Some observations on the reductive ring opening of 4,6-O-benzylidene acetals of hexopyranosides with the borane trimethylamine-aluminium chloride reagent

Article abstract of DOI:10.1016/j.carres.2011.04.046

Reductive ring openings of 3-O-benzoyl-4,6-O-benzylidene-d-glucopyranosides with BH₃·NMe₃-AlCl₃ are accompanied by side reactions, such as debenzoylation and reduction of the benzoate to benzyl ether. This phenomenon was r

Full text of DOI:10.1016/j.carres.2011.04.046

Carbohydrate Research 346 (2011) 1633–1637
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Some observations on the reductive ring opening of 4,6-O-benzylidene acetals
of hexopyranosides with the borane trimethylamine–aluminium chloride
reagent
Katalin Daragics a, Pál Szabó b, Péter Fügedi a,
⇑
a Department of Carbohydrate Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeri út 59-67, H-1025 Budapest, Hungary
b Department of Biochemical Pharmacology, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeri út 59-67, H-1025 Budapest, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Reductive ring openings of 3-O-benzoyl-4,6-O-benzylidene-
D
-glucopyranosides with BH3ÁNMe3–AlCl3 are
Received 6 February 2011
Received in revised form 22 April 2011
Accepted 27 April 2011
accompanied by side reactions, such as debenzoylation and reduction of the benzoate to benzyl ether.
This phenomenon was rationalized by aluminium chelate formation between the O-4 acetal and the ben-
zoyl carbonyl group oxygens. It was also shown that these side reactions can be eliminated by using
BH3ÁTHF as the reducing agent.
Available online 3 May 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Dedicated to Professor Dr. András Lipták on
the occasion of his 75th birthday
Keywords:
Benzylidene acetals
Reductive ring opening
Borane trimethylamine–aluminium chloride
By-products
Chelation
Regioselective protection of hydroxyl groups is an essential step
in the synthesis of complex carbohydrates. Benzylidene acetals are
formed regioselectively and they are commonly used for the simul-
taneous protection of O-4 and O-6 of hexopyranosides. The useful-
ness of benzylidene acetals in carbohydrate chemistry was further
increased by the introduction of reductive ring opening,1 which re-
leases one of the two hydroxyl groups involved in the cyclic acetal
while providing the other in protected form as a benzyl ether. The
first reagent system used for affecting this transformation was
LiAlH4–AlCl3.1 Reductive ring opening of benzylidene acetals with
this reagent was extensively investigated by Lipták and co-work-
ers2 and the method was widely used for the preparation of 4-O-
benzyl ethers from 4,6-O-benzylidene hexopyranosides. A draw-
back of the LiAlH4–AlCl3 reagent system is that it is incompatible
with the acyl groups. This problem was solved by Garegg and co-
workers3 by introducing borane trimethylamine and aluminium
chloride as reagents, as this combination can be used in the pres-
ence of acyl groups. The regioselectivity of ring openings with
BH3ÁNMe3–AlCl3 is dependent on the solvent: reactions in tetrahy-
drofuran give the 6-O-benzyl ethers, whereas the 4-O-benzyl
ethers are produced selectively using toluene as solvent. Though
the regioselectivities of these reactions are high, the yields of the
4-O-benzyl ethers are generally moderate, as the ring opening in
toluene is accompanied by extensive degradation.
To increase the yields of 4-O-benzyl ethers we have changed the
solvent from toluene to dichloromethane-diethyl ether.4 In this
solvent system the regioselectivity is somewhat compromised,
yet the yields of the 4-O-benzyl ethers are higher than in toluene,
as decomposition of the starting material is significantly reduced.
Before the development of our methodology for high-yielding 4-
O-benzyl selective ring opening,5 we have been using BH3ÁNMe3–
AlCl3 in dichloromethane-ether routinely in different projects and
performed a fairly large number of reductive ring openings on sub-
strates of diverse structures. Over the years, we have noticed that
in the case of some acyl-containing substrates, the yields of the
4-O-benzyl ethers are significantly reduced. This is not due to the
loss of regioselectivity, that is, increased formation of the corre-
sponding 6-O-benzyl ethers, as these ring openings tend to give
more complex reaction mixtures compared to the regular ones.
We have now studied this phenomenon in more detail and report
our results.
The effect of protecting groups at positions O-2 and O-3 on
the outcome of the reductive ring opening was studied on the
derivatives of methyl 4,6-O-benzylidene-
having various combinations of O-benzyl and O-benzoyl groups
a-D-glucopyranoside
⇑
Corresponding author. Fax: +36 1 438 1145.
E-mail address: pfugedi@chemres.hu (P. Fügedi).
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.04.046

1634
K. Daragics et al. / Carbohydrate Research 346 (2011) 1633–1637
at O-2, and O-3. The reductive ring openings were performed
under identical conditions, by conducting the reactions in dichlo-
romethane-ether (5:1 v/v) at 0 °C using 5 equiv of BH3ÁNMe3 and
2 equiv of AlCl3. The results are summarized in Table 1.
Reductive ring cleavage of the 2,3-di-O-benzyl derivative (1a)
gave the 4-O-benzyl (2a) and the 6-O-benzyl (3a) ethers in 77%
and 17% yields, respectively (Table 1, entry 1). In contrast, the ring
opening of the 2,3-di-O-benzoyl derivative (1b) afforded the 4-O-
(2b) and 6-O-benzyl (3b) ethers in significantly lower yields (Table
1, entry 2).
be methyl 2,6-di-O-benzyl-
sample of 3e was readily obtained by reductive opening of methyl
2-O-benzyl-4,6-O-benzylidene- -glucopyranoside (1e) (Table 1,
a-D-glucopyranoside (3e). An authentic
a
-D
entry 5). Another by-product, isolated in low yield, was 3a in which
the benzoyl was replaced by a benzyl group. The same types of by-
products were also found in the ring opening of the 2,3-di-O-ben-
zoyl derivative (1b): the 3-O-debenzoylated derivative (4) was ob-
tained in 13% yield, and, again, a small amount of a derivative
containing a 3-O-benzyl instead of the 3-O-benzoyl group (3c),
was isolated. The formation of these types of by-products, particu-
larly that of the 3-O-benzylated ones, was unexpected. As far as we
know, none of the reagents used for the reductive cleavage of ace-
tals is capable to reduce esters to ethers.
The differences in the ring opening of the 3-O-benzyl and 3-O-
benzoyl derivatives are most probably due to chelation. Coordina-
tion of the Lewis acid to the acetal oxygen is the initiating step of
the reductive ring cleavage. Complex formation with the acetal
oxygen O-4 gives complex 5, further transformation of 5 then leads
to the regular products (3b and 3d) (Scheme 2). In case of the 3-O-
benzoyl derivatives a chelate (6) may be formed with the electron
rich oxygen of the benzoyl carbonyl group. Chelate formation
polarizes the benzoyl group, cleavage of bond at a in 7 leads finally
to the debenzoylated derivatives (3e and 4), whereas cleavage of
the AlO-CHPh linkage (b, Scheme 2) and reduction followed by ring
opening of the benzylidene group finally afford the 3-O-benzyl
derivatives (3a and 3c).
To find out which of the benzoyl groups is responsible for this
effect, the ring opening of the monobenzoylated derivatives (1c
and 1d) was studied. Compounds 1c and 1d were readily obtained
by conventional benzoylation of methyl 3-O-benzyl- and 2-O-ben-
zyl-4,6-O-benzylidene-
these latter compounds were obtained by phase transfer-catalyzed
benzylation of methyl 4,6-O-benzylidene-
-glucopyranoside.6
a-D-glucopyranoside (1e), respectively,
a
-D
The yields of the 4-O- and 6-O-benzyl ethers obtained in the ring
opening of the 2-O-benzoyl-3-O-benzyl derivative (1c) were very
close to those obtained for the 2,3-di-O-benzyl derivative (Table
1, entries 1 and 3). The 3-O-benzoyl-2-O-benzyl derivative (1d),
on the other hand, gave the expected derivatives in lower yields,
similarly to the 2,3-di-O-benzoyl derivative (Table 1, entries 2
and 4). These data clearly support the role of the 3-O-acyl group
in reducing the yield, and we reasoned that the 3-O-benzoyl group
is probably involved in some side reactions.
The reductive ring openings of 1b and 1d indeed showed a more
complex pattern on TLC and various side products could also be
isolated from these reaction mixtures (Scheme 1.)
The major by-product isolated from the reaction of 1d was a
dibenzyl ether which contained no benzoyl group, and proved to
Chelation-controlled cleavage of acetals with various nucleo-
philes has previously been reported.7 The exact structure of the Le-
wis acid involved in the chelation is not completely clear.
Aluminium species have been demonstrated to be effective in che-
lation controlled cleavage of acetals.7b,e,f On the other hand, in a
series of detailed investigation on the reductive opening of acetals,
Ellervik and co-workers came to the conclusion that in BH3ÁNMe3–
AlCl3-mediated ring openings, AlCl3 activates BH3ÁNMe3 in the
presence of acetals, rendering BH3 to the most electrophilic spe-
cies.8 Consequently, the reaction is directed by the complexation
of the borane. For this reason we have performed the reductive ring
opening of 1d with BH3ÁTHF and AlCl3 in dichloromethane-ether.
The reaction gave the regular product 2d in almost quantitative
yield, with no appreciable amounts of the above by-products (3e,
3d and 3a) detectable (Table 2, entry 1).
Previously, we have shown that the regioselectivity of ring
openings with BH3ÁTHF–Lewis acid mixtures is independent of
the Lewis acid used.5 Reductions of the 3-O-benzoyl (1d) and the
2,3-di-O-benzoyl (1b) derivatives with BH3ÁTHF–TMSOTf gave the
normal ring opening products in excellent yields without signifi-
cant by-product formation (Table 2, entries 2 and 3).5 These result
clearly demonstrate that the active complexing species are
Table 1
Reductive ring openings of methyl 4,6-O-benzylidene-
a
-D-glucopyranosides
OBn
O
OH
O
Ph
O
.
O
BH3 NMe3
HO
BnO
R2O
O
R2O
R2O
+
R1O
AlCl3
R1O
R1O
OMe
OMe
OMe
1
2
3
Entry
Substrate
Isolated yield (%)
4-O-Benzyl (2)
6-O-Benzyl (3)
1
2
3
4
5
a R1 = Bn, R2 = Bn
b R1 = Bz, R2 = Bz
c R1 = Bz, R2 = Bn
d R1 = Bn, R2 = Bz
e R1 = Bn, R2 = H
77
41
76
55
33
17
8
15
6
22
OH
O
OBn
O
OBn
O
OBn
O
.
BH3 NMe3
HO
BnO
BnO
BzO
HO
HO
HO
BzO
1d
+
+
+
AlCl3
BnO
BnO
OMe
BnO
BnO
OMe
OMe
OMe
3a
3e
29%
3d
6%
2d
1%
55%
OH
OBn
O
OBn
O
OBn
O
.
BH3 NMe3
O
BnO
BzO
HO
HO
HO
1b
+
+
+
BnO
HO
BzO
AlCl3
BzO
BzO
BzO
BzO
OMe
OMe
OMe
OMe
2b
41%
4
3c
3b
8%
13%
1%
Scheme 1. Products isolated from the reductive ring cleavage of 3-O-benzoyl-4,6-O-benzylidene-D-glucopyranosides.

K. Daragics et al. / Carbohydrate Research 346 (2011) 1633–1637
1635
OBn
O
O
O
Ph
Al
O
O
Ph
Al
O
Ph
Al
δ+
O
HO
HO
O
O
O
O
O
δ+
O
O
O
RO
O
RO
RO
RO
OMe
OMe
OMe
OMe
a
Ph
Ph
Ph
b
7
3e, 4
6
5
OBn
O
OBn
O
HO
BnO
HO
O
O
RO
RO
OMe
3a, 3c
OMe
3b, 3d
Ph
Scheme 2. The effect of chelation on the reaction pathway.
were determined in capillary tubes on a Griffin melting point appa-
ratus and are uncorrected. Optical rotations were measured at
room temperature with an Optical Activity P-2000 (Jasco) polarim-
eter. The NMR spectra were recorded on Varian Unity Inova 3000
(1H: 300 MHz; 13C: 75 MHz) and Varian Unity Inova 2000 (1H:
200 MHz; 13C: 50 MHz) spectrometers at ambient temperature in
CDCl3, and assigned using 2D-methods (COSY, HSQC). The chemical
shifts were referenced to TMS (0.00 ppm for 1H) and to the central
line of CDCl3 (77.0 ppm for 13C). Elemental analyses were per-
formed with an Elementar Vario EL III instrument at the Analytical
Department of the Chemical Research Center, Hungarian Academy
of Sciences.
Table 2
Reductive ring openings with BH3ÁTHF
OH
O
Ph
O
BH3.THF
O
BnO
R2O
O
R2O
R1O
R1O
Lewis acid
OMe
OMe
1
2
Entry
Substrate
Lewis acid
Yield of 2 (%)
1
2
3
1d R1 = Bn, R2 = Bz
1d R1 = Bn, R2 = Bz
1b R1 = Bz, R2 = Bz
AlCl3
95
TMSOTf
TMSOTf
99a
87a
a
Ref. 5.
1.2. Methyl 2-O-benzoyl-3-O-benzyl-4,6-O-benzylidene-a-D-
glucopyranoside (1c)
different in BH3ÁNMe3 and BH3ÁTHF-mediated ring openings. From
the preparative aspect, the same data also support the superiority
of BH3ÁTHF–TMSOTf-mediated reductive ring openings5 over the
BH3ÁNMe3–AlCl3 mediated ones.
Benzoyl chloride (1.37 mL, 1.5 equiv) was added to a solution of
methyl 3-O-benzyl-4,6-O-benzylidene-
-glucopyranoside6 (2.92
a-D
g) in dry pyridine (15 mL) stirred at 0 °C. The mixture was stirred
at room temperature for 1 h, then water (1 mL) was added. The
mixture was diluted with dichloromethane, washed with 2 M aq
HCl, saturated aq NaHCO3 and water, was dried, and concentrated.
Recrystallization of the residue from ethyl acetate–hexanes gave
1c (3.40 g, 91%) as white crystals: mp 132–133 °C, lit.9 142–
In summary, we have found that reductive ring openings of 3-O-
benzoyl-4,6-O-benzylidene-
D
-glucopyranosides with BH3ÁNMe3–
AlCl3 are accompanied by side reactions, such as extensive deben-
zoylation and reduction of the benzoates to benzyl ethers. We have
rationalized this phenomenon by the formation of an aluminium
chelate complex with the O-4 acetal and the carbonyl oxygen of
the benzoyl group. We have also shown that these side reactions
do not occur to any significant extent by using BH3ÁTHF as the
reducing agent.
143 °C, lit.10 143–145 °C; [
a
]
+134 (c 0.46, chloroform), lit.9
D
+135, lit.11 +130.1 The 1H and 13C NMR data were in agreement
with those published.10,11
1.3. Methyl 3-O-benzoyl-2-O-benzyl-4,6-O-benzylidene-a-D-
glucopyranoside (1d)
1. Experimental
Benzoylation of 1e6 was performed the same way as described
above, and afforded 1d in 89% yield. White crystals: mp 129–
130 °C (from ethyl acetate–hexanes), lit.12 118–120 °C, lit.13 136–
1.1. General methods
137 °C; [
a
]
D
À11.7 (c 0.65, chloroform), lit.13 À6.3. 1H NMR
Evaporations were performed under reduced pressure on rotary
evaporators with bath temperatures not exceeding 40 °C. All reac-
tions sensitive to air or moisture were carried out under an argon
atmosphere with anhydrous solvents. Air- and moisture-sensitive
liquids and solutions were transferred via a syringe. Dichlorometh-
ane was distilled from CaH2, and stored over 4 Å molecular sieves.
Solvents used for column chromatography were of technical grade
and distilled before use. Thin layer chromatography (TLC) was per-
formed on Silica Gel 60 F254 plates (E. Merck, Darmstadt), the
compounds were detected under UV light and by spraying the
plates with a 0.02 M solution of resorcinol in 20% methanolic
H2SO4 followed by heating. For column chromatography, Silica
Gel 60 (0.040–0.063 mm) (E. Merck) was employed. Melting points
(300 MHz, CDCl3): d 3.43 (s, 3H, OMe), 3.69 (dd, 1H, J3,4 9.6 Hz,
J4,5 10.0 Hz, H-4), 3.72 (dd, 1H, J1,2 3.6 Hz, J2,3 9.6 Hz, H-2), 3.74
(dd, 1H, J5,6a ꢀ J6a,6b 10.0 Hz, H-6a), 3.97 (ddd, 1H, J4,5 ꢀ J5,6a
10 Hz, J5,6b 4.8 Hz, H-5), 4.29 (dd, 1H, J5,6b 4.8 Hz, J6a,6b 10.0 Hz,
H-6a), 4.62 (s, 2H, PhCH2), 4.75 (d, 1H, J1,2 3.6 Hz, H-1), 5.46 (s,
1H, PhCH), 5.84 (dd, 1H, J2,3 ꢀ J3,4 9.6 Hz, H-3), 7.20–7.30 (m, 8H,
aromatic), 7.36–7.46 (m, 4H, aromatic), 7.52–7.58 (m, 1H, aro-
matic), 8.02–8.06 (m, 2H, aromatic); 13C NMR (75 MHz, CDCl3): d
55.4 (OMe), 62.4 (C-5), 69.0 (C-6), 71.2 (C-3), 72.8 (PhCH2), 77.4
(C-2), 79.6 (C-4), 98.8 (C-1), 101.4 (PhCH), 126.1, 127.9, 128.1,
128.2, 128.4, 128.8, 129.8, 130.2, 137.0, 137.6 (aromatic), 165.3
(PhCO).

1636
K. Daragics et al. / Carbohydrate Research 346 (2011) 1633–1637
1.4. General procedure for reductive ring openings with
BH3ÁNMe3–AlCl3
J 11.5 Hz, 1/2PhCH2), 4.91 (d, 1H, J 11.5 Hz, 1/2PhCH2), 5.13 (d,
1H, J1,2 3.6 Hz, H-1), 5.17 (dd, 1H, J1,2 3.6 Hz, J2,3 9.5 Hz, H-2),
7.24–7.40 (m, 10H, aromatic), 7.46–7.51 (m, 2H, aromatic), 7.59–
7.63 (m, 1H, aromatic), 8.13–8.15 (m, 2H, aromatic); 13C NMR
(75 MHz, CDCl3): d 55.1 (OMe), 69.6 (C-6), 69.9 (C-5), 71.3 (C-4),
73.7 (C-2), 73.5 (PhCH2), 75.0 (PhCH2), 79.6 (C-3), 97.1 (C-1),
127.49, 127.53, 127.6, 127.7, 128.3, 129.6, 129.7, 133.1, 137.8,
138.2 (aromatic), 165.7 (PhCO). MS-ESI: [MÀOMe]+ 447.2,
[M+H]+ 479.2, [M+Na]+ 501.3, [M+K]+ 517.2.
A solution of aluminium chloride (1.07 g, 8.0 mmol, 2 equiv) in
dry diethyl ether (10 mL) was added during 10 min to a stirred
mixture of the benzylidene derivative (1a–1e) (4.0 mmol) and bor-
ane trimethylamine (1.46 g, 20 mmol, 5 equiv) in dry dichloro-
methane (50 mL) at 0 °C. After completion of the reaction, the
mixture was diluted with dichloromethane (100 mL) and stirred
with 2 M aq HCl (100 mL) for 2 h. The organic layer was washed
with saturated aq NaHCO3 and water, dried (MgSO4), and concen-
trated. The products were isolated by silica gel column chromatog-
raphy (toluene–acetone, 98:2?4:1).
Eluted next was methyl 2-O-benzoyl-3,4-di-O-benzyl-
glucopyranoside (2c) (1.461 g, 76%). White crystals: mp 99–
100 °C (from ethyl acetate–hexanes), lit.21 white solid; [
+148
a-D-
a]
D
(c 0.67, chloroform). 1H NMR (300 MHz, CDCl3): d 2.02 (dd, 1H,
J6a,OH 5.5 Hz, J6b,OH 7.3 Hz, OH), 3.35 (s, 3H, OMe), 3.67–3.88 (m,
4H, H-4, H-5, H-6a, H-6b), 4.21 (dd, 1H, J2,3 ꢀ J3,4 9.5 Hz, H-3),
4.69 (d, 1H, J 11.0 Hz, 1/2PhCH2), 4.83 (s, 2H, PhCH2), 4.89 (d, 1H,
J 11.0 Hz, 1/2PhCH2), 5.03 (d, 1H, J1,2 3.6 Hz, H-1), 5.08 (dd, 1H,
J1,2 3.6 Hz, J2,3 9.5 Hz, H-2), 7.16–7.32 (m, 10H, aromatic), 7.40–
7.46 (m, 2H, aromatic), 7.54–7.59 (m, 1H, aromatic), 8.05–8.07
(m, 2H, aromatic); 13C NMR (75 MHz, CDCl3): d 55.1 (OMe), 61.7
(C-6), 70.9 (C-5), 74.1 (C-2), 75.1 (PhCH2), 75.5 (PhCH2), 77.6 (C-
4), 79.9 (C-3), 97.2 (C-1), 127.6, 127.8, 128.0, 128.3, 128.4, 129.6,
129.8, 133.2, 138.0, 138.1 (aromatic), 165.9 (PhCO).
1.5. Reductive ring opening of methyl 2,3-di-O-benzyl-4,6-O-
benzylidene-a-D-glucopyranoside (1a)
Eluted first from the column was methyl 2,3,6-tri-O-benzyl-
a
+14
-
D
-glucopyranoside (3a) (0.317 g, 17%). Colorless syrup: [
(c 0.64, chloroform), lit.3 +9, lit.6 +11, lit.14
lit.15 +14, lit.16 +15.1. MS-ESI: [M+NH4]+ 482.3, [M+Na]+
[a]
D
a
]
D
[
a]
[
a]
[
a] +13,
D
D
D
[
a]
D
487.3, [M+K]+ 503.2. The 1H and 13C NMR data were in agreement
with those reported.16,17
Eluted second was methyl 2,3,4-tri-O-benzyl-a-D-glucopyrano-
side (2a) (1.432 g, 77%). White crystals: mp 50–51 °C (from ethyl
1.8. Reductive ring opening of methyl 3-O-benzoyl-2-O-benzyl-
4,6-O-benzylidene-a-D-glucopyranoside (1d)
acetate–hexanes), lit.6 mp 53–54 °C, lit.16 mp 43–44 °C, lit.17 oil;
lit.18 mp 65–67 °C, lit.19 mp 50–51 °C; [
a]D +24 (c 0.74, chloroform),
lit.6 [
a
]
D +22.5, lit.18
[a
]
D +24, lit.19
[a
]
D +22, lit.20
[a
]
D +26.3. The 1H
Eluted first was a syrup (0.017 g, 1%) which had 1H, 13C NMR
and MS spectra indistinguishable from those of methyl 2,3,6-tri-
and 13C NMR data were in agreement with those reported.16,20
O-benzyl-
The next compound obtained was methyl 3-O-benzoyl-2,6-di-
O-benzyl- -glucopyranoside (3d) (0.107 g, 6%). Colorless syrup:
+71 (c 0.47, chloroform). 1H NMR (300 MHz, CDCl3): d 3.06
a-D-glucopyranoside (3a).
1.6. Reductive ring opening of methyl 2,3-di-O-benzoyl-4,6-O-
benzylidene-
a
-D
-glucopyranoside (1b)
a-D
[a]
D
Eluted first from the column was a fraction, which turned out to
be a mixture of two compounds. The components were separated
by column chromatography using hexanes–acetone (9:1) as eluent.
The first compound proved to be methyl 2-O-benzoyl-3,6-di-O-
(br s, 1H, OH), 3.40 (s, 3H, OMe), 3.68 (dd, 1H, J1,2 3.5 Hz, J2,3
9.8 Hz, H-2), 3.70–3.80 (m, 4H, H-4, H-5, H-6a, H-6b), 4.55 (d,
1H, J 12.1 Hz, 1/2PhCH2), 4.59 (d, 1H, J 12.1 Hz, 1/2PhCH2), 4.61
(d, 1H, J 12.6 Hz, 1/2PhCH2), 4.64 (d, 1H, J 12.6 Hz, 1/2PhCH2),
4.75 (d, 1H, J1,2 3.5 Hz, H-1), 5.51 (dd, 1H, J2,3 ꢀ J3,4 9.8 Hz, H-3),
7.22–7.32 (m, 10H, aromatic), 7.40–7.45 (m, 2H, aromatic), 7.53–
7.58 (m, 1H, aromatic), 8.01–8.03 (m, 2H, aromatic); 13C NMR
(75 MHz, CDCl3): d 55.2 (OMe), 69.1 (C-6), 70.2 and 70.3 (C-4 and
C-5), 72.8 (PhCH2), 73.5 (PhCH2), 76.1 (C-3), 76.4 (C-2), 97.7 (C-
1), 127.5, 127.8, 127.9, 128.3, 129.7, 129.8, 133.1, 137.6, 137.8 (aro-
matic), 167.4 (PhCO). MS-ESI: [M+H]+ 479.3, [M+NH4]+ 496.4,
[M+Na]+ 501.5, [M+K]+ 517.2. Anal. Calcd for C28H30O7: C, 70.28;
H, 6.32. Found: C, 70.19, H, 6.35.
benzyl-a-D
-glucopyranoside (3c) (0.018 g, 1%). Its 1H, 13C NMR
and MS spectra were indistinguishable from the ones described
for this compound in Section 1.7. The second component of this
mixture was methyl 2,3-di-O-benzoyl-6-O-benzyl-
a-D-glucopy-
ranoside (3b) (0.149 g, 8%). Colorless syrup: [ D +123 (c 0.63, chlo-
a]
roform), lit.14
[
a]
+113. The 1H and 13C NMR data were in
D
agreement with those reported.20
Continued elution of the original column with toluene–acetone
gave next methyl 2,3-di-O-benzoyl-4-O-benzyl-
side (2b) (0.811 g, 41%). White crystals: mp 112–113 °C (from ethyl
acetate–hexanes), lit.3 mp 117–118 °C; [
+133 (c 0.80, chloro-
a-D-glucopyrano-
The following compound eluted was methyl 3-O-benzoyl-2,4-
a
]
D
di-O-benzyl-a-D-glucopyranoside (2d) (1.062 g, 55%). Colorless
form), lit.3
[
a]
+132, lit.20
[
a]
D
+140.9. The 1H and 13C NMR data
syrup: [a] [a]
+36 (c 0.62, chloroform), lit.5 +36. The 1H and 13C
D D
D
were in agreement with those reported.20
NMR data were in agreement with those reported.5
Further elution afforded a compound which proved to be
The next fraction proved to be methyl 2,6-di-O-benzyl-a-D-
methyl 2-O-benzoyl-6-O-benzyl-
a
-
D
-glucopyranoside (4) (0.206 g,
+99 (c 0.62, chloroform),
glucopyranoside (3e) (0.439 g, 29%). White crystals: mp 74–75 °C
13%). White crystals: mp 87–88 °C; [
a
]
D
(from ethyl acetate–hexanes), lit.18 mp 85–86 °C, lit.22 mp 80–
lit.20
[
a
]
+88.7. MS-ESI: [M+H]+ 389.4, [M+Na]+ 411.2, [M+K]+
82 °C; [
+58.7, lit.23
with those reported.22,23
a]
D
+63 (c 0.63, chloroform), lit.18
[a]
+62.6, lit.22
[a]
D D
D
427.0. The 1H and 13C NMR data were in agreement with those
reported.20
[a]
D +63.2. The 1H and 13C NMR data were in agreement
1.7. Reductive ring opening of methyl 2-O-benzoyl-3-O-benzyl-
1.9. Reductive ring opening of methyl 2-O-benzyl-4,6-O-
benzylidene- -glucopyranoside (1e)
4,6-O-benzylidene-
a
-D
-glucopyranoside (1c)
a-D
Eluted first was methyl 2-O-benzoyl-3,6-di-O-benzyl-
glucopyranoside (3c) (0.288 g, 15%). Colorless syrup: [ +98 (c
0.60, chloroform), lit.9 +99. 1H NMR (300 MHz, CDCl3): d
2.92 (br s, 1H, OH), 3.42 (s, 3H, OMe), 3.80–3.92 (m, 4H, H-4, H-
5, H-6a, H-6b), 4.11 (dd, 1H, J2,3 ꢀ J3,4 9.5 Hz, H-3), 4.63 (d, 1H, J
12.0 Hz, 1/2PhCH2), 4.69 (d, 1H, J 12.0 Hz, 1/2PhCH2), 4.82 (d, 1H,
a
-
D
-
Eluted first from the column was methyl 2,4-di-O-benzyl-a-D-
a]
D
glucopyranoside (2e) (0.488 g, 33%). White crystals: mp 64–65 °C
[a]
D
(from ethyl acetate–hexanes), lit.18 mp 75 °C, lit.24 mp 71–72 °C,
lit.25 mp 74–75 °C; [
a
[
]
a
+100 (c 0.72, chloroform), lit.18
]
[a]
+87,
D
D
lit.24
[
a]
D
+98.3, lit.25
+88. The 1H and 13C NMR data were in
D
agreement with those reported.24

K. Daragics et al. / Carbohydrate Research 346 (2011) 1633–1637
1637
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1.10. Reductive ring opening of methyl 3-O-benzoyl-2-O-
benzyl-4,6-O-benzylidene-
BH3ÁTHF–AlCl3
a-D-glucopyranoside (1d) with
To a solution of 1d (0.953 g, 2.0 mmol) in dry dichloromethane
(30 mL) stirred under argon at 0 °C, a 1 M solution of BH3ÁTHF
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washed with 2 M aq HCl, saturated aq NaHCO3 and water; dried,
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Acknowledgments
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