Sc(OTf)3-catalyzed acetolysis of 1,6-anhydro-β-hexopyranoses and solvent-free per-acetylation of hexoses

Article abstract of DOI:10.1016/S0040-4039(01)02253-5

Acetolysis of 1,6-anhydro-β-hexopyranoses and solvent-free per-acetylation of hexoses with acetic anhydride at room temperature in excellent yields employing 0.5 mol% scandium(III) trifluoromethanesulfonate as an extremely efficient catalyst are, respectively, described here.

Full text of DOI:10.1016/S0040-4039(01)02253-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 851–855
Sc(OTf)3-catalyzed acetolysis of 1,6-anhydro-b-hexopyranoses
and solvent-free per-acetylation of hexoses
Jinq-Chyi Lee,b Cheng-An Taic and Shang-Cheng Hunga,*
aInstitute of Chemistry, Academia Sinica, Taipei 115, Taiwan
bDepartment of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan
cDepartment of Chemistry, National Chung Cheng University, Chiayi 621, Taiwan
Received 29 October 2001; revised 20 November 2001; accepted 22 November 2001
Abstract—Acetolysis of 1,6-anhydro-b-hexopyranoses and solvent-free per-acetylation of hexoses with acetic anhydride at room
temperature in excellent yields employing 0.5 mol% scandium(III) trifluoromethanesulfonate as an extremely efficient catalyst are,
respectively, described here. © 2002 Elsevier Science Ltd. All rights reserved.
1,6-Anhydro-b-hexopyranoses are potent synthons
toward the synthesis of oligosaccharides, glycoconju-
gates, and natural products.1 Their [3.2.1]bicyclic skele-
tons ensure that not only two less protecting groups at
C1 and C6 are needed than their corresponding
pyranoses, but also none of the anomeric isomers are
required to be differentiated. After cleavage of the
internal acetal, further functional group transformation
and glycosylation at the C6 and C1 positions, respec-
tively, can be carried out. Typical acetolysis is mainly
used to open the 1,6-anhydro ring via treatment with
acetic anhydride in the presence of either excess tri-
fluoroacetic acid at room temperature2 or a catalytic
amount of triethylsilyl trifluoromethanesulfonate
(TESOTf) at 0°C.3 Acetic anhydride acts as both reac-
tant and solvent, which often causes tedious workup in
the neutralization processes. Since the traditional Lewis
acids (TESOTf, BF3/OEt2, TiCl4, etc.) are extremely
moisture sensitive, there is a need to search for new
catalysts. To tackle these problems, we have explored
herein a practical and mild procedure that is applicable
to a wide variety of substrates.
O-glycosylations,11 allylations,12 cyanations,13 ketaliza-
tions,14 esterifications,15 deacetylations,16 and so on.17
We describe herein our studies in acetolysis and acetyla-
tion–acetolysis of 1,6-anhydro-b-hexopyranoses with
minimum amounts of acetic anhydride at room temper-
ature using 0.5 mol% scandium(III) trifluoromethane-
sulfonate [Sc(OTf)3] as an extremely efficient catalyst.
The conditions and results are illustrated in Table 1. In
order to test the compatibility of different protecting
groups, the
D
-gluco derivatives 1 and 2 were examined
(entries 1 and 2), and the expected products 818 and 9
were isolated in almost quantitative yields, respectively.
The reaction rate of compound 2, which contains three
electron-donating protecting groups, is faster than 1. In
entry 3, 1,6-anhydro-b- -glucopyranose 3 was treated
D
with 4 equiv. of acetic anhydride, and the triacetate 1
was obtained in excellent yield in a very short period.
When the amount of acetic anhydride was increased to
12 equiv., one-pot acetylation–acetolysis was success-
fully carried out in 5 h. In the cases of the -manno (4),
D
D
-galacto (5),
L
-ido (6),1a and -altro (7)1a sugars, simi-
L
lar results were observed, respectively.18
Lanthanide and group III metal trifluoromethanesul-
fonates are known as valuable, water-stable, and
reusable Lewis acids.4 They exhibit excellent catalytic
activities in the Diels–Alder reactions,5 Mukaiyama–
aldol reactions,6,7 Michael reactions,7 Ferrier rearrange-
ments,8 Ene reactions,9 Friedel–Crafts acylations,10
The mechanism of one-pot acetylation–acetolysis of the
1,6-anhydro-b-hexopyranosyl sugars is proposed in
Scheme 1. Sc(OTf)3 seems to be involved in two consecu-
tive cycles. In the first acetylation-cycle, acetic anhy-
dride is activated by Sc(OTf)3, perhaps forming a polar-
ized complex 14, which is then rapidly attacked by the
free hydroxyl group of the sugar molecule 15 to gener-
ate two charged species 16 and 17. A rapid proton
exchange takes place between the two to furnish the
acetate 18 and acetic acid, liberating the Lewis acid in
Keywords: acetolysis; acetylation; Sc(OTf)3; carbohydrates.
* Corresponding author. Fax: 886-2-2783-1237; e-mail: schung@
chem.sinica.edu.tw
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02253-5

852
J.-C. Lee et al. / Tetrahedron Letters 43 (2002) 851–855
Table 1. Sc(OTf)3-catalyzed acetolysis of 1,6-anhydrohexopyranoses with acetic anhydride at room temperature
entry
1
SM
Ac2O (eq) t (h)
product
OAc
yield (%)
>95
AcO
O
O
AcO
AcO
4
4
5.5
O
O
O
OAc
OAc
OAc
OAc
AcO
8
1
BnO
OAc
O
O
BnO
BnO
2
3
4
5
6
7
1
>95
OBn
OBn
BnO
9
2
HO
O
4
<0.2
5
>95
>95
1
8
OH
HO
12
3
HO
HO
AcO
AcO
OAc
O
O
15
15
5
5
5
>95
>95
>95
>95
O
O
AcO
OAc
OAc
OH
10
4
OAc
O
AcO
AcO
HO
OH
O
OAc
HO
11
5
OBn
O
AcO
OAc
O
HO
BnO
20
24
BzO
AcO
OBz
O
12
6
7
HO
OBn
O
O
AcO
AcO
OAc
BnO
5
BzO
O
OBz
13
its free form. With the data in hand, it appears that the
progress of the second acetolysis-cycle needs a higher
concentration of acetic anhydride and a prolonged time
scale. The ring oxygen atom at C6 captures the acyloin
ion from the complex 14 to form the positively charged
intermediate 19 and its counter ion 17. This highly
unstable species 19 readily undergoes cleavage of the
C1ꢀO6 bond to relieve the ring strain generating a new
positive charge at the anomeric center of the pyranosyl
compound 20, which is then readily attacked by 17 to
deliver the fully acylated sugar 21 and the Lewis acid in
its original form.
Sc(OTf) ,15a,b In(OTf) ,15c Bi(OTf) ,15d or V(O)-
−
−
3
−
3
(OTf)2-catalyzed19 esterifications of al3cohols with acid
anhydrides in a variety of solvents have been reported.
However, treatment of
D-glucose with acetic anhydride
General procedure of acetolysis and per-acetylation. A
mixture of starting material, fleshly dried scandium
trifluoromethanesulfonate (0.5 mol%), and acetic anhy-
dride was stirred at room temperature under nitrogen
in dichloromethane in the presence of 0.5 mol%
Sc(OTf)3 for 2 days afforded a mixture of esters and
starting material. Since acetylation of 3 in neat condi-

J.-C. Lee et al. / Tetrahedron Letters 43 (2002) 851–855
853
O
HO
O
15
Sc(OTf)3
δ-
O
O
O
O-
Sc(OTf)3
O
+
O
δ+
14
+
O
O
O
H
16
17
I
O
O
O
O
+
AcOH
AcO
O
OAc
O
18
Sc(OTf)3
AcO
Ac2O
OAc
21
17
OAc
O
14
II
AcO
+
20
+
O
Ac
AcO
17
O
19
Scheme 1.
Table 2. Sc(OTf)3-catalyzed solvent-free per-acetylation of hexoses with acetic anhydride at room temperature
Ac2O (eq.)
entry
1
hexose
t (h)
product
yield (%)
OH
O
HO
HO
8
4.5
1.5
5.1
6
99
96
OH
OH
22
HO
HO
HO
OH
O
2
3
4
5
1
91
88
5.1
5.1
10
11
OH
OH
23
OH
O
HO
6.5
HO
OH
24
OAc
OAc
OH
OH
O
O
<10min
4.5
4.1
4.1
78
92a
OAc
OH
25
AcO
HO
27
OH
OAc
O
O
5
0.5
97
HO
AcO
HO
26
AcO
28
OH
OAc
a The reaction was carried out at 0 oC.

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J.-C. Lee et al. / Tetrahedron Letters 43 (2002) 851–855
atmosphere. The amount of acetic anhydride and reac-
tion time are listed in Tables 1 and 2. After the reaction
is done, methanol was added to quench the rest of
acetic anhydride, and the whole solution was kept
stirring at room temperature for another 0.5 h. The
resulting mixture was concentrated in vacuo to remove
methyl acetate and acetic acid, and the residue was
dissolved in ethyl acetate followed by sequential wash
with saturated sodium bicarbonate aqueous solution,
water, as well as brine. The organic phase was dried
over magnesium sulfate, filtered and concentrated in
vacuo to afford the expected product in excellent yield.
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Acknowledgements
We thank Professor Chun-Chen Liao for his helpful
discussions and the National Science Council of Repub-
lic of China for financial support.
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6.32 (d, J=1.7 Hz, 1.2H), 6.16 (s, 1.0H), 5.48 (dd, J=4.9,
1.7 Hz, 1.2H), 5.40 (dd, J=3.7, 1.6 Hz, 1.1H), 5.23–5.19
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