Permethacrylated carbohydrates: synthesis and reactivity in glycosidation reaction

Article abstract of DOI:10.1016/j.tet.2009.08.083

The synthesis of various permethacrylated mono- and disaccharides in acceptable yields is reported. The reactivity of these unusual polymerizable compounds has been investigated in diverse glycosidation reaction conditions. New original polymerizable dono

Full text of DOI:10.1016/j.tet.2009.08.083

Tetrahedron 65 (2009) 9395–9402
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Permethacrylated carbohydrates: synthesis and reactivity in
glycosidation reaction
*
Christelle Zandanel, Charles Mioskowski, Rachid Baati , Alain Wagner
University of Strasbourg, Laboratory of Functional ChemoSystems, Faculty de Pharmacy, CNRS-UMR 7199, 74 Route du Rhin, 67000 Illkirch, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 June 2009
Received in revised form 27 August 2009
Accepted 29 August 2009
Available online 4 September 2009
The synthesis of various permethacrylated mono- and disaccharides in acceptable yields is reported. The
reactivity of these unusual polymerizable compounds has been investigated in diverse glycosidation
reaction conditions. New original polymerizable donor sugars have been prepared successfully in good to
excellent yields.
Ó 2009 Elsevier Ltd. All rights reserved.
In the memory of Dr. C. Mioskowski
OAcr
OAcr
1. Introduction
OAcr
OAcr
O
OAcr
O
O
O
O
AcrO
AcrO
OR
AcrO
AcrO
AcrO
OR
OR
AcrO
OR
AcrO
OR
AcrO
OAcr
OAcr
OAcr
OAcr
As a part of our ongoing program devoted to the development of
molecular imprinted polymers (MIP), functionalized polymerizable
mono- and disaccharides (Fig. 1) were needed.1 To date different
approaches have been employed for the preparation of polymer-
izable carbohydrates. Of particular interest, is the strategy based on
the use of styrilboronic esters described for monosaccharides by
Wulff et al.2 This approach, however, is limited to 1,2-cis diols and
suffers from severe drawbacks such as their sensitivity toward
aqueous hydrolysis, precluding their use in suspension, pre-
cipitation or emulsion polymerization techniques. Glucopyrano-
side-6-(mono)acrylate derivatives have been also synthesized, as
the functional component for the preparation of diverse imprinted
matrix.3 The synthesis of cyclodextrin methacrylate monomers,
cinnamic carbohydrates esters, as well perallylated sugars have also
been mentioned in the literature.4–6 However, efficient methods for
the preparation mono- and disaccharides polyacrylates remain
elusive, and have received only little attention.7 The development
of new approaches for the preparation of such molecules still
stands as an important synthetic challenge. Such compounds not
only represent fundamentally new molecular structures, but also
offer the potential opportunity for creating novel functional
polymers.
OAcr
R = R1 : 1
R = R2 : 2
R = R3 : 3
R = R4 : 4
R = R1 : 5
R = R1 : 8
R = R3 : 9
R = R1 : 11
R = R2 : 12
R = R1 : 13
R = R2 : 14
R = R3 : 6
R = R4 : 7
R = R4 : 10
OAcr
O
OAcr
OAcr
OAcr
O
OAcr
OAcr
O
AcrO
AcrO
O
OAcr
O
OAcr
AcrO
AcrO
OR
AcrO
OR
O
AcrO
O
O
O
OAcr
OR
AcrO
AcrO
OAcr
AcrO
OAcr
OAcr
R = R1 : 15
R = R2 : 16
R = R1 : 17
R = R3 : 18
R = R4 : 19
R = R1 : 20
R = R3 : 21
O
-Acr
R1 =
R2 =
OAcr
OAcr
O
AcrO
AcrO
10 OBn
O
OAcr
AcrO
O
H
R3 =
R4 =
AcrO
OAcr
Herein we wish to report the development of new methodolo-
gies for the synthesis of permethacrylated carbohydrates (Fig. 1),
and their reactivity toward direct glycosidation reactions.
Due to the potential propensity of permethacrylated sugars to
polymerize, we envisioned first to use mild experimental
NH
CCl3
R = R1 : 22
Figure 1. General structure of mono- and disaccharides targeted in this study
(Acr¼Methacryl).
conditions to guide our optimization strategy. Inspired by the
profuse literature for sugar peracetylation reactions, we tested
conditions that employ weak bases such as triethylamine/DMAP
* Corresponding author. Tel.: þ33 368 854 301; fax: þ33 368 854 306.
E-mail address: baati@bioorga.u-strasbg.fr (R. Baati).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.08.083

9396
C. Zandanel et al. / Tetrahedron 65 (2009) 9395–9402
and sodium acetate in the presence of acrylic anhydride at room
temperature.8,9 The literature survey revealed also that per-
acetylation of sugar in solution, might afford two regioisomers, the
pyranose and furanose forms by virtue of the existing mutarotation
spectrum, the a anomer 5 being the major product (undetermined
ratio). No traces of the furanose regioisomer were detected. The
permethacrylated xylose 5 was best obtained when Method 2 was
used. In these conditions, the pure
exclusively, with 71% of isolated yield. To reverse the
selectivity toward the desired -pyranose anomer, the per-
a
-pyranose form is formed
equilibrium. Moreover, the
a
/b
ratio of the pyranose forms appears
a
stereo-
to depend on the nature of the base used for the peracetylation
reactions.10,11 The purpose of our optimization study, for the per-
methacrylation of sugars was directed to favor, at best, the forma-
b
methacrylation of xylose was tested in more drastic conditions
with Method 4. Unfortunately, a complex mixture of the pyranose/
furanose forms was obtained, as identified upon analysis of the
crude 13C NMR spectrum of the reaction. Indeed, the signal at
98.6 ppm was identified and assigned, unambiguously, to the
furanose anomeric carbon form (major isomer). Consequently, only
Method 2 could be used for the efficient synthesis of per-
tion of the
b-pyranose anomer, which is, theoretically the most
reactive for further envisioned direct glycosidation reactions.
2. Permethacrylation reactions: results and discussions
At first, the permethacrylation reaction was tested for glucose in
different conditions. In Method 1, the reaction was performed at
room temperature for 12 h, in the presence of Et3N/DMAP as base
and catalyst, and with methacrylic anhydride in DCM. The reaction
was monitored by TLC, and a usual work up procedure was
employed (see Experimental section). The crude product of the
reaction was then simply purified by column chromatography us-
ing silica gel. In the second method (Method 2), the reaction, as well
as the work up procedure, were carried out in the same conditions
as Method 1, except for the temperature that has been fixed at
ꢀ10 ꢁC. Finally, two other conditions were also tested. In Methods 3
and 4, the reactions were performed in neat conditions, and in the
presence of NaOAc as base, and with methacrylic anhydride. The
reaction in Method 3 was performed at 110 ꢁC for 30 min, while
Method 4 was conducted at 140 ꢁC for 5 min and under microwave
conditions.12 In the latter cases, no work up procedure was neces-
sary and direct purification was effected.
methacrylated xylose as the
The treatment of mannose under Method 1 permethacrylation
conditions gave selectively the pure -pyranose form 8, however,
with a modest isolated yield of 23% (Table 1, entry 3). Because of the
anomeric effect, the -pyranose is largely preferred compared to
the -pyranose anomer. Furthermore, while the peracetylation of
mannose is reported to be problematic and unselective at higher
temperature (complex mixture of pyranose/furanose forms),9a we
decided, however, to perform the permethacrylation reaction at
140 ꢁC under microwave (Method 4). Unexpectedly, the reaction
was highly regioselective in delivering the pyranoside form 8
a-pyranoside 5.
a
a
b
exclusively, as the initially unwanted
a-anomer (25% of yield). Even
though the reaction did not afford the desired
b
-anomer, it is
worthwhile to note the high stereoselectivity of the transformation.
Ribose permethacrylation at room temperature using Method 1
afforded after 12 h of reaction a complex mixture containing both
the pyranose and the furanose regioisomers (Table 1, entry 4). Even
though the furanose form was the major compound (undetermined
In the case of glucose, the b/a ratio of the pyranose form was
determined based on the 1H NMR of the purified product by
quantitative integration of the characteristic anomeric proton
signals of permethacrylated glucose at 5.87 ppm for anomer
ratio) the product was contaminated with the a and b-pyranose
anomers. The decrease of the temperature to ꢀ10 ꢁC for 12 h by
using Method 2, delivered cleanly and selectively the pyranose
b
(J¼8.0 Hz), and at 6.46 ppm for anomer
a
(J¼4.0 Hz). As shown in
form of permethacrylated ribose 11, with a favorable b/a ratio of 5/1,
Table 1, for glucose as substrate (Table 1, entry 1), we were pleased
to observe that, all the four methods afforded the permethacrylated
glucose as the pyranose isomer 1, exclusively, in an acceptable
isolated yields (40–59%). The undesired permethacrylated furanose
regioisomer was not detected. The better
form is obtained when Method 4 was used (
the microwave influences the mutarotation equilibrium toward the
formation of -glucopyranoside is known, and is probably due to
the increase of the temperature.13 Identically, when the reaction is
performed at 110 ꢁC (Method 3) the
ratio of the pyranose form
in 43% of isolated yield. The fact, that the pyranose is obtained
exclusively, is ascribed to the temperature effect on the ribose
mutarotation blockade, known to favor the pyranose form.14 As
a consequence, permethacrylation at higher temperature (Methods
4) was anticipated to be tedious. Expectedly, under microwave
conditions at 140 ꢁC for 5 min a complex mixture was obtained
with the undesired furanoside as the major compound.
b
/a
ratio of the pyranose
b/a
¼5/1). The fact that
b
In the case of galactose the application of Method 1 afforded,
with a disappointing selectivity, a 2/1 mixture of pyranose/furanose
b
/a
regioisomers 13 in 69% of yield. Indeed, the
b
/a
ratio of the major
remains high (
b
/
a
¼4/1), although it is slightly decreased. In sharp
pyranose form was unsatisfactory (
b/a
¼2/1) (Table 1, entry 5). The
contrast, lower temperatures (ꢀ10 ꢁC, Method 2) favored, as major
decrease of the reaction temperature to ꢀ10 ꢁC or the use of
Method 3 at 110 ꢁC, did not improve both, the pyranose/furanose
selectivity and the chemical yields were decreased (Methods 2 and
3). In sharp contrast, increasing the temperature to 140 ꢁC under
microwave irradiation gave, albeit in modest yield (15%), as the
anomer the
a
-pyranose 1 (
b/a
¼1/4). The reaction carried out at
room temperature was the less selective and a 1/1 (b/a) ratio of the
pyranoside 1 was formed.
To extend the scope of the permethacrylation conditions to
a wider set of saccharides, xylose, mannose, ribose, galactose,
maltose, lactose, cellobiose, and saccharose were then tested
(Table 1). As a general experimental observation, when the re-
actions afforded permethacrylated sugars, including the desired
product, the initial heterogeneous suspension always became
homogeneous, most likely due to the increased solubility of the
products, suggesting total conversion of the starting materials. As
mentioned previously for glucose, the furanose/pyranose ratio
major product, the desired
of the furanose regioisomer and 20% of the
When maltose disaccharide was subjected to Method 1 per-
methacrylation conditions, the -pyranose form 15 was success-
fully obtained as the predominant product with 42% of yield, and
a good ratio (5/1) (Table 1, entry 6). It is of paramount impor-
tance to point out that the
configuration of the 4C1 linkage of the
b-galactopyranoside 13, along with 5%
a-galactopyranoside.
b
b/a
a
disaccharide was preserved during the reaction, and no isomeri-
zation of the anomeric stereocenter was observed in these condi-
tions. Since the desired product was obtained in a satisfactory yield,
and the preservation of the stereochemical integrity of 4C1, the
other three initially envisioned conditions were not tested.
The permethacrylation of lactose under Method 1 conditions
was not total as could be observed by the heterogenic suspension of
the reaction mixture even after 12 h of reaction (Table 1, entry 7).
and the b/a ratio of the pyranose form, for all the new compounds,
were determined based on the integration of the specific signals
on the 1H NMR of the purified products. For xylose, lactose, ribose,
and saccharose, HSQC NMR analysis was necessary for the accu-
rate identification of the anomeric proton signals.
For xylose (Table 1, entry 2), application of Method 1 afforded
a mixture of b/a
pyranose 5 as evidenced by analysis of the 13C NMR

Table 1
Permethacrylation of carbohydrates
AcrO
AcrO
O
O
conditions
O
OAcr
+
OAcr
OH
AcrO
HO
AcrO
Furanoside (Fur)
Pyranoside (Pyr)
Entry
SMa
Glc
Product
Method 1
Yield (%)
Method 2
Method 3
Method 4
Yield (%)
Pyr/Fur
1/0
Pyr
1/1
b
/
a
Yield (%)
Pyr/Fur
1/0
Pyr
1/4
b
/a
Yield (%)
Pyr/Fur
1/0
Pyr
4/1
b
/a
Pyr/Fur
Pyr b/a
OAcr
O
AcrO
AcrO
1
59
40
40
41
1/0
5/1
OAcr
OAcr
OAcr
1
O
AcrO
AcrO
2
3
4
5
6
7
8
Xylose
Man
d
1/0
a
Major
71
1/0
0/1
Not tested
Not tested
Not tested
28
d
Furanoside major
d
OAcr
5
OAcr
OAcr
O
AcrO
AcrO
23
1/0
0/1
Not tested
25
1/0
0/1
8
OAcr
OAcr
O
AcrO
Ribose
d
Furanoside major
d
43
1/0
5/1
d
Furanoside major
d
OAcr
OAcr
11
OAcr
OAcr
O
OAcr
Gal
69
2/1
1/0
1/0
7/4
5/1
1/3
25
2/1
1/1
2/1
1/1
15
95/5
5/1
AcrO
OAcr
13
OAcr
O
AcrO
AcrO
OAcr
Glc (
a
1/4) Glc
1/4) Glc
42
Not tested
Not tested
Not tested
Not tested
Not tested
Not tested
32
O
AcrO
O
OAcr
OAcr
AcrO
OAcr
15
OAcr
OAcr
O
OAcr
O
Gal (
b
36
60
0/1
d
AcrO
AcrO
O
AcrO
OAcr
17
OAcr
OAcr
O
AcrO
AcrO
AcrO
O
O
Glc (
b1/4) Glc
OAcr
OAcr
Traces
Not tested
1/0
1/0
AcrO
20
(continued on next page)

9398
C. Zandanel et al. / Tetrahedron 65 (2009) 9395–9402
The
a
-pyranose form 17 was isolated predominantly in 36% of yield
¼1/3). As observed for maltose, the stereochemistry of the
anomeric stereocenter between both galactose and glucose units
was preserved. To increase the proportion of -pyranose anomer of
(b/a
b
17, the permethacrylation of lactose was envisioned at higher
temperature with Method 3. Unfortunately, these drastic condi-
tions did not allow the formation of the desired
contrast, we observed the exclusive formation of a
the furanose regioisomer in 60% of yield (undetermined
b
-pyranose form. In
mixture of
ratio).
b/a
b/a
This somehow interesting result, but disappointing for our pur-
poses, excluded Method 4 as a potential alternative for the for-
mation of the b-pyranose form of the reducing sugar, due to the low
selectivity induced by high temperatures.
While only traces of the desired product (20) was detected for
the permethacrylation of cellobiose at room temperature, with
Method 1 (Table 1, entry 8), the use of more drastic conditions
(Method 4), afforded, selectively and unexpectedly, the b-pyranose
form 20 in an acceptable yield of 32%. This lack of reactivity
exhibited at room temperature for cellobiose was also noticed for
saccharose (Table 1, entry 9), which was totally unreactive under
Method 1 conditions. The use of higher temperature by using
Method 3, and in neat conditions was not satisfactory, because only
5% of the
a-furanose form of 22 was isolated, due to a partial
polymerization of the crude mixture. In sharp contrast, the use of
microwave at 140 ꢁC was beneficial and the permethacrylation
of saccharose with Method 4 was effective, and gave the per-
methacrylated product 22 with 35% of yield, selectively.
Analysis of the previous permethacrylation results for lactose
(Method 1, Table 1, entry 7), that contains a galactose and a glucose
unit, revealed that galactose sugar reacted with retention of the
b
-configuration of the glycosidic bond between the sugars (4C1).
Consequently, we hypothesized that the permethacrylation of
-galactopyranoside, such as 25, should yield to the selective for-
mation of the corresponding permethacrylated -galactopyrano-
b
b
side selectively, by virtue of the mutarotation blockade.
Accordingly, the treatment of compound 25 with Method 1 con-
ditions, gave the expected product 14 in reasonably good yield
(35%), without any traces of the furanose isomer or the
form either (entry 10).
a-pyranose
As can be evaluated by the overall results reported in Table 1, it
clearly appeared that each sugar (mono- or disaccharide) exhibits
an intrinsic reactivity in the studied permethacrylation conditions.
Therefore, based on our experimental data a general protocol
cannot be ruled out and each sugar needs specific reaction condi-
tions. The permethacrylation at room temperature, with Method 1,
was the most effective for mannose, galactopyranoside 25, maltose,
and lactose. The
for mannose (Table 1, entry 3) and lactose (Table 1, entry 7) while
the -anomer is observed for galactopyranoside 25 (Table 1, entry
a-pyranose form is obtained as the major product
b
10), and maltose (Table 1, entry 6). Method 2 was advantageous for
the permethacrylation of xylose and ribose (Table 1, entries 2 and
4). A quite high selectivity is observed for xylose since the
ranose form is isolated exclusively in high yield, while ribose
afforded the -pyranose as the major anomer. The use of Method 4
was effective for the preparation of permethacrylated -glucoside 1
as the major anomer (Table 1, entry 1). Exclusive per-
a-py-
b
b
b
methacrylated cellobioside 20 could also be synthesized by this
protocol (Table 1, entry 8).
3. Reactivity of permethacrylated carbohydrates
With the permethacrylated sugars in hands, we then in-
vestigated their chemical reactivity in diverse reactions conditions
for the synthesis of our targeted intermediates (Fig. 1). We were
surprised by the fact that the reactivity and the chemistry of such
functionalized sugars are unknown. Therefore we decided to

C. Zandanel et al. / Tetrahedron 65 (2009) 9395–9402
9399
investigate this field that would contribute in broadening the
challenging chemistry of sugars.
derivatized or activated. The offered alternatives were to explore
the reactivity of these sugars toward halogenation conditions
(Koenigs–Knorr reaction)18,10b and hydrolysis conditions.19 While
Initially, it was anticipated that such polymerizable molecules
would be sensitive and could probably be difficult to work with,
without observing partial polymerization. The first attempts were
to test classical selective reactions reported for the peracetylated
sugars, such as direct glycosidation, halogenations, and hydrolysis
of the anomeric position.10 Direct glycosidation reactions were first
performed on selected permethacrylated sugars, that have been
the halogenation reactions tested on permethacrylated
a-gluco-
pyranoside 1, failed to give any traces of the desired products 26
and 27 (Table 3, entries 1 and 2), we were pleased to notice that the
hydrolysis of substrates 1, 5, 8, and 17 employing BnNH2 afforded
the expected compounds in acceptable yields, for such function-
alized molecules. Except for substrate 5 (Table 3, entry 5), which
was accompanied with small amount of the furanose form, the
reagents were hydrolyzed smoothly without complication.
obtained as major b-pyranoside isomers. Consequently, substrates
1, 11, 15, and 20 were reacted with alcohol 2315 in the presence of
BF3$Et2O as activator in DCM, and at room temperature for 12 h. We
observed that compounds 12, 16, and 21 (Table 2, entries 2–4) were
obtained with reasonable yields (37–46%), while substrate 2 (Table
2, entry 1) was obtained with a poor isolated yield (15%). It is as-
sumed that the moderate yields are ascribed to possible removal or
loss of methacrylate(s) function(s) during the glycosidation re-
action affording, eventually, more polar partially deprotected
sugars. However, it is interesting to point out that the products 2
Table 3
Halogenation and hydrolysis reactions
Entry
Reagent
Product
Yield (%)
0
Ratio (b/a)
OAcr
O
1
AcrO
1
d
AcrO
b
/
a
a
¼ 1/1
AcrO
26
Br
and 21 gave the
meric assistance of the methacrylate group, while a 3/1 ratio of
is obtained for compound 16.16 In the case of 12, the
-anomer
b-anomer exclusively, probably due to the anchi-
OAcr
b
/a
a
O
1
was obtained selectively.
AcrO
2
3
0
d
AcrO
b/
¼ 1/1
AcrO
I
27
Table 2
Glycosidation reaction in the presence of BF3$Et2O at room temperature in DCM for
12 h with alcohol 23
OAcr
O
OH
OBn
Compound 23:
1
AcrO
AcrO
10
48
0/1
b
/
a
a
¼ 1/1
AcrO
OH
Entry Reagent
Product
Yield (%) Ratio (b/a)
3
OAcr
OAcr
OAcr
O
O
1
AcrO
AcrO
8
1
15
46
1/0
0/1
O
OBn
12
AcrO
AcrO
4
5
36
0/1
0/1
b
b
/
a
a
¼ 5/1
b/
¼ 0/1
OAcr
2
OH
9
O
AcrO
O
AcrO
AcrO
11
¼ 5/1
5
OAcr
2
3
38a
O
OBn
/
AcrO
OAcr
b
/
a
a
¼ 0
OH
12
6
12
17
¼ 1/3
OAcr
OAcr
OAcr
OAcr
O
b/
O
AcrO
AcrO
O
OAcr
6
AcrO
AcrO
O
54
1/3
OH
15
¼ 5/1
AcrO
O
O
AcrO
37
40
3/1
1/0
O
OBn
OAcr
b
b
/
a
a
AcrO
18
OAcr
12
a
13C NMR analysis revealed the presence of small amount of furanose form.
16
20
¼ 1/0
OAcr
AcrO
OAcr
O
/
AcrO
AcrO
The intermediates 3, 6, 9, and 18 were finally used for the
preparation of Schmidt reagents, well known for their ability to be
used in glycosidation reactions.20 As expected good to excellent
O
O
4
AcrO
O
OAcr
OBn
12
21
yields of the corresponding trichloroacetimidate
a-anomer de-
rivatives 4, 7, 10, and 19 were isolated (Table 4), without observing
epimerization of the anomeric center or detectable degradation of
the disaccharide substrate.
It is worthwhile to mention that these functionalized glycosyl
donors can be handled easily and are stable at room temperature.
The uses of these new reagents for further transformations are
underway in our laboratory and will be reported in due course.
In conclusion, each sugar behaved differently and requires
specific reaction permethacrylation conditions. Three main prob-
lems were encountered: the presence of the furanose isomer form,
The direct glycosidation reaction was then attempted with
permethacrylated -pyranosides. When the substrate 8 was sub-
jected to the same conditions as the one used for -pyranosides
(1, 11, 15, and 20), the expected products were not obtained and
the conversion of the starting material 8 was low, even after
prolonged reaction time at 45 ꢁC or the use of microwave irra-
diation. This lack of reactivity is reminiscent of the reactivity
a
b
reported for
the
-anomer remains kinetically unreactive.17
Consequently, prior to direct glycosylation reactions, the
anomeric center of all permethacrylated -anomers (glucose 1,
xylose 5, mannose 8, and lactose 17 derivatives) was first
a-peracetylated sugars in glycosidation conditions;
the possibility of producing
a and b pyranose form, and the lack of
a
reactivity for some saccharides. In most cases, the control of the
regioselectivity was achieved and the pyranose forms were
obtained as the major products. The lack of reactivity could be
a

9400
C. Zandanel et al. / Tetrahedron 65 (2009) 9395–9402
n
(cmꢀ1) 2928, 1733, 1637, 1456, 1318, 1294, 1146, 1077;
Table 4
18.3; IR:
MM-ES: 543.3 [MþNa]þ, mp: 66–68 ꢁC.
Synthesis of trichloroacetimidate with trichloroacetonitrile, DBU at room temper-
ature in DCM for 2 h
Entry Reagent
Product
Yield (%) Ratio (b/a)
4.1.2. Synthesis of permethacrylated mannose 8. From 4.0 g of
mannose, 2.6 g of compound 8 as a colorless oil (yield: 23%) was
recovered (SiO2, cyclohexane/EtOAc¼7/3, Rf¼0.56). 1H NMR (CDCl3,
OAcr
O
AcrO
AcrO
3
300 MHz) d (ppm): 6.24 (s, 1H), 6.22 (s, 1H), 6.21 (s, 1H), 6.13 (s, 1H),
1
73
66
60
0/1
0/1
0/1
b
b
/
a
a
¼ 0/1
AcrO
NH
CCl3
6.05 (s, 1H), 5.73–5.42 (m, 8H), 4.30–4.21 (m, 3H), 1.98 (s, 3H), 1.96
O
(s, 3H), 1.93 (s, 3H), 1.92 (s, 3H), 1.86 (s, 3H), 1.81 (s, 3H); 13C NMR
4
(APT) (CDCl3, 75 MHz)
d (ppm): 166.9, 166.1, 165.9, 165.8, 164.3,
OAcr
135.9–135.2, 127.8–126.1, 91.1, 70.9, 69.6, 69.0, 65.7, 62.1, 18.2; IR:
n
OAcr
O
(cmꢀ1) 2980, 1728, 1637, 1458, 1319, 1294, 1147; MM-ES: 543.1
AcrO
AcrO
9
[MþNa]þ, 559.2 [MþK]þ.
2
3
/
¼ 0/1
NH
CCl3
O
10
4.1.3. Synthesis of permethacrylated maltose 15. From 5.0 g of
maltose, 10.4 g of compound 15 as a white solid (yield: 42%) was
recovered (SiO2, cyclohexane/EtOAc¼7/3, Rf¼0.53). 1H NMR (CDCl3,
O
AcrO
AcrO
300 MHz)
5.73 (d, 1H, J¼7.5 Hz, Hano
2H), 5.10–4.90 (m,1.2H), 4.55 (m,1.1H), 4.40 (m,1.1H), 4.26–4.01 (m,
5.5H),1.98–1.80 (m, 31H); 13C NMR (CDCl3, 75 MHz)
(ppm): 167.1–
165.4, 128.3–126.7, 136.0–135.3, 96.5, 92.2, 75.2, 73.6, 72.4, 71.2,
d
(ppm): 6.33 (d, J¼3.7 Hz, 0.20H), 6.26–5.85 (m, 8.8H),
6
AcrO
O
NH
CCl3
b
b
/
a
a
¼ 0/1
b
), 5.68–5.42 (m, 12.8H), 5.30–5.13 (m,
7
d
18
¼ 1/3
OAcr
70.7, 69.9, 69.3, 68.6, 63.2, 62.3, 27.2, 18.4; IR:
n
(cmꢀ1) 2978, 1731,
OAcr
OAcr
ArO
/
O
1638, 1454, 1319, 1295, 1154, 1082; API-ES. Pos: 909.4 [MþNa]þ;
O
AcrO
AcrO
O
AcrO
4
55
0/1
mp: 81–83 ꢁC.
O
NH
CCl3
19
4.1.4. Synthesis of permethacrylated lactose 17. From 2.0 g of com-
pound lactose, 1.7 g of compound 17 as a colorless oil (yield: 34%)
was recovered (SiO2, cyclohexane/EtOAc¼7/3, Rf¼0.60). 1H NMR
circumvented in some instance, by modifying the reaction condi-
tions. For instance, decreasing the reaction temperature to ꢀ10 ꢁC,
allowed the formation of permethacrylated ribose (Method 2),
while permethacrylated galactose 16, is obtained only from galac-
toside 25 and not from the free sugar. The use of microwave re-
solved the problem of reactivity for cellobiose and saccharose
(Method 4). For all the permethacrylated carbohydrates obtained as
-anomer as the major product, direct glycosidation with BF3$Et2O
was possible and gave moderate yields of glycosylated products. All
the carbohydrates where the anomer was predominant the direct
(CDCl3, 200 MHz)
d
(ppm): 6.35 (d, J¼3.2 Hz, 1H), 6.25–5.93 (m,
15H), 5.81 (m, 0.5H), 5.77 (d, J¼8.7 Hz, 0.5H), 5.72–5.48 (m, 18H),
5.30–5.25 (m, 2H), 5.16–5.08 (m, 2H), 4.64–4.41 (m, 3H), 4.24–3.90
(m, 8.5H), 2.10–1.76 (m, 24H); 13C NMR (CDCl3, 50 MHz)
d (ppm):
172.9, 166.6–165.2, 135.1–134.9, 129.0–126.3, 100.9, 100.6, 92.5,
89.6, 75.4, 75.2, 73.7, 72.6, 71.6, 71.4, 71.1, 70.6, 70.2, 69.9, 69.7, 69.6,
67.3, 62.0, 61.8, 61.4, 61.2, 18.3–17.9; IR:
n
(cmꢀ1) 2961, 1731, 1637,
b
1456, 1319, 1294, 1150, 1076; HRMS: m/z: calcd for C44H54O19Li:
893.3419 [MþLi]þ; found: 893.3412.
a
glycosidation was uneffective. Gratifyingly, two-step activations of
the anomeric position by the preparation of the Schmidt reagent
was possible in good to excellent yields. These activated building
blocks are now investigated for diverse reactions that will be
published elsewhere.
4.1.5. Synthesis of compound 14. From 446.7 mg of compound 25,
248.7 mg of compound 14 as a colorless oil (yield: 35%) was re-
covered (SiO2, cyclohexane/EtOAc¼8/2, Rf¼0.70). 1H NMR (CDCl3,
200 MHz)
d (ppm): 7.27 (m, 5H), 6.18 (s, 1H), 6.05 (s, 1H), 5.99 (s,
1H), 5.92 (s, 1H), 5.60–5.44 (m, 5H), 5.29–5.17 (m, 2H), 4.53 (d,
J¼7.9 Hz, 1H,), 4, 49 (s, 2H), 4.33–4.28 (m, 1H), 4.12–3.98 (m, 2H),
3.80 (m, 1H), 3.40 (m, 3H), 1.91 (s, 3H), 1.86 (s, 3H), 1.83 (s, 3H), 1.75
(s, 3H), 1.53 (m, 4H), 1.17 (m, 17H); 13C NMR (CDCl3, 50 MHz)
4. Experimental section
d
(ppm): 166.9–166.0, 128.5–126.2, 101.5, 73.0, 71.5, 71.0, 70.7, 70.4,
4.1. General procedure for the permethacrylation of glucose,
xylose, mannose, maltose, lactose, and compound 14 at room
temperature: Method 1
69.6, 67.8, 61.7, 29.9–29.5, 26.3, 25.9, 18.4; IR:
n
(cmꢀ1) 2927, 2854,
1730, 1457, 1320, 1154; HRMS: m/z: calcd for C25H42O7Li: 733.4139
[MþLi]þ, found 733.4130.
4.1.1. Synthesis of permethacrylated glucose 1. Glucose (5.0 g,
27.70 mmol, 1 equiv) was suspended in dichloromethane (100 mL);
methacrylic anhydride (40 mL, 268.4 mmol, 9.6 equiv), triethyl-
amine (40 mL, 284.6 mmol, 10.3 equiv), and a catalytic amount of
DMAP were added. The reaction mixture was stirred at rt overnight
(12 h), then quenched with water (3ꢂ50 mL). The organic phase
was separated, dried over Na2SO4, and evaporated. The crude
product was purified by column chromatography (SiO2, cyclohex-
ane/EtOAc¼7/3, Rf¼0.63) to give a sticky solid (8.5 g, yield: 59%). 1H
4.2. General procedure for the permethacrylation of ribose
at L10 8C: Method 2
4.2.1. Synthesis of permethacrylated ribose 11. The procedure is
identical as Method 1, except the temperature of the reaction was
fixed at ꢀ10 ꢁC. From 500.0 mg of ribose, 1.14 g of compound 11 as
a white solid (yield: 70%) was recovered (SiO2, cyclohexane/
EtOAc¼7/3, Rf¼0.67). 1H NMR (CDCl3, 300 MHz)
d (ppm): 6.26 (d,
J¼4.3 Hz, 0.2H), 6.19 (m, 1H), 6.16 (d, J¼5.6 Hz, 1H), 6.12–6.05 (m,
NMR (CDCl3, 200 MHz)
d
(ppm): 6.46 (d, J¼3.6 Hz, 0.5H), 6.28–6.04
(m, 5H), 5.86 (d, J¼8.0 Hz, 0.5H), 5.78–5.42 (m, 6H), 5.42–5.22 (m,
3H), 5.70–5.58 (m, 5H), 5.31–5.25 (m, 2H), 4.17–4.00 (m, 2H), 1.97–
2H), 4.40–4.03 (m, 3H), 2.02–1.85 (m, 15H); 13C NMR (APT) (CDCl3,
1.92 (m, 12H); 13C NMR (CDCl3, 75 MHz)
d
(ppm): 166.0–164.6,
135.6–135.0, 127.2–125.6, 91.4( ), 67.3( ), 67.1, 67.1( ),
66.5( ), 65.7, 62.5( ), 17.9–17.6; IR: n
(cmꢀ1) 2960, 1724, 1637, 1434,
50 MHz)
d
(ppm): 167.0, 166.4, 165.8, 135.8–134.9, 128.3–126.5,
b
), 88.7(
a
b
b
92.5, 89.8, 73.1, 72.7, 70.6, 70.4, 70.2, 70.0, 68.5, 68.3, 62.3, 62.2,
b
b

C. Zandanel et al. / Tetrahedron 65 (2009) 9395–9402
9401
1318, 1292, 1115, 1079; HRMS: m/z: calcd for C21H26O9Li1: 429.1737
[MþLi]þ; found 429.1732; mp: 100–102 ꢁC.
2926, 1737, 1637, 1456, 1320, 1294, 1152, 1078; HRMS: m/z: calcd for
C
36H52O9Li: 635.3771 [MþLi]þ; found 635.3755.
4.2.2. Synthesis of permethacrylated xylose 5. From 500.0 mg of
xylose, 1.12 g of compound 5 as a colorless oil (yield: 70%) was re-
covered (SiO2, cyclohexane/EtOAc¼7/3, Rf¼0.68). 1H NMR (CDCl3,
4.4.2. Synthesis of compound 16. From 617.8 mg of compound 15,
332.7 mg of compound 16 as yellow oil (yield: 54%) was recovered
(SiO2, cyclohexane/EtOAc¼8/2, Rf¼0.62). 1H NMR (CDCl3, 300 MHz)
300 MHz)
d
(ppm): 6.40 (d, J¼3.7 Hz, 1H), 636–6.04 (m, 5H), 5.75–
d
(ppm): 7.27 (m, 5H), 6.06 (m, 7H), 5.52 (m, 10H), 5.32 (t, J¼7.5 Hz,
5.56 (m, 6H), 5.25–5.16 (m, 2H), 4.11–4.06 (m, 1H), 3.78 (t, J¼9.0 Hz,
1H); 13C NMR (CDCl3, 75 MHz)
(ppm): 165.6–164.5, 135.5–135.3;
126.7–126.3, 89.4, 69.5, 69.3, 68.5, 60.6, 17.6–17.3; IR:
(cmꢀ1
1H), 5.20 (m, 1H), 4.95 (m, 1H), 4.52 (m, 1H), 4.44 (s, 2H), 4.32 (m,
1H), 4.10 (m, 4H), 4.70 (m, 2H), 3.40 (m, 3H), 1.93–1.74 (m, 21H),
d
n
)
1.52 (m, 4H), 1.20–1.16 (m, 16H); 13C NMR (CDCl3, 75 MHz)
d (ppm):
2926, 1726, 1637, 1454, 1319, 1290, 1146, 1120; HRMS: m/z: calcd for
C21H26O9Li1: 429.1737 [MþLi]þ; found 429.1732.
166.9–165.7, 135.8–135.2, 128.5, 127.7, 127.5–126.5, 100.6, 96.1, 95.5,
75.1, 73.0, 72.4, 71.0, 70.7, 70.2, 69.6, 69.0, 68.5, 67.9, 63.3, 62.1,
29.9–29.4, 26.3, 21.1, 20.9, 18.4–18.1; IR: n
(cmꢀ1) 2928, 2855, 1732,
1638, 1454, 1319, 1295, 1159, 1043, 1019; MM-ES: 1089 [Mꢀ27].
4.3. General procedure for the permethacrylation of
cellobiose and saccharose under microwave irradiation:
Method 4
4.4.3. Synthesis of compound 21. From 510.0 mg of compound 20,
255.0 mg of compound 21 as yellow oil (yield: 40%) was recovered
(SiO2, cyclohexane/EtOAc¼7/3, Rf¼0.63). 1H (CDCl3, 300 MHz)
4.3.1. Synthesis of permethacrylated cellobiose 20. Cellobiose (2.0 g,
5.55 mmol, 1 equiv) was charged in a vial containing methacrylic
anhydride (10 mL, 67.1 mmol, 12.1 equiv), and sodium acetate
(600.0 mg, 7.31 mmol, 1.3 equiv) was added. The reaction mixture
was stirred at 140 ꢁC for 5 min in the presence of microwave. The
crude product was purified by column chromatography (SiO2, cy-
clohexane/EtOAc¼7/3, Rf¼0.48) to give a white solid (1.7 g, yield:
d
(ppm): 7.32 (m, 5H), 6.08 (m, 7H), 5.58 (m, 7H), 5.36 (m, 2H), 5.15
(m, 2H), 5.02 (m, 1H), 4.63 (m, 1H), 4.53 (m, 3H), 4.13 (m, 4H), 3.91
(m, 1H), 3.76 (m, 3H), 3.44 (m, 3H), 1.99–1.80 (7s, 21H), 1.52 (m, 4H),
1.26–1.22 (m, 16H); 13C NMR (CDCl3, 75 MHz)
d (ppm): 136.1–135.2,
128.5, 127.7, 127.2–126.2, 100.9, 100.6, 76.1, 73.0, 72.9, 72.6, 72.4,
71.9, 71.8, 70.7, 70.3, 68.9, 62.9, 62.4, 29.9–29.5, 25.9, 18.4; IR:
n
(cmꢀ1) 2927, 2854, 1730, 1637, 1456, 1320, 1295, 1151, 1068.
35%). 1H NMR (CDCl3, 300 MHz)
d (ppm): 6.17–6.00 (m, 7H), 5.77 (d,
J¼7.8 Hz, 1H), 5.25 (m, 8H), 5.35 (t, J¼9.2 Hz, 1H), 5.18 (m, 2H), 4.64
4.4.4. Synthesis of compound 24. Peracetylated galactose derivate:
from 1.0 g of peracetylated galactose, 802.4 mg of compound 24 as
a colorless oil (yield: 46%) was recovered (SiO2, cyclohexane/
(m, 1H), 4.52 (m, 1H), 4.20 (m, 2H), 4.13 (m, 2H), 3.85 (m, 1H), 3.75
(m, 1H), 2.00–1.80 (7s, 21H); 13C NMR (CDCl3, 75 MHz)
d
(ppm):
18.4, 62.3, 62.9, 68.8, 70.7, 71.6, 72.4, 73.6, 75.5, 92.3, 100.6, 126.7–
EtOAc¼7/3, Rf¼0.35).1H(CDCl3, 300 MHz)
d(ppm): 7.27 (m, 5H), 5.33
129.1, 135.1; IR:
n
(cmꢀ1) 2978, 1735, 1638, 1454, 1319, 1294, 1153,
(m,1H), 5.13 (m,1H), 4.96 (m,1H), 4.40 (s, 2H), 4.38 (d, J¼8.0 Hz,1H),
1080; API-ES. Pos: 909.3 [MþNa]þ; temperature of degradation:
4.10 (m, 2H), 3.84 (m, 2H), 3.40 (m, 3H), 2.08–1.92 (3s, 12H), 1.53 (m,
266 ꢁC.
4H), 1.20 (m, 16H); 13C NMR (CDCl3, 75 MHz)
d
(ppm): 170.4–170.2,
138.8, 128.4, 127.6, 127.5, 101.4, 72.9, 71.0, 70.6, 70.5, 70.3, 69.0, 67.1,
4.3.2. Synthesis of permethacrylated saccharose 22. From 100.0 mg
of saccharose, 87.0 mg of compound 22 as a colorless oil (yield:
34%) was recovered (SiO2, cyclohexane/EtOAc¼7/3, Rf¼0.51). 1H
61.3; IR:
n
(cmꢀ1) 2926, 2854, 1733, 1454, 1319, 1295, 1150; HRMS:
m/z: calcd for C33H50O11Li: 629.3513 [MþLi]þ; found 629.3505.
NMR (CDCl3, 300 MHz)
d (ppm): 6.25–5.97 (m, 8H), 5.76 (d,
4.5. General procedure for the hydrolysis of the anomeric
position
J¼5.8 Hz, 1H), 5.71–5.49 (m, 11H), 5.32 (t, J¼8.0 Hz, 1H), 5.07–
5.03 (m, 1H), 4.44–4.23 (m, 8H), 2.03–1.81 (m, 26H); 13C NMR
(CDCl3, 75 MHz)
104.2, 90.3, 79.1, 76.7, 75.9, 70.7, 70.0, 68.9, 68.5, 64.5, 64.0, 62.1,
d
(ppm): 167.7–166.3, 135.8–135.4, 127.7–126.2,
4.5.1. Hydrolysis of compound 1. Compound 1 (1.0 g, 1.90 mmol,
1 equiv) was dissolved in tetrahydrofuran (20 mL) and benzyl-
amine (250 mL, 2.30 mmol, 1.2 equiv) was added. The reaction
18.4–18.2; IR:
1016.
n
(cmꢀ1) 2961, 1727, 1637, 1453, 1319, 1296, 1151,
mixture was stirred at rt for 24 h, then evaporated. The crude
product was purified by column chromatography (SiO2, cyclohex-
ane/EtOAc¼8/2, Rf¼0.51) to give a yellow solid as compound 3
4.4. General procedure for direct glycosidation reaction
(365.0 mg, yield: 42%). 1H NMR (CDCl3, 300 MHz)
d (ppm): 6.18 (s,
4.4.1. Synthesis of compound 12. Compound 11 (1.14 g, 2.69 mmol,
1 equiv) was dissolved in dichloromethane (40 mL) and mono-
protected dodecane diol (946.0 mg, 3.23 mmol, 1.2 equiv) was
added. The reaction mixture was cooled down to 0 ꢁC then
BF3$EtO2 (1 mL 8.07 mmol, 3 equiv) was slowly added. The reaction
mixture was stirred 5 min at 0 ꢁC then allowed to warm up to room
temperature and stirred overnight. The reaction mixture was then
cooled down to 0 ꢁC and quenched with a saturated NaHCO3 so-
lution (1ꢂ10 mL), the organic phase extracted, the aqueous phase
extracted with dichloromethane (1ꢂ10 mL). The organic layers
combined were dried over Na2SO4 and evaporated. The crude
product was purified by column chromatography (SiO2, cyclohex-
ane/EtOAc¼8/2, Rf¼0.57) to give a colorless oil (778.4 mg, yield:
1H), 6.12 (s,1H), 6.07 (s,1H), 6.01 (s,1H), 5.78 (t, J¼10.3 Hz,1H), 5.55
(m, 5H), 5.29 (t, J¼10.3 Hz, 1H), 4.96 (m, 1H), 4.37 (m, 2H), 4.19 (m,
1H), 1.96 (s, 3H), 1.89 (s, 3H), 1.87 (s, 3H), 1.84 (s, 3H); 13C DEPT 135
NMR (CDCl3, 50 MHz)
67.7, 62.6, 18.3; IR:
d (ppm): 127.4–126.5, 90.4, 71.9, 70.0, 69.0,
n
(cmꢀ1) 3450,þ2960, 1730, 1636, 1456, 1320,
1294, 1155; MM-ES: 435.1 [MꢀOH] ; mp: 56–58 ꢁC.
4.5.2. Hydrolysis of compound 8. From 2.6 g of compound 8,
813.7 mg of compound 9 as yellow solid (yield: 36%) was recovered
(SiO2, cyclohexane/EtOAc¼8/2, Rf¼0.55). 1H NMR (CDCl3, 300 MHz)
d
(ppm): 6.23–6.01 (m, 4H), 5.68–5.34 (m, 8H), 4.43–4.22 (m, 3H),
3.34 (m, 1H), 1.98 (s, 6H), 1.89 (s, 3H), 1.84 (s, 3H); 13C NMR (CDCl3,
75 MHz) d (ppm): 167.4,166.4–166.2,136.0–135.4,126.9–126.3, 92.3,
46%). 1H NMR (CDCl3, 200 MHz)
d
(ppm): 7.27 (m, 5H), 6.09 (m, 3H),
70.8, 69.6, 68.5, 66.5, 62.6, 18.3–18.1; IR:
n
(cmꢀþ1) 3470, 2980, 1732,
5.53–5.46 (m, 4H), 5.20 (m, 1H), 5.08 (m, 1H), 4.81 (d, J¼3.6 Hz,
1637, 1456, 1295, 1152; MM-ES: 435.1 [MꢀOH] ; mp: 89–92 ꢁC.
1H), 3.81 (m, 1H), 3.83–3.66 (m, 2H), 3.40 (m, 3H), 1.87–1.82 (m,
9H), 1.53 (m, 4H), 1.21 (m, 16H); 13C NMR (CDCl3, 50 MHz)
d
(ppm):
166.8, 166.6, 165.8, 138.8, 136.1, 136.0, 135.9, 128.4, 127.7, 127.5,
126.4, 126.2, 126.1, 98.5, 72.9, 68.9, 68.7, 67.3, 66.3, 61.1; IR:
(cmꢀ1
4.5.3. Hydrolysis of compound 5. From 361.8 mg of compound 5,
115.5 mg of compound 6 as a white solid (yield: 36%) was recovered
(SiO2, cyclohexane/EtOAc¼7/3, Rf¼0.46). 1H NMR (CDCl3, 200 MHz)
n
)

9402
C. Zandanel et al. / Tetrahedron 65 (2009) 9395–9402
d
(ppm): 6.09 (s, 1H), 6.04 (s, 1H), 6.02 (s, 1H), 5.73 (t, J¼8.0 Hz, 1H),
5.56–5.44 (m, 4H), 5.06–4.87 (m, 2H), 1.84 (s, 9H); 13C NMR (CDCl3,
50 MHz) (ppm): 166.7–166.3, 135.5–135.3, 127.2–126.4, 96.0 (
furanose), 90.4 ( pyranose), 73.4 (furanose), 71.8, 69.7, 69.5, 62.8
(furanose), 58.4, 18.2; IR:
(cmꢀ1) 3467, 2960, 1724, 1637, 1455,
recovered (SiO2, cyclohexane/EtOAc¼7/3, Rf¼0.55). 1H NMR
(CDCl3, 300 MHz)
d (ppm): 6.38–5.97 (m, 8H), 5.77–5.48 (m, 9H),
d
a
5.35–5.29 (m, 1H), 5.17–5.11 (m, 1H), 4.65–4.59 (m, 1H), 4.47–4.27
(m, 1H), 4.28–4.13 (m, 2H), 4.09–3.89 (m, 4H), 1.99–1.80 (m, 22H);
a
n
13C NMR (CDCl3, 50 MHz)
d
(ppm): 166.6–165.2, 135.9–135.1,
1322, 1293, 1151, 1054; HRMS: m/z: calcd for C17H22O8Li: 361.1475
[MþLi]þ; found 361.1459; mp: 116–118 ꢁC.
128.0–126.1, 101.0, 89.6, 75.5, 71.6, 71.1, 70.2, 69.9, 69.7, 67.2, 61.7,
61.3; IR:
1047.
n
(cmꢀ1) 3314, 2960, 1731, 1639, 1459, 1322, 1295, 1116,
4.5.4. Hydrolysis of compound 17. From 1.5 g of compound 17,
790.0 mg of compound 18 as a white solid (yield: 54%) was re-
covered (SiO2, cyclohexane/EtOAc¼6/4, Rf¼0.40). 1H NMR (CDCl3,
4.7. General procedure for the hydrolysis of the acetate
groups
200 MHz) d (ppm): 6.22–5.96 (m, 5H), 5.72–5.47 (m, 7H), 5.29–5.22
(m, 0.5H), 5.12–5.08 (m, 0.5H), 4.82–4.92 (m, 0.5H), 4.65–4.60 (m,
0.5H), 4.53–4.45 (m, 1H), 4.26–4.15 (m, 2H), 4.06–3.89 (m, 2H),
Compound 24 was dissolved in MeOH (10 mL) and NaOMe
(35.0 mg, 0.64 mmol, 0.5 equiv) was added. The reaction mixture
was stirred at rt for 1 h then quenched with Dowex and filtered off
on Celite to give compound 25 as a white solid (446.7 mg, yield:
2.02–1.79 (m, 21H); 13C NMR (CDCl3, 50 MHz)
d
(ppm): 166.8–
furanose), 90.3 (
pyranose), 75.8, 71.9, 71.6, 71.1, 69.9, 69.7, 68.5, 67.3, 62.2, 61.4, 18.4;
165.5, 136.0–135.1, 129.9–125.9, 100.7, 95.7 (
a
a
77%). 1H NMR (MeOD, 300 MHz)
d
(ppm): 7.27 (m, 5H), 4.43 (m,
2H), 4.13 (d, J¼7.9 Hz, 1H), 3.85–3.68 (m, 5H), 3.30–3.26 (m, 2H),
1.55 (m, 4H), 1.24 (m, 16H); 13C NMR (MeOD, 75 MHz)
(ppm):
129.3, 128.8, 128.6, 105.0, 76.5, 75.0, 73.8, 72.6, 71.4, 70.8, 62.4,
IR:
n
(cmꢀ1) 3435, 2960, 1727, 1637, 1455, 1321, 1294, 1155, 1076;
HRMS: m/z: calcd for C40H50O18Li: 825.3157 [MþLi]þ; found
825.3131; mp: 100–102 ꢁC.
d
30.8–30.5, 27.2; IR:
n
(cmꢀ1) 3384, 2927, 1597, 1454; HRMS: m/z:
4.6. General procedure for the synthesis of the Schmidt
reagent
calcd for C25H42O7Li: 4601.3091 [MþLi]þ; found 461.3086; mp:
68–70 ꢁC.
4.6.1. Preparation of compound 4. Compound
0.97 mmol, 1 equiv) was dissolved in dichloromethane (20 mL) and
trichloroacetonitrile (290 L, 2.92 mmol, 3 equiv), followed by DBU
(15 L, 0.10 mmol, 0.1 equiv) were added. The reaction mixture was
3
(440.0 mg,
Acknowledgements
m
m
This work was supported by University of Strasbourg and the
CNRS (grant to Z.D.).
stirred at rt for 2 h, then evaporated. The crude product was puri-
fied by column chromatography (SiO2, cyclohexane/EtOAc¼6/4,
Rf¼0.72) to give a white solid (426.0 mg, yield: 73%). 1H NMR
(CDCl3, 300 MHz)
d
(ppm): 8.68 (s, 1H), 6.63 (d, J¼4.0 Hz, 1H), 6.15–
Supplementary data
6.04 (m, 12H), 5.81 (t, J¼10.8 Hz, 1H), 5.55 (m, 5H), 5.34 (t,
J¼10.3 Hz, 1H), 5.27 (m, 1H), 4.35 (m, 2H), 4.24 (m, 1H), 1.84 (s, 3H),
1.82 (s, 3H), 1.75 (s, 3H), 1.69 (s, 3H); 13C NMR (CDCl3, 75 MHz)
Supplementary data associated with this article can be found in
online version, at doi:10.1016/j.tet.2009.08.083.
d
(ppm): 166.9–165.8, 160.7, 135.2–135.0, 127.5–126.4, 93.1, 90.8,
70.6, 70.2, 70.1, 68.2, 62.2, 18.3; IR: n
(cmꢀ1) 3318, 2959, 1724, 1637,
1453, 1317, 1292, 1137, 1020; MM-ES: 622.0 [MþNa]þ, 435.1
References and notes
[MꢀCNHCCl3]; mp: 105–107 ꢁC.
1. Curcio, P.; Zandanel, C.; Wagner, A.; Mioskowski, C.; Baati, R. Macromol. Biosci.
2009, 9, 596.
2. (a) Wulff, G.; Poll, H. G. Makromol. Chem. 1987, 188, 741; (b) Wulff, G.; Schauhoff,
S. J. Org. Chem. 1991, 56, 395.
4.6.2. Preparation of compound 10. From 1.4 g of compound 9, 1.2 g
of compound 10 as a yellow solid (yield: 66%) was recovered (SiO2,
cyclohexane/EtOAc¼7/3, Rf¼0.67). 1H NMR (CDCl3, 300 MHz)
3. (a) Dergunov, S. A.; Pinkhassik, E. Angew. Chem., Int. Ed. 2008, 47, 1; (b) Xiao-
Chuan, L.; Dordick, J. S. J. Polym. Sci. A 1999, 37, 1665.
4. Bachmann, F.; Ho¨pken, J.; Kohli, R.; Lohmann, D.; Schneider, J. J. Carbohydr. Res.
1998, 17, 1359.
5. (a) Mukkamala, R.; Burns, C. L., Jr.; Catchings, R. M., III; Weiss, R. G. J. Am. Chem.
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Ca´novas, F.; Garcı´a-Ruiz, P. A. Carbohydr. Polym. 2004, 58, 79.
6. Kieburg, C.; Dubber, M.; Lindhorst, T. K. Synlett 1997, 1447.
7. Treadway, R. H.; Yanovsky, E. J. Am. Chem. Soc. 1945, 67, 1038.
8. Steglich, W.; Ho¨fle, G. Angew. Chem., Int. Ed. Engl. 1969, 8, 981.
9. (a) Wang, Z.; Matin, M.; Sheikh, S. Molecules 2005, 10, 1325; (b) Franchimont,
A. P. N. Chem. Ber. 1938, 12, 1879.
10. (a) Osborn, H. M. I. Carbohydrates; Academic: UK, 2003; p 23; (b) Osborn; H. M.
I. Carbohydrates; Academic: UK, 2003; pp 82–95.
11. Braun, D. H. J. Am. Chem. Soc. 1926, 48, 2776.
12. Das, S. K.; Reddy, K. A.; Krovvidi, V. L. N. R.; Mukkanti, K. Carbohydr. Res. 2005,
340, 1387.
13. Pagnotta, M.; Pooley, C. L. F.; Gurland, B.; Choi, M. J. Phys. Org. Chem. 1993,
6, 407.
d
(ppm): 8.81 (s, 1H), 6.38 (s, 1H), 6.24 (s, 1H), 6.16 (s, 1H), 6.09 (s,
1H), 6.01 (s, 1H), 5.73–5.54 (m, 7H), 4.40–4.25 (m, 3H), 1.99 (s, 3H),
1.95 (s, 3H), 1.89 (s, 3H), 1.83 (s, 3H); 13C NMR (CDCl3, 75 MHz)
d
(ppm): 166.9, 166.1–165.9, 160.0, 136.0–135.3, 127.4–126.2, 94.7,
90.7, 71.5, 69.5, 68.6, 65.7, 62.3, 18.3; IR: n
(cmꢀ1) 3315, 2960, 1729,
1638, 1459, 1322, 1295, 1114, 1044; mp: 82–86 ꢁC.
4.6.3. Preparation of compound 7. From 306.2 mg of compound 6,
334.4 mg of compound 7 as a yellow oil (yield: 87%) was recovered
(SiO2, cyclohexane/EtOAc¼7/3, Rf¼0.59). 1H NMR (CDCl3, 300 MHz)
d
(ppm): 8.66 (s, 1H), 6.57 (d, J¼4.0 Hz, 1H), 6.16 (s, 2H), 6.11 (s, 1H),
5.82 (t, J¼4.0 Hz, 1H), 5.63–5.55 (m, 4H), 5.28–5.17 (m, 2H), 4.17–
4.09 (m, 1H), 3.89 (m, 1H), 1.89 (m, 11H); 13C NMR (CDCl3, 75 MHz)
d
(ppm): 166.1–165.9, 160.7, 135.3–135.0, 127.3–126.5, 93.3, 90.7,
(cmꢀ1) 3310, 2959, 1730, 1637, 1460,
14. Frank, F. J. Chem. Soc., Faraday Trans. 1989, 85, 2417.
15. Shimojo, M.; Matsumoto, K.; Hatanaka, M. Tetrahedron 2000, 56, 9281.
16. Levy, D. E.; Fu¨ gedi, P. The Organic Chemistry of Sugars; CRC: New York,
NY, 2006; Chapter 2.
17. Zhu, X.; Schmidt, R. R. Angew. Chem., Int. Ed. 2009, 48, 1900.
18. Ko¨nigs, W.; Knorr, E. Chem. Ber. 1901, 34, 957.
70.1, 69.5, 68.9, 61.1, 18.1; IR:
n
1321, 1296, 1115, 1046; HRMS: m/z: calcd for C19H22Cl3O8NLi:
506.0542 [MþLi]þ; found 506.0529.
4.6.4. Preparation of compound 19. From 461.8 mg of compound
18, 299.6 mg of compound 19 as a yellow oil (yield: 55%) was
19. Boger, D. L.; Teramoto, S.; Zhou, J. J. Am. Chem. Soc. 1995, 117, 7344.
20. Jayakanthan, K.; Vankar, Y. D. Carbohydr. Res. 2005, 340, 2688.