Highly chemo- and stereoselective glycosidation of permethacrylated O-glycosyl trichloroacetimidate reagents promoted by TMSNTf2

Article abstract of DOI:10.1016/j.tet.2010.02.068

TMSNTf₂ has been used efficiently as a promoter in glycosidation reaction involving permethacrylated Schmidt reagents. While TMSNTf₂ is known to be a powerful activator for C{double bond, long}O double bonds, we have discovered that this reagent can activate C{double bond, long}N double bond selectively, even in the presence of excess C{double bond, long}O groups of permethacrylated O-glycosyl trichloroacetimidate substrates. Glycosides are synthesized in moderate to reasonable yields with an excellent overall β-stereoselectivity.

Full text of DOI:10.1016/j.tet.2010.02.068

Tetrahedron 66 (2010) 3365–3369
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Highly chemo- and stereoselective glycosidation of permethacrylated O-glycosyl
trichloroacetimidate reagents promoted by TMSNTf2
*
Christelle Zandanel, Laure Dehuyser, Alain Wagner, Rachid Baati
University of Strasbourg, Faculty of Pharmacy CNRS/UMR 7199, Laboratory of Functional ChemoSystems, 74 route du Rhin BP 60024, 67 401 Illkirch, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 October 2009
Received in revised form 18 February 2010
Accepted 18 February 2010
Available online 25 February 2010
TMSNTf2 has been used efficiently as a promoter in glycosidation reaction involving permethacrylated
Schmidt reagents. While TMSNTf2 is known to be a powerful activator for C]O double bonds, we have
discovered that this reagent can activate C]N double bond selectively, even in the presence of excess
C]O groups of permethacrylated O-glycosyl trichloroacetimidate substrates. Glycosides are synthesized
in moderate to reasonable yields with an excellent overall
b
-stereoselectivity.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
permethacrylated Schmidt reagents as useful glycosyl donors, upon
activation with various Lewis acids, including TMSNTf2. To date,
TMSNTf2 has exclusively been used as carbonyl activator, in dif-
ferent transformation such as Diels–Alder (DA) reactions,19
The increased knowledge and understanding of the crucial roles
of oligosaccharides in diverse biological processes, have stimulated
tremendous synthetic efforts for the development of efficient and
selective methods in glycoside synthesis.1 Since the first glycoside
preparation by Michael2 and Fisher,3 a great number of glyco-
sidation strategies have been developed and constantly optimized.
Among them, glycoside syntheses based on O-glycosyl tri-
chloroacetimidates, discovered by Sinay¨,4 and known as ‘Schmidt
glycosidation’ has emerged as the most popular approach, due to
their remarkable donor properties, ease of formation, reactivity,
and general applicability.5 Nowadays a large number of catalysts for
glycosidation reactions of trichloroacetimidates are known. Acti-
vation using BF3$Et2O,6 TMSOTf,7 TBDMSOTf,8 Tf2O,9 ZnBr2,10
AgOTf,11 and several moisture-stable activating reagents such as
I2/Et3SiH12 or HClO4/silica,13 have been used successfully. Beside
these promoters, it is also worthwhile to mention the use of 4 Å
acid washed molecular sieves,14 Amberlyst 1515 and a cationic
palladium16 for the efficient activation of O-glycosyl
trichloroacetimidates. More recently, the use of N-phenyl
trifluoroacetimidate has contributed to expand considerably the
imidate chemistry.17 However, the majority of glycosidation re-
actions involving Schmidt reagents as glycosyl donor requires the
use of robust compatible protecting groups such as ethers or esters,
and little attention has been paid to the use of protected poly-
Mukayaima–aldol condensations,20 alkylations of
a
,b
-unsaturated
compounds,21 and Friedel–Crafts alkylation. While TMSNTf2 has
been shown to activate efficiently -unsaturated esters such as
a,b
trans-methyl crotonate in DA reaction, this catalyst was also found
to be chemically compatible with 2-azadiene.22 This observation
demonstrated the capabilities of TMSNTf2 to activate selectively
carbonyl group in the presence of C]N bond. During
our investigations we have discovered that glycosidation reactions
involving permethacrylated Schmidt glycosyl donors (Fig. 1) pro-
moted by TMSNTf2 afforded the expected glycosides, in good to
moderate yields, with an excellent overall
b-stereoselectivity. These
unprecedented results demonstrate, for the first time that the
OAcr
OAcr
OAcr
O
O
AcrO
AcrO
AcrO
AcrO
AcrO
NH
CCl3
NH
CCl3
O
O
2
1
OAcr
OAcr
O
OAcr
ArO
AcrO
AcrO
O
O
AcrO
O
AcrO
AcrO
AcrO
O
NH
CCl3
merizable Schmidt reagents bearing
a
,
b-unsaturated esters. In
O
NH
CCl3
continuation of our efforts to investigate the chemistry of per-
4
3
methacrylated carbohydrates,18 we wish to report on the use of
O
Acr =
* Corresponding author. Fax: þ33 368 854 306; e-mail address: baati@
Figure 1. Activated permethacrylated O-glycosyl trichloroacetimidate reagents
investigated.
bioorga.u-strasbg.fr.
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.068

3366
C. Zandanel et al. / Tetrahedron 66 (2010) 3365–3369
trichloroacetimidate function could be activated by TMSNTf2 se-
lectively to generate the oxocarbenium ion, even in the presence of
excess methacrylate functions on the substrates. Since, all the
common other Lewis acid tested behaved similarly to TMSNTf2 in
terms of efficiency, kinetics and stereoselectivity in the glyco-
sidation, we decided to investigate the scope and the reactivity
of TMSNTf2, which has no literature precedent for this trans-
formation, specially with substrates bearing compatible poly-
acrylate functions 1–4.
methacrylate groups with TMSNTf2. Reactions carried out in the
presence of 2,6-bis-tert-butyl-4-methylpyridine for neutralizing
residual traces of TfOH in TMSNTf2 gave also the expected product,
however, with a decreased yield (36%) (Table 1, entry 7).23 Attempts
to reduce the amount of TMSNTf2 to 10 mol % was detrimental to
the conversion of 1 and only 23% of 6 was isolated (Table 1, entry 8).
Identically, using 1 equiv or excess of TMSNTf2 was unsatisfactory,
due to partial polymerization of both the starting material 1 and the
desired product 6. In all cases, the product 6 of the reaction was
easily detected by TLC monitoring, and full conversion of 1 was
always observed. Traces of other more polar byproducts were
observed, however, identification of their structures by NMR
remained difficult. These side products might arise from the
hydrolysis of the anomeric position of compound 1 or from the
activation of the acrylate functions. Partial polymerization of 1 and
6 was only detected when 1 equiv of TMSNTf2 was used.
The identification of the unknown reactivity and chemo-
compatibility of TMSNTf2 with permethacrylated and peracetylated
O-glycosyl trichloroacetimidate reagents prompted us to finally
evaluate the substrate scope and the limitations of the reaction, as
well as its influence on the stereoselectivity (Table 2).
We have found that permethacrylated O-glycosyl tri-
chloroacetimidate mannose 2 and xylose 3 derivatives behaved
similarly to 1, and provided 7 and 8 in good yield (Table 2, entries 1
and 2). While the reaction was highly stereoselective and delivered
2. Result and discussion
TMSNTf2 was first prepared according to reported procedures
that use the protodesylilation of allyltrimethylsilane with com-
mercially available HNTf2 at room temperature.22,23 It is important
to mention, that all the glycosidation reactions were carried out
under an inert atmosphere and any other precautions were nec-
essary for the handling of permethacrylated carbohydrates.18b
Permethacrylated O-glycosyl trichloroacetimidate reagent 1
was first used in glycosidation reaction with alcohol 524 in the
presence of the most commonly used activators such as TMSOTf
and BF3$Et2O in standard conditions (DCM at 0 ꢀC, for 1 h).6 The
reactions afforded stereoselectively the b-glycoside in reasonable
yields, 44% and 51%, respectively (Table 1, entries 1, 2). We then
experienced the reactivity of 1 in the presence of a catalytic amount
of protic acids, such as TfOH and HNTf2 (Table 1, entries 3 and 4).
The reactions delivered cleanly and stereoselectively the expected
exclusively the
ratio of the
8. Permethacrylated Schmidt dissacharide such as the lactose de-
rivative 4 gave satisfactorily the -anomer 9, although the yield was
a
-glycoside for permethacrylated mannose 7, a 5/2
b/a anomers was obtained for permethacrylated xylose
b
-glycoside 6 in comparable yields with the results obtained with
TMSOTf and BF3$Et2O. Triflic anhydride behaved similarly and
afforded 6, in moderate yield with a complete stereoselectivity
b
decreased to 23% (Table 2, entry 3). In this conditions, unactivated
alcohol such as phenol 10 could also react with 1 in a stereo-
selective manner giving rise to 11 (41%) (Table 2, entry 4). While the
b
(Table 1, entry 5). It is important to point out that there was no
literature precedent mentioning the use of these Lewis acids with
permethacrylated O-glycosyl trichloroacetimidate reagents. How-
ever, only recently HNTf2 has been reported for glycosidation re-
actions in ionic liquid for the activation of a glucopyranosyl diethyl
phosphite25 and glucopyranosyl fluoride.26 With the goal of im-
proving the overall efficiency of the reaction we envisioned to test
other Lewis acid, that is, stronger than TMSOTf,6 and that would
still remain selective with methacrylate functions. To our delight,
glycosidation of 1 with 5 performed with TMSNTf2 yielded to
reaction with primary alcohol 5 and phenol with 1 afforded the
glycoside, we observed that the glycosidation with cyclohexanol 12
was not as selective and gave a 1/1 mixture of glycoside 13 and
b-
b/a
in a less efficient manner (Table 2, entry 5). This lack of selectivity is
not understood yet and might eventually, be ascribed to incomplete
anchimeric assistance of the 2-methacrylate group of 1. This result
was partially corroborated when peracetylated Schmidt reagent 14
was submitted in strictly identical conditions. In this particular case
the b-anomer was formed as the unique product 15 exclusively
(Table 2, entry 6).
b-glycoside 6 with 42% (Table 1, entry 6). Even though TMSNTf2 is
known to act as a strong C]O bond activator, the desired glycoside
is obtained without alteration of the stereoselectivity and with
comparable yield to the classical catalyst activators used previously.
These results demonstrated the chemical compatibility of
Finally we envisaged to extend the use of TMSNTf2 as activator
for peracetylated O-glycosyl trichloroacetimidate reagents. It
appeared that the efficiency of the glycosidation was dependent on
the structure of the nucleophilic alcohol acceptor. Indeed, while
cyclohexanol 12 was successfully coupled with 14 (Table 2, entry 6),
primary alcohol gave poor yield, 18% for the compound 16 (Table 2,
entry 7) and the use of low nucleophilic phenol 10 afforded only
traces amount of the expected product 17 (Table 2, entry 8). We
have eventually found that more complex peracetylated O-glycosyl
trichloroacetimidate disaccharides 18 and 21 reacted with func-
tionalized alcohol 20 and yielded to 19 and 22 in acceptable yields
for such complex functionalized sugars (Table 2, entries 9 and 10).
Table 1
Glycosidation of 1 with different promoters
OAcr
OAcr
HO
OBn
12
5:
O
O
AcrO
AcrO
AcrO
AcrO
O
OBn
12
AcrO
NH
CCl3
OAcr
O
DCM, 0°C, 1h
1
6
It is worthwhile to mention that pure
formed exclusively when peracetylated substrates were used.
However, as general trend, peracetylated O-glycosyl tri-
b anomers were also
a
Entry
Promoters
Equiv
Isolated yield (%)
Ratio (b/a)
chloroacetimidate were less stable in the glycosidation conditions,
since the hydrolyzed peracetylated carbohydrates were always
formed as byproducts in large amounts. All together, these results
demonstrate for the first time, the chemocompatibility of TMSNTf2
in glycosidation reactions involving either permethacrylated O-
glycosyl trichloroacetimidates, and to some extent with peracety-
lated O-glycosyl trichloroacetimidate.
1
2
3
4
5
6
7
8
TMSOTf
BF3$Et2O
TfOH
HNTf2
Tf2O
TMSNTf2
TMSNTf2
TMSNTf2
0.5
0.5
0.1
0.1
0.5
0.5
0.5a
0.1a
44
51
35
48
44
42
36
23
1/0
1/0
1/0
1/0
1/0
1/0
1/0
1/0
a
In summary, we have reported the use of TMSNTf2 for the selective
activation of permethacrylated O-glycosyl trichloroacetimidates. The
0.1 Equiv of 2,6-bis-tert-butyl-4-methylpyridine was added in the reaction
mixture.

C. Zandanel et al. / Tetrahedron 66 (2010) 3365–3369
3367
Table 2
Glycosidation of permethacrylated O-glycosyl trichloroacetimidate carbohydrates with TMSNTf2
a
Entry
O-Glycosyl trichloroacetimidate
Alcohol
Product
Yield (%)
40
Ratio (
b/a)
OAcr
OAcr
OAcr
OAcr
O
O
AcrO
AcrO
AcrO
1
AcrO
5
0/1
NH
CCl3
O
O
O
OBn
12
7
2
O
AcrO
AcrO
O
AcrO
O
OBn
12
AcrO
AcrO
2
3
5
5
35
23
5/2
1/0
NH
CCl3
OAcr
8
3
OAcr
OAcr
O
OAcr
O
OAcr
AcrO
OAcr
ArO
OAcr
O
AcrO
O
O
AcrO
O
AcrO
O
OBn
12
AcrO
OAcr
O
NH
CCl3
OAcr
9
4
OAcr
OAcr
OH
O
O
O
AcrO
AcrO
AcrO
4
5
6
7
8
9
AcrO
41b
1/0
1/1
1/0
1/0
/
O
AcrO
NH
CCl3
AcrO
10
1
11
OAcr
OAcr
O
O
OH
O
O
AcrO
AcrO
AcrO
AcrO
O
23
AcrO
NH
CCl3
AcrO
12
1
13
OAc
OAc
O
O
AcO
AcO
AcO
AcO
O
12
37
AcO
AcO
NH
CCl3
14
15
OAc
OAc
O
O
O
AcO
AcO
AcO
AcO
O
OBn
12
5
18
AcO
NH
CCl3
OAc
16
14
OAc
OAc
O
O
O
AcO
AcO
AcO
AcO
O
10
Traces
AcO
AcO
NH
CCl3
14
17
OAc
O
OAc
AcO
OAc
OAc
O
OAc
AcO
OAc
O
HO
O
O
O
N3
24
1/0
AcO
O
OAc
3
O
AcO
AcO
OAc
O
N3
O
NH
CCl3
20
AcO
18
3
19
OAc
OAc
OAc
O
O
OAc
AcO
AcO
AcO
O
AcO
AcO
O
O
10
20
30
1/0
AcO
O
OAc
O
AcO
AcO
OAc
O
N3
O
NH
CCl3
0.5 Equiv of TMSNTf2 was used in DCM at 0 ꢀC, for 1 h.
21
3
22
a
b
The product 11 was contaminated with phenol 10 due to the same Rf of the compounds for purification carried out by column chromatography on silica.
reactions were highly stereoselective and favoured
b
-glycosides due
chemocompatibility of the permethacrylated, as well as the acetate
functions of the substrates with TMSNTf2. Besides this we have also
shown that protic acid such as HNTf2 can also be used successfully to
promote the glycosidation reactions for Schmidt reagents.
to anchimeric assistance of the methacrylate group. The overall effi-
ciencyinterms of isolatedyields, iscomparablewithotherpromoters,
and the most important feature of these conditions still remain the

3368
C. Zandanel et al. / Tetrahedron 66 (2010) 3365–3369
3. Experimental
1639, 1452, 1322, 1294, 1155, 1076; HRMS (m/z): calcd for
C
59H80O19Li: 1099.5454 [MþLi]þ; found 1099.5407; mp: 82–
3.1. General
85 ꢀC.
The general procedure for the preparation of O-glycosyl tri-
chloroacetimidates 1, 2, 3 and 4 can be found in Ref. 18a. Compound
14 was prepared accordingly to the protocol described in the Ref. 27
and compounds 18 and 21 were synthesized following reported
procedures.28 Alcohol 20 was synthesized according to Ref. 29. The
preparation of TMSNTf2 has been performed following the Ghosez’s
protocol.21
3.2.5. Synthesis of compound 11. From 100 mg of 1, 36.1 mg of 11
was recovered as a white solid (yield: 41%) (SiO2, cyclohexane/
EtOAc¼7/3, Rf¼0.60). 1H NMR (CDCl3, 400 MHz)
d (ppm):
7.27–6.81(m, 7H), 6.15–6.04 (m, 4H), 5.60–5.50 (m, 5H), 5.44–5.40
(m, 1H), 5.31 (t, J¼9.1 Hz, 1H), 5.17 (d, J¼8.0 Hz, 1H), 4.35–4.15 (m,
2H), 3.99–3.94 (m, 1H), 1.89–1.75 (m, 12H); 13C NMR (CDCl3,
100 MHz)
135.2, 135.1, 129.7, 127.3, 127.2, 126.8, 126.5, 120.7, 117.3, 99.6, 72.8,
72.5, 71.5, 69.2, 63.0,18.4; IR:
(cmꢁ1) 2959, 2929,1726,1637,1591,
d (ppm): 167.0, 166.5, 165.9, 165.8, 157.1, 135.9, 135.5,
3.2. General procedure for the glycosidation reactions of
O-glycosyl trichloroacetimidates 1, 2, 3, 4, 14, 18 and 21
promoted by TMSNTf2
n
1495, 1453, 1404, 1379, 1319, 1295, 1231, 1144, 1075, 1045, 1016;
HRMS (m/z): calcd for C28H36O1N: 546.2339 [MþNH4]þ; found
546.2338; mp: 104–106 ꢀC.
The glycosyl donor (1 equiv) was dissolved in dichloromethane
(concentration fixed at 50 mM) and alcohol 5, 10, 12 or 20
(1.2 equiv) was added. The reaction mixture was cooled down to
0 ꢀC and TMSNTf2 (0.5 equiv, freshly prepared DCM solution at
0.7 M) was slowly added. The mixture became brown after 10 min.
After stirring for 1 h at 0 ꢀC in DCM, the solvent was evaporated and
the purification is performed by column chromatography with the
indicated solvents.
3.2.6. Synthesis of compound 13. From 110.0 mg of 1, 22.0 mg of
13 was recovered as a white solid (yield: 23%) (SiO2, cyclohex-
ane/EtOAc¼7/3, Rf¼0.55). 1H NMR (CDCl3, 400 MHz)
d (ppm):
6.14–6.11 (3s, 4H), 5.60–5.51 (m, 4H), 5.42 (t, J¼9.6 Hz, 1H), 5.21
(t, J¼10.0 Hz, 1H), 5.12 (t, J¼7.6 Hz, 1H), 4.70 (d, J¼8.0 Hz, 1H),
4.37–4.20 (m, 2H), 3.88–3.82 (m, 1H), 3.62–3.59 (m, 1H), 1.94–
1.72 (m, 12H), 1.75–1.62 (m, 4H), 1.47–1.20 (m, 7H); 13C NMR-
APT (CDCl3, 100 MHz)
d (ppm): 166.6, 166.1, 165.9, 165.8,
3.2.1. Synthesis of compound 6. From 600.0 mg of 1, 411.4 mg of 6
was recovered as colourless oil (yield: 56%) (SiO2, cyclohexane/
EtOAc¼8/2, Rf¼0.46). For 1H and 13C NMR see Ref. 17b.
136.0–135.2, 127.0–126.2, 99.8, 94.6, 77.5, 76.8, 73.1, 72.1, 71.9,
71.8, 70.6, 69.6, 69.4, 67.8, 63.1, 63.0, 33.4, 31.6, 25.5, 24.0, 23.7,
18.5–18.3; IR:
n
(cmꢁ1) 2933, 2856, 1731, 1638, 1453, 1320, 1295,
1150, 1018; MM-ES (m/z): 435.1 [M-cyclohexanol]þ; mp:
3.2.2. Synthesis of compound 7. From 1.4 g of 2, 1.1 g of 7 was re-
covered as yellow oil (yield: 40%) (SiO2, cyclohexane/EtOAc¼7/3,
92–93 ꢀC.
Rf¼0.75). 1H NMR (CDCl3, 300 MHz)
d
(ppm): 7.27 (m, 5H),
3.2.7. Synthesis of compound 15. From 100 mg of 14, 32.0 mg of
15 was recovered as a white solid (yield: 37%) (SiO2, cyclohex-
6.15–5.93 (4s, 4H), 5.58–5.29 (m, 8H), 4.83 (s, 1H), 4.44 (s, 2H),
4.30–4.19 (m, 3H), 3.64 (m, 1H), 3.40 (m, 3H), 1.90–1.76 (m, 12H),
ane/EtOAc¼7/3, Rf¼0.50). 1H NMR (CDCl3, 400 MHz)
d (ppm):
1.57 (m, 4H), 1.21 (m, 16H); 13C NMR (CDCl3, 75 MHz)
d
(ppm):
5.19 (t, J¼9.6 Hz, 1H), 5.08 (t, J¼9.6 Hz, 1H), 4.98–4.93 (m, 1H),
4.58 (d, J¼8.0 Hz, 1H), 4.28–4.21 (m, 1H), 4.13–4.07 (m, 1H),
3.70–3.59 (m, 2H), 2.07 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H), 2.01 (s,
3H), 1.91–1.65 (m, 5H), 1.53–1.40 (m, 2H), 1.35–1.18 (m, 5H); 13C
167.0, 166.3, 166.2, 166.1, 136.2, 135.8, 135.6, 135.5, 128.4, 127.6,
126.8,126.7,126.6,126.0, 97.7, 73.0, 70.7, 70.5, 69.9, 68.8, 66.8, 62.9,
29.9–29.4, 26.3, 18.3–18.1; IR:
n
(cmꢁ1) 2927, 2854, 1728, 1638,
1454, 1321, 1294, 1135, 1081; HRMS: (m/z): calcd for C41H58O11Li:
NMR (CDCl3, 100 MHz) d (ppm): 170.9, 170.5, 169.6, 169.4, 99.5,
733.4139 [MþLi]þ; found 733.4139.
78.2, 73.1, 71.8, 68.8, 62.3, 33.3, 31.6, 25.6, 23.7, 20.9–20.7; IR:
n
(cmꢁ1) 2935, 1732, 1558, 1541, 1456, 1230,1037; HRMS (m/z):
calcd for C20H30O10Naþ: 453.1737 [MþNa]þ; found 453.1735;
mp: 80–81 ꢀC.
3.2.3. Synthesis of compound 8. From 334.4 mg of 3, 296.0 mg of 8
was recovered as colourless oil (yield: 35%) (SiO2, cyclohexane/
EtOAc¼7/3, Rf¼0.60). 1H NMR (CDCl3, 300 MHz)
d (ppm): 7.27 (m,
5H), 6.12–6.03 (m, 3H), 5.73 (t, 0.3H, J¼9.0 Hz), 5.59–5.52 (m, 3H),
5.38 (t, 0.3H, J¼7.8 Hz), 5.09–4.99 (m, 2H), 4.92 (m, 0.3H), 4.58 (d,
1H, J¼6.7 Hz); 4.51 (s, 2H), 4.23 (m, 0.7H), 3.92–3.65 (m, 1.7H),
3.51–3.38 (m, 3.8H), 1.91–1.88 (m, 9.8H), 1.69–1.51 (m, 5H), 1.26 (m,
3.2.8. Synthesis of compound 16. From 105.0 mg of 14, 24.0 mg of
16 was recovered as colourless oil (yield: 18%) (SiO2, cyclohexane/
EtOAc¼7/3, Rf¼0.32). For 1H and 13C NMR, see Ref. 17b.
17H); 13C NMR (CDCl3, 75 MHz)
d
(ppm): 166.4, 165.9, 162.3, 138.9,
3.2.9. Synthesis of compound 19. From 574.0 mg of 18, 148.0 mg of
19 was recovered as colourless oil (yield: 24%) (SiO2, cyclohexane/
135.7, 135.5, 128.5, 127.7, 127.6, 126.9, 126.5, 100.8, 96.0, 73.0, 71.7,
71.3, 70.9, 70.7, 70.0, 69.8, 69.4, 68.7, 62.0, 58.6, 30.1–29.5, 27.0–
EtOAc¼3/7, Rf¼0.3). 1H NMR (CDCl3, 300 MHz)
d (ppm): 5.32 (d,
26.0, 18.4; IR:
n
(cmꢁ1) 2927, 2854, 1729, 1639, 1453, 1322, 1293,
J¼3.0 Hz, 1H), 5.18 (t, J¼9.3 Hz, 1H), 5.07 (t, J¼7.8 Hz, 1H), 4.96–4.87
(m, 2H), 4.50 (t, J¼8.4 Hz, 3H), 4.13–4.06 (m, 6H), 3.89–3.61 (m,
14H), 3.42 (t, J¼6.0 Hz, 2H), 2.12–1.94 (m, 21H); 13C NMR-APT
1151, 1048; HRMS (m/z): calcd for C36H52O9Li: 635.3771 [MþLi]þ;
found 635.3770; mp: 82–85 ꢀC.
(CDCl3, 75 MHz)
d (ppm): 171.0–169.5, 101.5, 101.2, 76.4, 73.3,
3.2.4. Synthesis of compound 9. From 380.0 mg of 4, 100.0 mg of 9
was recovered as a white solid (yield: 23%) (SiO2, cyclohexane/
72.7, 72.2, 71.4, 71.1, 70.7–70.2, 69.5, 69.2, 67.0, 62.2, 61.1, 51.0, 21.2–
20.9; MM-ES (m/z): 855.2 [MþNH3]þ.
EtOAc¼7/3, Rf¼0.53). 1H NMR (CDCl3, 300 MHz)
d (ppm): 7.27
(m, 5H), 6.12–5.89 (6s, 7H), 5.58–5.42 (m, 7H), 5.31 (t, 1H,
J¼8.5 Hz), 5.21 (m, 1H), 5.05–4.95 (m, 2H), 4.54 (d, 1H, J¼8.5 Hz),
4.47–4.42 (m, 3H), 4.17–3.95 (m, 3H), 3.95 (m, 2H), 3.75 (m, 1H),
3.63 (m, 1H), 3.39 (m, 3H), 1.98–1.72 (m, 21H), 1.55 (m, 4H), 1.15
3.2.10. Synthesis of compound 22. From 159 mg of 21, 52.4 mg of 22
was recovered as a colourless oil (yield: 30%) (SiO2, cyclohexane/
EtOAc¼2/8, Rf¼0.3). 1H NMR (CDCl3, 300 MHz)
d (ppm): 5.21–5.06
(m, 3H), 4.94–4.87 (m, 2H), 4.57–4.48 (m, 3H), 4.40 (dd, J¼4.5 Hz,
16.2 Hz, 1H), 4.25 (t, J¼4.5 Hz, 1H), 4.15–4.13 (m, 1H), 4.03 (dd,
J¼1.8 Hz, 12.3 Hz, 1H), 3.95–3.82 (m, 2H), 3.74–3.59 (m, 14H), 3.44
(t, J¼6.0 Hz, 2H), 2.12–1.97 (m, 21H); 13C NMR-APT (CDCl3, 75 MHz)
(m, 16H),; 13C NMR-APT (CDCl3, 75 MHz)
d (ppm): 166.6–165.7,
136.0–135.1, 128.4, 127.6, 127.5, 127.2, 127.1, 126.9, 126.7, 126.2,
100.9, 100.6, 75.8, 72.8, 71.7, 71.4, 71.1, 70.6, 70.2, 69.6, 67.3, 62.3,
61.4, 29.8–29.4, 26.2, 25.8, 18.3; IR:
n
(cmꢁ1) 2929, 2856, 1750,
d (ppm): 171.2–169.5, 101.3, 101.2, 76.5, 73.4, 72.3–71.9, 70.4–70.1,

C. Zandanel et al. / Tetrahedron 66 (2010) 3365–3369
3369
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Acknowledgements
This work was supported by the University of Strasbourg, (grant
to C.Z.) and the Ministe`re de l’Education National et de la Recherche
for a grant to L.D.
Supplementary data
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9395; (b) Curcio, P.; Zandanel, C.; Wagner, A.; Mioskowski, C.; Baati, R. Macromol.
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Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2010.02.068.
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