DBN-Catalyzed Regioselective Acylation of Carbohydrates and Diols in Ethyl Acetate

Article abstract of DOI:10.1002/ejoc.201900776

The 1,5-diazabicyclo[4.3.0]non-5-ene (DBN)-catalyzed regioselective acylation of carbohydrates and diols in ethyl acetate has been developed. The hydroxyl groups can be selectively acylated by the corresponding anhydride in EtOAc in the presence of a catalytic amount (as low as 0.1 equiv.) of DBN at room temperature to 40 °C. This method avoids metal catalysts and toxic solvents, which makes it comparatively green and mild, and it uses less organic base compared with other selective acylation methods. Mechanism studies indicated that DBN could catalyze the selective acylation of hydroxyl moieties through a dual H-bonding interaction.

Full text of DOI:10.1002/ejoc.201900776

A Journal of
Accepted Article
Title: DBN-Catalyzed Regioselective Acylation of Carbohydrates and
Diols in Ethyl Acetate
Authors: Bo Ren, Mengyao Zhang, Shijie Xu, Lu Gan, Li Zhang, and
Lin Tang
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900776
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10.1002/ejoc.201900776
European Journal of Organic Chemistry
FULL PAPER
DBN-Catalyzed Regioselective Acylation of Carbohydrates and
Diols in Ethyl Acetate
Bo Ren*[a], Mengyao Zhang[a], Shijie Xu[a], Lu Gan[a], Li Zhang[a] and Lin Tang*[a]
Abstract: The 1,5-diazabicyclo[4.3.0]non-5-ene (DBN)-catalyzed
regioselective acylation of carbohydrates and diols in ethyl acetate
has been developed. The hydroxyl groups can be selectively
acylated by the corresponding anhydride in EtOAc in the presence of
a catalytic amount (as low as 0.1 equiv.) of DBN at room
temperature to 40 °C . This method avoids metal catalysts and toxic
solvents, which makes it comparatively green and mild, and it uses
less organic base compared with other selective acylation methods.
Mechanism studies indicated that DBN could catalyze the selective
acylation of hydroxyl moieties through a dual H-bonding interaction.
and enzyme catalysts have the advantage of high efficiency and
high regioselectivity.[41] In 2004, Kattnig and colleagues
developed a DMAP-catalyzed selective acetylation of octyl-β-D-
glucopyranoside, but this method requires rigorous conditions
(Scheme 1a).[33] Then, in 2007, Kawabata and colleagues also
developed a DMAP-catalyzed selective acylation of octyl-6-O-
methyl-β-D-glucopyranoside, but this method uses 1.5
equivalents of collidine as base (Scheme 1a).[32] In 2013, Tan
and coworkers developed N-methylimidazole-derived catalysts
for the selective functionalization of carbohydrates, which is a
great progress for represents a great advance in the recognition
regioselective derivatization of complex polyhydroxyl species.[17]
Recently, a phosphonium ylide was developed as a catalyst for
the highly regioselective acetylation of primary hydroxyl groups,
but its substrate scope is restricted.[42] Some peptides can also
catalyze the regioselective acylation of carbohydrates, and they
Introduction
The preparation of high value-added carbohydrates and building
blocks for oligosaccharide synthesis still remains the most
important scientific problem in carbohydrate chemistry.[1-11]
Regioselective acylation is of great importance in the synthesis
of valuable oligosaccharide structural units because it facilitates
the protection and deprotection of hydroxyl groups and the
synthesis of target building blocks.[12-18] Recently, many methods
have been developed to make regioselective acylations highly
efficient, green, and even controllable, and some metal catalysts
and organic small molecules have been used for the
regioselective acylation of carbohydrates and diols; for example,
tin (IV),[19-21] boron (IV),[22] copper (II),[23-25] silver (I),[26] and iron
catalysts have been recently reported.[27, 28] Organotin reagents
are the most widely used reagents for the selective protection of
carbohydrates because over the years, they have been
developed into easy to handle and generally highly
regioselective reagents for the derivatization of diols and polyols.
often provide good selectivities with
substrate.[37-39]
a particular kind of
In summary, most of these promoters and catalysts have
disadvantages in the selective acylation of carbohydrates,
including environmental toxicity, expensive reagents, moisture
intolerance, limited substrate scope and requiring the pre-
protection of secondary hydroxyl groups. Here, we report an
organic small molecule catalyst, 1,5-diazabicyclo[4.3.0]non-5-
ene (DBN) that can be used for the selective acylation of more
than 25 carbohydrates and diols in the presence of an anhydride
and EtOAc as solvent (Scheme 1b). These reactions do not
require stoichiometric or superstoichiometric amount of base,
and the amount of DBN can even be reduced to only 0.1 equiv.,
making this method very economical and highly efficient
compared with other acylation reactions.[17, 23] The solvent was
optimized to EtOAc, which is relatively green and
environmentally friendly compared with MeCN. It is clear that we
provide an alternative highly efficient method for the
regioselective acylation of carbohydrates and diols. In addition,
based on our mechanism studies, we proposed that DBN could
catalyze the selective acylation of hydroxyls through dual H-
bonding interactions.
However, the organotin reagents are toxic and environmentally
30]
unfriendly, and thus their use has been restricted.[29,
The
organoboron catalysts can catalyze regioselective acylations of
carbohydrates, but they are green but not suitable for trans-
31]
diols.[22,
Recently, Fe(acac)3 was developed for the site-
selective acylation of 1,2-cis-diols;[28] it is an efficient and green
catalyst and has great research potentiality.
Many enzymes and small organic molecular catalysts are also
often used for the regioselective acylation of the hydroxyl groups
Scheme 1. Comparison of this method with previously reported methods.
a) Org. Lett. 2004, 6, 945; Tetrahedron Lett. 2007, 48, 5031
33]
of sugars, these catalysts include functional DMAP,[32,
TBAOAc,[34, 35] organic amines,[36] and peptides,[37-39] and most of
OP
OP
O
O
Ac2O, DMAP (5 mol%)
Base, -78 oC - 0 o
these reactions are catalyzed by the formation of strong H-
HO
HO
HO
AcO
32, 34, 35, 40]
bonds.[17,
In 2005, Bornscheuer and coworkers
HO
HO
OP
OP
C
developed a lipase-catalyzed glucose fatty acid ester synthesis,
b) This work
OP
OP
[a]
Dr. Bo Ren, Mengyao Zhang, Shijie Xu, Lu Gan, Li Zhang and Dr.
Lin Tang
College of Chemistry & Chemical Engineering, Xinyang Normal
University, Nanhu Road 237, Xinyang, Henan 464000, P. R. China.
E-mail: renbo@xynu.edu.cn, lintang@xynu.edu.cn.
Ac2O, DBN (10~20 mol%)
O
O
HO
HO
AcO
HO
HO
OP
OP
rt.~40 o
C
EtOAc
HO
Mild Conditions, Wide scope of substrates, Non-toxic reagents, Green Solvents
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201900776
European Journal of Organic Chemistry
FULL PAPER
Results and Discussion
the observed conversion was even lower (Table 1, Entry 12).
When MeCN was the solvent, we can also obtain very good
regioselectivity, but it is obviously not green enough (Table 1,
Entry 13). For the acetylation of carbohydrates, room
temperature is sufficient for obtaining the same high isolated
yields that were achieved at 40 °C (Table 1, Entry 14). When 0.3
equiv. of TBAOAc replaces 0.1 equiv. of DBN as catalyst, the
conversion reaches 70% after 12 hours, this means DBN
strongly activates and accelerates these reactions compared
with TBAOAc (Table 1, Entry 15). When we change the
acylation reagent to AcCl and add DBN to 1.0 equiv., only 55%
of the acylation product was obtained (Table 1, Entries 16); the
conversion rate does not increase but the selectivity is still very
good. For some regioselective benzoylation reactions, we
needed to raise the temperature to 40 °C and speed up the
reaction. Finally, the best reaction conditions for the substrate
were optimized; EtOAc is the best choice of solvent, and DBN is
the best catalyst (Table 1, Entries 1 and 2).
First, we used carbohydrates and diols to test the catalytic
efficiency and substrate scope of this method; in contrast,
reactions using MeCN as solvent were also evaluated (Table 2).
For substrate 3, most of the acylated products are obtained with
poor selectivities; when EtOAc was the solvent, the
regioselective acetylation of 3 was achieved with a good isolated
yield of 75% (Table 2, Entries 1 and 2). For terminal hydroxyl
carbohydrate substrates 6 and 9, good isolated yields (75%-
89%) were obtained under these conditions (Table 2, Entries 3-
6). To test the substrate scope, 1,2-diols 12 and 15 were used
as substrates, and high regioselectivities for the terminal
hydroxyl acylated product were observed in all reactions, and
the isolated yields were 79%-90% (Table 2, Entries 7–10). For
1,3-diols 18 and 21, good acetylation and benzoylation isolated
yields of 83%-88% were obtained for all reactions (Table 2,
Entries 11–14). All the results prove that this method has high
catalytic activity for the acylation of diols, especially terminal
hydroxyl groups.
Organotin- and organoboron-catalyzed selective protections of
hydroxyls have been studied for many years. Mechanistic
studies have shown that good regioselectivities are obtained
through cyclic intermediates and then selectively ring-opening
the catalysts and hydroxyl groups.[19] Based on these results,
Dong's group also predicted that any reagent that can form
cyclic dioxolane-analogue intermediates with hydroxyl groups
can achieve selectivities similar to organotin reagents.[43]
Inspired by this idea, a TBAOAc-catalyzed[34,
selective
35]
acylation and a self-catalyzed selective acylation initiated by a
catalytic amount of N,N-diisopropylethylamine (DIPEA) were
developed recently.[36] However, the solvents in these reactions
are not green, and the reaction times are often relatively long.
Therefore, we initially hoped to develop a greener and more
efficient organic small molecule-catalyzed selective acylation. To
verify our hypothesis, we first chose methyl 6-O-(tert-
butyldimethylsilyloxy)-α-D-mannopyranoside, 1, as the main
substrate (Table 1). As EtOAc is a good solvent for substrates, it
is very common and inexpensive, and it’s a recommended
solvent by green chemistry.[44, 45] Thus, 1 was treated with 1.1
equiv. of acetic anhydride and 0.1 equiv. of DIPEA in EtOAc at rt.
for 8 h. To our disappointment, the isolated yield was not as
good as what was obtained in MeCN, and most of the substrate
could be recovered (Table 1, Entry 5). Then, we changed the
catalyst to other organic bases, DBN, TEA (triethylamine) and
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) (Table 1, Entries 1
and 6-7). Only the DBN catalyzed reactions achieved a very
good regioselectivity. Interestingly, when we changed the
acylation reagent to AcCl, only 50% of the acylation product was
obtained (Table 1, Entries 8); perhaps the generated HCl blocks
the reaction. The blank control experiment showed that almost
no product is obtained without the DBN catalyst (Table 1, Entry
9). Here, we prove that DBN may be a good catalyst for the
regioselective acylation of carbohydrates.
Table 1. Comparison of results using variations of the “standard conditions”.
OTBS
OH
O
OTBS
OH
O
0.1~ 0.2 equiv. DBN,
1.1 equiv. (RCO)2O
Table 2. DBN-Catalyzed Regioselective Acetylation and Benzoylation of Diols.
HO
HO
HO
ROCO
1
OMe
2
EtOAc, rt.
OMe
Entry
(RCO)2O
Ac2O
Bz2O
Ac2O
Bz2O
Ac2O
Ac2O
Ac2O
AcCl
Ac2O
Ac2O
Ac2O
Ac2O
Ac2O
Ac2O
Ac2O
AcCl
Various Conditions
0.1 equiv. DBN.
0.2 equiv. DBN.
0.2 equiv. DBN.
0.1 equiv. DBN.
0.1 equiv. DIPEA.
0.1 equiv. TEA.
0.1 equiv. DBU.
0.2 equiv. DBN.
Without DBN.
EtOH as solvent.
CH2Cl2 as solvent.
H2O as solvent.
MeCN as solvent.
React at 40 °C
Isolated Yield %
Entry Conditions
A
Reactant
O
Product
Isolated yield (%)
1
2
3
4
5
6
7
8
86
80
87
70
30
20b
50b
50
Ph
O
O
Ph
Ph
a/b (47/46)
a/b (75/22)
O
O
O
R1O
4a,b
OMe
HO
3
R2O
HO
1
OMe
a:R1=H,R2=Ac
b:R1=Ac,R2=H
B
Ph
O
O
O
HO
a/b (47/45)
a/b (46/46)
O
O
O
C
R1O
5a,b
OMe
3
R2O
HO
c
OMe
2
9
-
a:R1=H,R2=Bz
b:R1=Bz,R2=H
10
11
12
13
14
15
16
30b
20b
10b
87
D
OH
OAc
HO
86
85
HO
BnO
A
O
O
O
OMe
6
OMe
7
3
BnO
BnO
88
70
55
BnO
B
0.3 equiv. TBAOAc.
1.0 equiv. DBN.
OH
OBz
HO
84
84
a
HO
C
Reactant (50 mg), (RCO)2O (1.1 equiv.), DBN (0.1~ 0.2 equiv.), solvent (1
O
mL), rt.~ 40 °C, 8~12 h. b Poor or no selectivity. c Low conversion (5-10% of 2).
OMe
OMe
4
BnO
BnO
BnO
8
6
BnO
D
Then, we optimized the solvent for both environmental
friendliness and regioselectivity. When EtOH and CH2Cl2 were
used as the solvent, the conversion was very low (Table 1,
Entries 10 and 11). H2O is the greenest solvent; unfortunately,
OH
OAc
A
75
75
O
O
HO
HO
BnO
BnO
BnO
10
OMe
9
5
BnO
B
OMe
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10.1002/ejoc.201900776
European Journal of Organic Chemistry
FULL PAPER
OH
OBz
OTBS
OTBS
C
85
89
O
O
O
A
B
80
85
HO
HO
BnO
O
HO
HO
HO
6
BnO
11
OMe
9
7
8
AcO
33
OMe
32
OMe
BnO
BnO
HO
D
OMe
HO
HO
OH
HO
Ph
OAc
A
B
C
D
A
82
80
79
79
81
OTBS
OTBS
O
7
8
12
13
14
Ph
C
D
O
87
78
HO
HO
HO
BzO
32
34
HO
HO
OMe
OMe
HO
Ph
OBz
HO
Ph
OH
OH
OH
12
15
OTBS
OTBS
O
35
OMe
36
OMe
A
B
81
60
O
HO
HO
HO
AcO
HO
HO
HO
OAc
OBz
9
HO
HO
9
16
17
B
C
D
A
80
90
90
85
OTBS
OTBS
O
HO
35
OMe
37
OMe
C
D
75
75
O
HO
HO
HO
BzO
10
10
15
HO
HO
OAc
OH
OH OAc
19
OH OH
18
OH
OH
11
12
13
14
O
A
B
78
80
O
HO
HO
B
C
D
A
B
C
D
87
88
88
80
80
85
83
BnO
11
12
13
39
BnO
38
OMe
OMe
OH OH
18
OH OBz
20
OH
OBz
HO
BnO
HO
41
OMe
C
D
40
OMe
84
86
O
O
BnO
HO
HO
OH OAc
22
OH OH
21
OAc
OH
HO
BnO
HO
BnO
A
B
83
82
O
O
43
42
HO
HO
OMe
OMe
OH OBz
23
OH OH
21
OH
OBz
HO
HO
C
D
O
84
80
O
14
BnO
BnO
Reaction conditions: A.50 mg of substrate, 1 mL of MeCN, 0.1 equiv. of DBN,
1.1 equiv. of Ac2O, rt., 8-12 h. B. 50 mg of substrate, 1 mL of EtOAc, 0.1 equiv.
of DBN, 1.1 equiv. of Ac2O, rt., 8-12 h. C. 50 mg of substrate, 1 mL of MeCN,
0.2 equiv. of DBN, 1.1 equiv. of Bz2O, 40 °C, 8-12 h. D. 50 mg of substrate, 1
mL of EtOAc, 0.2 equiv. of DBN, 1.1 of equiv. Bz2O, 40 °C, 8-12 h.
42
44
HO
HO
OMe
OMe
OH
OBz
OH
OH
O
O
HO
HO
HO
BzO
15
16
17
G
E
84
72
93
45
46
OMe
OMe
Table 3. DBN-Catalyzed Regioselective Acylation of Polyols.
OAc
OH
HO
HO
HO
O
O
O
Entry Conditions
Reactant
Product
Isolated yield (%)
OMe
48
OMe
47
AcO
HO
HO
OTBS
OTBS
OH
O
OH
O
OBz
OH
HO
HO
AcO
HO
HO
HO
BzO
A
87
86
HO
HO
24
1
1
O
OMe
OMe
OMe
49
B
G
OMe
47
HO
OTBS
OH
OTBS
OH
OAc
OH
HO
AcO
HO
HO
C
O
87
75
O
HO
HO
O
E
F
60
65
2
O
BzO
25
HO
1
18
19
51
OMe
D
OMe
OMe
50
HO
HO
OMe
OTBS
O
OTBS
O
HO
HO
OH
OBz
26
OMe
27
A
85
85
HO
HO
HO
BzO
3
OMe
HO
AcO
BzO
O
O
HO
B
HO
G
73
52
OMe
50
HO
HO
OMe
OTBS
O
OTBS
HO
HO
HO
28
26
O
C
D
88
55
OMe
OMe
4
Reaction conditions: A. 50 mg of substrate, 1 mL of MeCN, 0.1 equiv. of DBN,
1.1 equiv. of Ac2O, rt., 8-12 h. B. 50 mg of substrate, 1 mL EtOAc, 0.1 equiv.
of DBN, 1.1 equiv. of Ac2O, rt., 8-12 h. C. 50 mg of substrate, 1 mL of MeCN,
0.2 equiv. of DBN, 1.1 equiv. of Bz2O, 40 °C, 8-12 h. D. 50 mg of substrate, 1
mL of EtOAc, 0.2 equiv. of DBN, 1.1 equiv. of Bz2O, 40 °C, 8-12 h. E. 50 mg of
substrate, 1 mL of MeCN, 0.2 equiv. of DBN, 2.2 equiv. of Ac2O, 40 °C, 8-12 h.
F. 50 mg of substrate, 1 mL of EtOAc, 0.2 equiv. of DBN, 2.2 equiv. of Ac2O,
40 °C, 8-12 h. G. 50 mg of substrate, 1 mL of MeCN, 0.4 equiv. of DBN, 2.2
equiv. of Bz2O, 40 °C, 8-12 h.
HO
HO
OTBS
OTBS
O
HO
HO
HO
AcO
A
83
45
O
5
29
30
HO
HO
B
OMe
OMe
OTBS
O
OTBS
O
HO
BzO
HO
HO
C
75
50
6
31
OMe
29
OMe
HO
D
HO
The DBN catalyst was then used for the acylation of polyols and
carbohydrates with polyol structures to test its substrate scope
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10.1002/ejoc.201900776
European Journal of Organic Chemistry
FULL PAPER
(Table 3). For 6-OH silicane protected glycoside substrates (1,
26, 29, 32 and 35), the 3-OH of most substrates was acylated in
75–88% isolated yields (Table 3, Entries 1-10). Only four
reactions resulted in relatively low isolated yields of 45%-60% in
EtOAc, and the reason for this is unclear. For 3-OBn-protected
carbohydrates (38, 40 and 42), the 6-OH moiety is acylated or
benzoylated in isolated yields of 78%-86% (Table 3, Entries 11-
14). Then, free glycosides 45, 47 and 50 were treated with 2.2
equiv. of anhydride and 0.2-0.4 equiv. of DBN, and in most
cases, the 3,6-diacylated products were generated with good
isolated yields (72%-93%), and only substrate 50 had a
relatively low isolated yield of 60%-65% (Table 3, Entries 15-19).
Good regioselectivities were observed for the acylations of all
the polyols, and these results prove that this method is
applicable for polyols.
then released to the solvent and goes on to catalyze the reaction
of another substrate. This may explain why as little as 0.1 equiv.
of DBN can highly efficiently catalyze the regioselective
acylation without an additional base. In addition, from the three-
dimensional molecular structures (Figure 1), we find that DBN
has a face that is not sterically hindered, but DBU has relatively
large steric hindrance on both faces due to its larger ring, which
may be why only DBN is a suitable catalyst.
Then, we performed simple competition reactions to support our
proposed mechanism. When diols 12 and 15 and 1.0 equiv. of
their corresponding monohydric alcohol (53 and 54) are co-
reacted with 1.0 equiv. of acetic anhydride, the outcomes
support the H-bond-activated mechanism (Table 4, Entries 1-2).
No products from the monohydric alcohols were observed (53
and 54), while mono-acylated products 13 and 16 were obtained
from 12 and 15 in 80% and 78% isolated yields, respectively. As
suggested by the mechanism, only 1,2-diols and 1,3-diols could
form the stable double H-bonded intermediates that lead to
highly regioselective acylations. These results also support the
proposed mechanism in which DBN initiates the regioselective
acylation by forming two H-bonds.
According to the experiments with these substrates, this is a
highly efficient and relatively green regioselective acylation
method for carbohydrates and diols, but the catalytic mechanism
remained unclear. As with our previously reported TBAOAc- and
DIPEA- activated acylation reactions,[34, 35, 46] we sought to clarify
the mechanism by variable-temperature NMR experiments to
determine whether the substrates form strong H-bonds with the
catalysts.[47] The catalyst (0.2 equiv. of DBN or 0.2 equiv. of DBU
or without catalyst) was added to a solution of 1-phenyl-1,2-
ethanediol (10 mg) in dry CD3CN (0.5 mL), and then a series of
Scheme 2. Proposed DBN-catalyzed acylation mechanism.
Possible mechanism
R3
O
R3
O
Partial
1
N
DBN + (R3CO)2O
variable-temperature H NMR tests were performed from 20 °C
O
N
to 60 °C (Figure S4 to Figure S15 in the Supporting Information).
When no catalyst was added to the solution, 0.2 equiv. of DBU
was added, or 0.2 equiv. of DBN was added to the solution, the
transformation constants of the OH chemical shift as a function
of temperature were 3.4*10-3 K-1, 6.3*10-3 K-1 and 9.1*10-3 K-1,
respectively (Figures S1 to S3 in the Supporting Information).
These results prove that DBN and DBU form intermolecular H-
bonds with the substrate, as predicted in the previous work in
which TBAOAc formed intermolecular H-bonds with the
substrates.[34] This also means that the formation of strong H-
bonds between DBN and the substrates initiates the reaction,
and the experimental results and NMR studies better support the
double H-bond mechanism than the single H-bond mechanism.
Further experiments were performed to compare the H-bond
effects in the presence of 1.0 equiv. of Ac2O, 0.2 equiv. of DBN
or 0.2 equiv. of DBU (Figure S16 in the Supporting Information);
the H-bonds were found to be stronger, the H-bond is stronger,
and the hydroxyl-H resonances shifted downfield. By mixing
equal amounts of acetic anhydride and DBN and testing 1H NMR,
we find that a new carboxylate peak is formed quickly, which
indicates that the reaction mechanism may be catalyzed by
carboxylate ions as previously reported (Figure S17 in the
Supporting Information). When 0.3 equiv. of TBAOAc replaces
0.1 equiv. of DBN as catalyst, the conversion reaches 90% after
24 hours, this means DBN strongly activates and accelerates
these reactions.
f
e
R3
O
HO
R2
O
N
HO
R2
OH
1,2
1,2
R1
N
d R1
Cat.
a
+
R3COOH or DBN
Acyl reagent 1
N
N
N
R3
O
R3
N
H
H
O
H
O
H
O
O
O
R
O
Catalyzed Acylation
1,2
R1
1,2
O
R3
R2
R3
R2
R1
b
O
c
Less steric effect
N
f
N
Acyl reagent 2
Figure 1. 3D structures of DBN and DBU
Finally, we propose a simple mechanism by which DBN
catalyses the regioselective acylation by strong dual H-bonds in
Scheme 2. First, the catalyst (DBN) forms intermediate b, which
possesses strong H-bonds, with diols and carbohydrates. From
the control experiments, we can propose that partial DBN forms
carboxylate ions f with anhydride. Then, the acid anhydride or
DBN carboxylate ions f attacks the less hindered hydroxyl group
to selectively generate acylation product d and regenerate the
corresponding carboxylic acid or DBN. The catalyst (DBN) is
Table 4. Competitive acylation of hydroxyl groups.
Entry
1
Reactant
Product Isolated yield (%)
HO
Ph
OH
OH
HO
OAc
53
80
12
13
Ph
Ph
and
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10.1002/ejoc.201900776
European Journal of Organic Chemistry
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HO
OH
HO
OAc
OH
Doctoral Research Foundation of Xinyang Normal University
(Grant Number: 16070). The authors would like to thank Dr.
Qiuju Zhou and the Analysis and Testing Center of XYNU for
support with the NMR instruments.
2
78
15
54
16
and
Reaction conditions: 50 mg of substrate, 1 mL of EtOAc, 0.1 equiv. of
DBN, 1.0 equiv. of Ac2O, 40 °C, 8-12 h.
Keywords: DBN • EtOAc • acylation • H-bonding • carbohydrate
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European Journal of Organic Chemistry
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
R3
O
R3
The 1,5-diazabicyclo[4.3.0]non-
5-ene (DBN) -catalyzed, highly
efficient and relatively green
Carbohydrate Chemistry
O
O
O
R3
HO
R2
OH
Cat. (10~20 mol% DBN) HO
EtOAc, rt~40 o
R2
O
Bo Ren*, Mengyao Zhang,
Shijie Xu, Lu Gan, Li Zhang,
and Lin Tang*
1,2
R1
1,2
R1
C
regioselective
acylation
of
1. Green solvent, mild and highly efficient
2. Strong H-bond activated catalysis
3. Metal-free, low loading of catalyst
4. Homogeneous catalysis
carbohydrates and diols is firstly
developed. The hydroxyl groups
can be selectively acylated by
the corresponding anhydride in
75 - 93% yields for
over 25 examples
Page No. – Page No.
DBN-Catalyzed
Regioselective Acylation of
Carbohydrates and Diols in
Ethyl Acetate
EtOAc in the presence of
a
catalytic amount (as low as 0.1
equiv.) of DBN at room
temperature to 40 °C.
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