Photoreaction of methyl and phenyl 4,6-O-benzylidene-2,3-dideoxy-2-C-p-tolylsulfonyl-β-D-erythro-hex-2- enopyranosides in methanol

Article abstract of DOI:10.1016/S0008-6215(02)00231-8

The title compounds were irradiated with a high-pressure mercury lamp in methanol to give 2-C-hydroxymethyl derivatives having the gluco, altro, and allo configurations as well as an S_N2′ product. Equatorial attack of a hydroxymethyl radical slightly predominated over axial attack. During chromatographic separation on a silica gel column, partial migration of the 4,6-O-benzylidene group in the gluco and altro products occurred to yield the 3′,4-O-benzylidene derivatives.

Full text of DOI:10.1016/S0008-6215(02)00231-8

Carbohydrate Research 337 (2002) 2061–2067
www.elsevier.com/locate/carres
Photoreaction of methyl and phenyl
4,6-O-benzylidene-2,3-dideoxy-2-C-p-tolylsulfonyl-b-
enopyranosides in methanol
D-erythro-hex-2-
Tohru Sakakibara,* Tetsuya Shindo, Hiroshi Hirai
Graduate School of Integrated Science, Yokohama City Uni6ersity, 22-2, Seto, Kanazawa-ku, Yokohama 236-0027, Japan
Received 2 April 2002; accepted 22 May 2002
Dedicated to Professor Derek Horton on the occasion of his 70th birthday
Abstract
The title compounds were irradiated with a high-pressure mercury lamp in methanol to give 2-C-hydroxymethyl derivatives
having the gluco, altro, and allo configurations as well as an SN2% product. Equatorial attack of a hydroxymethyl radical slightly
predominated over axial attack. During chromatographic separation on a silica gel column, partial migration of the 4,6-O-benzyl-
idene group in the gluco and altro products occurred to yield the 3%,4-O-benzylidene derivatives. © 2002 Elsevier Science Ltd. All
rights reserved.
Keywords: Photoreaction; Sulfonyl sugars; Benzylidene group
1. Introduction
have performed such reactions by irradiation of 1 and 2
in methanol in the presence of benzophenone.
a,b-Unsaturated sulfones are compounds of potential
utility because a host of nucleophiles added to the
electron-deficient b-carbon atom.1 The sulfonyl group is
replaced by a hydrogen atom2 or changed to other
functional group.3
Previously, we showed that nucleophiles added from
the equatorial side of methyl 4,6-O-benzylidene-2,3-
dideoxy-2-C-p-tolylsulfonyl-b-D-erythro-hex-2-enopy-
ranoside (1) with high stereoselectivity to give the gluco
adducts.4 On the other hand, a similar reaction of the
phenyl analog 2 afforded the SN2% products, that is, the
glucal derivatives.4 Sodium borodeuteride also added
from the equatorial side of 1, and the stereochemistry
of the subsequent protonation was strongly affected by
the solvents employed.5
2. Results and discussion
2-Sulfonyl-2-enopyranoside 1 was irradiated with a
high-pressure mercury lamp in methanol in the presence
of benzophenone (added as a sensitizer) for 10 h at
ꢀ8 °C to give three new spots on TLC. By silica gel
column chromatography, the glucal 3 (4%), the b-
product 6 (9%), and a mixture (55%) of the b- -gluco 7
-altro 9 products were isolated. After acetyla-
D-allo
D
and b-
D
tion of the mixture, compounds 7 and 9 could be
separated by column chromatography. The isolated
acetates, b-
D
-gluco 8 and b- -altro isomers 10, were
D
deacetylated to afford the alcohols 7 and 9, respec-
However, photoaddition reactions to a,b-unsaturated
4
tively. The allo and gluco configurations with the C1
conformations for 6 and 7, respectively, were readily
sulfones have been extremely limited.6 Therefore, we
assigned by the coupling constants; J1,2 8.7, J2,3
=
J
3,4=5.0, J4,5 9.6 Hz for 6 and J1,2 6.7, J2,3 9.2 Hz,
* Corresponding author. Tel. +81 45 787 2183; fax: +81
45 787 2370
E-mail address: baratoru@yokohama-cu.ac.jp (T. Sakak-
ibara).
J3,4=J4,5=10.1 Hz for 7. The twist-boat conformation
(1S5) for the altro isomer 9 was suggested by the
coupling constants (J1,2 2.6, J2,3 8.1, J3,4 7.9, and J4,5
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00231-8

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T. Sakakibara et al. / Carbohydrate Research 337 (2002) 2061–2067
10.4 Hz) and confirmed by correlation between H-2 and
H-5 in the NOESY spectrum. The altro configuration
for 9 was chemically confirmed by treatment of the allo
isomer 6 with DBU in THF, in which a 1:2 mixture of
6 and 9 was obtained. The same treatment, except in
the presence of small amount of deuterium oxide, gave
a similar result in which H-1 appeared as singlet, indi-
cating the epimerization at C-2. The glucal structure for
3 was determined by IR (hydroxyl group at 3490 cm−1
and strong absorption band at 1605 cm−1 for O–
CꢀC–SO2Tol) and H NMR spectra (olefinic proton at
l 7.74, J3,4 10.9 Hz). The configuration at C-3 was
confirmed by transformation of 3 into the b-D-glucopy-
ranoside 7 as a major product by treatment with
methanolic sodium methoxide.
After acetylation of a fraction that mainly consisted
of 7, a small amount of the transbenzylidenated altro
product 16 was isolated. Different from the alternative
altro isomer 10, compound 16 has the 1C4 conformation
(J2,3 11.8 Hz). The altro configuration for 16 was confi-
rmed by transformation into the peracetate 17, identical
with a sample prepared from the b- -allopyranoside 10.
D
The peracetate 17 and trihydroxy derivative 18 exist in
1
the C4 conformation. Benzylidenation of 18 afforded
the 3%,4-O-benzylidene derivative 15 in 89% yield.
Similar photoreaction of the phenyl analog 2, fol-
lowed by acetylation and subsequent separation by
column chromatography afforded the glucal 4, allal 5,
and the gluco adduct 19 in 37%, 24%, and 11% yields,
respectively. The gluco structure for 19 was assigned by
the coupling constants (J1,2 5.0, J2,3 7.9, J3,4=J4,5 9.9
Hz). The allal structure for 5 was suggested by the IR
1
Although the amounts were variable, another gluco
isomer 11 was almost always isolated as crystals from
1
the fraction mainly containing the b-
D-gluco isomer 7
(1620 cm−1 for O–CꢀC–SO2Tol) and H NMR spec-
after column chromatography. Before column chro-
matography, however, compound 11 could not be de-
tected. The gluco structure for 11 was determined from
the coupling constants and confirmed chemically as
follows. Debenzylidenation and subsequent acetylation
of the monoacetates 8 and 12 (derived by acetylation of
11) gave the same peracetate 13. Thus compound 11
should be formed from 7 by migration of the 4,6-O-
benzylidene group to O-4 and the newly introduced
hydroxymethyl group (3%,4-O-benzylidene). It was note-
worthy that the benzylidenation of trihydroxy deriva-
tive 14, followed by acetylation, afforded a 1:3 mixture
of the 4,6-O-benzylidene 8 and 3%,4-O-benzylidene
derivative 12.
tra (olefinic proton at l 7.74, J3,4 5.9 Hz) and confirmed
by conversion into the a- -altropyranoside 20 (J1,2 0,
D
J2,3B1.0 Hz) in almost quantitative yield by treatment
with methanolic sodium methoxide. Thus a methoxide
ion predominantly added from the same side of the
substituent at C-3 of 1-enitols 4 and 5. Similar stereose-
lectivity was observed in the SN2% reaction of 3-O-ace-
tyl-1,5-anhydro-4,6-O-benzylidene-2-deoxy-2-C-p-tolyl-
sulfonyl-D-arbino- and -ribo-hex-1-enitol with methano-
lic sodium methoxide.7
The ratios of glycal derivatives (SN2% product) to
adducts were 1:16 for the methyl derivative 1 and 5.5:1
for the phenyl derivative 2. These results are reasonable
because a phenoxy radical generated by formation of

T. Sakakibara et al. / Carbohydrate Research 337 (2002) 2061–2067
2063
glycal derivatives is much more stable than a methoxy
radical.8
4.43–4.35 (m, 2 H, H-3%, H-3%%), 2.89 (dd, 1 H, J3%,OH
5.8, J3%%,OH 8.2 Hz, OH), 5.56 (s, 1 H, PhCH), 3.30 (s, 3
H, OMe), and 2.44 (s, 3 H, SO2Tol). Anal. Calcd for
C22H26O7S: C, 60.81; H, 6.03; S, 7.38. Found: C, 60.69;
H, 5.98; S, 7.32.
The stereoselectivities of the present hydroxymethyl
radical addition reaction to methyl and phenyl deriva-
tives (1 and 2) were 2.4:1 and 2.0:1, respectively, where
equatorial attack slightly predominated over axial
attack.
Separation of 7 and 9 could be achieved after acety-
lation. To a mixture (300 mg, 0.69 mmol) of 7 and 9 in
CH2Cl2 (60 mL) was added alternatingly and portion-
wise AcCl (900 mg, 11.46 mmol) and pyridine (900 mg,
11.38 mmol). After stirring for 2 h at room tempera-
ture, the mixture was partitioned between AcOEt and
H2O. The organic layer was separated and washed with
H2O, dried, and evaporated to give a residue that was
chromatographed to afford successively 8 (235 mg,
71%) and 10 (59 mg, 18%).
3. Experimental
General methods.—Melting points are uncorrected.
Optical rotations were determined with a Horiba High
Sensitive Polarimeter (SEPA-200). 1H NMR spectra
were recorded with JEOL EX-270 or Bruker AVANCE
400 instruments in CDCl3 with Me4Si as the internal
standard. Only important correlations for structural
determination observed in the NOESY spectrum are
described. The integration values in NOE difference
spectra are roughly estimated, because measurement
conditions were not completely optimized. IR spectra
were recorded for KBr pellets. Solutions were dried
over MgSO4 and evaporated under diminished pres-
sure. Column chromatography was conducted on silica
gel (Wakogel C-300) with 12:1 toluene–EtOAc.
Physical data for 8: mp 121–122 °C (2-PrOH), [h]D25
−54° (c 1, CHCl3); wmax 1740 (OAc), 1300, and 1140
1
cm−1 (SO2); H NMR (400 MHz): l 4.91 (d, 1 H, J1,2
6.2 Hz, H-1), 3.59 (dd, 1 H, J2,3 9.2 Hz, H-2), 2.74 (m,
1 H, H-3), 3.75 (t, 1 H, J3,4 9.7, J4,5 9.3 Hz, H-4), 3.60
(sextet, 1 H, J5,6a 10.1, J5,6e 4.3 Hz, H-5), 3.66 (t, 1 H,
J6a,6e 10.0 Hz, H-6a), 4.31 (dd, 1 H, H-6e), 4.44 (dd, 1
H, J3,3% 3.1, J3%,3%% 11.4 Hz, H-3%), 4.62 (dd, 1 H, J3,3%% 3.4
Hz, H-3%%), 5.51 (s, 1 H, PhCH), 3.30 (s, 3 H, OMe),
and 2.46 (s, 3 H, SO2Tol), and 1.99 (s, 3 H, OAc).
Anal. Calcd for C24H28O8S: C, 60.49; H, 5.92; S, 6.73.
Found: C, 60.40; H, 5.83; S, 6.92.
Irradiation of 1 in methanol.—To a solution of 1
(Ref. 9, 500 mg, 1.24 mmol) in methanol (distilled over
Mg, 160 mL) in the presence of benzophenone (37 mg,
0.20 mmol) was cooled at ꢀ8 °C and irradiated in a
Riko photoreactor with a high-pressure mercury lamp
in an H2O–ethylene glycol cooled Pyrex immersion-
well for 10 h under N2. The mixture was then evapo-
rated, and the resulting syrup was chromatographed to
give the 1-enitol derivative 3 (22 mg, 4%) as the front-
running fraction, the allo isomer 6 (46 mg, 9%) as the
second one, and a 4:1 mixture (298 mg, 55%) of the
Physical data for 10: mp 141–142 °C (EtOH), [h]D25
−46° (c 1, CHCl3); wmax 1730 (OAc), 1315, and 1150
cm−1 (SO2); 1H NMR: l 5.03 (d, 1 H, J1,2 2.6 Hz, H-1),
3.83 (dd, 1 H, J2,3 7.3 Hz, H-2), 3.11 (m, 1 H, H-3),
4.38 (dd, 1 H, J3,4 7.6, J4,5 10.2 Hz, H-4), 3.86 (td, 1 H,
J5,6a 10.2, J5,6e 4.6 Hz, H-5), 3.60 (t, 1 H, J6a,6e 10.2 Hz,
H-6a), 4.31 (dd, 1 H, H-6e), 4.55 (dd, 1 H, J3,3% 4.6 Hz,
J3%,3%% 11.6 Hz, H-3%), 4.39 (dd, 1 H, J3,3%% 4.0 Hz, H-3%%),
5.50 (s, 1 H, PhCH), 3.35 (s, 3 H, OMe), 2.46 (s, 3 H,
SO2Tol), and 2.04 (s, 3 H, OAc). Anal. Calcd for
C24H28O8S: C, 60.49; H, 5.92; S, 6.73. Found: C, 60.69;
H, 5.78; S, 6.81.
1
gluco and altro isomers (7 and 9), as judged from H
NMR spectroscopy as the third one.
Physical data for 3: mp 185–186 °C (EtOH), [h]D25
+141° (c 0.6, CHCl3); wmax 3490 (OH), 1605 (O–CꢀC–
Although no evidence for formation of 11 was ob-
1
1
SO2), 1280 and 1140 cm−1 (SO2); H NMR: l 7.74 (d,
tained by H NMR spectroscopy and TLC of the crude
1 H, J1,3 1.7 Hz, H-1), 2.28 (m, 1 H, J3,4 10.9 Hz, H-3),
4.10 (broad t, 1 H, J4,5 10.9 Hz, H-4), 4.46 (dd, 1 H,
ABX, H-6e), 3.90–3.83 (m, 2 H, H-5, H-6a), 4.02 (dd,
1 H, J3,3% 3.0, J3%,OH 4.6 Hz, H-3%), 3.82 (m, 1 H, J3,3%%
ꢀ0, J3%%,OH 10.9 Hz, H-3%%), 2.73 (dd, 1 H, OH), 5.62 (s,
1 H, PhCH), and 2.44 (s, 3 H, SO2Tol). Anal. Calcd for
C21H22O6S: C, 62.67; H, 5.51; S, 7.97. Found: C, 62.87;
H, 5.61; S, 7.78.
product just after evaporation, transbenzylidenation of
7 into 11 frequently occurred during crystallization of
the mixture of 7 and 9 or during separation by column
chromatography on silica gel. While the conditions for
the transbenzylidenation have not yet been established,
the rearrangement also occurred in chloroform-d. An
analytical sample of 11, which readily crystallized from
the mixture, was prepared by recrystallization from
ethanol: mp 198–199 °C, [h]2D5 +3° (c 1, CHCl3); wmax
Physical data for 6: mp 157–158 °C (EtOH), [h]D25
−76° (c 1, CHCl3); wmax 3520 and 3475 (OH), 1280,
1
3480 (OH), 1285, and 1140 cm−1 (SO2); H NMR (400
1
and 1130 cm−1 (SO2); H NMR (400 MHz): l 5.21 (d,
MHz): l 4.69 (d, 1 H, J1,2 7.2 Hz, H-1), 3.07 (dd, 1 H,
J2,3 11.9 Hz, H-2), 2.63 (qd, 1 H, J3,4 10.5 Hz, H-3),
3.82 (dd, 1 H, J4,5 9.0 Hz, H-4), 3.65 (ddd, 1 H, J5,6 4.2,
J5,6% 3.1 Hz, H-5), 3.76 (ddd, 1 H, J6,6% 12.1 Hz, H-6%),
3.83 (m, 1 H, H-6), 3.89 (t, 1 H, J3,3%a 10.5, J3%a,3%e 11.6
1 H, J1,2 8.7 Hz, H-1), 3.40 (dd, 1 H, J2,3 5.0 Hz, H-2),
3.06 (m, 1 H, H-3), 3.71 (dd, 1 H, J3,4 5.0, J4,5 9.6 Hz,
H-4), 4.17 (sextet, 1 H, J5,6a 10.1, J5,6e 5.0 Hz, H-5),
3.62 (t, 1 H, J6a,6e 10.5 Hz, H-6a), 4.32 (dd, 1 H, H-6e),

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T. Sakakibara et al. / Carbohydrate Research 337 (2002) 2061–2067
Hz, H-3%a), 5.17 (dd, 1 H, J3,3%e 4.1 Hz, H-3%e), 5.59 (s,
1 H, PhCH), 3.17 (s, 3 H, OMe), 2.46 (s, 3 H, SO2Tol),
and 1.92 (dd, 1 H, J6,OH 5.3, J6%,OH 7.8 Hz, OH). Anal.
Calcd for C22H26O7S: C, 60.81; H, 6.03; S, 7.38. Found:
C, 60.74; H, 5.93; S, 7.28.
The same compound 11 was prepared by benzylide-
nation of 14 as described later.
The filtrate was evaporated and acetylated by AcCl
and pyridine to give the acetate 12, together with a
small amount of the altro isomer 16, identical with an
authentic sample prepared from 15.
Deacetylation of 8.—To a solution of 8 (20 mg, 0.04
mmol) in methanol (8 mL) was added 1.8 M NaOMe (3
mL). After stirring for 3 h at room temperature, the
mixture was partitioned between H2O and AcOEt, and
then the organic layer was washed with dil aq HCl and
H2O, dried, and evaporated to give 7 in almost quanti-
tative yield.
Physical data for 7: mp 110–111 °C (2-PrOH), [h]D25
−36° (c 1, CHCl3); wmax 3550–3400 (OH), 1290, and
1
1130 cm−1 (SO2); H NMR (400 MHz): l 4.78 (d, 1 H,
J1,2 6.7 Hz, H-1), 3.66 (dd, 1 H, J2,3 9.2 Hz, H-2), 2.59
(m, 1 H, H-3), 3.82 (t, 1 H, J3,4=J4,5 10.1 Hz, H-4),
3.55 (sextet, 1 H, J5,6a 10.1, J5,6e 4.8 Hz, H-5), 3.67 (t, 1
H, J6a,6e 10.2 Hz, H-6a), 4.28 (dd, 1 H, H-6e), 4.17 (dd,
1 H, J3,3% 3.7, J3%,3%% 11.5 Hz, H-3%), 3.99 (dd, 1 H, J3,3%%
2.3 Hz, H-3%%), 5.56 (s, 1 H, PhCH), 3.14 (s, 3 H, OMe),
and 2.46 (s, 3 H, SO2Tol). Anal. Calcd for C22H26O7S:
C, 60.81; H, 6.03; S, 7.38. Found: C, 61.00; H, 5.99; S,
7.39.
Acetylation of 11.—Similar acetylation of 11 (45 mg,
0.10 mmol) with AcCl and pyridine in CH2Cl2 as had
been described for the preparation of 8 and 10 gave a
crystalline residue of 12 in almost quantitative yield.
Physical data for 12: mp 142–143 °C (EtOH), [h]D25
+14° (c 1, CHCl3); wmax 1735 (OAc), 1295, and 1150
1
cm−1 (SO2); H NMR (400 MHz): l 4.70 (d, 1 H, J1,2
6.6 Hz, H-1), 3.09 (dd, 1 H, J2,3 11.8 Hz, H-2), 2.60 (m,
1 H, H-3), 3.8–3.7 (m, 2 H, H-4 -5), 4.18 (dd, 1 H, J5,6
5.5, J6,6% 12.0 Hz, H-6), 4.35 (dd, 1 H, J5,6% 2.1 Hz, H-6%),
3.88 (dd, 1 H, J3,3%a 10.5, J3%a,3%e 11.6 Hz, H-3%a), 5.12
(dd, 1 H, J3,3%e 4.1 Hz, H-3%e), 5.56 (s, 1 H, PhCH), 3.18
(s, 3 H, OMe), 2.46 (s, 3 H, SO2Tol), and 2.04 (s, 3 H,
OAc); the n.O.e. difference spectrum (270 MHz), H-5
(11%), H-3 (6%), and OMe (10%) appeared by irradia-
tion at H-1. Anal. Calcd for C24H28O8S:C, 60.49; H,
5.92; S, 6.73. Found: C, 60.49; H, 5.95; S, 6.59.
Deacetylation of 10.—Similar deacetylation of 10 (20
mg, 0.04 mmol) afforded 9, identical with an authentic
1
sample by its H NMR spectrum and TLC.
Reaction of 3 with methanolic sodium methoxide.—To
a solution of 3 (10 mg, 0.02 mmol) in methanol (5 mL)
was added 1.2 M NaOMe (2 mL) and the mixture was
heated under reflux for 2 h and allowed to stand
overnight at room temperature. The mixture was parti-
tioned between AcOEt and H2O. The organic layer was
washed with dil aq HCl and H2O, dried, and evapo-
rated, from which 7, identical with an authentic sample,
was separated in 57% yield, as the major product, after
column chromatography.
Epimerization of 6.—To a solution of the allo isomer
6 (15 mg, 0.03 mmol) in oxolane (5 mL) was added
DBU (720 mg, 4.73 mmol), and the mixture was al-
lowed to stand for 1 week at room temperature. The
mixture was then partitioned between AcOEt and H2O.
The organic layer was washed with dil aq HCl and
Methyl
4,6-di-O-acetyl-3-C-acetoxymethyl-2-C-p-
tolylsulfonyl-i-D-glucopyranoside (13).—A solution of
1
H2O, dried, and evaporated. The H NMR spectrum
8 (30 mg, 0.06 mmol) in 70% aq AcOH (10 mL) was
kept for 2 h at 80–90 °C. After cooling, the mixture
was evaporated, and the evaporation was repeated
azeotropically with ethanol, toluene, and ethanol. The
residue was then dried over P2O5 in vacuo at 40 °C. Its
1H NMR was different from that obtained from 12. To
the syrup dissolved in CH2Cl2 (5 mL) was added Ac2O
(300 mg, 2.94 mmol) and BF3·OEt2 (50 mg, 0.35 mmol).
After keeping for 1 h at room temperature, the mixture
was partitioned between AcOEt and H2O. The organic
layer was washed with dil aq HCl and H2O, dried, and
evaporated. The residue was chromatographed to give
23 mg (77%) of 13 as syrup; [h]2D5 −4° (c 1.2, CHCl3);
wmax 1740 (OAc), 1290, and 1140 cm−1 (SO2); 1H NMR
(400 MHz): l 4.87 (d, 1 H, J1,2 5.4 Hz, H-1), 3.53 (dd,
1 H, J2,3 8.1 Hz, H-2), 2.69 (m, 1 H, H-3), 5.19 (t, 1 H,
showed that it was a 1:2 mixture of 6 and the altro
isomer 9. The same reaction was performed one more
time, and the combined residue was chromatographed
to give 6 (9 mg, 30%) as the fast-running fraction and
9 (20 mg, 67%) as the second one.
Physical data for 9; syrup, [h]2D5 −38° (c 0.8, CHCl3);
1
wmax 3520 (OH), 1300, 1140 and 1130 cm−1 (SO2); H
NMR (400 MHz): l 5.00 (d, 1 H, J1,2 2.6 Hz, H-1), 3.66
(dd, 1 H, J2,3 8.1 Hz, H-2), 2.89 (m, 1 H, H-3), 4.49 (dd,
1 H, J3,4 7.9, J4,5 10.4 Hz, H-4), 3.91 (td, 1 H, J5,6a 10.4,
J5,6e 4.9 Hz, H-5), 3.58 (t, 1 H, J6a,6e 10.5 Hz, H-6a),
4.34 (dd, 1 H, H-6e), 4.02 (m, 2 H, H-3%, -3%%), 2.35
(broad s, 1 H, OH), 5.49 (s, 1 H, PhCH), 3.34 (s, 3 H,
OMe), and 2.47 (s, 3 H, SO2Tol); NOESY: correlation
between H-2 and H-5; PhCH and H-4; PhCH and
H-6a. Anal. Calcd for C22H26O7S·0.5 H2O: C, 59.58; H,
6.14; S, 7.23. Found: C, 59.56; H, 5.87; S, 7.00.
Similar treatment of 6, except for addition of D2O
(200 mg), gave a similar result in which deuteration at
C-2 occurred; this is indicated by appearance of H-1
signals as a singlet in both products.
J3,4=J4,5 9.6 Hz, H-4), 3.77 (ddd, 1 H, H-5), 4.20 (dd,
1 H, J5,6 4.9, J6,6% 12.2 Hz, H-6), 4.03 (dd, 1 H, J5,6% 2.9
Hz, H-6%), 4.49 (dd, 1 H, J3,3% 3.6, J3%,3%% 11.7 Hz,
H-3%), 4.09 (dd, 1 H, J3,3%% 4.4 Hz, H-3%%), 3.30 (s, 3 H,
OMe), 2.46 (s, 3 H, SO2Tol), 2.09 (s, 3 H, OAc), 2.06 (s,
3 H, OAc), and 1.99 (s, 3 H, OAc). Anal. Calcd. for

T. Sakakibara et al. / Carbohydrate Research 337 (2002) 2061–2067
2065
C21H28O10S: C, 53.38; H, 5.97; S, 6.79. Found: C, 53.58;
H, 5.85; S, 6.96.
(0.04 mL, 0.49 mmol), and the mixture was cooled to
−20 °C. To the cooled solution was added dropwise
AcCl (0.04 mL, 0.56 mmol). After 2 h, the mixture was
extracted with CH2Cl2, and the extracts were washed
with aq HCl, aq NaCl, dried, and evaporated. The
contaminating benzaldehyde was removed by column
chromatography with toluene and then toluene and
AcOEt (15:1) to give a 1:3 mixture (18 mg, 96%) of 8
and 12, as judged from NMR spectroscopy.
The same debenzylidenation of 12, except the reac-
tion time was prolonged to 3 h, and subsequent acetyla-
tion gave in 80% yield the peracetate 13, which was
identical with an authentic sample by its 1H NMR
spectrum and TLC.
Methyl
3-C-acetoxymethyl-4,6-di-O-acetyl-2,3-
-altropyranoside (17).—
dideoxy-2-C-p-tolylsulfonyl-i-
D
A solution of 10 (15 mg, 0.03 mmol) in 70% aq AcOH
(10 mL) was heated for 2 h at 80–90 °C. After cooling
and evaporation, the mixture was azeotropically evapo-
rated with ethanol and then toluene. The resulting
syrup was dissolved in CH2Cl2 (5 mL), to which Ac2O
(300 mg, 1.65 mmol) and BF3·OEt2 (50 mg) was added.
The same workup described for the preparation of 13
gave 17 in 78% yield; syrup, [h]2D5 −73° (c 1.8, CHCl3);
wmax 1740 (CꢀO), 1310, and 1130 cm−1 (SO2); 1H NMR
(400 MHz, C6D6): l 4.80 (d, 1 H, J1,2 3.3 Hz, H-1), 3.88
(dd, 1 H, J2,3 11.9 Hz, H-2), 3.31 (m, 1 H, H-3), 5.49
(broad t, 1 H, J3,4 2.6, J4,5 2.0 Hz, H-4), 5.06 (dd, 1 H,
J3,3% 4.5, J3%,3%% 11.4 Hz, H-3%), 4.25–4.30 (m, 2 H, H-6,
-6%), 4.60 (dd, 1 H, J3,3%% 10.2 Hz, H-3%%), ꢀ4.20 (m, 1 H,
H-5), 2.97 (s, 3 H, OMe), 1.88 (s, 3 H, SO2Tol), 1.74 (s,
3 H, OAc), 1.71 (s, 3 H, OAc), and 1.66 (s, 3 H, OAc);
NOESY: correlation between H-3 and H-6; H-1 and
OMe. Anal. Calcd for C21H28O10S·H2O: C, 51.42; H,
6.16; S, 6.54. Found: C, 51.84; H, 5.63; S, 7.02.
Methyl 2,3-dideoxy-2-3-C-hydroxymethyl-C-p-tolyl-
sulfonyl-i- -altropyranoside (18).—A solution of 9
D
(163 mg, 0.38 mmol) in 70% aq AcOH (48 mL) was
kept for 2 h at 80 °C. After cooling, the mixture was
evaporated, and evaporation was repeated azeotropi-
cally three times with toluene. The residue was then
dried over P2O5 in vacuo at 40 °C to give 18 as a syrup
(112 mg, 84%).
Physical data for 18; syrup, [h]2D5 −35° (c 1.0,
CHCl3); wmax 3330 (OH), and 1280 cm−1 (SO2); 1H
NMR (D2O): l 4.37 (d, 1 H, J1,2 3.6 Hz, H-1), 3.87 (dd,
1 H, J2,3 10.4 Hz, H-2), 2.60 (m, 1 H, H-3), 4.19 (t, 1 H,
J
3,4=J4,5 3.0 Hz, H-4), 3.82–3.52 (m, 4 H, H-5, -6, -6%,
3%%), 3.98 (dd, 1 H, J3,3% 5.0, J3%,3%% 11.2 Hz, H-3%), 3.09 (s,
3 H, OMe), and 2.35 (s, 3 H, SO2Tol). Anal. Calcd for
C15H22O7S·0.5H2O: C, 50.69; H, 6.52; S, 9.02. Found:
C, 50.80; H, 6.17; S, 9.49.
Benzylidenation of 18.—Similar benzylidenation of
18 (110 mg, 0.31 mmol) afforded 200 mg of 15 that was
contaminated with small amount of benzaldehyde. Half
amount of the syrup was similarly chromatographed to
give 60 mg (89%) of 15, which was pure as judged from
1H NMR spectroscopy.
Similar debenzylidenation, except that the reaction
time was 3 h, and subsequent acetylation of 16 gave the
same peracetate 17 in ꢀ80% yield.
Methyl 2,3-dideoxy-3-C-hydroxymethyl-2-C-p-tolyl-
sulfonyl-i-
D
-glucopyranoside (14).—A solution of 7 (15
Physical data for 15: mp 173.5–175 °C (2-PrOH–
mg, 0.03 mmol) in 70% aq. AcOH (10 mL) was kept for
2 h at 80–90 °C. After cooling, the mixture was evapo-
rated, and evaporation was repeated azeotropically
with toluene and with EtOH. The residue was dried
over P2O5 in vacuo at 40 °C to give 14 in 90% yield.
Physical data for 14; syrup, [h]2D5 −10° (c 1.6,
CHCl3); wmax 3370 (OH), 1280, and 1140 cm−1 (SO2);
1H NMR (CD3OD): l 4.83 (d, 1 H, J1,2 7.3 Hz, H-1),
3.82–3.70 (m, 3 H, H-2, -4, -6%), 2.34 (tt, 1 H, J2,3=J3,4
10.2, J3,3% 3.3, J3,3%% 2.3 Hz, H-3), 4.34 (dd, 1 H, J3,3%% 10.9
Hz, H-3%), 4.13 (dd, 1 H, H-3%%), 3.46 (m, 1 H, H-5), 3.99
(dd, 1 H, J5,6 2.7, J6,6% 12.2 Hz, H-6), 3.30 (s, 3 H, OMe)
and 2.59 (s, 3 H, SO2Tol). Anal. Calcd for C15H22O7S:
C, 52.01; H, 6.40; S, 9.26. Found: C, 51.89; H, 6.24; S,
8.97.
Benzylidenation of 14.—To a solution of 14 (15 mg,
0.04 mmol) in DMF (2 mL) and benzaldehyde dimethyl
acetal (0.05 mL, 0.33 mmol) was added TsOH until pH
ꢀ2, and the mixture was stirred at 60 °C under dimin-
ished pressure. After 2 h, the mixture was extracted
with AcOEt, and the extracts were washed with aq
NaHCO3, aq NaCl, dried, and evaporated. To the
syrup dissolved in CHCl3 (3 mL) was added pyridine
acetone), [h]D25 −81° (c 1.1, CHCl3); wmax 3460 (OH),
1
1290, and 1130 cm−1 (SO2); H NMR (400 MHz): l
4.85 (d, 1 H, J1,2 3.4 Hz, H-1), 4.30 (dd, 1 H, J2,3 11.8
Hz, H-2), 2.60 (dd, 1 H, H-3), 4.28 (broad s, 1 H, J3,4
2.2, J4,5 ꢀ0 Hz, H-4), 3.94 (t, 1 H, J5,6=J5,6% 4.5 Hz,
H-5), 3.7–3.85 (m, 2 H, H-6, -6%), 4.78 (d, 1 H, J3,3%e
ꢀ0, J3%a,3%e 12.3 Hz, H-3%e), 3.99 (dd, 1 H, J3,3%a 2.4 Hz,
H-3%a), 5.55 (s, 1 H, PhCH), 3.38 (s, 3 H, OMe), and
2.45 (s, 3 H, SO2Tol), 2.72 (bdd, J6,OH 4.1, J6%,OH 8.2
Hz, OH); NOESY: correlation between PhCH and
H-3%a; H-1 and OMe; H-3 and H-6. Anal. Calcd for
C22H26O7S: C, 60.81; H, 6.03; S, 7.38. Found: C, 61.06;
H, 6.01; S, 7.21.
The remaining syrup was dissolved in CH2Cl2 (5
mL), and pyridine (0.04 mL, 0.49 mmol) and AcCl
(0.04 mL, 0.56 mmol) were added at −20 °C. After 2 h
at ambient temperature, similar workup gave 16 (45
mg, 61% from 18).
Physical data for 16: mp 84–85 °C (2-PrOH), [h]D25
−69° (c 1.1, CHCl3); wmax 1740 (CO), 1315, and 1140
1
cm−1 (SO2); H NMR (400 MHz, C6D6): l 4.76 (d, 1
H, J1,2 3.3 Hz, H-1), 4.57 (dd, 1 H, J2,3 11.8 Hz, H-2),
3.53 (broad dd, 1 H, J3,4 1.7, J3,3%e ꢀ0, J3,3%a 2.0 Hz,

2066
T. Sakakibara et al. / Carbohydrate Research 337 (2002) 2061–2067
Anal. Calcd for C23H24O7S: C, 62.15; H, 5.44; S, 7.21.
Found: C, 61.89; H, 5.20; S, 7.05.
H-3), 3.83 (dd, 1 H, J4,5 ꢀ0 Hz, H-4), 4.2–4.4 (3 H, m,
H-5, -6, 6%), 5.09 (d, 1 H, J3%a,3%e 12.0 Hz, H-3%e), 3.53
(dd, 1 H, H-3%a), 5.28 (s, 1 H, PhCH), 3.03 (s, 3 H,
OMe), 1.86 (s, 3 H, SO2Tol), and 1.68 (s, 3 H, OAc);
NOESY: correlation between H-2 and H-3%e; PhCH
and H-3%a. Anal. Calcd for C24H28O8S: C, 60.49; H,
5.92; S, 6.73. Found: C, 60.70; H, 5.92; S, 6.60.
Irradiation of 2 in methanol.—To a solution of 2
(Ref. 9, 570 mg, 1.23 mmol) in methanol (distilled over
Mg, 540 mL) in the presence of benzophenone (36 mg,
0.20 mmol) was cooled at ꢀ10 °C and irradiated in a
Riko photoreactor with a high-pressure mercury lamp
in an H2O–ethylene glycol cooled Pyrex immersion-
well for ꢀ10 h under N2. After evaporation, the syrup
was dissolved in CH2Cl2 (50 mL) and pyridine (1.84
mL, 22.7 mmol) and cooled to −20 °C. AcCl (1.63
mL, 22.9 mmol) was added dropwise to the solution.
After 2.5 h, the mixture was extracted with CH2Cl2,
and the extracts were washed with aq HCl, aq NaCl, aq
NaHCO3, dried, and evaporated. The syrup was chro-
matographed with 30:1 hexane–AcOEt to give 19 (75
mg, 11%) and a 3:2 mixture (334 mg, 61%) of 4 and 5.
Compounds 4 and 5 were separated by fractional crys-
tallization from 2-propanol; the first crop was 5.
Reaction of 3 with methanolic sodium methoxide.—To
a solution of 3 (10 mg, 0.025 mmol) in methanol (5 mL)
was added 1.2 M NaOMe (2 mL), and the mixture was
heated under reflux for 2 h and allowed to stand
overnight. The mixture was partitioned between AcOEt
and H2O. The organic layer was washed with dil aq
HCl and H2O, dried, and evaporated to give a 4:1
mixture (8 mg, 74%) of 7 and an unidentified product
1
as judged from the H NMR spectrum.
Reaction of 5 with methanolic sodium methoxide.—To
a solution of 5 (15 mg, 0.034 mmol) in methanol (10
mL) was added 1.8 M NaOMe (3 mL), and the mixture
was heated under reflux for 2 h. The mixture was
partitioned between AcOEt and H2O. The organic layer
was washed with dil aq HCl and H2O, dried, and
evaporated to give 15 mg (98%) of 20, which was pure
1
as judged from H NMR spectroscopy.
Physical data for 20; syrup, [h]2D5 +49° (c 1.8,
1
CHCl3); wmax 3520 (OH), 1300, 1120 cm−1 (SO2); H
NMR: l 5.28 (s, 1 H, H-1), 3.46 (broad s, 1 H,
J2,3B1.0 Hz, H-2), 2.84 (broad dd, 1 H, H-3), 4.36 (dd,
1 H, J3.4 5.9, J4,5 9.7 Hz, H-4), 4.07 (td, 1 H, J5,6a 9.7,
J5,6e 5.1 Hz, H-5), 3.77 (t, 1 H, J6a,6e 10.2 Hz, H-6a),
4.28 (dd, 1 H, H-6e), 4.17 (dd, 1 H, J3,3% 6.1, J3%,3%% 9.8
Hz, H-3%), 3.60 (broad dd, 1 H, J3,3%% 7.5 Hz, H-3%%), 5.53
(s, 1 H, PhCH), 3.37 (s, 3 H, OMe), and 2.48 (s, 3 H,
STol). Anal. Calcd for C22H26O7S·H2O: C, 58.39; H,
6.24; S, 7.09. Found: C, 57.91; H, 5.81; S, 7.12.
Physical data for 19: mp 146–148 °C (EtOH), [h]D25
−63° (c 1.0, CHCl3); wmax 1740 (OAc), 1300, 1140
cm−1 (SO2); 1H NMR: l 5.84 (d, 1 H, J1,2 5.0 Hz, H-1),
3.87 (dd, 1 H, J2,3 7.9 Hz, H-2), 2.85 (m, 1 H, H-3),
3.95 (t, 1 H, J3,4=J4,5 9.9 Hz, H-4), 3.78 (dt, 1 H, J5,6a
10.1, J5,6e 4.6 Hz, H-5), 3.60 (t, 1 H, J6a,6e 10.2 Hz,
H-6a), 4.29 (dd, 1 H, H-6e), 4.47 (dd, 1 H, J3,3% 4.0 Hz,
J3%,3%% 11.5 Hz, H-3%), 4.60 (dd, 1 H, J3,3%% 4.0 Hz, H-3%%),
5.51 (s, 1 H, PhCH), 2.43 (s, 3 H, SO2Tol), and 2.02 (s,
3 H, OAc). Anal. Calcd for C29H30O8S: C, 64.67; H,
5.61; S, 5.95. Found: C, 64.70; H, 5.68; S, 5.80.
References
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Physical data for 4: mp 159–161 °C (2-PrOH), [h]D25
+19° (c 1.0, CHCl3); wmax 1740 (OAc), 1610 (O–CꢀC–
1
SO2), 1300, 1140 cm−1 (SO2); H NMR (C6D6): l 7.77
(d, 1 H, J1,3 1.7 Hz, H-1), 2.75 (m, 1 H, H-3), 3.69 (t,
1 H, J3,4=J4,5 9.5 Hz, H-4), 3.15 (dt, 1 H, J5,6a 10.4,
J5,6e 4.9 Hz, H-5), 3.26 (t, 1 H, J6a,6e 10.1 Hz, H-6a),
3.95 (dd, 1 H, H-6e), 4.63 (dd, 1 H, J3,3% 3.8 Hz, J3%,3%%
11.9 Hz, H-3%), 4.50 (dd, 1 H, J3,3%% 2.6 Hz, H-3%%), 5.15
(s, 1 H, PhCH), 1.85 (s, 3 H, SO2Tol), and 1.42 (s, 3 H,
OAc). Anal. Calcd for C23H24O7S: C, 62.15; H, 5.44; S,
7.21. Found: C, 62.38; H, 5.49; S, 7.45.
Physical data for 5: mp 220–222 °C (2-PrOH), [h]D25
+121° (c 0.5, CHCl3); wmax 1740 (OAc), 1620 (O–
1
CꢀC–SO2), 1300, 1150 cm−1 (SO2); H NMR: l 7.74
(d, 1 H, J1,3 1.7 Hz, H-1), 3.07 (m, 1 H, J3,4 5.9 Hz,
H-3), 3.81 (dd, 1 H, J4,5 9.9 Hz, H-4), 4.30–4.21 (m, 3
H, H-5, H-3%×2), 3.74 (t, 1 H, J5,6a=J6a,6e 10.5 Hz,
H-6a), 4.50 (dd, 1 H, J5,6e 5.3 Hz, H-6e), 5.52 (s, 1 H,
PhCH), 2.44 (s, 3 H, SO2Tol), and 1.83 (s, 3 H, OAc).
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