A facile preparation of peracylated α-aldopyranosyl chlorides with thionyl chloride and tin tetrachloride

Article abstract of DOI:10.1016/j.carres.2008.08.037

Aldopyranose peracetates react with thionyl chloride and tin tetrachloride, producing the corresponding peracylated aldopyranosyl chlorides in very good to excellent yields (88-100%) with exclusive α-anomeric selectivity and short reaction times. The use of peracylated sugars as the substrate in large scale reactions also proceeds in high yield. Crown Copyright

Full text of DOI:10.1016/j.carres.2008.08.037

Carbohydrate Research 343 (2008) 2989–2991
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Note
A facile preparation of peracylated
a-aldopyranosyl chlorides
with thionyl chloride and tin tetrachloride
Qingbing Wang, Jie Fu, Jianbo Zhang *
Department of Chemistry, East China Normal University, Shanghai 200062, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 June 2008
Received in revised form 28 August 2008
Accepted 31 August 2008
Available online 15 September 2008
Aldopyranose peracetates react with thionyl chloride and tin tetrachloride, producing the correspond-
ing peracylated aldopyranosyl chlorides in very good to excellent yields (88–100%) with exclusive
a-
anomeric selectivity and short reaction times. The use of peracylated sugars as the substrate in large scale
reactions also proceeds in high yield.
Crown Copyright Ó 2008 Published by Elsevier Ltd. All rights reserved.
Dedicated to Professor Yongzheng Hui on
the occasion of his 70th birthday
Keywords:
Stereoselective
Glycosyl chloride
Aldopyranosyl
SnCl
Thionyl chloride
4
Glycosyl halides are a very valuable and versatile group of syn-
thetic intermediates widely used in the field of carbohydrate
reaction time. The development of new methodologies for their
preparation has been a challenging task.
1
,2
chemistry. Although their reactivity is lower as synthetic donors,
glycosyl chlorides are superior to the bromides as their thermal
and chemical stabilities are higher. In addition, they can be easily
We first tried the conversion of 1,2,3,4,6-penta-O-acetyl-b-D-
glucopyranose (1, Scheme 1) using tin tetrachloride alone as the
chlorination reagent, as the glycosyl chloride has been postulated
as the intermediate in the tin tetrachloride-catalyzed glycosylation
with glycosyl acetate donors. When a solution of 1 in dichloro-
methane was treated with tin tetrachloride, and allowed to attain
ambient temperature over a period of 4 h, TLC revealed only the
presence of one component. If the reaction time is prolonged, the
starting material is not fully consumed and the yield of product de-
creases gradually. Under these conditions, a 76% yield of the
3
converted into O-glycosides, C-glycosylic compounds (C-glyco-
4
,5
6
sides) or glycals via the generation of intermediate anomeric
carbocations, radicals, or cabanions.6 Methods for the synthesis
7
of these important compounds include treatment of sugar perace-
8
–AcOH.9 The reaction of 1,2-trans-
tates with PCl
5
or with SOCl
2
peracetates with anhydrous titanium tetrachloride is also used fre-
1
0
quently, though the efficiency is very low. Thionyl chloride–zinc
chloride had earlier been suggested as a useful reagent combina-
tion for the formation of 1,2-cis-glycopyranosyl chlorides from
either of the corresponding anomeric peracetates.11 However, the
use heavy metal salts in these conversions is not environmentally
2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl chloride could be iso-
lated and identified.
Treatment of
for 1, furnished the corresponding
yield. However, peracetates of -mannopyranose,
nose, and -arabinopyranose hardly reacted and gave many by-
products when treated in the same manner as for 1. Ghosh et al.
synthesized a variety of -chlorides from the corresponding
monosaccharide peracetates, employing a mixture of thionyl chlo-
D
-galactopyranose peracetates, as was described
-chloride also in very good
-rhamnopyra-
a
-D
12
friendly. Peromo and Krepinsky used BCl
3
as chlorine source and
D
L
several groups utilized dichloromethyl methyl ether in the synthe-
sis of glycosyl chlorides.13 However, these reagents are powerful
lachrymators and are highly toxic. Thus, the reported methods
have limitations in terms of yield and selectivity of the products
or in respect of the stability, toxicity and cost of the promoter or
D
a
1
4
ride and BiOCl as a procatalyst. The method compares favorably
with all of those described hitherto, especially with respect to the
ease of availability of the reagents and simplicity of the reaction
conditions. However, the literature method uses BiOCl as the
promoter, which is not common in carbohydrate chemistry and
*
Corresponding author. Tel./fax: +86 21 62233853.
E-mail address: jbzhang@chem.ecnu.edu.cn (J. Zhang).
0
008-6215/$ - see front matter Crown Copyright Ó 2008 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.08.037

2
990
Q. Wang et al. / Carbohydrate Research 343 (2008) 2989–2991
R5
R5
R7 R1
R1
O
R7
SOCl (2 eq)/SnCl4(1 eq)
O
2
R
6
R
6
R
OAc
CH2Cl /amb.temp
2
3
R
3
R8
R2
R8R2Cl
R4
R4
α-only
1
2
3
5
6
R =R =R =OAc,R =R =R =R =H,R =CH OAc
2 3 6 1 4 5 8 7 2
R =R =R =OAc,R =R =R =R =H,R =CH OAc
2
1
3
3
3
5
6
6
1
2
1
4
4
4
6
5
5
8
8
7
7
7
2
2
R =R =R =OAc,R =R =R =R =H,R =CH OAc
R =R =R =OAc,R =R =R =R =R =H
2
8
R =R =R =OAc,R =R =R =R =R =H
1
4
6
1
3
5
7
8
Cl
SOCl (2 eq)/SnCl (1 eq)
H C
OAc
2
4
H C
3
3
O
O
AcO
AcO
AcO
CH Cl /amb. temp
2
2
AcO
OAc
OAc
α-only
4
AcO
AcO
OAc
OAc
OAc
O
OAc
O
O
OAc
SOCl (4 eq)/SnCl (2 eq)
O
2
4
O
AcO
O
AcO
AcO
OAc
CH Cl /amb. temp
2 2
OAc
OAc
AcO
AcO
Cl
α-only
7
Scheme 1.
Table 1
Synthesis of peracylated
a
-aldopyranosylchlorides
SnCl4
reaction time is very long. We, therefore, studied the use of thionyl
chloride as a procatalyst for the tin-mediated chlorination of sugar
peracetates. Fortunately, the conversion went well, and in good
yield and stereoselectivity, and the reaction proved to be very
reliable.
Entry
Products
SOCl2
(equiv)
Time
(h)
Yield
(%)
(equiv)
1
2
3
4
5
6
7
8
9
2,3,4,6-Tetra-O-acetyl-
glucopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-
glucopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-
glucopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-
glucopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-
a
-
-
-
-
-
D
D
D
D
D
-
-
-
-
-
-
-
-
-
1
—
2
2
2
—
2
2
2
2
2
2
2
2
2
2
4
4
4.0
1.3
1.5
2.0
4.5
1.2
1.2
3.0
3.0
4.0
4.0
1.0
2.0
1.5
2.5
8.0
8.0
76
a
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
98
To establish optimal conditions, a number of experiments were
performed. These experiments identified that reaction of 1,2,3,4,6-
98a
a
penta-O-acetyl-
2 equiv) in the presence of tin tetrachloride (1 equiv) in dry
dichloromethane at ambient temperature furnishes exclusively
the 2,3,4,6-tetra-O-acetyl- -glucopyranosyl chloride in 98% yield
Table 1, entry l). Similarly, 1,2,3,4,6-penta-O-acetyl- -galactopyr-
anose (entry 6), 1,2,3,4,6-penta-O-acetyl- -mannopyranose penta-
acetate (entry 8) and 1,2,3,4-tetra-O-acetyl- -rhamnopyranose
entry 10) were converted into the corresponding -glycosyl chlo-
ride derivatives quickly, and in very good to excellent yields. Pen-
tose sugars such as 1,2,3,4-tetra-O-acetyl- -xylopyranose (entry
2) and 1,2,3,4-tetra-O-acetyl- -arabinopyranose (entry 14) also
reacted efficiently with thionyl chloride in the presence of tin tet-
rachloride resulted in the formation of the corresponding -chlo-
D-glucopyranose 1 (1 equiv) with thionyl chloride
a
98b
82
(
a
a-D
galactopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-
galactopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-
galactopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-
mannopyranosyl chloride
2,3,4,6-Tetra-O-acetyl-
mannopyranosyl chloride
2,3,4-Tri-O-acetyl-
rhamnopyranosyl chloride
2,3,4-Tri-O-acetyl-
rhamnopyranosyl chloride
2,3,4-Tri-O-acetyl-
xylopyanosyl chloride
2,3,4-Tri-O-acetyl-
xylopyanosyl chloride
2,3,4-Tri-O-acetyl-
arabinopyanosyl chloride
2,3,4-Tri-O-acetyl-
arabinopyanosyl chloride
(
D
a-
D
98
D
a-D
98a
D-
L
(
a
a-
D
88
D
88a
a-D
1
D
1
0
1
a
-
L
-
88
a
1
a
-L
-
86a
100
95a
99
0
0
0
0
rides in almost quantitative yield. Similarly, reaction of 2 ,3 ,4 ,6 -
tetra-O-acetyl-b- -galactopyranosyl-(1?4)-1,2,3,6-tetra-O-acetyl-
-glucopyranose (lactose octaacetate, entry 16) proceeded
D
12
a-D-
D
1
3
4
a-D-
smoothly in the presence of thionyl chloride and tin tetrachloride.
Due to the larger size of the lactose octaacetate, we doubled the
amount of a thionyl chloride–tin tetrachloride complex. Using this
improved method, the yield of the desired product is much more
than the existing methods. Furthermore, there is no cleavage of
1
a-D-
15
16
a
-D
-
90a
0
0
0
0
1
5,16
2,3,6,2 ,3 ,4 ,6 -Hepta-O-acetyl-
a
-
-
90
the glycosidic bond compared to the reported methods.
It
lactosyl chloride
was found that a thionyl chloride–tin tetrachloride complex is a
mild chlorinating reagent and it can speed up the chlorination
reaction.
0
0
0
0
88a
17
2,3,6,2 ,3 ,4 ,6 -Hepta-O-acetyl-
a
lactosyl chloride
a
4
2
0-fold increase in scale of starting carbohydrate substrate (from 50 mg to 2 g).
00-fold increase in scale of starting carbohydrate substrate (from 50 mg to
In the reactions described above, thionyl chloride and SnCl
were added to the appropriate sugar (50 mg, 1 equiv) in CH Cl
4
b
2
2
10 g).
giving excellent yields of the product. To examine further the effi-
cacy of the present procedure, the scale of the reaction was in-
1
,2,3,4,6-penta-O-acetyl-
D-galactopyranose 2 from 50 mg to 2 g
creased for 1,2,3,4,6-penta-O-acetyl-D-glucopyranose
1
and
(
5.1 mmol). At this scale, the reactions proceeded efficiently fur-

Q. Wang et al. / Carbohydrate Research 343 (2008) 2989–2991
2991
nishing the desired product in excellent yield and with
a
-selectiv-
2.2. General procedure for chlorination of aldopyranose
peracetates a small scale
ity as in the case of 1 (Table 1, entries 3 and 7). Subsequently, com-
pounds 3, 4, 5, 6 and 7 were also further evaluated at larger scale
and in all cases the reactions furnished the desired products in
excellent yield, 88%, 86%, 95%, 90% and 88%, respectively. However,
as the reaction times were prolonged, a few by-products appeared
from TLC. The same methodology was also shown to be reliable on
scales as large as 10 g (26 mmol) of 1 (Table 1, entry 4).
To a solution of aldopyranose peracetate (50 mg, 1 equiv) in
dichloromethane (2 mL), was added first thionyl chloride (2 equiv)
and then SnCl (1 equiv). The mixture was stirred at ambient tem-
4
perature until completion (monitored by TLC, EtOAc–petroleum
ether as eluant). The reaction mixture was then poured onto cold
The conversion of monosaccharides and disaccharides to the
3
saturated NaHCO solution and the product was extracted with
corresponding
a
-chlorides proceeds irrespective of the stereo-
dichloromethane (3 ꢀ 10 mL). The combined organic layer was
chemistry of the anomeric and C-2 of the starting materials.
The results indicate that participation of the C-2 acetoxy group
washed with cold saturated salt water (1 ꢀ 15 mL) and then dried
2 4
over anhydrous Na SO . After evaporation of the solvent under
is not involved in the exclusive formation of the
One of the by-products in this process, acetyl chloride, was also
trapped successfully with p-nitrophenol as p-nitrophenyl acetate
a
-products.
vacuum, the crude residue was purified by column filtration,
where necessary. All products were characterized by NMR by com-
paring the physical data with those in the literature.
1
1,17–20
(
data not shown). Therefore, we proposed the mechanism is
similar to that proposed by Ghosh.14 In this mechanistic
scheme, the C-l acetoxy group is removed by thionyl chloride
Acknowledgments
and SnCl
4
via anomeric participation, and then attacked by
We thank the Analytic Center of East China Normal University
for data measurement. The authors gratefully acknowledge helpful
discussions from Dr. Wei Zou at NRCC and the kind donation of
some starting materials from Mr. Xiaohu Wang. The project was
supported by Shanghai Rising-Star Program (06QA14018) and the
Natural Science Foundation of Shanghai (04ZR14042).
the chloride ion at C-l with concomitant regeneration of SnCl4.
Thus, we chose to add thionyl chloride to the reaction system
first.
In summary, we have demonstrated a new, highly efficient ster-
eoselective synthesis of peracylated-
from aldopyranose peracetates using a mixture of thionyl chloride
and SnCl in anhydrous CH Cl . The advantages of the present pro-
cedure are that the method is simple and high yielding, and the
reactions proceed with exclusive -selectivity. The applied re-
agents, SnCl and thionyl chloride are easily available. Moreover,
a-aldopyranosyl chlorides
4
2
2
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distilled before use. TLC plates (10–40
applied to monitor reactions.
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