), 62.21 (C-6), 55.55 (OMe), 20.74, 20.86,
30.35 (OCOCH3, COCH3, Me), 170.58
(OCOCH3), and 195.76 (COCH3); 1JC-1,H-1 175
Hz. Anal. Calcd for C14H19NO8: C, 51.06; H,
5.82; N, 4.25. Found: C, 51.05; H, 5.80; N,
4.28.
1
and 1560 cm−1 (NO2); H NMR: l 4.93 (d, 1
H, J1,2 1.7 Hz, H-1), 3.50 (ddd, 1 H, J2,2% 6.6,
J2,3 5.0 Hz, H-2), 5.10 (dd, 1 H, J3,4 9.6 Hz,
H-3), 4.02 (dt, 1 H, J4,5 9.9, J4,OH 5.0 Hz, H-4),
ꢀ3.8 (H-5), 4.45 (dd, 1 H, J5,6 4.6, J6,6% 12.2
Hz, H-6), 4.38 (dd, 1 H, J5,6% 2.6 Hz, H-6%),
3.65 (d, 1 H, H-2%), 3.46 (s, 3 H, OMe), 2.20
(s, 3 H, OAc), 3.76 (s, 3 H, CO2Me), and 3.81
(s, 3 H, CO2Me). Anal. Calcd for C14H21NO11:
C, 44.33; H, 5.58; N, 3.69. Found: C, 44.53;
H, 5.48; N, 3.66.
Methyl
6-O-acetyl-2-C-dibenzoylmethyl-
-threo-hex-3-
2,3,4-trideoxy-3-C-nitro-h-
D
enopyranoside (12).—A stirred suspension of
NaH (20 mg, 0.5 mmol) in oxolane (5 mL)
was cooled to −20 °C under N2. To the
solution dibenzoylmethane (195 mg, 0.87
mmol) in oxolane (1 mL) and 4 (50 mg, 0.17
mmol) in oxolane (1 mL) were successively
added. After stirring for 30 min at −20 °C,
the mixture was diluted with EtOAc and the
organic layer was washed with aq satd NaCl
(twice), dried, and evaporated. The resulting
syrup was chromatographed with 100:1
toluene–EtOAc to give 70 mg (89%) of 12 as
a syrup; [h]2D5 −22° (c 0.9, CH2Cl2); wmax 1740
(OAc), 1690, 1670 (COPh) and 1530 cm−1
1
(CꢀCꢁNO2); H NMR: l 5.30 (s, 1 H, H-1),
4.02 (t, 1 H, J2,2%=J2,5 3.0 Hz, H-2), 7.14 (d, 1
H, J4,5 1.3 Hz, H-4), 4.36 (br td, 1 H, J5,6=
J5,6% 6.6 Hz, H-5), 3.59 (dd, 1 H, J6,6% 11.2 Hz,
By shortening the reaction time by 5 min
and quenching the reaction at −20 °C a mix-

496
T. Sakakibara et al. / Carbohydrate Research 327 (2000) 489–496
ture of 13 and the SN2% product corresponding
Acknowledgements
1
to 11 was obtained, as judged from H NMR
spectroscopy {4.68 (1 H, d, J1,2 2.0 Hz, H-1),
ꢀ3.97 (overlapped with H-2 of 13, H-2), and
7.39 (1 H, d, J4,5 2.4 Hz, H-4)}.
This work was supported in part by the
Grants in Support of the Promotion of Re-
search at Yokohama City University.
(1R,5S,6S,8R,9R)-8-Acetoxymethyl-4-eth-
oxycarbonyl-6-methoxy-3-methyl-9-nitro-2,7-
dioxabicyclo[3.3.1]non-3-ene (14).—Similar
treatment of 4 (50 mg, 0.17 mmol) with ethyl
acetoacetate (115 mg, 0.88 mmol) in the pres-
ence of NaH (20 mg, 0.5 mmol) gave 61 mg
(98%) of 14; mp 130.5–132 °C (toluene–hex-
ane), [h]2D5 −0° (c 1.4, CH2Cl2); wmax 1740
(OAc), 1710 and 1620 (CꢀCꢁCOOEt), and
References
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1
1550 cm−1 (NO2); H NMR: l 4.78 (d, 1 H,
J1,2 2.0 Hz, H-1), 3.91 (dt, 1 H, J2,3 3.3, J2,4 2.0
Hz, H-2), 4.97 (dd, 1 H, J3,4 2.0 Hz, H-3), 5.04
(br s, 1 H, H-4), 4.05 (t, 1 H, J5,6 6.6, J5,6% 6.3
Hz, H-5), 4.28 (dd, 1 H, J6,6% 11.6 Hz, H-6),
4.22 (dd, 1 H, H-6%), 3.43 (s, 3 H, OMe), 2.12
(s, 3 H, OAc), 1.30 (s, 3 H, OCH2CH3), 4.20
(q, 2 H, OCH2CH3), and 2.29 (s, 3 H,
CꢀCꢁMe); NOE difference spectrum: H-4
(12%), H-3 (12%), and H-6 and H-6% (7%)
irradiated at H-5; 13C NMR: l 101.19 (C-1)
36.00 (C-2), 74.11 (C-3), 69.53 (C-4), 71.52
(C-5), 62.36 (C-6), 55.81 (OMe), 60.65
(OCH2CH3), 20.97 (OAc or Me), 19.98 (Me
1
or OAc), and 14.58 (OCH2CH3); JC-1,H-1 172
[10] H.H. Baer, C.W. Chiu, Can. J. Chem., 52 (1974) 111–
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[11] H.H. Baer, T. Neilson, Can. J. Chem., 43 (1965) 840–
846.
Hz. Anal. Calcd for C15H21NO9: C, 50.14; H,
5.89; N, 3.90. Found: C, 50.16; H, 5.91; N,
3.93.
.