H-bonding activation in highly regioselective acetylation of diols

Article abstract of DOI:10.1021/jo402036u

H-bonding activation in the regioselective acetylation of vicinal and 1,3-diols is presented. Herein, the acetylation of the hydroxyl group with acetic anhydride can be activated by the formation of H-bonds between the hydroxyl group and anions. The reaction exhibits high regioselectivity when a catalytic amount of tetrabutylammonium acetate is employed. Mechanistic studies indicated that acetate anion forms dual H-bonding complexes with the diol, which facilitates the subsequent regioselective monoacetylation.

Full text of DOI:10.1021/jo402036u

Note
pubs.acs.org/joc
H‑Bonding Activation in Highly Regioselective Acetylation of Diols
Yixuan Zhou,† Martin Rahm,‡ Bin Wu,† Xiaoling Zhang,† Bo Ren,† and Hai Dong*,†
†School of Chemistry & Chemical Engineering, Huazhong University of Science & Technology, Luoyu Road 1037, Wuhan 430074, P.
R. China
‡Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, Los Angeles, California
90089, United States
S
* Supporting Information
ABSTRACT: H-bonding activation in the regioselective acetylation of vicinal
and 1,3-diols is presented. Herein, the acetylation of the hydroxyl group with
acetic anhydride can be activated by the formation of H-bonds between the
hydroxyl group and anions. The reaction exhibits high regioselectivity when a
catalytic amount of tetrabutylammonium acetate is employed. Mechanistic
studies indicated that acetate anion forms dual H-bonding complexes with the
diol, which facilitates the subsequent regioselective monoacetylation.
egioselective protection of carbohydrates under mild and
supported by experiments and preliminary quantum-chemical
Renvironmentally sustainable conditions is necessary in studies.
First, acetylation of the diol methyl 4,6-O-benzylidene-α-D-
glucoside (1) by the addition of anions was examined using 1.1
equiv of acetic anhydride (Table 1). Without the addition of
order to meet the requirements for preparation of value-added
intermediates and building blocks in efficient protecting group
strategies, and it remains a prominent challenge in synthetic
carbohydrate chemistry.1,2 Several protection methods have
been developed to this end by making use of certain reagents to
enlarge small differences in reactivity of hydroxyl groups for
diols and polyols. For example, methods employing organo-
tin,3−8 organoboron,9−11 organosilicon,12−15 and metal
salts,16−18 organo-catalytic methods,19−21 and enzymatic
methods22−24 have been exemplified, all with their respective
advantages and shortcomings. In the present study, we report
on the application of H-bonding activation principles in a
highly regioselective carbohydrate acetylation. Herein, a
catalytic amount of tetrabutylammonium acetate was employed
to promote the regioselective acylation of diols by acetic
anhydride under mild conditions without the assistance of any
other reagents. Different from the general pyridine-catalyzed
acylation,25−30 our mechanistic studies suggest that the catalytic
acetylation owes its increased reactivity to hydroxyl groups
engaged in H-bonding.
In our earlier studies, we found that new and improved
reaction routes may be found by the application of
intermolecular non-covalent forces.31−33 For example, in
intramolecular acetyl group migration with anions in aprotic
solvents under mild conditions, which was recently reported by
us, the leading cause for this process was found to be the
formation of hydrogen bonds between the neighboring
hydroxyl group and anions.33 The catalytic effect of anions
follows the corresponding H-bond formation tendencies, where
more basic anions lead to faster migration. These results
inspired us to think that H-bonds between hydroxyl groups and
anions might also be able to activate the acylation of hydroxyl
groups. We have found this H-bond activation principle to be
Table 1. Acetylation of Methyl 4,6-O-Benzylidene-α-D-
a
glucoside (1) upon the Addition of Anions
entry
reagent
T (°C)
conversion
1
2
3
4
5
−
HOAc
80
80
80
r.t.
r.t.
no reaction
no reaction
TBAB
low conversion
b
TBAOAc
TBAF
2a (90%)
c
2a/2b (68/32)
a
Reaction conditions: reactant (100 mg), Ac2O (1.1 equiv), TBAX
b
c
(0.3−0.6 equiv), 8−12 h. Isolated yield. NMR ratio.
anions, the acetylation of 1 did not proceed, even at 80 °C.
With the addition of 0.6 equiv of tetrabutylammonium bromide
(TBAB), the acetylation of 1 was very slow at 80 °C. However,
when 0.6 equiv of tetrabutylammonium acetate (TBAOAc) was
used, the reaction proceeded at room temperature, and the 2-
hydroxyl group of diol 1 was regioselectively acetylated after 12
h, leading to a 90% isolated yield of methyl 2-O-acetyl-4,6-O-
benzylidene-α-D-glucoside (2a). There no acetyl group
migration occurred, since compound 2b is the migration
product. The reason must be that only a catalytic amount of
TBAOAc was used in this case. The reaction showed higher
Received: September 13, 2013
Published: October 28, 2013
© 2013 American Chemical Society
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reactivity but lower selectivity with 0.3 equiv of tetrabutylam-
monium fluoride (TBAF). The results indicate that H-bonds
between hydroxyl groups and anions are indeed able to activate
the acylation of hydroxyl groups, and the catalytic effect of
anions followed the corresponding H-bond formation tenden-
cies. However, high regioselectivities were obtained when
acetate anion was employed as the catalyst.
In light of these results, TBAOAc was chosen and tested
together with a range of diols (cf. Table 2): methyl 4,6-O-
benzylidene-α-D-mannoside (3) and methyl 2,6-di-O-benzyl-β-
D-galactoside (4), two cis-diols; methyl 4,6-O-benzylidene-β-D-
galactoside (5), a trans-diol where one of the substituents
adjacent to the hydroxyl group is equatorial and the other is
axial; methyl 4,6-O-benzylidene-α-D-galactoside (6) and -β-D-
glucoside (7), trans-diols where both substituents adjacent to
the hydroxyl group are equatorial or axial; methyl 2,6-di-O-
benzyl-β-D-glucoside (8), a trans-diol; methyl 2,3-di-O-benzyl-
α-D-glucoside (9), -galactoside (10), and -mannoside (11),
three 1,3-diols with one primary (1°) hydroxyl group; and 1,2-
propanediol (12) and 1-phenyl-1,2-ethanediol (13), two 1,2-
diols with one 1° hydroxyl group. These compounds were
allowed to react with 1.1 equiv of Ac2O in the presence of 0.6
equiv of TBAOAc in acetonitrile at 40 °C for 8 h. The results
(cf. Table 2) show high regioselectivities in most cases and
excellent isolated yields (85−93%). However, when the
reactions were performed at room temperature, a longer
reaction time (24−48 h) was necessary to reach the same
isolated yields. For acetylation of compounds 3, 5, and 8 at
lower temperatue, no noticeably improved selectivities were
observed.
Table 2. Acetate-Promoted Regioselective Acetylation of 1,2-
a
and 1,3-Diols
Comparisons with the outcomes from organosilicon-,
organotin-, and Ag2O-mediated methods are shown in Table
S1 in the Supporting Information (SI). The di-OAc products
did not form in any of the reactions, even for the acetylations of
compounds 3 and 8 in which poor selectivities were observed.
This suggests that acetylation of one of the hydroxyl groups
dramatically decreases the reactivity of its neighbors. Thus,
overacetylation should not be of concern. Our method showed
selectivities for compounds 1 and 4 and diols with one 1°
hydroxyl group similar to those reported for organotin/
organosilicon-mediated methods (Table S1). Interestingly, in
contrast to the poor selectivities usually observed in organotin/
organosilicon-mediated methods, our method showed very
good selectivities for trans-diols 6 and 7 (Table 2, entries 5 and
6).4,15 In comparison with the Ag2O-mediated method,16 our
method enabled the reversed protection pattern of compounds
1, 6, and 7. When 0.3 equiv of TBAOAc was employed, a
longer reaction time was necessary to reach the same isolated
yield. The acetylation of compound 5 appears to be a special
case, as no reaction occurred at 40 °C and 24% of the starting
material remained even after 48 h at 80 °C (Table 2, entry 4).
All of these experimental results support our hypothesis that
anions enable regioselective acetylation of hydroxyl groups by
H-bonding. The 1H NMR spectra of the protons involved in H-
bonding (see the SI) further support this. For example, the
resonances of the protons on the 3- and 4-hydroxyl groups of 4
shifted from 2.57 and 2.47 ppm in CDCl3 to 3.27 and 3.02 ppm
in CD3CN and to 4.91 and 4.64 ppm in DMSO-d6 as a result of
the formation of hydrogen bonds between the hydroxyl groups
and the solvent molecules. Anions form stronger hydrogen
bonds with hydroxyl groups than these solvent molecules,
leading to greater downfield chemical shifts of the protons.33
For example, the addition of 0.6 equiv of TBAB into the
solution of 4 in CD3CN caused the chemical shifts of the
protons on the 3- and 4-hydroxyl groups to change from 3.27
and 3.02 ppm to 3.40 and 3.15 ppm, respectively (see the SI).
We found that the hydroxyl groups with greatest downfield
chemical shift were preferentially acetylated (compounds 1, 4,
6, and 7 in CD3CN; see the SI). When the acetate anion was
used, the proton signals originating from the hydroxyl groups
disappeared because of rapid proton interchange in all solvents.
However, the H-bonding effect was observable by proton
chemical shifts on carbons adjacent to the hydroxyl groups.
a
Reaction conditions: (A) reactant (100 mg), Ac2O (1.1 equiv),
TBAOAc (0.6 equiv), 40 °C, 8−12 h; (B) reactant (100 mg), Ac2O
(1.1 equiv), TBAOAc (0.3 equiv), 40 °C, 16−24 h; (C) reactant (100
b
mg), Ac2O (1.1 equiv), TBAOAc (0.6 equiv), 80 °C, 48 h. Isolated
c
d
yields. NMR ratio; raw materials could hardly be observed. NMR
ratio; 24% of the raw material was observed.
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These chemical shifts also moved downfield. We performed a
preliminary quantum-chemical study (see the SI and Figure 1),
group (compounds 9−13), the regioselectivity might be more
dependent on steric effects. The poor selectivities for
compounds 3, 5, and 8 might arise because two hydroxyl
groups in each compound are in similar steric and stereo-
electronic situations. Further support for the dual H-bonding
mechanism was found when the diols were coreacted with their
corresponding monohydric alcohols in competitive acetylation
of 1.1 equiv of acetic anhydride (see Table 3). The conversion
rates for acetylation of these diols were 3−4 times higher than
those of the corresponding monohydric alcohols. Especially for
the case in entry 2, the secondary hydroxyl group in compound
7 was preferentially acetylated as a result of dual H-bonding.
Usually the primary hydroxyl group is preferentially acetylated
because of the small steric effects. Thus, different from the two-
step reaction approaches in organotin, organoboron, and
organosilicon methods, this straightforward one-step reaction
proceeds efficiently with all reactants tested, producing the
predicted monoacylated products in all cases. Anhydrous
conditions are not necessary when using in this method,
since moisture does not noticeably disrupt the formation of the
H-bonds.
Figure 1. Four investigated possibilities (a−d) for binding of 1,2-
propanediol to an acetate anion. SMD-PCM-M06-2X/aug-cc-pVTZ
energies relative to the free species in acetonitrile solution (1 M, 298
K) are shown.
which demonstrated that the formation of dual H-bonding
between the acetate anion and the diols is favorable by ∼4 kcal/
mol relative to separate solvated species in 1 M acetonitrile
solution at 298 K. This corresponds to an equilibrium constant
of ca. 900. Thus, in contrast to the cases of catalysis using
bromide and fluoride anions, the high selectivity when using the
acetate anion for catalysis might be attributed to the specific
dual H-bonding prereaction complex between the diol reagent
and the acetate catalyst.
Different from the DMAP-catalyzed regioselective acetylation
mechanism,26−28 a suggested mechanism for the regioselective
acetylation of diols catalyzed by acetate anions is shown in
Figure 2. For the acetylation of diols with one primary hydroxyl
In conclusion, we propose that H-bonding plays an
important role in the acylation of alcohols, in which hydroxyl
groups are first bound to anions through the formation of H-
bonds. On the basis of this principle, a highly regioselective
acetylation of diols in which acetylation is enabled by a catalytic
amount of acetate was developed. The roles of the acetate
1
anion have been disclosed by mechanistic studies involving H
NMR experiments and preliminary quantum-chemical calcu-
lations. The larger scope of this methodology is currently under
investigation, as regioselective acetylations of polyols and
benzyolations are being tested and the mechanism is being
explored by theoretical calculations and kinetic isotope effect
measurements.
EXPERIMENTAL SECTION
■
General Method for Regioselective Acylation of Diols. The
1,2- or 1,3-diol reactant (100 mg) was allowed to react with acetic
anhydride (1.1 equiv) in dry acetonitrile (1 mL) at 40 °C for 8−12 h
in the presence of tetrabutylammonium acetate (0.3−0.6 equiv). The
reaction mixture was directly purified by flash column chromatography
(hexanes/EtOAc = 5:1 to 1:2), affording the pure selectively protected
derivatives.
General Method for Obtaining the 1H NMR Ratio of
Products. The 1,2- or 1,3-diol reactant (100 mg) was allowed to
react with acetic anhydride (1.1 equiv) in dry acetonitrile (1 mL) at 40
°C for 8−12 h in the presence of tetrabutylammonium acetate (0.3
equiv). A 0.2 mL sample of the reaction mixture was taken and dried
in vacuum. The dried mixture was directly tested by 1H NMR analysis.
Figure 2. Highly regioselective acetylation of diols activated by dual H-
bonding.
a
Table 3. Competitive Acetylation of Hydroxyl Groups
a
Conditions: reactants (1:1 mixture), Ac2O (1.1 equiv), TBAOAc (0.3 equiv), 40 °C, 16−24 h.
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General Method for Testing the Formation of H-Bonds
between Glycosides and Anions. The anion salt (0.3 equiv of
TBAB or 0.6 equiv of TBAOAc) was added to a solution of methyl
2,6-OBn-β-D-galactopyranoside (10 mg) in dry CD3CN (0.5 mL), and
PhCH2), 4.59−4.51 (m, 2H, PhCH2), 4.33 (d, 1H, J = 8 Hz, H1), 3.67
(t, J1 = 8.1 Hz, J2 = 8.2 Hz, H3), 3.59 (m, 6H, H5, H6a, H6b, OMe), 3.30
(t, 1H, J1 = 7.6 Hz, J2 = 7.6 Hz, H2), 3.59 (s, 1H, OMe), 1.99 (s, 1H,
OAc).
1
Data for 19b: 1H NMR (CDCl3, 400 MHz): δ 7.33−7.26 (m, 10H,
Ph × 2), 5.00 (t, 1H, J1 = 7.6 Hz, J2 = 9.6 Hz, H3), 4.85 (d, 1H, J = 12
Hz, PhCH2), 4.63−4.56 (m, 3H, PhCH2), 4.37 (d, 1H, J = 7.6 Hz,
H1), 3.78−3.77 (m, 2H, H5, H6a), 3.65−3.58 (m, 4H, OMe, H4),
3.52−3.47 (m, 1H, H6b), 3.34 (t, 1H, J1 = 9.2 Hz, J2 = 7.6 Hz, H2),
2.02 (s, 1H, OAc).
then an H NMR test was performed.
General Method for Testing the Formation of H-Bonds
between Glycosides and Solvents. The 1,2-diol reactant (10 mg)
was dissolved in dry CD3Cl, CD3CN, or DMSO-d6 (0.5 mL), and the
1
dried mixture was directly used to perform H NMR tests.
Syntheses. Methyl 2-O-Acetyl-4,6-O-benzylidene-α-D-glucopyr-
anoside (2a).15 Methyl 4,6-O-benzylidene-α-D-glucopyranoside (100
mg) was allowed to react with acetic anhydride (37 μL, 1.1 equiv) in
dry acetonitrile (1 mL) at 40 °C for 12 h in the presence of
tetrabutylammonium acetate (64 mg, 0.6 equiv). The reaction mixture
was directly purified by flash column chromatography (hexane/EtOAc
Methyl 2,3-Di-O-benzyl-6-O-acetyl-α-D-glucopyranoside (20).15
Methyl 2,3-di-O-benzyl-α-D-glucopyranoside (100 mg) was allowed to
react with acetic anhydride (28 μL, 1.1 equiv) in dry acetonitrile (1
mL) at 40 °C for 8 h in the presence of tetrabutylammonium acetate
(48 mg, 0.6 equiv). The reaction mixture was directly purified by flash
column chromatography (hexane/EtOAc = 2:1), affording 101 mg of
1
= 2:1), affording 101 mg of compound 2 (88%). H NMR (CDCl3,
1
400 MHz): δ 7.49−7.26 (m, 5H, Ph), 5.56 (s, 1H, CH), 4.97 (d, 1H, J
= 4 Hz, H1), 4.83−4.79 (dd, 1H, J1 = 3.6 Hz, J2 = 9.6 Hz, H2), 4.32−
4.29 (dd, 1H, J1 = 3.6 Hz, J2 = 10 Hz, H6a), 4.19 (t, 1H, J1 = 9.6 Hz, J2
= 9.2 Hz, H3), 3.89−3.79 (m, 1H, H5), 3.77 (t, 1H, J1 = 10 Hz, J2 =
10.4 Hz, H6b), 3.57 (t, 1H, J1 = 9.6 Hz, J2 = 9.2 Hz, H4), 3.41 (s, 1H,
OMe), 2.16 (s, 1H, OAc).
compound 20 (91%). H NMR (DMSO-d6, 400 MHz): δ 7.40−7.28
(m, 10H, Ph × 2), 5.04−4.67 (m, 4H, PhCH2 × 2), 4.65 (d, 1H, J =
3.6 Hz, H1), 4.46−4.41 (dd, 1H, J1 = 4.8 Hz, J2 = 12 Hz, H6a), 4.25−
4.22 (dd, 1H, J1 = 2.4 Hz, J2 = 12 Hz, H6b), 3.84−3.74 (m, 2H, H3,
H5), 3.53 (dd, 1H, J1 = 3.6 Hz, J2 = 9.6 Hz, H2), 3.47−3.41 (m, 4H,
H4, OMe), 2.51 (s, 1H, OH), 2.10 (s, 1H, OAc).
Methyl 3-O-Acetyl-2,6-di-O-benzyl-β-D-galactopyranoside (15).15
Methyl 2,6-di-O-benzyl-β-D-galactopyranoside (100 mg) was allowed
to react with acetic anhydride (28 μL, 1.1 equiv) in dry acetonitrile (1
mL) at 40 °C for 8 h in the presence of tetrabutylammonium acetate
(48 mg, 0.6 equiv). The reaction mixture was directly purified by flash
column chromatography (hexane/EtOAc = 2:1), affording 100 mg of
compound 15 (90%). 1H NMR (CDCl3, 400 MHz): δ 7.31−7.26 (m,
10H, Ph × 2), 4.89 (dd, 1H, J1 = 3.2 Hz, J2 = 10 Hz, H3), 4.85 (d, 1H,
J = 12 Hz, PhCH2), 4.64−4.55 (m, 3H, PhCH2), 4.36 (d, 1H, J = 8 Hz,
H1), 4.13 (d, 1H, J = 3.2 Hz, H4), 3.81−3.64 (m, 4H, H2, H5, H6a,
H6b), 3.59 (s, 1H, OMe), 2.05 (s, 1H, OAc).
Methyl 2,3-Di-O-benzyl-6-O-acetyl-α-D-galactopyranoside (21).15
Methyl 2,3-di-O-benzyl-α-D-galactopyranoside (100 mg) was allowed
to react with acetic anhydride (28 μL, 1.1 equiv) in dry acetonitrile (1
mL) at 40 °C for 8 h in the presence of tetrabutylammonium acetate
(48 mg, 0.6 equiv). The reaction mixture was directly purified by flash
column chromatography (hexane/EtOAc = 2:1), affording 103 mg of
1
compound 21 (93%). H NMR (DMSO-d6, 400 MHz): δ 7.41−7.27
(m, 10H, Ph × 2), 4.96 (d, 1H, J = 4.8 Hz, OH), 4.79 (d, 1H, J = 3.6
Hz, H1), 4.72−4.56 (m, 4H, PhCH2 × 2), 4.15−4.11 (m, 2H, H6a,
H6b), 4.08−4.03 (m, 1H, H4), 3.80−3.74 (m, 2H, H2, H5), 3.69−3.65
(dd, 1H, J1 = 10.4 Hz, J2 = 3.0 Hz, H3), 3.26 (s, 3H, OCH3), 2.02 (s,
3H, OAc).
Methyl 3-O-Acetyl-4,6-O-benzylidene-α-D-galactopyranoside
(17).24 Methyl 4,6-O-benzylidene-α-D-galactopyranoside (100 mg)
was allowed to react with acetic anhydride (37 μL, 1.1 equiv) in dry
acetonitrile (1 mL) at 40 °C for 12 h in the presence of
tetrabutylammonium acetate (64 mg, 0.6 equiv). The reaction mixture
was directly purified by flash column chromatography (hexane/EtOAc
Methyl 2,3-Di-O-benzyl-6-O-acetyl-α-D-mannopyranoside (22).15
Methyl 2,3-di-O-benzyl-α-D-mannopyranoside (100 mg) was allowed
to react with acetic anhydride (28 μL, 1.1 equiv) in dry acetonitrile (1
mL) at 40 °C for 8 h in the presence of tetrabutylammonium acetate
(48 mg, 0.6 equiv). The reaction mixture was directly purified by flash
column chromatography (hexane/EtOAc = 2:1), affording 101 mg of
compound 22 (91%). 1H NMR (CDCl3, 400 MHz): δ 7.39−7.28 (m,
10H, Ph × 2), 5.32 (d, 1H, J = 6.0 Hz, OH), 4.77 (d, 1H, J = 0.8 Hz,
H1), 4.65−4.62 (m, 4H, PhCH2 × 2), 4.35−4.31 (dd, 1H, J1 = 12.0
Hz, J2 = 1.8 Hz, H6a), 4.10−4.03 (m, 1H, H6b), 3.81−3.80 (m, 1H,
H2), 3.69−3.61 (m, 1H, H4), 3.66−3.51 (m, 2H, H3, H5), 3.26 (s, 3H,
OCH3), 2.02 (s, 3H, OAc).
1
= 2:1), affording 104 mg of compound 17 (90%). H NMR (CDCl3,
400 MHz): δ 7.54−7.28 (m, 5H, Ph), 5.54 (s, 1H, CH), 5.15 (dd, 1H,
J1 = 3.2 Hz, J2 = 10.4 Hz, H3), 4.98 (d, 1H, J = 3.6 Hz, H1), 4.40 (s,
1H, H4), 4.32 (dd, 1H, J1 = 2 Hz, J2 = 12.4 Hz, H6a), 4.29−4.17 (m,
1H, H5), 4.09 (dd, 1H, J1 = 1.6 Hz, J2 = 12.4 Hz, H6b), 3.75 (s, 1H,
H2), 3.50 (s, 1H, OMe), 2.19 (s, 1H, OAc), 2.01 (d, 1H, J = 10.8 Hz,
OH).
2-Phenyl-2-hydroxyethyl Acetate (24).15 1-Phenyl-1,2-ethanediol
(50 mg) was allowed to react with acetic anhydride (38 μL, 1.1 equiv)
in dry acetonitrile (1 mL) at 40 °C for 8 h in the presence of
tetrabutylammonium acetate (66 mg, 0.6 equiv). The reaction mixture
was directly purified by flash column chromatography (hexane/EtOAc
Methyl 2-O-Acetyl-4,6-O-benzylidene-β-D-glucopyranoside
(18).24 Methyl 4,6-O-benzylidene-β-D-glucopyranoside (100 mg) was
allowed to react with acetic anhydride (37 μL, 1.1 equiv) in dry
acetonitrile (1 mL) at 40 °C for 12 h in the presence of
tetrabutylammonium acetate (64 mg, 0.6 equiv). The reaction mixture
was directly purified by flash column chromatography (hexane/EtOAc
1
= 2:1), affording 59 mg of compound 24 (90%). H NMR (CDCl3,
1
400 MHz): δ 7.42−7.28 (m, 5H, Ph), 4.98−4.95 (dd, 1H, J1 = 8.4, J2 =
3.2 Hz, CH), 4.32−4.15 (m, 2H, CH2), 2.12 (s, 3H, OAc).
= 2:1), affording 98 mg of compound 18 (85%). H NMR (CDCl3,
400 MHz): δ 7.51−7.26 (m, 5H, Ph), 5.55 (s, 1H, CH), 4.92 (t, 1H, J1
= 8 Hz, J2 = 9.2 Hz, H2), 4.43 (d, 1H, J = 8 Hz, H1), 4.37 (dd, 1H, J1 =
5.2 Hz, J2 = 10.8 Hz, H6a), 3.91−3.85 (m, 1H, H3), 3.80 (t, J1 = 10.4
Hz, J2 = 10.4 Hz, H6b), 3.59 (t, 1H, J1 = 9.2 Hz, J2 = 9.6 Hz, H4), 3.51
(s, 1H, OMe), 3.48−3.42 (m, 1H, H5), 2.67 (s, 1H, OH), 2.15 (s, 1H,
OAc).
ASSOCIATED CONTENT
■
S
* Supporting Information
1
General methods; Table S1; H NMR spectra of compounds
Methyl 4-O-Acetyl-2,6-di-O-benzyl-β-D-glucopyranoside (19a)
and Methyl 3-O-Acetyl-2,6-di-O-benzyl-β-D-glucopyranoside
(19b).34 Methyl 2,6-di-O-benzyl-β-D-glucopyranoside (100 mg) was
allowed to react with acetic anhydride (28 μL, 1.1 equiv) in dry
acetonitrile (1 mL) at 40 °C for 8 h in the presence of
tetrabutylammonium acetate (48 mg, 0.6 equiv). The reaction mixture
was directly purified by flash column chromatography (hexane/EtOAc
= 2:1), affording 53 mg of compound 19a (48%) and 47 mg of
compound 19b (42%).
2a, 15, 17, 18, 19a, 19b, 20, 21, 22, and 24; H-bond tests of
compounds 1, 4, 6, and 7 by 1H NMR; computational
methods; and Cartesian coordinates and total energies. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
■
Data for 19a: 1H NMR (CDCl3, 400 MHz): δ 7.32−7.26 (m, 10H,
Ph × 2), 4.95−4.87 (m, 2H, PhCH2, H4), 4.67 (d, 1H, J = 11.2 Hz,
Corresponding Author
*E-mail: hdong@mail.hust.edu.cn.
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The Journal of Organic Chemistry
Note
(30) Xu, S.; Held, I.; Kempf, B.; Mayr, H.; Steglich, W.; Zipse, H.
Notes
Chem.Eur. J. 2005, 11, 4751−4757.
The authors declare no competing financial interest.
(31) Dong, H.; Rahm, M.; Brinck, T.; Ramstrom, O. J. Am. Chem.
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Soc. 2008, 130, 15270−15271.
(32) Dong, H.; Rahm, M.; Thota, N.; Deng, L.; Brinck, T.;
ACKNOWLEDGMENTS
■
This study was supported by the Fundamental Research Funds
for the Central Universities (HUST: 2012QN146), the
National Natural Science Foundation of China (21272083),
the Chutian Project Sponsored by Hubei Province and the
Project Sponsored by the SRF for ROCS, SEM. The authors
are also grateful to the staff in the Analytical and Test Center of
HUST for support with the NMR instruments.
Ramstrom, O. Org. Biomol. Chem. 2013, 11, 648−653.
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(33) Dong, H.; Pei, Z. C.; Ramstrom, O. Chem. Commun. 2008,
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1359−1361.
(34) Dong, H.; Pei, Z. C.; Ramstrom, O. J. Org. Chem. 2006, 71,
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3306−3309.
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