Dehydrative glycosylation in water using a Broonsted acid-surfactant-combined catalyst

Article abstract of DOI:10.1246/cl.2006.238

Bronsted acid-surfactant-combined catalyst, dodecylbenzenesulfonic acid (DBSA), was used in catalytic dehydrative glycosylation reactions in water. 1-Hydroxy sugars, such as O-benzyl-protected furanose and pyranose, reacted with alcohols and a nitrogen nu

Full text of DOI:10.1246/cl.2006.238

238
Chemistry Letters Vol.35, No.2 (2006)
Dehydrative Glycosylation in Water Using a Brꢀnsted Acid–Surfactant-Combined Catalyst
Naohiro Aoyama and Shu¯ Kobayashiꢀ
Graduate School of Pharmaceutical Sciences, The University of Tokyo, The HFRE Division, ERATO,
Japan Science and Technology Agency (JST), Hongo, Bunkyo-ku, Tokyo 113-0033
(Received November 17, 2005; CL-051429; E-mail: skobayas@mol.f.u-tokyo.ac.jp)
Brꢀnsted acid–surfactant-combined catalyst, dodecylben-
general, D-ribofuranose was prepared from the corresponding
methyl D-ribofuranoside via hydrolysis under acidic conditions.6
Although the reactivities of 1c and 1d were lower than those of
1a and 1b respectively, direct use of methyl furanosides allowed
the omission of the tedious hydrolysis steps.
N-Protected ribofuranosylamines are important scaffolds for
the synthesis of 2-deoxy-D-ribonucleotides, a unit of DNA or
RNA. The present reaction system could be applied to N-glyco-
sylation of ribofuranose as well (Table 2). A nitrogen nucleo-
phile such as benzyl carbamate reacted with 1a or 1b to give
the corresponding product in good yield.
zenesulfonic acid (DBSA), was used in catalytic dehydrative
glycosylation reactions in water. 1-Hydroxy sugars, such as O-
benzyl-protected furanose and pyranose, reacted with alcohols
and a nitrogen nucleophile in the presence of a catalytic amount
of DBSA to afford the desired adducts in good yields. Detailed
study of the glycosylation of 2-deoxy-D-ribofuranose showed
that hydrophobicity of the substrates was important to attain
higher yields. Regarding the ꢀ=ꢁ selectivities, D-ribose and
D-mannose derivatives gave the products in high ꢁ- and ꢀ-selec-
tivities, respectively.
Next, we examined the effects of varying the hydrophobicity
of alcohols (Table 3). When alcohols having various length of
alkyl chains were used, the alcohols with longer alkyl chains
afforded the corresponding glycosides in higher yields. A similar
tendency was observed in the DBSA-catalyzed dehydrative
esterifications in water.7
The origin of the ꢀ=ꢁ ratio in dehydrative glycosylation
in water was investigated in a model reaction of 1a with 2a
(Table 4). The ꢀ=ꢁ ratio was found to be almost unchanged dur-
ing the reaction course. This result may suggest that the glyco-
sylation reactions proceed under kinetic control.8
Recently, organic reactions in water have attracted much
attention in synthetic organic chemistry.1 Water is a cheap, safe,
and environmentally benign solvent. In addition, water has
unique physical and chemical properties (high polarity, high
boiling point, and tight hydrogen-bonding network), which
sometimes induce reactivities and selectivities that can not be
attained in organic solvents.
Although various efficient catalytic systems in water have
been developed so far, dehydration reactions in water are among
the most challenging research topics. In the course of our inves-
tigations on dehydration reactions in water, we have recently
reported DBSA (dodecylbenzenesulfonic acid)-catalyzed dehy-
dration reactions (esterification, etherification, thioetherification,
and dithioacetalization) in water.2 In these reactions, DBSA and
substrates form emulsion droplets whose interior is hydrophobic
enough to exclude water molecules generated during the reac-
tions. To expand the utility and applicability of this work, we
next focused on dehydrative glycosylation in water. Brꢀnsted
acid-catalyzed dehydrative glycosylation of 1-hydroxy sugars
with alcohols is among the most important and efficient reactions
to prepare glycosides.3 Although the reaction is known as
Fischer glycosylation, excess amounts of Brꢀnsted acids or alco-
hols are necessary in many cases.4 Therefore, further exploration
of a more efficient process is desired. Here, we report DBSA-cat-
alyzed dehydrative glycosylation in water. Under the reaction
conditions, O-protected furanoses and pyranoses reacted with
hydrophobic alcohols in water to afford the desired products in
good yields.
Finally, several examples of dehydrative glycosylation of
pyranose in water were examined (Table 5). As for O-benzyl-
protected glucopyranose 4a, the reaction mixture did not form
Table 1. DBSA-catalyzed dehydrative glycosylation of D-ribo-
furanose
BnO
BnO
DBSA (10 mol%)
H2O
O
O
OR2
+
OnC12H25
nC12H25OH
(1.5 equiv)
2a
OBn R1
1
OBn R1
3
Glycosyl donor
R1
Entry
Condition Product Yield/% ꢀ=ꢁ
R2
1
2
3
4
H
OBn
H
H
H
1a 40 ꢁC, 3 h
1b 40 ꢁC, 12 h
3a
3b
3c
3d
88
83
73
82
36/64
9/91
Me 1c 40 ꢁC, 12 h
39/61
6/94
OBn Me 1d 80 ꢁC, 12 h
First, we carried out the reactions using 1-dodecanol 2a as a
glycosyl acceptor (Table 1). In the presence of 10 mol % of
DBSA,5 the reaction with O-benzyl-protected 2-deoxy-D-ribo-
furanose 1a proceeded smoothly albeit with low ꢀ=ꢁ selectivity
(Entry 1). While O-benzyl-protected D-ribofuranose 1b also re-
acted with 2a to afford the desired product in high ꢁ-selectivity
(Entry 2), a longer reaction time was needed due to its low reac-
tivity. It is noteworthy that not only D-ribofuranose but also
methyl D-ribofuranoside reacted with 2a; in the latter case the
reaction proceeded by releasing methanol (Entries 3 and 4). In
Table 2. Reaction with benzyl carbamate
O
BnO
BnO
O
DBSA (10 mol%)
O
O
+
OH
N
OBn
BnO
NH2
H
H2O
OBn R1
OBn R1
(1.5 equiv)
Entry
R1
Condition
40 ꢁC, 3 h
60 ꢁC, 18 h
Yield/%
1
2
H
OBn
1a
1b
75a
70a
aꢀ=ꢁ Selectivity was not determined.
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.2 (2006)
239
Table 3. Effect of the hydrophobicity of glycosyl acceptors
reacted with hydrophobic alcohols in water to afford the desired
products in good to high yields. It is note that dehydrative glyco-
sylation proceeded smoothly in water. Detailed study of the gly-
cosylation of 2-deoxy-D-ribofuranose showed that hydrophobic-
ity of substrates was important to attain higher yields. Regarding
the ꢀ=ꢁ selectivities, D-ribose and D-mannose derivatives were
found to give the corresponding products in high ꢁ- and ꢀ-selec-
tivities, respectively. Further investigations on stereoselective
dehydrative glycosylation in water are in progress.
BnO
BnO
DBSA (10 mol%)
O
O
OH
OR
+
ROH
H2O, 40 °C, 1 h
(1.5 equiv)
OBn
OBn
3
1a
2
Entry
ROH
Yield/%
ꢀ=ꢁ
1
2
3
4
5
C2H5OH
n-C3H7OH
n-C4H9OH
15
28
50
63
85
42/58
39/61
40/60
38/62
35/65
This work was partially supported by a Grant-in-Aid for
Scientific Research from Japan Society of the Promotion of
Science (JSPS). N.A. thanks JSPS for the position of a fellow-
ship for Japanese Junior Scientists.
n-C5H11OH
n-C12H25OH
Table 4. Reaction profile
References and Notes
BnO
BnO
1
2
3
For a review, see: C.-J. Li, T.-H. Chan, Organic Reactions
in Aqueous Media, John Wiley & Sons, New York, 1997;
P. A. Grieco, Organic Synthesis in Water, Blackie Academic
and Professional, London, 1998.
DBSA (10 mol%)
O
O
OnC12H25
nC12H25OH
(1.5 equiv)
2a
+
OH
H2O, 40 °C
OBn
OBn
1a
3a
a) K. Manabe, X.-M. Sun, S. Kobayashi, J. Am. Chem. Soc.
2001, 123, 10101. b) K. Manabe, S. Iimura, X.-M. Sun, S.
Kobayashi, J. Am. Chem. Soc. 2002, 124, 11971. c) S.
Kobayashi, S. Iimura, K. Manabe, Chem. Lett. 2002, 10.
For recent examples of catalytic glycosylations of 1-hydroxy
sugars, see: a) T. Mukaiyama, K. Matsubara, M. Hora,
Synthesis 1994, 1368. b) H. Uchiro, K. Miyazaki, T.
Mukaiyama, Chem. Lett. 1997, 403. c) H. Uchiro, T.
Mukaiyama, Chem. Lett. 1996, 79. d) H. Uchiro, T.
Mukaiyama, Chem. Lett. 1996, 271. e) K. Toshima, H.
Nagai, S. Matsumura, Synlett 1999, 1420. f) J. Inanaga, Y.
Yokoyama, T. Hashimoto, J. Chem. Soc., Chem. Commun.
1993, 1090. g) B. Wagner, M. Heneghan, G. Schnabel,
B. Ernst, Synlett 2003, 1303. h) T. Suzuki, S. Watanabe, T.
Yamada, K. Hiroi, Tetrahedron Lett. 2003, 44, 2561. i) H.
Jona, H. Mandai, T. Mukaiyama, Chem. Lett. 2001, 426.
j) D. Gin, J. Carbohydr. Chem. 2002, 21, 645.
Entry
Time/h
Yield/%
ꢀ=ꢁ
1
2
3
4
0.33
44
85
88
91
39/61
35/65
36/64
38/62
1
3
12
Table 5. DBSA-catalyzed glycosylation of pyranose
O
O
DBSA (10 mol%)
H2O
nC12H25OH
(2 equiv)
OnC12H25
+
OH
2a
5
4
Pyranose
Temperature/°C
Time/h
Yield/%
10
α/β
reflux
150a
150a
6
6
60/40
61/39
61/39
BnO
O
BnO
4a
55
4
5
E. Fischer, Chem. Ber. 1893, 2400.
BnO
BnO OH
For DBSA-catalyzed carbon-carbon bond-forming reactions,
see: a) K. Manabe, S. Kobayashi, Org. Lett. 1999, 1, 1965.
b) K. Manabe, Y. Mori, S. Kobayashi, Synlett 1999, 1401.
c) K. Manabe, Y. Mori, S. Kobayashi, Tetrahedron 2001,
57, 2537.
12
66
OBn
reflux
reflux
12
48
70
67
55/45
61/39
BnO
O
4b
4c
BnO
BnO
6
a) S. Tejima, H. G. Fletcher, Jr., J. Org. Chem. 1963, 28,
2999. b) K. Jansson, G. Noori, G. Magnusson, J. Org. Chem.
1990, 55, 3181. c) O. R. Martin, C. A. V. Hendricks, P. P.
Deshpande, A. B. Cutler, S. A. Kane, S. P. Rao, Carbohydr.
Res. 1990, 196, 41. d) N. Hossain, H. van Halbeek, E. D.
Clercq, P. Herdewijin, Tetrahedron 1998, 54, 2209.
For example, lauric acid and 3-phenyl-1-propanol gave the
ester in 84% yield, whereas lauric acid and ethanol gave
the ester in 15% yield (10 mol % of DBSA in water at
40 ꢁC). For details, see Ref. 2b.
When each isolated anomeric product was treated under the
reaction conditions, anomeric isomerization occurred. While
the ꢀ anomer gave an anomeric mixture with the ratio of
ꢀ=ꢁ ¼ 49=51, the ꢁ anomer provided the ratio of ꢀ=ꢁ ¼
29=71 during 12 h.
BnO OH
OBn
O
reflux
reflux
12
48
51
64
87/13
94/6
BnO
BnO
OH
aThe reaction was carried out in a sealed tube.
7
8
emulsion droplets under reflux conditions, presumably because
of its high melting point. The reaction proceeded by increasing
the reaction temperature to 150 ꢁC in a sealed tube. On the other
hand, O-benzyl-protected galactopyranose 4b and mannose 4c
are colorless oils at room temperature, and the reaction with
2a gave the corresponding products in moderate yields under
reflux conditions. It should be noted that high ꢀ-selectivity
was attained in the reaction of 4c.9
9
4c reacted with cyclohexanol (reflux, 48 h) to afford the
desired glycoside in 26% yield (ꢀ=ꢁ ¼ 92=8).
In conclusion, O-benzyl-protected furanoses and pyranoses
Published on the web (Advance View) January 25, 2006; DOI 10.1246/cl.2006.238