A green and convenient method for regioselective mono and multiple benzoylation of diols and polyols

Article abstract of DOI:10.1016/j.tet.2015.12.074

An efficient method for regioselective benzoylation of diols and polyols was developed. The benzoylation is catalyzed by only 0.2 equiv of benzoate anion in acetonitrile with the addition of a stoichiometric amount of benzoic anhydride under very mild condition, leading to high yields. Compared with all other methods, this method shows particular advantage in regioselective multiple benzoylation of polyols, and in avoiding the use of any metal-based catalysts and any amine bases, which is more environment-friendly.

Full text of DOI:10.1016/j.tet.2015.12.074

Tetrahedron 72 (2016) 1005e1010
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A green and convenient method for regioselective mono and
multiple benzoylation of diols and polyols
,
a,
Xiaoling Zhang a, Bo Ren a, Jiantao Ge a, Zhichao Pei b , Hai Dong
*
*
a Key laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education, School of Chemistry & Chemical Engineering,
Huazhong University of Science & Technology, Luoyu Road 1037, Wuhan, 430074, PR China
b State Key Laboratory of Crop Stress Biology in Arid Areas and College of Science, Northwest A&F University, Yangling, Shaanxi, 712100, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient method for regioselective benzoylation of diols and polyols was developed. The benzoylation
is catalyzed by only 0.2 equiv of benzoate anion in acetonitrile with the addition of a stoichiometric
amount of benzoic anhydride under very mild condition, leading to high yields. Compared with all other
methods, this method shows particular advantage in regioselective multiple benzoylation of polyols, and
in avoiding the use of any metal-based catalysts and any amine bases, which is more environment-
friendly.
Received 3 November 2015
Received in revised form 19 December 2015
Accepted 28 December 2015
Available online 30 December 2015
Keywords:
Ó 2015 Elsevier Ltd. All rights reserved.
Regioselectivity
Benzoylation
H-bonding
Green chemistry
Carbohydrate
1. Introduction
friendly. However, in all these methods, the uses of a large amount
of organic amine bases are usually inevitable. In addition, most of
Studies on the roles of carbohydrates in life require various ol-
igosaccharides. In order to synthesize the oligosaccharides, one of
the most prominent challenges is to develop environment-friendly,
convenient, efficient and high regioselective carbohydrate pro-
tection methods.1e5 Selectively protected monosaccharides can be
obtained through these methods and can act as either value-added
intermediate products, or building blocks for the synthesis of
oligosaccharides.6e10 The most frequently used protection methods
involve acetylation and benzoylation. Generally the benzoylated
carbohydrates are more stable due to lower rates of both acyl group
migration and neighboring group participation compared to acet-
ylated carbohydrates. Accordingly, many regioselective benzoyla-
tion methods have been developed. The initial methods involve the
use of stoichiometric amounts of organotins11e16 and a large
amount of heavy metal salts.17e22 However, these methods have to
be abandoned today due to the inherent potential toxicity of them.
It seems that the methods using reduced amounts of organo-
tins23,24 or heavy metal-based complexes25e31 as catalysis, or using
certain nonmetallic catalysis,32e34 are more environmental
the developed methods except for using organotin35 are only ap-
propriate to selective mono-benzoylation of polyols. For the
organotin-mediated multiple carbohydrate esterification, more
than two hydroxyl groups were regioselectively acylated by use of
excess (2e3 equiv) organotin reagent in a one-pot process in light
of description.35 A regioselective acetylation method has been re-
ported by us recently, where acetylation is enabled by only
0.3e0.6 equiv of acetate anion without the assistance of any other
reagents (Fig. 1a).36,37 The method is based on a H-bonding
Fig. 1. a) Previous reported regioselective acetylation of diols catalyzed by acetate
anion. b) Present developed regioselective benzoylation of diols catalyzed by benzoate
anion.
* Corresponding authors. E-mail addresses: peizc@nwafu.edu.cn (Z. Pei), hdong@
mail.hust.edu.cn (H. Dong).
http://dx.doi.org/10.1016/j.tet.2015.12.074
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

1006
X. Zhang et al. / Tetrahedron 72 (2016) 1005e1010
activation mechanism where H-bonding between hydroxyl groups
and anions can activate acetylation in the absence of a pyridine
catalyst and lead to higher regioselectivities. We wondered if
a green and regioselective benzoylation method by the application
of this H-bonding activation principle could be developed. The
initial attempts were failed in previous studies when we still used
acetate anion as the catalyst. However, once we made clear the
reaction mechanism, the new regioselective benzoylation method
was developed by us when benzoate anion was used as the catalyst
instead of acetate anion in present studies. Consequently, com-
pared with all other methods, a more green method for regiose-
lective mono and multiple benzoylation of diols and polyols was
developed by us (Fig. 1b). The method avoids using any metal salts
and any amine bases, and only uses 0.1e0.2 equiv of tetrabuty-
lammonium benzoate (TBAOBz) as a catalyst in comparison with
previous report36,37 where 0.6 equiv acetate anion is necessary.
High isolated yields were obtained, especially, in regioselective
multiple benzoylation of polyols. The reason why benzoate shows
higher catalytic reactivity is also discussed (Fig. 2).
Table 1
Regioselective benzoylation of diols catalyzed by TBAOBza
Entry Acylation reagent Catalysis
Yieldb
dc
dc
1
2
3
4
5
6
7
8
AcCl
BzCl
TBAOAc
TBAOAc
Ac2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
Bz2O
TBAOAc
TBAOAc
TBAOBz
BzONa
0.2 equiv TBAOBz
0.1 equiv TBAOBz
0.1 equiv TBAOBz
Without catalyst
With 1 equiv TEA
2 (90%)
A mixture (2, 3)
3 (87%)
dc
3 (89%)
3 (75%)
3 (77%)
No reaction
No selectivity
9d
10
11
12
0.2 equiv BzONa, 0.2 equiv TBABr 3 (73%)
a
Reaction conditions: reactant (100 mg), acylation reagent (1.1 equiv), TBAX
(0.3 equiv), 8e12 h.
b
Isolated yield.
Low conversion (<20%).
Reaction time (24 h).
c
d
a)
b)
c)
Fig. 2. a) Generation of acetic anhydride and benzoate anion through acyltransfer reaction. b) Proposed catalytic mechanism of regioselective benzoylation by BzOꢀ. c) The effi-
ciency of the catalysis depending on the stability of the homo-conjugate H-bond complex.
2. Results and discussion
However, very low conversions were obtained (Entries 1 and 2).
The failed results could be explained by the formation of chlorine
hydride when acyl chlorides as acylation reagents instead of the
formation of acetic acid when acetic anhydride (Ac2O) as the ac-
ylation reagent. Therefore, acetic anhydride (Ac2O) and benzoic
anhydride (Bz2O) had to be as the acetylation reagents in the re-
action. Indeed, the acylation proceed smoothly with anhydrides
In light of the previous report,36,37 it is easy to think that acetate
anion as catalyst is used to fully explore the scope of electrophiles.
Therefore, our initial try is to use acetate anion as catalyst and
acetyl chloride or benzoyl chloride as acylation reagents in the
regioselective acylation of 1-phenyl-1,2-ethanediol 1 (Table 1).

X. Zhang et al. / Tetrahedron 72 (2016) 1005e1010
1007
Table 2
(Entry 3). However, a mixture of acetylation product 2 and ben-
Regioselective benzoylation of diols catalyzed by TBAOBza
zoylation product 3 was obtained when Bz2O was used as the ac-
ylation reagent (Entry 4). The reason might be explained by the
transferring of acyl groups between Bz2O and acetate anion (AcOꢀ)
(Fig. 2a). Ac2O and benzoate anion (BzOꢀ) might be generated
through the acyltransfer process. Consequently, BzOꢀ had to be
used as a catalyst in the regioselective benzoylation in order to
avoid forming acetylated products. The benzoylation product 3 was
obtained in 87% yield when compound 1 was allowed to react with
1.1 equiv of Bz2O in the presence of 0.3 equiv of TBAOBz in aceto-
nitrile at 40 ꢁC for 8 h (Entry 5). However, 0.3 equiv of BzONa led to
low conversion (Entry 6), likely due to its poor solubility in aceto-
nitrile. Through optimization of the used amount of TBAOBz (En-
tries 7e9), it was found that 0.2 equiv of TBAOBz was the best for
the reaction. 0.1 equiv of TBAOBz led to lower yields even when the
reaction time was prolonged to 24 h. There was no reaction oc-
curred without any catalyst (Entry 10). A mixture of 1-OBz, 2-OBz
and 1,2-di-OBz products were obtained when 1 equiv of triethyl-
amine was used instead of TBAOBz (Entry 11), indicating that there
is no selectivity without the catalysis of benzoate anion. In order to
verify the role of TBA cation, a combination of 0.2 equiv of BzONa
and 0.2 equiv of TBABr was used to catalyze the reaction (Entry 12).
It was found that the yield of 3 was increased by 73%. The reason
must be the better solubility of benzoate anion in acetonitrile by
the addition of TBA cation.
In light of the proposed mechanism showed in Fig. 2b, with
Bz2O as the acylation reagent, the catalysis BzOꢀ would form
homo-conjugate H-bond complex with BzOH formed in the re-
action. The formation and stability of homo-conjugate H-bond
complexes [BzOHOBZ]ꢀ (B) and [AcOHOAc]ꢀ (C) have been dis-
cussed in several papers.38e41 Thus, with the reaction proceeding
and BzOH generating, the homo-conjugate H-bond complex B was
becoming increasingly and the dual H-bonding complex A were
becoming decreasingly. Consequently, the efficiency of the catal-
ysis depends on the relative stability of the homo-conjugate H-
bond complex B and the dual H-bonding complex A. When the
used amount of BzOꢀ was decreased by 0.1 equiv of compound 1,
the dual H-bonding complex A was difficult to form with the
conversion rate reaching to approximate 80%. As a result, the yield
could not be increased even if the reaction time was prolonged to
24 h. With BzCl as the acylation reagent, the catalysis BzOꢀ would
be consumed by the formed HCl in the reaction since BzOH is
much weaker acid, leading to low conversion (<20%). The homo-
conjugate H-bond complex B may be less stable than the homo-
conjugate H-bond complex C formed by AcOꢀ and AcOH likely
due to the larger steric effect of benzoyl group than that of acetyl
group (Fig. 2c).40 The more stable complex C would decrease the
efficiency of the catalysis acetate anion. It may be one of the
reasons why 0.1e0.2 equiv of TBAOBz is used as catalysis in
present reaction whereas 0.3e0.6 equiv of TBAOAc is necessary in
previous report.
Entry
Reactant
Product
Yield (%)b
1
2
91
81
3
4
88
82
5
6
76
a/b (9/64)
7
8
88
90
9
94
10
a/b (70/14)
11
a/b (65/19)
12
13
a/b (48/30)
a/b (31/50)
14
15
a/b (30/52)
a/b (36/40)
Based on these studies, 0.2 equiv of TBAOBz was further tested
together with a range of diols (cf. Table 2): 1,2-diols 4 and 6, with
one primary hydroxyl group; 1,3-diols 8 and 10, with one primary
hydroxyl group; methyl glycoside 1,3-diols 12, 14, 16, 18 and 20,
with one primary hydroxyl group; and methyl glycoside 1,2-diols
22, 24, 26, 28, 30 and 32, without primary hydroxyl group. These
compounds were allowed to react with 1.1 equiv of Bz2O in the
presence of 0.2 equiv of TBAOBz in acetonitrile at 40 ꢁC for 8e12 h.
The results (cf. Table 2) show high regioselectivities to primary
hydroxyl group in most cases and excellent isolated yields
(64e94%). The regioselectivities showed to methyl glycoside 1,2-
diols 22, 24, 26, 28, 30 and 32, which contain two secondary hy-
droxyl groups, are not very good. However, this method still takes
advantageous since only very few over-benzoylated products were
formed during all these reactions.
a
Reaction conditions: reactant (100 mg), Bz2O (1.1 equiv), TBAOBz (0.2 equiv),
MeCN (1 mL), 40 ꢁC, 8e12 h.
b
Isolated yield.
In the further experiments, 0.2e0.4 equiv of TBAOBz was tested
together with a range of polyols (cf. Table 3): methyl glycosides 34,
36, 38, 40 and 42, in which the 6-OH groups were silylated; methyl
b-D-galactoside 44, in which the 3-OH group were benzylated; free
methyl glycosides 46, 48, 50, 52, 54 and 56; and glycerol 58. When
compounds 34, 36, 38, 40, 42, 44, 56 and 58 were allowed to react
with 1.1 equiv of Bz2O in the presence of 0.2 equiv of TBAOBz in

1008
X. Zhang et al. / Tetrahedron 72 (2016) 1005e1010
Table 3
for entry 6, entries 10e15 in Table 2, respectively). As the benzoy-
Regioselective benzoylation of polyols catalyzed by TBAOBza
lation is catalyzed by benzoate anion through a dual H-bonding
complex, once one of hydroxyl groups is benzoylated, the left
neighbor hydroxyl group will be difficult to be benzoylated due to
the lack of the dual H-bonding complex. We proposed the regio-
selectivities should be mainly controlled by steric effect of sub-
strates. Thus, for diols or polyols with a primary hydroxyl, the
primary hydroxyl groups were selective benzoylated due to their
minimum steric effect. For glycoside polyols in which the 6-OH
groups have been protected, 3-OH groups have the minimum ste-
ric effects since they neighbored two hydroxyl groups whereas 2-
and 4-OH groups neighbored a bulky group separately except for 3-
OH, leading to good selectivities to 3-OH. The acidity of hydroxyl
group for substrates should also play an important role on the
regioselectivity. It might be the reason why the 3-position of
compound 56 is highly selective benzoylated though 4-OH groups
of 56 have the minimum steric effect.
Entry
1
Reactant
Product
Condition
Yield(%)b
83
A
2
3
A
A
78
84
4
A
85
5
6
7
A
A
B
84
85
3. Conclusion
Based on dual H-bonding principle, we developed an efficient
method for regioselective benzoylation of diols and polyols. The
benzoylation is catalyzed by 0.2 equiv of benzoate anion for
benzoylation of one hydroxyl group in acetonitrile with the ad-
dition of a stoichiometric amount of benzoic anhydride under
very mild condition, leading to high selectivities and isolation
yields. Compared with other methods, this method shows par-
ticular advantage in regioselective multiple benzoylation of pol-
yols, and in avoiding the use of any metal-based catalysts and any
amine bases. Therefore, although the method requires more ca-
talysis (0.2 equiv), it is still advantageous compared to methods
using less catalysis (<0.1 equiv) but much more amine bases
(>1 equiv).
70c
8
9
B
B
72
79
10
B
B
83
91
11
12
4. Experimental section
4.1. General
A
A
84
All commercially available starting materials and solvents were
of reagent grade and dried prior to use. Chemical reactions were
monitored with thin-layer chromatography using precoated silica
gel 60 (0.25 mm thickness) plates. High-resolution mass spectra
HRMS where obtained by electrospray ionization (ESI) and Q-TOF
detection. Flash column chromatography was performed on silica
gel 60 (0.040e0.063 mm). 1H and 13C spectra were recorded with
a 400 MHz and 100 MHz instrument at 298 K in CDCl3, using the
67d
13
B
70
a
Reaction conditions: reactant (100 mg), A) Bz2O (1.1 equiv), TBAOBz (0.2 equiv),
CH3CN (1 mL), 40 ꢁC, 8e12 h; B) Bz2O (2.1 equiv), TBAOBz (0.4 equiv), CH3CN/DMF
(5:1), 40 ꢁC, 8e12 h.
residual signals from d-chloroform (1H:
d
¼7.25 ppm; 13C:
b
Isolated yield.
Mixed with 13% methyl 4,6-OBz
Mixed with 6% 2-OBz glycerol.
c
d
¼77.2 ppm), as internal standard. Assignments were made by first
a-D-glucoside.
order analysis of the spectra, supported by standard 1He1H corre-
d
lation spectroscopy (COSY).
acetonitrile, 3-OH groups were selectively benzoylated for com-
pounds 34, 36, 38, 40, 42 and 56 to obtain high isolation yields of
compounds 35, 37, 39, 41, 43 and 57 (78e85%), and primary hy-
droxyl groups were selectively benzoylated for compounds 44 and
58 to obtain high isolation yields of compounds 45 (85%) and 59
(73%). When compounds 46, 48, 50, 52 and 54 were allowed to
react with 2.1 equiv of Bz2O in the presence of 0.4 equiv of TBAOBz
in acetonitrile, 3, 6-di-OBz products 47, 49, 51, 53 and 55 were
obtained in high isolated yields (72e91%). Benzoylation of glycerol
58 led to selective benzoylation of two primary hydroxyl groups
under this condition.
The isolated yields of the major product in most examples
(Tables 2 and 3) are quite good (>80% yield), indicating high
regioselectivities of these reactions (>80%). For some examples
with yields lower than 70%, the product distribution is given as
isolation ratios (9/64, 70/14, 65/19, 48/30, 31/50, 30/52 and 36/40
4.2. General procedure for regioselective mono benzoylation
Diols and polyol reactants (100 mg) were allowed to react with
benzoic anhydride (1.1 equiv) in acetonitrile (1 mL) at 40 ꢁC for
8e12 h in the presence of TBAOBz (0.2 equiv). The reaction mixture
was directly purified by flash column chromatography (hexanes/
EtOAc¼2:1 to 1:1), affording the pure selectively protected
derivatives.
4.3. General procedure for regioselective multiple
benzoylation
Polyol reactants (100 mg) were allowed to react with benzoic
anhydride (2.1 equiv) in a mixture of 2 mL MeCN and 0.2 mL DMF at
40 ꢁC for 8e12 h in the presence of TBAOBz (0.4 equiv). The reaction

X. Zhang et al. / Tetrahedron 72 (2016) 1005e1010
1009
mixture was directly purified by flash column chromatography
(hexanes/EtOAc¼2:1 to 1:1), affording the pure selectively pro-
tected derivatives.
63.9, 55.3, 25.9, 18.4, ꢀ5.4. ESI-HRMS m/z calcd for C20H32O7Si
[MþNa]þ: 435.1815. Found 435.1809.
4.9. Methyl 3-O-benzoyl-6-O-(tert-butyldimethylsilyl)-bLD-
glucopyranoside 37
4.4. 2-Hydroxy-3-Allyloxypropyl benzoate 7
Colorless oil, 1H NMR (CDCl3, 400 MHz):
d
8.10 (d, 2H, J¼7.2 Hz,
Colorless oil, 1H NMR (400 MHz, CDCl3)
d¼8.05 (d, 2H, J¼7.2 Hz,
Ph), 7.57 (t, 1H, J¼7.6 Hz, Ph), 7.45 (t, 2H, J¼7.6 Hz, Ph), 5.22 (t, 1H,
J¼9.2 Hz, H-3), 4.34 (d, 1H, J¼8 Hz, H-1), 3.98 (dd, 1H, J¼10.4 Hz,
4.8 Hz, H-6a), 3.91 (dd, 1H, J¼10.4 Hz, 5.6 Hz, H-6b), 3.83 (t, 1H,
J¼9.2 Hz, H-4), 3.61 (m, 4H, H-2, OMe), 3.51e3.46 (m, 1H, H-5), 0.90
(s, 9H, SiC(Me)3, 0.11 (s, 6H, Si(Me)2). 13C NMR (CDCl3, 100 MHz)
Ph), 7.57 (t, 1H, J¼7.6 Hz, Ph), 7.45 (t, 2H, J¼7.6 Hz, Ph), 5.96e5.86
(m, 1H, CH2CH]CH2), 5.32e5.27 (m, 1H, CH2CH]CH2), 5.21 (dd,
1H, J¼1.2 Hz, 10.4 Hz, CH2CH]CH2), 4.46e4.38 (m, 2H, CH2OBz),
4.20e4.15 (m, 1H, CHOH), 4.05 (d, 2H, J¼5.6 Hz, CH2CH]CH2), 3.62
(dd, 1H, J¼4 Hz, 10 Hz, CH2OAllyl), 3.56 (dd, 1H, J¼6.4 Hz, 9.6 Hz,
CH2OAllyl). 13C NMR (100 MHz, CDCl3)
d
¼166.7, 134.2, 133.2, 129.7,
d
167.6, 133.4, 130.0, 129.6, 128.4, 103.7, 78.5, 74.7, 72.4, 71.6, 64.5,
57.2, 25.9, 18.3, ꢀ5.4; ESI-HRMS m/z calcd for C20H32O7Si[MþNa]þ:
128.4, 117.5, 77.4, 77.0, 76.7, 72.4, 70.9, 69.0, 66.0 ppm. ESI-HRMS m/
z calcd for C13H16O4[MþNa]þ: 259.0946. Found 259.0966.
435.1815. Found: 435.1826.
4.10. Methyl 3-O-benzyl-6-O-benzoyl-b-D-galactopyranoside
4.5. Methyl 2,3-di-O-benzyl-6-O-benzoyl-a-D-glucopyrano-
45
side 13
Colorless oil, 1H NMR (CDCl3, 400 MHz):
d
8.04 (d, 2H, J¼7.2 Hz,
Colorless oil, 1H NMR (400 MHz, CDCl3)
d
¼8.03 (d, 2H, J¼7.6 Hz,
Ph), 7.58 (t, 1H, J¼7.6 Hz, Ph), 7.45 (t, 2H, J¼7.6 Hz, Ph), 7.40e7.30
(m, 5H, Ph), 4.75 (t, 2H, J¼12 Hz, PhCH2), 4.63 (dd, 1H, J¼11.6, 6 Hz,
H-6a), 4.57 (dd, 1H, J¼11.6 Hz, 7.2 Hz, H-6b), 4.19 (d, 1H, J¼7.6 Hz, H-
1), 4.00 (d, 1H, J¼2.8 Hz, H-4), 3.83e3.77 (m, 2H, H-2, H-5), 3.55 (s,
3H, OMe), 3.48 (dd, 1H, J¼9.6 Hz, 3.2 Hz, H-3). 13C NMR (CDCl3,
Ph), 7.62e7.28 (m, 13H, Ph), 5.01 (d, 1H, J¼11.2 Hz, PhCH2),
4.80e4.75 (m, 2H, H-1, PhCH2), 4.68e4.60 (m, 3H, PhCH2, H-6a),
4.51 (dd, 1H, J¼2.0 Hz, 12 Hz, H-6b), 3.90e3.87 (m, 1H, H-5), 3.84 (t,
1H, J¼9.2 Hz, H-4), 3.56e3.51 (m, 2H, H-2, H-3), 3.40 (s, 3H, OMe).
13C NMR (100 MHz, CDCl3)
128.5,128.4,128.1,128.1,128.0,127.8, 98.2, 81.3, 79.7, 75.7, 73.2, 70.1,
69.5, 63.8, 55.3 ppm. ESI-HRMS m/z calcd for C28H30O7[MþNa]þ:
501.1890. Found 501.1895.
d
¼166.8, 138.6, 138.0, 133.2, 129.8, 128.7,
100 MHz)
d
¼166.4, 137.6, 133.2, 129.7, 128.7, 128.5, 128.2, 128.0,
103.8, 80.4, 72.4, 72.3, 71.0, 66.4, 63.3, 57.0; ESI-HRMS m/z calcd for
C
21H24O7[MþNa]þ: 411.1420. Found: 411.1429.
4.11. Methyl 3,6-di-O-benzoyl-b-D-glucopyranoside 49
4.6. Methyl 2,3-di-O-benzyl-6-O-benzoyl-
b-D
-glucopyrano-
side 15b
Colorless oil, 1H NMR (CDCl3, 400 MHz):
d
8.09e8.06 (m, 4H,
Colorless oil, 1H NMR (CDCl3, 400 MHz):
d
8.04 (d, 2H, J¼7.6 Hz,
Ph), 7.60e7.55 (m, 2H, Ph), 7.47e7.42 (m, 4H, Ph), 5.24 (t, 1H,
J¼9.2 Hz, H-3), 4.71 (dd, 1H, J¼4 Hz, 12 Hz, H-6a), 4.64 (dd, 1H,
J¼2 Hz, 12 Hz, H-6b), 4.38 (d, 1H, J¼8 Hz, H-1), 3.79e3.73 (m, 2H, H-
4, H-5),3.67 (dd,1H, J¼8 Hz, 9.6 Hz, H-2), 3.58 (s, 3H, OMe). 13C NMR
Ph), 7.63e7.30 (m, 13H, Ph), 4.90 (d, 1H, J¼11.2 Hz, PhCH2),
4.78e4.69 (m, 3H, PhCH2), 4.62 (dd, 1H, J¼6 Hz, 11.2 Hz, H-6a), 4.58
(dd, 1H, J¼6.8 Hz, 11.2 Hz, H-6a), 4.30 (d, 1H, J¼8 Hz, H-1), 3.99 (d,
1H, J¼2.8 Hz, H-4), 3.74 (t, 1H, J¼6.4 Hz, H-5), 3.65 (dd, 1H, J¼8 Hz,
(CDCl3, 100 MHz)
d
¼167.8, 167.0, 133.6, 133.3, 130.1, 129.8, 129.7,
9.6 Hz, H-2), 3.57 (s, 3H, OMe), 3.54 (dd, J¼3.2 Hz, 9.2 Hz, H-3), 13
C
129.3, 128.5, 128.4, 103.9, 78.4, 74.5, 72.3, 69.4, 63.7, 57.4; ESI-HRMS
m/z calcd for C21H22O8[MþNa]þ: 425.1213. Found: 425.1224.
NMR (CDCl3, 100 MHz)
d 166.5, 138.6, 137.8, 133.2, 129.7, 128.5,
128.4, 128.3, 128.1, 128.0, 127.9, 127.7, 104.7, 80.4, 78.9, 75.1, 72.8,
71.9, 66.7, 63.4, 57.0 ppm. ESI-HRMS m/z calcd for
C
4.12. Methyl 3,6-di-O-benzoyl-
a-D-galactopyranoside 53
28H30O7[MþNa]þ: 501.1890. Found 501.1893.
Colorless oil, 1H NMR (CDCl3, 600 MHz)
d
8.06 (d, 2H, J¼7.2 Hz,
Ph), 7.97 (d, 2H, J¼7.2 Hz, Ph), 7.53 (t, 1H, J¼7.2 Hz, Ph), 7.49 (t, 1H,
J¼7.2 Hz, Ph), 7.40 (t, 2H, J¼7.8 Hz, Ph), 7.36 (t, 2H, J¼7.8 Hz, Ph),
5.31 (dd, 1H, J¼3 Hz, 10.2 Hz, H-3), 4.88 (d, 1H, J¼3.6 Hz, H-1), 4.54
(dd, 1H, J¼5.4 Hz, 11.4 Hz, H-6a), 4.50 (dd, 1H, J¼7.2 Hz, 11.4 Hz, H-
6b), 4.24 (m, 2H, H-2, H-4), 4.16 (t, 1H, J¼6 Hz, H-5), 3.42 (s, 3H,
4.7. Methyl 2,3-di-O-benzyl-6-O-benzoyl-a-D-mannopyrano-
side 17
Colorless oil, 1H NMR (CDCl3, 400 MHz):
d
8.06 (d, 2H, J¼7.6 Hz,
Ph), 7.62e7.28 (m, 13H, Ph), 4.82 (s, 1H, H-1), 4.70e4.62 (m, 5H,
PhCH2, H-6a, H-6b), 4.53 (d, J¼12 Hz, 1H, PhCH2), 4.13 (t, 1H,
J¼9.6 Hz, H-5), 3.90e3.83 (m, 2H, H-3, H-4), 3.77 (dd, 1H, J¼2.8,
OMe). 13C NMR (CDCl3, 100 MHz)
d 166.5, 166.4, 133.6, 133.4, 133.3,
129.9, 129.7, 129.6, 128.5, 99.7, 73.8, 68.17, 68.0, 67.3, 63.3, 55.6; ESI-
HRMS m/z calcd for C21H22O8[MþNa]þ: 425.1213. Found: 425.1220.
9.2 Hz H-2), 3.39 (s, 3H, OMe). 13C NMR (CDCl3, 100 MHz):
d 166.7,
138.1,138.0,132.9,130.1,129.8,128.6,128.4,128.3,127.9,127.8,127.7,
127.6, 99.1, 79.5, 74.0, 72.6, 71.8, 70.8, 66.6, 64.0, 54.9. ESI-HRMS m/z
calcd for C28H30O7[MþNa]þ: 501.1890. Found 501.1898.
4.13. Glycerol 1,3-dibenzoate 60
Colorless oil, 1H NMR (CDCl3, 400 MHz)
d 8.07e8.05 (m, 4H, Ph),
7.58 (t, 1H, J¼7.2 Hz, Ph), 7.46e7.43 (m, 7H, Ph), 4.78e4.57 (m, 4H,
4.8. Methyl 3-O-benzoyl-6-O-(tert-butyldimethylsilyl)-a-D-
glucopyranoside 35
CH2ꢂ2), 4.42e4.37 (m, 1H, CH). 13C NMR (CDCl3, 100 MHz)
¼166.7,
d
133.4, 129.8, 129.6, 128.5, 68.6, 65.9; ESI-HRMS m/z calcd for
17H16O5[MþNa]þ: 323.0895. Found: 323.0878.
Colorless oil, 1H NMR (CDCl3, 400 MHz): 1H NMR (CDCl3,
400 MHz)
C
d
¼8.09 (d, 2H, J¼7.2 Hz, Ph), 7.56 (t,1H, J¼7.4 Hz, Ph), 7.44
(t, 2H, J¼7.7 Hz, Ph), 5.35 (t,1H, J¼9.6 Hz, H-3), 4.81 (d, 1H, J¼3.6 Hz,
H-1), 3.92 (dd, 1H, J¼10.6 Hz, 4.9 Hz, H-6a), 3.88 (dd, 1H, J¼10.6 Hz,
5.6 Hz, H-6b), 3.80e3.69 (m, 3H, H-2, H-4, H-5), 3.46 (s, 3H, OMe),
0.91 (s, 9H, SiC(Me)3, 0.11 (s, 6H, Si(Me)2). 13C NMR (CDCl3,
Acknowledgements
This study was supported by the National Nature Science
Foundation of China (No. 21272083), and the Chutian Project-
Sponsored by Hubei Province. The authors are also grateful to the
100 MHz)
d 167.9, 133.3, 130.0, 129.8, 128.4, 99.3, 71.1, 71.0, 70.7,

1010
X. Zhang et al. / Tetrahedron 72 (2016) 1005e1010
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Supplementary data
Supplementary data (Synthesis method of substrates, Char-
acterization of known compounds, 1H NMR and 13C NMR-spectra
of known and new compounds) associated with this article can
be found in the online version, at http://dx.doi.org/10.1016/
j.tet.2015.12.074.
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