Variations on the SnCl4 and CF3CO2Ag-promoted glycosidation of sugar acetates: a direct, versatile and apparently simple method with either α or β stereocontrol

Article abstract of DOI:10.1016/j.carres.2009.06.004

Glycosidation of sugar peracetates (d-gluco, d-galacto) with SnCl₄ and CF₃CO₂Ag led to either 1,2-cis-, or 1,2-trans-glycosides, depending primarily on the alcohols used. In particular, 1,2-trans-glycosides, expected from acyl-protected glycosyl donors, were formed in high yields with alcohols sharing specific features such as bulkiness, presence of electron-withdrawing groups or polyethoxy motifs. In contrast, simple alcohols afforded ～1:1 mixtures of 2,3,4,6-tetra-O-acetyl, and 3,4,6-tri-O-acetyl 1,2-cis-glycosides due to anomerization and/or acid-catalyzed fragmentation of 1,2-orthoester intermediates. After reacetylation or deacetylation, acetylated or fully deprotected 1,2-cis-glycosides (α-d-gluco, α-d-galacto) were obtained in ～90% yields by a simple and direct method.

Full text of DOI:10.1016/j.carres.2009.06.004

Carbohydrate Research 344 (2009) 1646–1653
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Variations on the SnCl4 and CF3CO2Ag-promoted glycosidation of sugar
acetates: a direct, versatile and apparently simple method with either
a
or b stereocontrol
1
1
*
Jia Lu Xue , Samy Cecioni, Li He , Sébastien Vidal, Jean-Pierre Praly
Université de Lyon, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires associé au CNRS, UMR 5246, Laboratoire de Chimie Organique 2,
Bâtiment Curien, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France
Université Lyon 1, F-69622 Villeurbanne, France
CNRS, UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Laboratoire de Chimie Organique 2, Bâtiment Curien,
43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Glycosidation of sugar peracetates (D-gluco, D-galacto) with SnCl4 and CF3CO2Ag led to either 1,2-cis-, or
Received 23 April 2009
Received in revised form 27 May 2009
Accepted 1 June 2009
1,2-trans-glycosides, depending primarily on the alcohols used. In particular, 1,2-trans-glycosides,
expected from acyl-protected glycosyl donors, were formed in high yields with alcohols sharing specific
features such as bulkiness, presence of electron-withdrawing groups or polyethoxy motifs. In contrast,
simple alcohols afforded ꢀ1:1 mixtures of 2,3,4,6-tetra-O-acetyl, and 3,4,6-tri-O-acetyl 1,2-cis-glycosides
due to anomerization and/or acid-catalyzed fragmentation of 1,2-orthoester intermediates. After reacet-
Available online 6 June 2009
Keywords:
Peracetyl-aldopyranoses
Glycosylation
Tin tetrachloride
Silver trifluoroacetate
1,2-cis-Glycosides
1,2-trans-Glycosides
Anomerization
ylation or deacetylation, acetylated or fully deprotected 1,2-cis-glycosides (
obtained in ꢀ90% yields by a simple and direct method.
a-D-gluco, a-D-galacto) were
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
pyranoside and ethyl 3,4,6-tri-O-acetyl-a-D-glucopyranoside
(ꢀ1:1 ratio) without any trace of the corresponding b-anomers.
Based on the generally accepted idea that acyl-protected glycosyl
donors led to 1,2-trans glycosides due to neighbouring group partic-
ipation,1,7,8 the isolation of pure 1,2-cis anomers attracted our atten-
tion. Despitetheformationof productsregioselectively deacetylated
Most of the carbohydrates found in Nature display complex
structures, which primarily involve monosaccharides linked to
each other or to other types of aglycones by glycosidic bonds.
Although O-, S-, N-, C-glycosidic linkages are known to be present
in naturally occurring carbohydrates, O-glycosides play a promi-
nent role, due to their abundance and importance.1 In recent pro-
jects focusing on C-glycosyl aryls,2 we obtained C-glycosylated
hydro-, and benzo-quinones3 as well as analogues bearing either
one nitro group4 or two methyl substituents in either ortho or meta
disposition on the phenyl ring.5 These last compounds afforded
two series of C-glycosyl-chromane derivatives or C-glycosyl ana-
logues of vitamin E whose antioxidant activities were investi-
gated.5 A stereocontrolled C-glycosidation promoted by SnCl4 and
CF3CO2Ag in anhydrous CH2Cl2 was the key step for preparing such
C-aryl glycosides.6 Use of CH2Cl2 containing EtOH as stabilizer led
at O-2, single a-anomers would be expected if the mixture was sub-
sequently subjected to either acetylation or deacetylation. More-
over, due to the different polarities of the products obtained, the
tri-O-acetyl glycosides could be easily separated by chromatogra-
phy. Therefore, this method could provide a simple and rapid access
to 1,2-cis sugar-derivatives with a free hydroxygroup at C-2 and an
a
anomeric configuration opposite to that easily established by classi-
cal methods. Recent reports showed that such compounds9 are of
great interest in oligosaccharide synthesis as glycosyl acceptors10
and for stereocontrolled glycosidations based on either intramolec-
ular aglycon delivery11 or participation of a recently introduced
neighbouring group.9b All considered, our observation encouraged
us to study glycosidations promoted by SnCl4 and CF3CO2Ag for
achieving direct syntheses of acyl-protected 1,2-cis glycosides.12
From the earlier reports describing O-glycosidations of glycosyl
esters upon activation by Lewis acids,8a it appeared that SnCl4 has
found limited applications as a promoter, either alone13–15 or in
association with other salts, such as AgClO416 and Sn(OTf)2–LiClO4.17
to byproducts identified as ethyl 2,3,4,6-tetra-O-acetyl-a-D-gluco-
* Corresponding author.
E-mail address: jean-pierre.praly@univ-lyon1.fr (J.-P. Praly).
Present address: Institute of Fine Chemicals, East China University of Science and
Technology (ECUST), 130 Meilong road, P.O.Box 257, 200237 Shanghai, PR China.
1
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.06.004

J. L. Xue et al. / Carbohydrate Research 344 (2009) 1646–1653
1647
Glycosylation reactions of benzyl-protected
acetate with silylated alcohols and the Mukaiyama catalyst
(SnCl3ClO4) in Et2O afforded -glucosides with high stereoselectivi-
ty.16 In contrast, glycosidations of sugar peracetates afforded either
b-, or
-glycosides, due to anomerization,14,15 depending on struc-
D
-glucopyranose 1-O-
MeOH or EtOH in the presence of SnCl4 and CF3CO2Ag (entries 1,
4, 13 and 14),
-configured glycosides (ꢀ1:1 ratio) were obtained
exclusively, with the more polar product being deacetylated at
O-2. Compounds 80a 23 0a (for the b-anomer, see Ref. 24),
16’a 23a and 170a were isolated in yields ranging from 26% to
a
a
,
9
a
,
tural features and the reaction conditions. For example, it has been
noted that increased amounts of MeOH decreased the catalytic
efficiency of SnCl4.13 In the case of peracylated donors, it has been
proposed that the order of addition is important for anomeric selec-
tivity, and that combining acceptor and donor in solution followed
by addition of SnCl4 leads to mixtures of anomeric glycosides.18a
These early reports were limited and did not bring a clear analysis
of the stereoselectivity issue. Recently, glycosidations–anomeriza-
42%. Such moderate yields were comparable to those reported
for the regioselective deprotection of acetylated glycosides.25
When the reaction mixtures were subsequently subjected to acet-
ylation, the compounds 8a, 9a, 16a and 17a were obtained in
ꢀ90% yield. This yield is significantly higher than the 35% yield26
reported for a recent synthesis of 8a. Comparative experiments
without adding CF3CO2Ag (entries 2 and 3) afforded the methyl
tri-, and tetraacetylated glycosides, as anomeric mixtures.
tion of 1,6-anhydro-
b- -glucopyranuronic acids in the presence of SnCl4 has been re-
ported.19 Similarly, b-to-
anomerization has been put forward to
account for the exceptionally high :b selectivity of glycosidation
of a benzyl-protected
-mannopyranose ester20 with SnCl3ClO4 as
D
-glucopyranuronic acid and anomerization of
In our conditions, the a:b ratio increased from 3:1 to 10:1 after
7 h of reaction in the presence of 5 equiv of SnCl4 whereas use of
SnCl4 in lower amount (1 equiv) was reported to afford methyl tet-
D
a
a
ra-O-acetyl-b-D-glucopyranoside 8b in good yield, provided ano-
D
merization was avoided.27 Glycosidation of 1 with i-PrOH (entry
promoter.18b Other Lewis acids (e.g., BF3ꢁOEt221 or zeolite22) for the
glycosidation of sugar acetates led to more complex mixtures, com-
pared to our preliminary observations (high 1,2-cis stereoselectivi-
ty; deacetylation at O-2 mainly). We now report further data on
the glycosidation of accessible sugar peracetates with various alco-
hols upon reaction with SnCl4 and CF3CO2Ag or related Lewis acids,
as promoters.
6) occurred within 20 min, producing an anomeric mixture,28 but
when the reaction was allowed to proceed for 1 h, the
only was obtained in 60% yield. Use of allyl alcohol (entries 7
and 8) led mainly to
-glucosides21,29 (with 3-,21 or 4 OAc groups),
a-anomer
a
with only trace amount of the b-anomer. Donor 4 and 1,12-dode-
canediol (entry 17) led to a multicomponent mixture from which
the bis-a-galactoside 20a
, a bolaform precursor30 (Scheme 3)
could be isolated in 21% yield, based on the diol used. For glycosi-
dation of 3 and 5 with MeOH (entries 11, 12, 24 and 25), use of
SnCl4 and CF3CO2Ag led to multicomponent mixtures, but with
2. Results and discussion
3 equiv of SnCl4, the corresponding
a-anomers (a-D-manno
To establish the scope and limitations of the selected glycosida-
tion conditions, we chose differently configured pyranose acetates
(1–7) including activated donors of the 2-deoxy type (5) or a ben-
15 -arabino 25
a
),32 (2-deoxy- ),33 were produced in moderate
a
-
D
a
yields. This selectivity can be best explained by neighbouring
group participation (for 3) or anomerization. For 2-deoxy sugar 5,
the reaction was fast, as expected from the absence of electron-
withdrawing group at C-2 resulting in a high reactivity.34
zyl-protected analogue (7) (Scheme 1). Methyl b-D-glucopyrano-
side 8b was used in one experiment.
The glycosyl donors were reacted with various alcohols in the
presence of SnCl4 and CF3CO2Ag using pure CH2Cl2 as solvent.
The molar ratio of the reagents was generally 1:2.5:3:1.5 (sugar
donor/ROH/SnCl4/CF3CO2Ag), although SnCl4 (from commercially
available 1 M solution in CH2Cl2) used alone led sometimes to clea-
ner transformations (Table 1). In a few cases, the molar ratio sugar
donor/ROH was 1:1.5 (entries 15, 16, 19 and 26). With diols (en-
tries 17 and 20–22), the ratio was 1:0.33 and the yields were based
on the alcohol used. Generally, the reactions were stopped after
complete conversion of the substrate and possible intermediates
In the light of these glycosidations of sugar peracetates with
simple alcohols, the SnCl4–CF3CO2Ag couple appeared to produce
more active species, as compared to SnCl4 alone, thus permitting
anomerization of b-anomers. Interestingly, when glycosidation of
1 with MeOH was attempted using a 3:1 mixture of CH2Cl2–THF
as the solvent and SnCl4, the starting material remained un-
changed (entry 2, note c). The regioselectively O-2 deacetylated
glycosides observed probably arose from 1,2-orthoesters pro-
duced from bicyclic dioxocarbenium ion intermediates and ROH.
Acidic conditions are known to promote 1,2-orthoester transfor-
mation into ROAc and oxocarbenium intermediates, with a 2-
(the
a-anomerized substrate and especially the glycosyl chlo-
ride)3,14,15,27 and the products were subjected to chromatography
and checked by NMR (Scheme 2).
OH group, which undergo preferential
a
-glycosidation.15,22a,29d
Our attempts aiming at enhancing the yield of the O-2 deacety-
lated products were not successful. This fact further supports
the formation of O-2 deacetylated products from 1,2-orthoesters,
but, considering reports on SnCl4-promoted regioselective deben-
zylation,9h regioselective deacetylation of the fully protected gly-
cosides cannot be excluded.
Experiments carried out with EtOH and disarmed donors such
as
-anomer 2, because 1 and 2 afforded essentially the same mixture
of -glucosides, but at significantly different rates with complete
conversion achieved within 5 h versus 7 days, respectively (entries
4 and 5). When 1 (or its -galacto analogue 4) was reacted with
D-glucopyranose acetates confirmed the lower reactivity of the
a
a
D
OAc
OAc
OAc
OAc
AcO
AcO
O
O
O
O
AcO
AcO
AcO
AcO
AcO
OAc
AcO
OAc
OAc
OAc
AcO
AcO
AcO
AcO
4
OAc
1
2
3
OAc
AcO
AcO
OBn
O
OAc
O
OAc
O
O
AcO
AcO
BnO
BnO
O
OAc
AcO
AcO
AcO
BnO
OAc
5
6
7
Scheme 1. Aldopyranose acetates used as glycosyl donors.

1648
J. L. Xue et al. / Carbohydrate Research 344 (2009) 1646–1653
conditions
O
O
PO
O
+
ROH
OAc
OR
+
+
others
see Table 1
PO
HO
OR
1 - 6 (P = Ac)
(P = Bn)
8 - 27
8' - 11', 16',17'
7
Scheme 2. General picture of the Lewis acid-promoted glycosidation of 1–7.
Table 1
Glycosidation of sugar peracetates 1–7 and glycoside 8b with various alcohols and SnCl4, SnCl4+CF3CO2Ag, or BF3ꢁEt2O as promoter
Entry
Donor
ROH
Conditions,a time (h)b
Products (%)
8–27
, 36
80–110 160, 170
Others
1
2
3
1
1
1
MeOH
MeOH
MeOH
A, 4
8
a
8
0a, 42
B, 3.3c
C, 7
8, 36
8, 45
a
a
/b = 3:1
/b = 10:1
80, 38
80, 37
a
a
/b = 3:1
/b = 10:1
4
5
1
2
EtOH
EtOH
A, 5
A, 7 days
9
9
a
a
, 54
, 39
9
9
0a, 26
0a, 30
6
1
iPrOH
A, 20 min
10
a
, 50d 10b, 14
7
8
1
1
CH2CHCH2OH
CH2CHCH2OH
A, 3
B, 5
11
11
a
a
, 28d 11b, 3
, 28d 11b, 3
110a, 24
110a, 17
9
1
1
3
CF3CH2OH
BnO2CCH2OH
MeOH
A1, 75 min
A1, 2
12b, 47
13b, 45
Mixture
10
14b, 2
11
12
A, 5
B, 3
Other unidentified
15
16
17
a, 52
a, 35
a, 53
13
14
15
16
17
4
4
4
4
4
MeOH
A, 4
160a, 40
170a, 36
EtOH
A, 5
HOCH2CH2Cle
HOCH2CCHe
HO(CH2)12OHf
A, 2
18b, 82
A, 1.5
E, 5g
19b, 84
Multicomponent mixture
21b, 81
21, 66 a/b = 1:5
20a
, 21h
18
19
4
4
HO(CH2CH2O)2CH2CH2Cl
HO(CH2CH2O)2CH2CH2Cle
A, 2
G, 100 min
20
21
22
4
4
4
HO(CH2CH2O)5Hf
HO(CH2CH2O)5Hf
HO(CH2CH2O)5Hf
A2, 3
D, 24
G1, 5
Multicomponent mixture
22b, 23h
23b, 15h
23b, 45h
22b, 28h
23
4
HOCH2CH(NHFmoc)CO2Bnf
A3, 3
24b, 43
24
25
5
5
MeOH
MeOH
A, 1
B, 45 min
25
25
a
a
, 28
, 55
26
6
HO(CH2CH2O)2CH2CH2Cle
A, 2.5
26b, ꢀ80
27
28
7
7
CF3CH2OH
CF3CH2OH
F, 2
F, 72
27, 85
27, 76
a
a
/b = 6:4
/b = 7:3
29
8b
iPrOH
A, 19
10
a
, 28i
100a, 11
8, 12.5 a/b = 5:1
Conditions: aUnless otherwise stated, the reactions were performed at rt in CH2Cl2 using a glycosyl donor (1 equiv) [typically 1 mmol (390 mg) in 5 mL CH2Cl2 for entries 1–5,
7, 8, 10–14, 17 (CHCl3, 50 °C), 19 (4: 17 g), 21–22, or 0.256 mmol (100 mg) in 3 mL CH2Cl2 for entries 6, 9, 15 (4: 1 g), 16 (4: 2 g), 18 (4: 5 g), 23–25, 26 (6: 5 g), 27–29] and
2.5 equiv of the glycosyl acceptor ROH, with different promoters: SnCl4–CF3CO2Ag (3 equiv:1.5 equiv-conditions A; 1.5 equiv:1.5 equiv-conditions A1; 2 equiv:1 equiv-
conditions A2; 0.5 equiv:0.5 equiv-conditions A3); SnCl4 (3 equiv-conditions B; 5 equiv-conditions C; 1.73 equiv-conditions D; 2 equiv-conditions E; 0.1 equiv-conditions F);
BF3ꢁEt2O (5 equiv-conditions G; 1.7 equiv-conditions G1). Commercially available 1 M solutions of SnCl4 in CH2Cl2 were used. bUnless otherwise indicated. cUnreacted 1 was
recovered when using a 3:1 mixture of CH2Cl2–THF as the solvent (time: 3 h), or when adding 0.4 equiv THF (time 5 h). dProducts separated by chromatography. eThe acceptor
ROH was used in smaller excess (1.5 equiv). fCompared to the glycosyl donor (1 mol. equiv), the acceptor ROH was used in lower amount (0.33 mol. equiv). gDue to the poor
i
solubility of diol (0.5 mmol), the reaction was performed at 50 °C in CHCl3 (10 mL). hYield calculated based on the alcohol. Unoptimized yields.
AcO
AcO
OAc
OAc
O
O
O
AcO
AcO
O
O
C6H5
(CH2)12
O
O
AcO
OAc
O
14β
AcO
O
O
20α
OAc
OAc
AcO
AcO
AcO
O
OAc
OH
OAc
O
O
HO
O(CH2CH2O)5
OAc
OAc
O
HO
O
O
AcO
AcO
28β
HO
23β
Scheme 3. Other glycosides obtained.

J. L. Xue et al. / Carbohydrate Research 344 (2009) 1646–1653
1649
In sharp contrast with the previous results, the major products
O
OAc
1, 2, 4, 6
obtained with alcohols such as trifluoroethanol (entry 9), benzyl
glycolate BnO2CCH2OH (entry 10), chloroethanol (entry 15), prop-
argylic alcohol (entry 16), triethylene glycol monochlorohydrin
HO(CH2CH2O)2CH2CH2Cl (entries 18, 19 and 26), pentaethylene
AcO
glycol HO(CH2CH2O)5H (entries 20–22) and N-Fmoc-L-serine ben-
O
O
O
zyl ester HOCH2CH(NHFmoc)CO2Bn (entry 23), were b-glycosides,
which were obtained in moderate (ꢀ45%) to excellent (ꢀ80%)
yields (12b: 47%; 13b:35 45%; 18b:36 82%; 19b:37 84%; 21b:38 81%;
26b:39 ꢀ80%; 22b + 23b: 38%; 24b:40 43%). For comparison, 4 re-
acted with HOCH2CH(NHFmoc)CO2Bn in the presence of BF3ꢁEt2O
with a poor selectivity, yielding a mixture from which 24b was ob-
tained in ꢀ15% after column chromatography. Similarly, a lower
selectivity was observed for the BF3ꢁEt2O-promoted synthesis of
+
O
O
O
+
ROH bulky,
nucleophilic/acidic
ROH
small
O
O
O
O
- ROAc
OR
+
21 (1:5
a:b mixture in 66% yield, entry 19), although a 72% yield
AcO
HO
was reported for a large-scale preparation of pure b-anomer.38 Un-
der conditions A, 21b was prepared in an 81% yield on the 5-g scale
(entry 18), while the lactose derivative 26b (prepared on 0.4 and
5 g scale using 1.5 equiv of alcohol) was also produced in ꢀ80%
yield, which exceeded markedly the 43% yield previously pub-
O
H+
OR
anomerization
(R = ERG)
ROH
O
O
O
anomer.
lished.39 Benzyl glycolate (entry 10) led to b- -glucosides 13b35
D
OR
and a transesterified minor byproduct 14b, with no isolable
AcO
HO
HO
OR
OR
amounts of the corresponding
a-anomers, known to result from
oxidative degradation of isomaltulose.41 As expected, the armed
Scheme 4. Possible reaction pathways for Lewis acid-promoted glycosidation of
glycosyl donor 7 reacted under milder conditions20 to afford ano-
aldose acetates.43
mers 27a and 27b in high yield, purified in 43% and 25% yield,
respectively, after two successive chromatographic runs. Under
Zemplén deacetylation, compound 13b afforded the corresponding
methyl ester 28b42 (Scheme 3).
Conversely, glycosides displaying electron-withdrawing aglycons
should be reluctant to anomerization. In the presence of SnCl4
(0.1 equiv), the armed benzyl-protected donor 7 and trifluoroetha-
nol reacted to afford an anomeric mixture in high yield (entries 27
The preferential formation of b-anomers with no significant
amounts of partially deacetylated glycosides suggested that 1,2-
orthoesters may not be primarily involved in these reactions. This
should be related to the glycosyl acceptors employed, in terms of
structure and electronic properties. In 24b, the protected serine
moiety appeared bulky while 12b and 13b displayed aglycons with
electron-withdrawing groups. The polyethylene-derived alcohols
do not share these features but the chain oxygen atoms are ex-
pected to interact with tin cations, thereby leading to complexes
with milder Lewis acid properties. How this explains the observed
b-selectivity remains questionable, although it is conceivable that,
in the first mentioned cases, bulkiness and nucleophilicity (due to
acidity) should favour the preferred stereocontrolled b-attack of
the less-hindered oxocarbenium ion. In addition, due to either
bulkiness or unfavourable electronic properties of the aglycon,
the initially formed b-glycosides should not anomerize readily
(Scheme 4).
and 28), with the
Thus, for trifluoroethyl glucosides 12b and 27 (
a
:b ratio being 3:2 after 2 h, and 7:3 after 72 h.
:b mixture) and
a
under the applied conditions, cleavage of both endo-, and exo-cyclic
C–O bonds was limited.
In conclusion, glycosidation of sugar peracetates (D-gluco, D-ga-
lacto) with SnCl4 and CF3CO2Ag led to either 1,2-cis-, or 1,2-trans-
glycosides, depending primarily on the alcohols used. In particular,
1,2-trans-glycosides, expected from acyl-protected glycosyl do-
nors, were formed in high yields with alcohols sharing specific fea-
tures such as bulkiness, presence of electron-withdrawing groups
or polyethoxy motifs. In contrast, simple alcohols afforded ꢀ1:1
mixtures of 2,3,4,6-tetra-O-acetyl, and 3,4,6-tri-O-acetyl 1,2-cis-
glycosides due to anomerization and/or acid-catalyzed fragmenta-
tion of 1,2-orthoester intermediates. After reacetylation or deacet-
ylation, acetylated or fully deprotected 1,2-cis-glycosides (
a-D-
gluco,
direct method.
a
-
D
-galacto) were obtained in ꢀ90% yields by a simple and
Indeed, glycosides can anomerize by cleavage of either of the
C–O bonds (endo-, or exo-cyclic). Under the conditions applied,
cleavage of the endocyclic C–O bond is possible because this pro-
cess accounts for the anomerization of
to the more stable b-anomers.3 For 2,3,4,6-tetra-O-acetyl-C-
copyranosyl 1,4-dimethoxybenzene (and its -galacto analogue),
such an -to-b anomerization occurred over 4–5 h upon mild heat-
ing to 25–30 °C (CH2Cl2), while for 4-methoxy-3-(2,3,4-tri-O-acet-
yl-b-
-fucopyranosyl)toluene, the reaction proceeded at 0 °C.6 In
the first case, the somewhat stronger conditions can be readily
rationalized by invoking the disarming effect of the acetoxy group
at C6. It is also noteworthy that the b(1?4) interglycosidic link-
age43 in 6 was stable during the synthesis of 26b. We believe that
for the acetylated glycosides derived from simple alcohols (MeOH,
a
-C-glycopyranosyl aryls
3. Experimental
D
-glu-
D
3.1. General methods
a
Methanol was distilled under nitrogen and over Mg turnings
after adding few crystals of iodine. Dichloromethane was washed
with H2O, dried with K2CO3 and distilled over CaH2. Chloroform
was washed with H2O, dried with K2CO3 (stirring for 1–2 h) and
distilled over CaSO4. 2,2,2-Trifluoroethanol was dried with CaSO4,
then stirred with NaHCO3 to remove traces of acid and distilled.
Thin-layer chromatography (TLC) was carried out on aluminium
sheets coated with Silica Gel 60 F254 (Merck). TLC plates were in-
spected under UV light (k = 254 nm) and developed after spraying
a mixture of 10% H2SO4 in EtOH–H2O (1:1 v/v) followed by heating.
Silica gel column chromatography was performed with GeduranÒ
L
EtOH and i-PrOH), b-to-a anomerization occurred mainly by cleav-
age of the exo-cyclic C–O bond, due to the electron-releasing prop-
erties of the aglycons (R = ERG, Scheme 4). Such a cleavage was
evidenced by the fact that, when subjected to the glycosidation
conditions in the presence of i-PrOH, methyl glucoside 8b led to
silica gel Si 60 (40–63
Germany). NMR solvents were purchased from Euriso-Top
lm) purchased from Merck (Darmstadt,
the corresponding isopropyl glucosides 10
a
and 100a (entry 29).

1650
J. L. Xue et al. / Carbohydrate Research 344 (2009) 1646–1653
(Saint Aubin, France). 1H and 13C NMR spectra were recorded at
23 °C using Bruker Advance300, DRX300 or DRX500 spectrometers
with TMS or the residual solvent as the internal standard. 19F NMR
spectra were recorded with a Bruker Advance400 spectrometer
(376.24 MHz), with CFCl3 as the external reference. The following
abbreviations are used to explain the observed multiplicities: s,
singlet; d, doublet; dd, doublet of doublet; ddd, doublet of doublet
of doublet; t, triplet; td, triplet of doublet; q, quadruplet; m, mul-
tiplet; br, broad and p, pseudo. Structure elucidation was deduced
from 1D and 2D NMR spectroscopy which allowed, in most cases,
complete signal assignments based on COSY, HSQC and HMBC cor-
relations. Melting points were measured in open capillary tubes
with a Büchi apparatus. Optical rotations were determined with
a Perkin–Elmer 241 polarimeter at room temperature. MS (ESI)
mass spectra were recorded in the positive mode using a Thermo
Finnigan LCQ spectrometer. HRMS (LSIMS) mass spectra were
recorded in the positive mode using a Thermo Finnigan Mat 95
XL spectrometer. Elemental analyses were performed at the Ser-
vice Central d’Analyses du CNRS (Vernaison, France).
(dd, 1H, J5,6a = 4.5 Hz, J6a,6b = 12.2 Hz, H6a), 4.00 (dd, 1H,
J5,6b = 2.3 Hz, J6a,6b = 12.2 Hz, H6b), 3.93 (m, 1H, H5), 3.76 (m, 1H,
OCH2CH3), 3.58 (m, 1H, OCH2CH3), 3.58 (overlapped, H2), 2.26 (d,
1H, J2,OH = 11.2 Hz, OH), 2.05, 2.04, 1.99 (3s, 9 H, COCH3), 1.24 (t,
3H, J = 7.1 Hz, OCH2CH3); 13C NMR (CDCl3, 50 MHz) : d 171.1,
170.7, 169.7 (C@O, acetyl), 98.1 (C1), 73.5, 70.7, 68.1, 67.6 (C2,
C3, C4, C5), 64.3, 62.1 (C6, OCH2CH3), 20.9, 20.7, 20.6 (COCH3),
15.0 (OCH2CH3) ; MS (CI, isobutane) C14H22O9: MW 334.32, m/z :
335 [M+H]+ (5%), 289 [M+HꢃEtOH]+ (100%), 229 (25%), 169 (95%).
3.5. Trifluoroethyl 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside
(12b)
This compound was prepared from 1 (100 mg) according to the
typical procedure (Table 1, entry 9) and purified by column chro-
matography (EtOAc–petroleum ether, 2:3, v/v), as a white solid
(52 mg, 0.12 mmol, 47%). Other less mobile products (Rf = 0.24 to
Rf = 0.1) arising probably from partial deacetylation were not iden-
tified. Compound 12b: Mp 127–130 °C; Rf = 0.53, EtOAc–petroleum
ether, 2:3, v/
v
; ½a 2D0
ꢂ
ꢃ16.3 (c 1, CH2Cl2); 1H NMR (300 MHz, CDCl3):
3.2. Typical glycosidation procedure
d 5.23 (t, 1H, J = 9.6 Hz, H3), 5.11 (t, 1H, J = 9.6 Hz, H4), 5.04 (dd, 1H,
J1,2 = 7.8 Hz, J2,3 = 9.6 Hz, H2), 4.66 (d, 1H, J1,2 = 7.8 Hz, H1), 4.27
(dd, 1H, J5,6a = 4.6 Hz, J6a,6b = 12.4 Hz, H6a), 4.19–4.06 (m, 2H,
H6b, CH2CF3), 3.97 (qd, 1H, JH,F = 8.2 Hz, JH,H = 12.8 Hz, CH2CF3),
3.74 (ddd, 1H, J4,5 = 9.9 Hz, J5,6a = 4.6 Hz, J5,6b = 2.4 Hz, H5), 2.10,
2.05, 2.03, 2.02 (4s, 12H, CH3CO); 13C NMR (75 MHz, CDCl3): d
171.0, 170.6, 169.8, 169.7 (4s, 4C, CH3CO), 101.2 (C1), 72.7 (C3),
A mixture of peracetylated glycopyranose (usually 0.256 mmol
or 1 mmol, 1 equiv) and ROH (2.5 equiv) was dissolved in dry
CH2Cl2. CF3CO2Ag (1.5 equiv) was added and the mixture was stir-
red at room temperature under argon for 5 min. A 1M solution of
SnCl4 in CH2Cl2 (3 equiv) was added dropwise (addition time 20–
40 min) to the mixture upon stirring (see text and caption of Table
1 for details and similar conditions). After conversion of the sub-
strate, as indicated by TLC monitoring, the reaction was quenched
by adding saturated aqueous NaHCO3. After stirring briefly, the
mixture was filtered through a bed of Celite. The filtrate was
repeatedly extracted with CH2Cl2, and the organic phase was
washed with brine, before drying (MgSO4) and concentration un-
der reduced pressure. The residue was purified by silica gel column
chromatography.
3
2
2
72.6 (C5), 71.1 (C2), 68.5 (C4), 66.3 (q, JC,F = 34.6 Hz, CH2CF3),
62.1 (C6), 21.1, 21.0, 20.9 20.8 (4s, 4C, COCH3); 19F NMR
3
(282.38 MHz, CDCl3): d = –74.85 (t, 3F, JH,F = 8.2 Hz, CH2CF3); MS
(ESI, positive mode) m/z
:
453.0 [M+Na]+; Anal. Calcd for
C16H21F3O10 (MW: 430.33): C, 44.66; H, 4.92; F, 13.24. Found: C,
44.97; H, 5.07; F, 13.02.
3.6. (Benzyloxycarbonyl)methylene 2,3,4,6-tetra-O-acetyl-b-
glucopyranoside (13b) and (benzyloxycarbonyl-methoxycar-
bonyl)methyl 2,3,4,6-tetra-O-acetyl-b- -glucopyranoside (14b)
D-
D
3.3. Methyl 3,4,6-tri-O-acetyl-a-D )
-glucopyranoside (80a
These compounds were prepared from 1 (390 mg, 1 mmol) (2 h)
according to the typical procedure (Table 1, entry 10), whereby 1
This compound was prepared from 1 (390 mg, 1 mmol), accord-
ing to the general procedure and purified by silica gel chromatog-
(Rf = 0.45, EtOAc–petroleum ether, 2:3, v/v) was transformed into
several compounds (Rf = 0.38, Rf = 0.23, EtOAc–petroleum ether,
2:3, v/v), purified by silica gel chromatography (EtOAc–petroleum
raphy to afford 8
a
and 80a (Table 1). Compound 80a: colourless oil,
Rf = 0.11, EtOAc–petroleum ether, 2:3, v/
v
; ½a 2D2
ꢂ
+121.7 (c 1,
CH2Cl2); 1H NMR (CDCl3, 300 MHz): d 5.16 (t, 1H, J2,3 = J3,4
=
ether, 1:3, v/v) to afford 13b (223.5 mg, 45%) and 14b (10 mg,
9.6 Hz, H3), 4.93 (dd, 1H, J3,4 = 9.6 Hz, J4,5 = 9.9 Hz, H4), 4.76 (d,
1H, J1,2 = 3.7 Hz, H1), 4.20 (dd, 1H, J5,6a = 4.7 Hz, J6a,6b = 12.2 Hz,
H6a), 4.01 (dd, 1H, J5,6b = 2.3 Hz, J6a,6b = 12.2 Hz, H6b), 3.88 (dq,
1H, J4,5 = 9.9 Hz, J5,6a = 4.7 Hz, J5,6b = 2.3 Hz, H5), 3.62 (ddd, 1H,
J1,2 = 3.7 Hz, J2,3 = 9.6 Hz, J2,OH = 10.9 Hz, H2), 3.40 (s, 3H, OCH3),
2.40 (d, 1H, J2,OH = 10.9 Hz, OH), 2.03, 2.00, 1.96 (3s, 9H, acetyl);
13C NMR (CDCl3, 75 MHz) : d 171.4, 170.1, 170.0 (C@O, acetyl),
99.6 (C1), 73.7, 71.1, 68.4, 67.8 (C2, C3, C4, C5), 62.4 (C6), 60.0
(OCH3), 21.2, 21.1, 21.0 (COCH3); MS (CI, isobutane) C13H20O9
2%), both as colourless oil.
Compound 13b: Rf = 0.38, EtOAc–petroleum ether, 2:3, v/
v
; ½a 2D0
ꢂ
ꢃ26.8 (c 1, CH2Cl2); Lit.35: ½a D20
ꢂ
ꢃ22.4 (c 1.7, CHCl3); 1H NMR
(300 MHz, CDCl3): d 7.3 (br s, 5H, H-Ar), 5.24 (t, 1H, J = 9.6 Hz,
H3), 5.18 (s, 2H, OCH2Ph), 5.09 (t, 1H, J = 9.6 Hz, H4), 5.05 (dd,
1H, J1,2 = 7.8 Hz, J2,3 = 9.6 Hz, H2), 4.67 (d, 1H, J1,2 = 7.8 Hz, H1),
4.33 (s, 2H, OCH2C=O), 4.25 (dd, 1H, J5,6a = 4.6 Hz, J6a,6b = 12.4 Hz,
H6a), 4.12 (dd, 1H, J5,6b = 2.4 Hz, J6a,6b = 12.4 Hz, H6b), 3.68 (ddd,
1H, J4,5 = 9.9 Hz, J5,6a = 4.6 Hz, J5,6b = 2.4 Hz, H5), 2.08, 2.03, 2.02,
2.01 (4s, 12H, CH3CO); 13C NMR (75 MHz, CDCl3): d 171.1, 170.6,
170.1, 169.8, 169.4 (5s, 5C, C@O), 135.6, 129.1, 129.0, 128.9 (4s,
6C, phenyl), 100.5 (C1), 72.9 (C3), 72.4 (C5), 71.3 (C2), 68.7 (C4),
67.2 (OCH2Ph), 65.4 (OCH2C@O), 62.2 (C6), 21.2, 21.1, 21.0, 21.0
(4s, 4C, COCH3); MS (ESI, positive mode) m/z : 519.1 [M+Na]+; Anal.
Calcd for C23H28O12 (MW: 496.46): C, 55.64; H, 5.68. Found: C,
55.78; H, 5.96.
(MW 320.29): m/z
:
321 [M+H]+ (10%), 289 [M+HꢃMeOH]+
(100%), 229 (20%), 169 (55%) ; MS (ESI, positive mode) m/z :
343.1 [M + Na]+ (100%).
3.4. Ethyl 3,4,6-tri-O-acetyl-a-D )
-glucopyranoside (90a
This compound was prepared from 1 (390 mg, 1 mmol), accord-
ing to the general procedure and purified by silica gel chromatog-
Data for 14b: Rf = 0.23, EtOAc–petroleum ether, 2:3, v/
v
; ½a 2D0
ꢂ
raphy to afford 9
a
and 9’
a
(Table 1). Compound 9’
a
: colourless oil,
+120.9 (c 1,
ꢃ18.2 (c 1, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 7.40–7.34 m,
5H, H-Ar), 5.23 (t, 1H, J = 9.6 Hz, H3), 5.23 (d, 1H, J = 12.3 Hz,
OCH2Ph), 5.18 (s, 1H, J = 12.0 Hz, OCH2Ph), 5.09 (t, 1H, J = 9.6 Hz,
H4), 5.05 (dd, 1H, J1,2 = 8.1 Hz, J2,3 = 9.6 Hz, H2), 4.73 (d, 2H,
J = 4.2 Hz, OCH2C@O), 4.65 (d, 1H, J1,2 = 8.1 Hz, H1), 4.40 (d, 2H,
Rf = 0.15, EtOAc–petroleum ether, 1:2, v/
v
; ½a 2D2
ꢂ
CH2Cl2); lit.24 for b-anomer : Mp 121 °C ; ½a 2D2
ꢂ
+14.4 (EtOH); 1H
NMR (CDCl3, 200 MHz): d 5.20 (t, 1H, J2,3 = J3,4 = 9.7 Hz, H3), 4.96
(t, 1H, J3,4 = J4,5 = 9.7 Hz, H4), 4.89 (d, 1H, J1,2 = 3.9 Hz, H1), 4.23

J. L. Xue et al. / Carbohydrate Research 344 (2009) 1646–1653
1651
J = 1.2 Hz, OCH2C@O), 4.25 (dd, 1H, J5,6a = 4.5 Hz, J6a,6b = 12.3 Hz,
3.10. 1,12-Dodecyl bis-2,3,4,6-tetra-O-acetyl-
galactopyranoside (20
a-D-
H6a), 4.13 (dd, 1H, J5,6b = 2.4 Hz, J6a,6b = 12.3 Hz, H6b), 3.66 (ddd,
1H, J4,5 = 9.9 Hz, J5,6a = 4.5 Hz, J5,6b = 2.4 Hz, H5), 2.09, 2.07, 2.03,
2.01 (4s, 12H, CH3CO); 13C NMR (75 MHz, CDCl3): d 171.1, 170.6,
170.1, 169.9, 169.0, 167.5 (6s, 6C, C=O), 129.1, 128.9 (2s, 6C, phe-
nyl), 100.5 (C1), 72.9 (C3), 72.3 (C5), 71.3 (C2), 68.6 (C4), 67.8
(OCH2Ph), 65.0 (OCH2C@O), 62.1 (C6), 61.3 (OCH2C@O), 21.2,
21.1, 21.02, 21.01 (4s, 4C, COCH3); MS (ESI, positive mode) m/z :
577.1 [M+Na]+.
a)
This compound was prepared from 4 (577.9 mg, 1.482 mmol)
and 1,12-dodecanediol (100 mg, 0.494 mmol, 0.33 equiv) in dry
CHCl3 (10 mL) at 50 °C in the presence of SnCl4 (1 M solution in
CH2Cl2, 6 equiv) within 5 h (Table 1, entry 17) and purified by silica
gel chromatography (EtOAc–petroleum ether, 1:4, v/v, then EtOAc)
to afford 20
petroleum ether 1:1, v/
a (88 mg, 21%) as a colourless oil. Rf = 0.4, EtOAc–
v
; ½a 2D0
ꢂ
+121 (c 0.9, CH2Cl2); 1H NMR
3.7. Methyl 3,4,6-tri-O-acetyl-a-D )
-galactopyranoside (160a
(500 MHz, CDCl3): d 5.42 (dd, 2H, J3,4 = 3.4 Hz, J4,5 = 1.2 Hz, H4,
H40), 5.35 (m, 2H, J2,3 = ꢀ9 Hz, J3,4 = 3.4 Hz, H3, H30), 5.11 (m, 4H,
H1, H10, H2, H20), 4.25 (t, 2H, J = 6.2 Hz, H5, H50), 4.10 (m, 4H,
H6a, H6b, H6a0, H6b0), 3.68 (m, 2H, OCH2), 3.42 (m, 2H, OCH2),
2.11, 2.04, 2.02, 1.96 (4s, 24H, CH3CO), 1.57–1.49 (m, 4H, CH2),
1.25 (s, 16H, CH2). 3J1,2 (3.8 Hz) and 1JC1,H1 (170.5 Hz)31 were mea-
This compound was prepared from 4 (390 mg, 1 mmol), accord-
ing to the general procedure and purified by silica gel chromatog-
raphy to afford 16
oil, Rf = 0.11, EtOAc–petroleum ether, 2:3, v/
a and 16’a
(Table 1). Compound 160a: colourless
v
; ½a 2D2
ꢂ
+120.6 (c 0.6,
sured by a 2D NMR experiment (SAPHIR-HSQC)44
;
13C NMR
CH2Cl2); 1H NMR (CDCl3, 300 MHz): d 5.35 (d, 1H, J3,4 = 3.2 Hz,
H4), 5.09 (dd, 1H, J2,3 = 10.4 Hz, J3,4 = 3.2 Hz, H3), 4.84 (d, 1H,
J1,2 = 4.0 Hz, H1), 4.13 (t, 1H, J5,6 = 6.2 Hz, J5,6’ = 6.4 Hz, H5), 4.06
(d, 2H, J = 7.0 Hz, H6a, H6b), 3.40 (s, 3H, OCH3), 3.92 (br signal,
H2), 2.23 (s, 1H, OH), 2.10, 2.02, 2.01 (3s, 9H, acetyl); 13C NMR
(CDCl3, 75 MHz): d 171.1, 170.9, 170.6 (C@O, acetyl), 100.0 (C1),
71.0, 68.6, 67.4, 67.0 (C2, C3, C4, C5), 62.3 (C6), 56.0 (OCH3),
21.2, 21.0, 21.0 (3s, 3C, COCH3); Anal. Calcd for C13H20O9 (MW
320.29): C, 48.75; H, 6.29; O, 44.96. Found: C, 48.86; H, 6.35; O,
44.61.
(75 MHz, CDCl3): d 170.3, 170.3, 170.1, 169.9 (3s, 8C, CH3CO),
95.9 (s, 2C, C1, C10), 68.5 (s, 2C, OCH2), 68.1 (s, 2C, C2, C20), 68.0
(s, 2C, C4, C40), 67.5 (s, 2C, C3, C30), 66.0 (s, 2C, C5, C50), 61.7 (s,
2C, C6, C60), 29.5, 29.3, 29.2, 29.2, 26.0 (5s, 10C, CH2), 20.7,
20.6, 20.5 (3s, 8C, CH3CO); MS (ESI, positive mode) m/z : 885.3
[M+Na]+.
3.11. [2-[2-[2-[2-(2-Hydroxy)ethoxy]ethoxy]ethoxy]ethoxy]-
ethyl 2,3,4,6-tetra-O-acetyl-b-
3,6,9,12-Tetraoxatetradecan-1,14-di-yl bis-2,3,4,6-tetra-O-
acetyl-b- -galactopyranoside (23b)
D-galactopyranoside (22b) and
D
3.8. Ethyl 3,4,6-tri-O-acetyl-a-D )
-galactopyranoside (170a
These compounds were prepared from 4 (491.4 mg, 1.26 mmol)
and pentaethylene glycol (70 L, 0.42 mmol, 0.33 equiv), in CH2Cl2
(8 mL) in the presence of SnCl4 (1 M solution in CH2Cl2, 1.68 mL,
1.68 mmol, 1.33 equiv) (Table 1, entry 21). After 17 h, more SnCl4
(0.5 mL, 0.5 mmol, 0.4 equiv) was added. After conversion of 4
(24 h), silica gel chromatography (EtOAc–petroleum ether, 1:3,
This compound was prepared from 4 (390 mg, 1 mmol), accord-
l
ing to the general procedure and purified by silica gel chromatog-
raphy to afford 17
a
and 170a (Table 1). Compound 170a: white
crystals, Mp 95.5–96.5 °C (petroleum ether-EtOAc); Rf = 0.1,
EtOAc–petroleum ether, 2:3, v/
v
; ½a 2D2
ꢂ
+143.7 (c 0.65, CHCl3); 1H
NMR (CDCl3, 300 MHz) : d 5.39 (dd, 1H, J3,4 = 3.4 Hz, J4,5 = 0.9 Hz,
H4), 5.13 (dd, 1H, J2,3 = 10.4 Hz, J3,4 = 3.4 Hz, H3), 4.99 (d, 1H,
J1,2 = 4.0 Hz, H1), 4.20 (t, 1H, J = 7.0 Hz, H5), 4.09 (m, 2H, H6a,
H6b), 3.93 (ddd, 1H, J1,2 = 4.0 Hz, J2,3 = 10.4 Hz, H2), 3.80 (m, 1H,
OCH2CH3), 3.60 (m, 1H, OCH2CH3), 2.14, 2.05, 2.05 (3s, 9 H, acetyl),
2.10 (s, 1H, OH), 1.28 (t, 3H, J = 7.1 Hz, OCH2CH3); 13C NMR (CDCl3,
75 MHz) : d 171.1, 170.8, 170.6 (C@O, acetyl), 98.8 (C1), 71.2, 68.7,
67.4, 67.0 (C2, C3, C4, C5), 64.7, 62.2 (C6, OCH2CH3), 21.2, 21.0, 21.0
(3s, 3C, COCH3), 15.4 (OCH2CH3) ; Anal. Calcd for C14H22O9
(334.32): C, 50.30; H, 6.63; O, 43.07. Found: C, 50.60; H, 6.58; O,
43.37.
1:1, v/
(55.4 mg, 23%), both as colourless oil. In another run (Table 1, entry
22), 4 (491.4 mg, 1.26 mmol) and pentaethylene glycol (70 L,
0.42 mmol, 0.33 equiv) in CH2Cl2 (8 mL) were stirred at rt for 5 h
after addition of BF3ꢁEt2O (0.266 mL, 2.1 mmol, 1.67 equiv) to af-
ford after purification 23b (168.6 mg, 45%) and 22b (67 mg, 28%)
as colourless oils.
v; EtOAc) afforded 23b (55 mg, 15%) followed by 22b
l
Compound 22b: Rf = 0.23, EtOAc–MeOH, 10:1, v/
v
; ½a 2D0
ꢃ6.4 (c
ꢂ
0.88, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 5.39 (bd, J3,4 = 3.0 Hz,
1H, H4), 5.21 (dd, 1H, J1,2 = 7.9 Hz, J2,3 = 10.4 Hz, H2), 5.03 (dd,
1H, J2,3 = 10.4 Hz, J3,4 = 3.3 Hz, H3), 4.59 (d, 1H, J1,2 = 7.9 Hz, H1),
4.2–3.6 (m, 23H, H5, H6a, H6b, OCH2CH2O), 2.16, 2.07, 2.06, 1.99
(4s, 12H, CH3CO); 13C NMR (75 MHz, CDCl3): d 170.4, 170.3,
170.1, 169.5 (4s, 4C, CH3CO), 101.3 (C1), 72.5, 70.65, 70.56, 70.53,
70.52, 70.49, 70.28, 70.24, 69.1, 61.7, 61.3 (11s, 11C, OCH2CH2O,
C6), 70.9, 70.6, 68.8, 67.1 (4s, 4C, C2, C3, C4, C5), 20.76, 20.67,
20.65, 20.57 (CH3CO); MS (ESI, positive mode) m/z : 591.2 [M+Na]+.
3.9. Chloroethyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyranoside
(18b)
This compound was prepared from 4 (1.0 g) and freshly dis-
tilled 2-chloroethanol (260 L, 3.84 mmol, 1.5 equiv) in anhy-
l
Compound 23b: Rf = 0.67, EtOAc–MeOH, 10:1, v/
v
; ½a 2D0
ꢃ8.3
ꢂ
drous CH2Cl2 (30 mL) according to the typical procedure (Table
1, entry 15), whereby the crude product was purified by flash
chromatography (EtOAc–petroleum ether 1:1). Crystallization
from CH2Cl2–petroleum ether afforded 18b (868 mg, 82%) as a
(c 1, CH2Cl2); 1H NMR (500 MHz, CDCl3):
d
5.38 (dd, 2H,
J3,4 = 3.3 Hz, J4,5 = 0.5 Hz, H4), 5.18 (dd, 2H, J1,2 = 8.0 Hz,
J2,3 = 10.4 Hz, H2), 4.99 (dd, 2H, J2,3 = 10.4 Hz, J3,4 = 3.3 Hz, H3),
white powder. Mp 102–105 °C (CH2Cl2–petroleum ether). Lit36
:
4.54 (d, 2H, J1,2 = 8.0 Hz, H1), 4.16 (dd, 2H, J5,6
=
; ½a 2D0
ꢂ
+1.22 (c
6.6 Hz, J06;6 = 11.3 Hz, H6), 4.12 (dd, 2H, J50 ;6 = 6.9 Hz, H60), 3.95–
3.88 (m, 3H, H5, OCH2), 3.74–3.70 (m, 3H), 3.75–3.61 (m, 16H,
OCH2CH2O), 2.13, 2.04, 2.03, 1.96 (4s, 24H, CH3CO); 13C NMR
(125 MHz, CDCl3): d 170.3, 170.2, 170.1, 169.4 (4s, 8C, CH3CO),
101.3 (s, 2C, C1, C10), 70.8 (s, 2C, C3, C30), 70.6 (s, 2C, CH2CH2O),
70.55 (s, 2C, C5, C50), 70.5, 70.4, 70.2, 69.0 (4s, 8C, CH2CH2O),
68.7 (s, 2C, C2, C20), 67.0 (s, 2C, C4, C40), 61.2 (s, 2C, C6, C60),
20.7, 20.6, 20.6, 20.5 (4s, 8C, CH3CO); MS (ESI, positive mode)
m/z : 921.3 [M+Na]+.
syrup ; Rf = 0.51, EtOAc–petroleum ether, 1:1, v/
v
1, CH2Cl2); 1H NMR (300 MHz, CDCl3):
d
5.35 (dd, 1H,
J4,5 = 0.9 Hz, J3,4 = 3.4 Hz, H4), 5.18 (dd, 1H, J1,2 = 7.9 Hz,
J2,3 = 10.5 Hz, H2), 4.98 (dd, 1H, J3,4 = 3.4 Hz, J2,3 = 10.5 Hz, H3),
4.50 (d, 1H, J1,2 = 7.9 Hz, H1), 4.14–4.03 (m, 3H, H6a, H6b, 1H
from OCH2), 3.89 (td, 1H, J4,5 = 0.9 Hz, J5,6 = J5,6’ = 6.6 Hz, H-5),
3.73 (ddd, 1H, J = 6 Hz, J = 7 Hz, J = 11 Hz, 1H from OCH2), 3.63–
3.57 (m, 2H, –CH2Cl), 2.11, 2.03, 2.00, 1.94 (4s, 12H, CH3CO); for
13C NMR, see Ref. 36.

1652
J. L. Xue et al. / Carbohydrate Research 344 (2009) 1646–1653
3.12. Trifluoroethyl 2,3,4,6-tetra-O-benzyl-
(27a and trifluoroethyl 2,3,4,6-tetra-O-benzyl-b-D-glucopyrano-
side 27b
a
-
D
-glucopyranoside
ARCUS Chine 2005, financed jointly by the Ministry of Foreign
Affairs, is gratefully acknowledged, as well as support from the
University Claude-Bernard for cotutored Ph.D. thesis. Région
Rhône-Alpes is also thanked for financial support and a stipend
(to SC, ADR 2007 du Cluster Chimie).
These compounds were prepared from 745 (238 mg, 0.407 mmol)
and 2,2,2-trifluoroethanol (74.5 L, 1.02 mmol, 2.5 equiv) in the
l
presence of SnCl4 (Table 1, entries 27 and 28) and purified by silica
gel chromatography (two successive runs with 35:65 then 3:7
References
petroleum ether–CH2Cl2 as the mobile phase) to afford 27
(109 mg, 43%) then 27b (62 mg, 25%).
a
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Compound 27
a
: colourless oil, Rf = 0.52, CH2Cl2; ½a D20
ꢂ
+50.6 (c
0.92, CH2Cl2); 1H NMR (300 MHz, CDCl3): d 7.34–7.26 (m, 18H,
Ph), 7.14–7.11 (m, 2H, Ph), 4.98 (d, 1H, J = 11 Hz, CH2-Ar), 4.83 (d,
1H, J = 10.8 Hz, CH2-Ar), 4.83 (d, 1H, J = 11 Hz, CH2-Ar), 4.81 (d,
1H, J1,2 = 3.7 Hz, H1), 4.78 (d, 1H, J = 12 Hz, CH2-Ar), 4.62 (d, 1H,
J = 11.8 Hz, CH2-Ar), 4.59 (d, 1H, J = 12 Hz, CH2-Ar), 4.47 (d,
1H, J = 10.8 Hz, CH2-Ar), 4.46 (d, 1H, J = 12.1 Hz, CH2-Ar), 3.98 (t,
3
1H, J = 9.2 Hz, H3), 3.88 (q, 2H, JH,F = 8.7 Hz, CH2CF3), 3.77–3.62
(m, 4H, H4, H5, H6a, H6b), 3.58 (dd, 1H, J1,2 = 3.7 Hz, J2,3 = 9.6 Hz,
H2); 13C NMR (75 MHz, CDCl3): d 139.1, 138.4, 138.1 (3s, 4C,
C-ar), 128.8, 128.7, 128.4, 128.3, 128.2, 128.1, 128.0 (7s, 20C, CH-
1
Ar), 123.8 (q, 1C, JC,F = 278.7 Hz, CF3), 98.1 (1JC,H = 169.4 Hz, C1),
81.9 (C3), 80.0 (C2), 77.6 (C4), 76.1, 75.5, 73.9, 73.7 (4s, 4C, CH2-
2
Ar), 71.3 (C5), 68.5 (C6), 65.0 (q, 1C, JC,F = 38 Hz, CH2CF3); 19F
NMR (376.24 MHz, CDCl3): d ꢃ74.0 (CF3); MS (ESI, positive mode)
m/z : 645.3 [M+Na]+ (100%).
Compound 27b: white needles, Mp 94–96 °C (petroleum ether);
Rf = 0.41, CH2Cl2; ½a D20
ꢂ
+8.4 (c 0.38, CH2Cl2); 1H NMR (300 MHz,
CDCl3): d 7.34–7.26 (m, 18H, Ph), 7.16–7.12 (m, 2H, Ph), 4.93 (d,
1H, J = 10.9 Hz, CH2-Ph), 4.92 (d, 1H, J = 10.7 Hz, CH2-Ar), 4.81 (d,
1H, J = 10.7 Hz, CH2-Ar), 4.78 (d, 1H, J = 10.9 Hz, CH2-Ar), 4.68
(d, 1H, J = 10.7 Hz, CH2-Ar), 4.60 (d, 1H, J = 12.3 Hz, CH2-Ar), 4.53 (d,
1H, J = 12 Hz, CH2-Ar), 4.52 (d, 1H, J = 10.7 Hz, CH2-Ar), 4.50 (d, 1H,
2
3
J1,2 = 7.5 Hz, H1), 4.21 (dq, 1H, JH,H = 12.3 Hz, JH,F = 9 Hz, CH2CF3),
3.96 (dq, 1H, 2JH,H = 12.3 Hz, 3JH,F = 9 Hz, CH2CF3), 3.70 (m, 2H, H6a,
H6b), 3.62 (m, 2H, H3, H4), 3.50 (br t, 1H, J = 7.8 Hz, H2), 3.45 (m,
1H, H5); 13C NMR (75.47 MHz, CDCl3): d 138.8, 138.32, 138.28 (3s,
4C, C-Ar), 128.8, 128.7, 128.3, 128.2, 128.1, 128.1, 128.0 (7s, 20C,
1
CH-Ar), 124.2 (q, 1C, JC,F = 278.3 Hz, CF3), 104.1 (1JC,H = 160.5 Hz,
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d
4.48 (d, 1H, J = 16.3 Hz, OCH2C@O), 4.37 (d, 1H,
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