Synthesis of some 2-alkoxy glyco-[2,1-d]-2-oxazolines and evaluation of their glycosylation reactivity

Article abstract of DOI:10.1016/j.carres.2012.03.026

The synthesis of the title compounds using intramolecular nucleophilic substitution reactions in the molecules of the corresponding 2-alkoxycarbonylamino-2-deoxy glucosyl halides was studied. It was found that in contrast to the 2-alkyl (aryl) glyco-[2,1-d]-2-oxazolines, the synthesis of the target 2-alkoxy glyco-[2,1-d]-2-oxazolines was possible only in highly basic media. The synthesized 2-alkoxy oxazoline derivatives turned out to be active glycosyl donors and were used for stereoselective 1,2-trans glycosylation reactions catalyzed by weak protic acid under very mild conditions, thus preventing anomerization and other side reactions. As a result of this glycosylation, the glycoside and oligosaccharide derivatives containing urethane N-protecting groups were formed.

Full text of DOI:10.1016/j.carres.2012.03.026

Carbohydrate Research 356 (2012) 172–179
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis of some 2-alkoxy glyco-[2,1-d]-2-oxazolines and evaluation
of their glycosylation reactivity
Sergey S. Pertel a, , Leonid O. Kononov b, Alexander I. Zinin b, Vasily Ja. Chirva a, Elena S. Kakayan a
⇑
a Department of Organic and Biological Chemistry, V.I. Vernadsky Taurida National University, Vernadsky ave. 4, 95007 Simferopol, Crimea, Ukraine
b N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky prosp., 47, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of the title compounds using intramolecular nucleophilic substitution reactions in the mol-
ecules of the corresponding 2-alkoxycarbonylamino-2-deoxy glucosyl halides was studied. It was found
that in contrast to the 2-alkyl (aryl) glyco-[2,1-d]-2-oxazolines, the synthesis of the target 2-alkoxy glyco-
[2,1-d]-2-oxazolines was possible only in highly basic media. The synthesized 2-alkoxy oxazoline deriv-
atives turned out to be active glycosyl donors and were used for stereoselective 1,2-trans glycosylation
reactions catalyzed by weak protic acid under very mild conditions, thus preventing anomerization
and other side reactions. As a result of this glycosylation, the glycoside and oligosaccharide derivatives
containing urethane N-protecting groups were formed.
Received 31 January 2012
Received in revised form 21 March 2012
Accepted 23 March 2012
Available online 2 April 2012
Keywords:
Glycosaminide bond
Oligosaccharide synthesis
2-Alkoxy glyco-[2,1-d]-2-oxazolines
1,2-trans Stereoselectivity
2,2,2-Trichloroethoxycarbonyl group
Glycosylation in neutral media
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
The effectiveness of a glycosylating agent is determined by
reactivity of oxazolinium intermediate. Inasmuch as only poorly
Considering that 2-amino-2-deoxy sugars are abundant in nat-
urally occurring oligosaccharides which play important biological
roles,1 the preparation of sugar derivatives with glycosaminide
bonds is of great interest. However, the achievement of this goal
is often complicated, because the glycosaminide synthesis, as a
rule, is less effective than the preparation of other glycosides.2
Many glycosyl donors have been suggested for the synthesis of
glycosaminides and those bearing 2-phthalimido group are proba-
bly the best in terms of reactivity, 1,2-trans-stereoselectivity and
overall efficiency of glycosylation.3,4 This group is compatible with
a vast number of leaving groups. However, it is notoriously difficult
or sometimes even impossible to remove the N-phthaloyl protect-
ing group in the presence of some functional groups like esters,
reactive halogens or multiple bonds since this process requires
rather harsh conditions.3,4 Therefore, introduction of new efficient
glycosylation methods obviating these difficulties can be consid-
ered useful.
reactive 2-methyl glycooxazoline derivatives (R = CH3) arise during
activation of 2-acetamido-2-deoxy glycosyl donors, they are used
rarely at the present time in spite of the fact that their use provides
high stereoselectivity and considerable decrease in the number of
synthetic steps.3,6
More reactive glycooxazolines possess electron withdrawing
substituents at the second position of oxazoline cycle. In particular,
the corresponding 2-trichloromethyl7–11 (R = CCl3) and trifluoro-
methyl12,13 (R = CF3) glycooxazolines were synthesized and shown
to be able to glycosylate poorly reactive secondary carbohydrate
hydroxyls.9,14 It was assumed3,6 that analogous oxazoline deriva-
tives arose during glycosylation when highly reactive glycosyl do-
nors, which bear urethane N-protecting groups, are used. Such
glycosyl donors are valuable glycosylating agents due to their high
reactivity.3,4 In particular, a comparative study of glycosylation
activity of widely used 2-phtalimido derivatives and their 2-
(2,2,2-trichloroethoxycarbonylamino) (N-Troc) analogs showed
that N-Troc derivatives were approximately 30 times more reac-
tive.15 The isolation of the corresponding oxazoline intermediates
is of interest because this may confirm the expected glycosylation
mechanism. On the other hand, the synthesized glycooxazolines, in
the case of their sufficient stability, could be used as new promis-
ing glycosyl donors, which would be not only highly reactive but
also stereoselective, similarly to the 2-alkyl (aryl) glyco-[2,1-d]-
2-oxazolines. The use of isolated 2-alkoxy glyco-[2,1-d]-2-oxazo-
lines as glycosylating agents, rather than their generation in situ,
It is thought that the synthesis of 2-acylamino-2-deoxy sugar
glycosides, which mostly occurs as nucleophilic substitution at
the anomeric center of a glycosyl donor, is usually accompanied
by participation of neighboring acylamino group. This participation
leads to the intermediate oxazoline derivatives and favors forma-
tion of 1,2-trans glycoside bonds (Scheme 1).3–6
⇑
Corresponding author. Tel.: +380 652 608 379; fax: +380 652 637589.
E-mail addresses: orgchem@crimea.edu, sergepertel@yahoo.com (S.S. Pertel).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.03.026

S. S. Pertel et al. / Carbohydrate Research 356 (2012) 172–179
173
O
O
O
O
R'OH
Promoter
LG
OR
HN
HN
O
HN
HN
O
O
O
R
R
R
R
Scheme 1. Formation of the oxazolinium intermediate during the synthesis of glycosides of 2-acylamino-2-deoxy sugars.
offers additional possibilities for controlling glycoside synthesis in
terms of effectiveness, stereoselectivity, and minimization of side
reactions. As a result of such glycosylation, glycosaminides with
the corresponding urethane N-protecting groups could be obtained
under new conditions that are different from those used to gener-
ate the oxazolines in situ.
Here we attempted to synthesize 2-alkoxy glycooxazolines
using intramolecular nucleophilic substitution reactions in the
molecules of the corresponding glycosyl halides containing ure-
thane N-protecting groups and studied their ability to act as glyco-
syl donors.
As it turned out, N-alkoxycarbonyl glycosyl halides 4–6 do not
interact with weak bases in acetonitrile under the conditions of ha-
lide ion catalysis according to Lemieux30 method, but quickly react
with AgClO4 or AgOTf in acetonitrile in the presence of pyridine un-
der the conditions of Khorlin and Zurabyan31–33 method. Neverthe-
less, 2-alkoxy glycooxazolines cannot be isolated from the reaction
mixture even in the latter case. We believe that in the presence of
silver salts the intramolecular nucleophilic substitution does occur,
but highly reactive intermediate oxazolinium cations quickly un-
dergo side reactions and do not form the target compounds. There-
fore, for prevention of side reactions and isolation of target 2-
alkoxy glyco-[2,1-d]-2-oxazolines it was necessary to deprotonate
completely the intermediate oxazolinium derivatives in the reac-
tion mixture. 2-Alkoxy oxazolines, being the isoelectronic analogs
of guanidines, are expected to possess higher basicity than 2-alkyl
oxazolines which are isoelectronic to amidines. Thus, for the
deprotonation of 2-alkoxy oxazolinium cations bases stronger than
pyridine are required.
For this reason, we attempted to prepare the target oxazoline
derivatives by the reaction of glycosyl halides 4–6 with silver per-
chlorate or triflate in CH2Cl2–C6H6 mixture at ꢀ25 °C in the pres-
ence of the excess of Et3N (Scheme 2). Indeed, under these
conditions 2-(2,2,2-trichloroethoxycarbonylamino) and 2-(isobu-
tyloxycarbonylamino) glycosyl bromides 5 and 6 cleanly gave
CCl4-soluble products which were isolated from the reaction mix-
tures in high yields. Their ESI mass spectra contain peaks of ions
with m/z values that agree with the calculated ones for the corre-
sponding oxazoline derivatives 1 and 2. However, when 2-(benzyl-
2. Results and discussion
Since 2-alkoxy glycooxazolinium ions can easily eliminate alkyl
carbenium ions with formation of oxazolidinone derivatives,16–18
isolable 2-alkoxy glycooxazolines must contain alkyl substituents
which are unable to form stable carbocations. The stability of carb-
ocations can be considerably decreased when introducing electron
withdrawing group into their structure. On the other hand, the
presence of electron withdrawing fragments in alkyl substituents,
as already mentioned, increases the glycosylating activity of 2-al-
kyl glycooxazolines. Therefore, taking into account availability of
many well developed methods for introduction and removal of
2,2,2-trichloroethoxycarbonyl N-protecting groups,19–25 2-(2,2,2-
trichloroethoxy) oxazolines, for example 1, may be considered as
the most promising synthetic targets. It is worth mentioning that
a similar 2-(2,2,2-trichloroethoxy) glycooxazoline derivative with
galacto-configuration was obtained, albeit in low yield, as a side
product of the reaction of a 4,6-O-(di-tert-butylsilylene)-2-deoxy-
2-(2,2,2-trichloroethoxycarbonylamino) glycosyl donor with
4-methylumbelliferone under Mitsunobu conditions.26 For the
comparative analysis of the properties of 2-alkoxy oxazolines, the
preparation of oxazolines 2 and 3 with isobutyloxy and benzyloxy
substituents was also attempted in this work (Fig. 1).
oxycarbonylamino) glycosyl bromide
4 was involved in this
reaction, neither the target 2-(benzyloxy) glycooxazoline nor the
known oxazolidinone 716,34 could be identified in the reaction
mixture.
Oxazolines 1 and 2 can be purified by chromatography on neu-
tral alumina by elution with benzene–triethylamine or diethyl
ether–triethylamine mixtures. It should be noted that purification
of these compounds could not be accomplished using silica gel col-
umn chromatography, even if triethylamine was used as an addi-
tive in the eluent, because they are completely decomposed
under these conditions.
The absorption band, corresponding to stretching vibrations of
N–H bond (3200–3450 cmꢀ1) is absent in the IR spectra of the iso-
lated derivatives 1 and 2, while the absorption band of C@N bond
(1665 cmꢀ1) is present. These spectra are analogous to the spec-
trum of the known oxazoline 8.30–33,35,36 1H NMR spectra of ob-
Several approaches for the preparation of 2-alkyl or 2-aryl gly-
cooxazolines from N,O-acylated 2-amino-2-deoxy glycosyl halides
are described in the literature.3 All these approaches are based on
formation of a good leaving group at the anomeric center of amino
sugar derivative as a result of a catalyst action. In this work, we
have studied the applicability of these methods for the synthesis
of 2-alkoxy glyco-[2,1-d]-2-oxazolines using the known glycosyl
bromides 4,17,27 5,28 and 629 as the starting compounds (Fig. 2).
tained products
1 and 2 correspond well to the proposed
structures and are analogous to the spectrum of oxazoline 8 (Ta-
ble 1). The values of coupling constants in these spectra correspond
to the 0S2 conformation of the pyranose ring in molecules of the
prepared oxazoline derivatives 1 and 2. Such conformation is also
known36,37 to be characteristic of 2-alkyl (aryl) glyco-[2,1-d]-2-
oxazolines in solution, in particular, of 2-methyl oxazoline 8.
Thus, the synthesized compounds were identified as 2-isobut-
oxy and 2-(2,2,2-trichloroethoxy) glycooxazolines 2 and 1. The
synthesized oxazolines 1 and 2 are quite stable compounds and
in the absence of traces of moisture they can be stored in CCl4
OAc
O
1
2
3
R = Cl3CCH2
R = (CH3)2CHCH2
R = PhCH2
OAc
AcO
O
N
C
OR
Figure 1. Structures of the target compounds.

174
S. S. Pertel et al. / Carbohydrate Research 356 (2012) 172–179
OAc
OAc
OAc
O
O
O
AcO
AcO
AcO
AcO
AcO
AcO
NH
NH
NH
O
O
Br
O
Br
Br
Cl3C
Bzl
O
O
O
4
5
6
Figure 2. N-Alkoxycarbonyl glycosyl halides that were used for the synthesis of the target 2-alkoxy oxazolines.
OAc
O
AcO
AcO
NH
O
Br
R
O
4-6
a
b
OAc
AcO
OAc
O
O
O
AcO
AcO
AcO
AcO
c
c
NH
NH
O
AcO
OAc
O
Br
O
Br
N
R
R
O
O
OR
5, 6
1 (63 %)
2 (81 %)
4
OAc
O
AcO
AcO
2, 6
1, 5
4
O
HN
R
-CH2CH(CH3)2 -CH2CCl3 -CH2Ph
7
O
Scheme 2. The synthesis of the target 2-alkoxy glyco-[2,1-d]-2-oxazolines. Reagents and conditions: (a) Et4NBr, NaHCO3, CH3CN; (b) AgOTf, Py, CH3CN; (c) AgClO4, Et3N,
CH2Cl2–C6H6, ꢀ25 °C.
solutions at ꢀ15 °C for several months without considerable
decomposition.
with oxazolines 1 and 2 in dichloromethane was catalyzed effec-
tively with sym-collidinium perchlorate; the concentration of the
catalyst could be as low as 0.1 mg/mL for the catalyst to exhibit
the catalytic effect (Scheme 3).
In this case the glycosylation was performed in practically neu-
tral medium and, as could be expected, anomerization and other
side reactions did not occur. Under these conditions the reaction
of 1 or 2 with benzyl alcohol led exclusively to the 1,2-trans benzyl
glycosides 9 and 10 in very good yields (85–95%). In this context it
is interesting to note that the reaction of the related 2-(2,2,2-tri-
Having prepared glycooxazolines 1 and 2, we attempted to deter-
mine whether synthesized 2-alkoxy oxazoline derivatives possess
glycosylating properties, analogously to 2-alkyl (aryl) glyco-[2,1-
d]-2-oxazolines, and to estimate effectiveness and stereoselectivity
of such glycosylation, if it occurs. Because the 2-alkyl (aryl) glyco-
[2,1-d]-2-oxazoline glycosyl donors interact with glycosyl acceptors
under the conditions of acidic catalysis,3 it should be expected that
the glycosylation of alcohols with 2-alkoxy glyco-[2,1-d]-2-oxazo-
lines also can be catalyzed by both protic and Lewis acids. Indeed,
the synthesized oxazolines 1 and 2, similarly to 2-alkyl (aryl) gly-
co-[2,1-d]-2-oxazolines, can quickly interact with alcohols at rt in
the presence of protic acids (TfOH, HClO4) to give the corresponding
1,2-trans glucosaminides with N-isobutyloxycarbonyl and N-Troc
urethane N-protecting groups. However, under these conditions
the yields of the products were low, even when the reactive accep-
tors, such as benzyl alcohol were used. Besides, an increase in con-
centration of acidic catalyst or time of reaction resulted in
formation of considerable quantities of anomeric 1,2-cis glucosami-
chloroethoxy)-[3-O-(2,3,4,6-tetra-O-acetyl-b- -galactopyranosyl)-
D
4,6-O-(di-tert-butylsilylene)-1,2-dideoxy- -D-galacto-pyrano]-
a
[2,1-d]-2-oxazoline,26 mentioned above, with 4-methylumbellifer-
one, although occurred under mild conditions too (no additional
acidic catalyst was required), led to the formation of aryl glycoside
with 1,2-cis configuration at the anomeric center probably due to
anomerization promoted by the acidic phenol.
At the same time, in diethyl ether the 2-(2,2,2-trichloroethoxy)
oxazoline 1 was more stereoselective than 2-isobutoxy oxazoline
2. Because the yields of the benzyl glycosides 9 and 10 were both
high and nearly equal, we chose the weakly nucleophilic 2,2,2-tri-
chloroethanol 11 to estimate relative reactivity of glycooxazolines
1 and 2. The corresponding 1,2-trans-(2,2,2-trichloroethyl) glyco-
side 14 could be obtained only when 2-(2,2,2-trichloroethoxy)
oxazoline 1 was used as the glycosyl donor (Scheme 4), thus indi-
cating the lower reactivity of 2-isobutoxy oxazoline 2.
nides (a-isomer 9a was formed in 80% yield when 1 equiv of TfOH
was used), apparently due to anomerization of initially formed 1,2-
trans glycosides in highly acidic medium. Side reactions of reactive
2-alkoxy oxazolinium salts could be the cause of low yields of glyco-
sylationproducts. Decreasingconcentrationofacidiccatalystshould
lead to minimization of side processes. On the other hand, owing to
presumed high basicity of 2-alkoxy glycooxazolines, they should be
protonated with quite weak acids. Indeed, glycosylation of alcohols
For evaluation of prospects of application of synthesized 2-alk-
oxy glyco-[2,1-d]-2-oxazolines to the formation of 1,2-trans

S. S. Pertel et al. / Carbohydrate Research 356 (2012) 172–179
175
Table 1
1H NMR data of synthesized 2-alkoxy oxazolines 1, 2, and 2-methyl oxazoline 8 (d, ppm)
AcO
AcO
AcO
O
O
O
O
O
O
AcO
OAc
AcO
OAc
AcO
OAc
N
N
N
CCl3
CH3
O
O
1
2
8
Compound (solvent)
8 (CDCl3)
2 (CDCl3)
1 (C6D6)
H-1 (J1,2 Hz)
H-3 (J3,2 Hz)
H-4 (J4,3 Hz)
H-6a (J6a,6b Hz)
5.98 d (7.5)
6.00 d (7.0)
5.20 br t (2.7)
4.93 ddd (2.4)
4.22 dd (12.5)
(J6a,5 4.0 Hz)
4.19 dd (4.6)
4.13 ddd (1.1)
3.80 br dt (9.0)
2.05 s, 2.08 s, 2.09 s
0.97 d (6H)
(JCH3,CH 6.8 Hz)
4.07 dd (6.6)
3.99 dd (10.1)
(JCHb,CH 7.0 Hz)
—
5.62 d (7.0)
5.27 dd (2.5)
4.93 ddd (2.0)
4.20 dd (12.0)
(J6a,5 4.0 Hz)
4.17 dd (5.0)
4.14 ddd (1.3)
3.60 br dt (9.3)
5.48 br t (2.7)
5.15 ddd (2.5)
4.19 dd (12.3)
(J6a,5 3.6 Hz)
4.12 dd (4.8)
3.82 ddd (1.1)
3.91 br dt (9.4)
H-6b (J6b,5 Hz)
H-2 (J2,4 Hz)
H-5 (J5,4 Hz)
CH3CO
2.08 s, 2.11 s, 2.12 s
2.10 br s
1.64 s, 1.62 s, 1.56 s
—
CH3
CHaCH(CH3)2 (JCHa,CH Hz)
CHbCH(CH3)2 (JCHa,CHb Hz)
—
—
—
—
CHaCCl3 (JCHa,CHb Hz)
CHbCCl3
CH(CH3)2
—
—
—
4.81 d (11.8)
4.57 d
—
—
2.13–2.00 m
AcO
OAc
O
O
AcO
AcO
a
O
AcO
OAc
NH
N
AlkO
OBzl
OAlk
O
(80%)
2
9α
OAc
AcO
OAc
O
O
O
AcO
AcO
AcO
AcO
b
c
Ph
OH
NH
NH
OBzl
O
OBzl
AcO
OAc
AlkO
AlkO
N
O
O
OAlk
9
β
(90%; only)
1, 2
9
α β
(80%; 1:85 ( / ))
10 (95%; β only)
10 (80%; β only)
2, 9
Alk = CH2CH(CH3)2
Alk = CH2CCl3
1, 10
Scheme 3. Estimation of effectiveness and stereoselectivity of glycosylation using 2-alkoxy glyco-[2,1-d]-2-oxazoline glycosyl donors. Reagents and conditions: (a) TfOH, MS
4 Å, CH2Cl2, rt; (b) s-collidineꢁHClO4, MS 4 Å, Et2O, rt; (c) s-collidine ꢁHClO4, MS 4 Å, CH2Cl2, rt.
glucosaminide bond in oligosaccharides we used carbohydrate
glycosyl acceptors. The reactivities of sugar hydroxyls are known
to differ considerably and to depend on their nature (primary or
secondary hydroxyl), orientation (axial or equatorial), position in
the cycle and neighborhood in general.38,39 One of the least reac-
tive hydroxyl groups of sugars is the hydroxyl group at C-4 of
Thus, for estimation of reactivity of 2-alkoxy glycooxazolines 1
and 2 we used 4-OH glycosyl acceptor 13,11 and also carbohydrate
alcohol 12, which was shown43 to be poor 3-OH glycosyl acceptor
in reactions with some glycosyl donors, for example, it could not be
glycosylated with 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bro-
mide43 (see Scheme 4). As it turned out, 1,2-trans glycosylation
of these sugar alcohols could be performed by 2-(2,2,2-trichloro-
ethoxy) oxazoline 1 in the presence of catalytic amounts of sym-
collidinium perchlorate. As a result, the corresponding N-Troc pro-
tected disaccharide derivatives with 1,2-trans glycosidic linkages
15 and 16 were formed in good yields, which confirms effective-
ness of this approach to 1,2-trans glycosaminide synthesis.
glucopyranose cycle in the molecules of N-acetyl-D-glucosamine
(GlcNAc) derivatives.40–42 It is believed42 that the lack of reactiv-
ity of these alcohols arises from combination of steric hindrance
of pyranose 4-OH group and ability of acetamido function to
participate in strong intra- and/or intermolecular hydrogen
bonding.

176
S. S. Pertel et al. / Carbohydrate Research 356 (2012) 172–179
AcO
O
OAc
s-collidine · HClO4
O
AcO
AcO
ROH
OR
O
°
AcO
OAc
MS 4Α, CH2Cl2, r.t.
N
NH
11, 12, 13
O
O
Cl3C
14
15
16
(35%)
(70%)
(57%)
O
1
CCl3
11, 14
12, 15
13, 16
OBz
O
Ph
O
R
CCl3
O
O
OAll
BzlO
AcNH
OAll
HNAc
Scheme 4. Glycosylation of poorly reactive glycosyl acceptors using 2-(2,2,2-trichloroethoxy) glycooxazoline 1 as the glycosyl donor.
Thus, 2-alkoxy glyco-[2,1-d]-2-oxazolines, especially oxazoline
AM300 spectrometer (75.48 MHz) or on a Bruker AVANCE 600
spectrometer (150.90 MHz). The chemical shifts were referred
either to the signal of internal Me4Si (dH 0.0) or to the residual sig-
nals of protonated solvent. Assignments of the signals in the NMR
spectra were performed using 2D-spectroscopy (COSY, HSQC,
HMQC) and DEPT-135 experiments. Optical rotation was measured
with a Carl-Zeiss Polamat-S polarimeter. Melting points were
determined in capillaries and were uncorrected. IR spectra were re-
corded on a Carl-Zeiss Specord IR-75 spectrometer in the 400–
4000 cmꢀ1 range for solutions in CCl4. Mass spectra (electrospray
ionization, ESI) were recorded on a Bruker micrOTOF II mass spec-
trometer for 2 ꢃ 10ꢀ5 M solutions in MeCN.
1, in contrast to the corresponding 2-alkyl (aryl) glyco-[2,1-d]-2-
oxazolines, proved to be effective glycosylating agents and may
be considered as new valuable glycosyl donors for oligosaccharide
synthesis due to their high stereoselectivity and the ability to per-
form glycosylation in practically neutral media.
3. Conclusions
In summary, we have developed an approach to the synthesis of
2-isobutoxy and 2-(2,2,2-trichloroethoxy) glyco-[2,1-d]-2-oxazo-
lines 2 and 1. The oxazolines 1 and 2 were shown to be reactive
and 1,2-trans stereoselective glycosyl donors, which could be used
for the synthesis of N-alkoxycarbonyl protected glycosaminide and
oligosaccharide derivatives under very mild conditions as com-
pared to many other methods of glycosaminide synthesis. While
new nitrogen protecting groups compatible with glycosylation
conditions and capable of nucleophilic participation continue to
emerge, the 2-alkoxy glyco-[2,1-d]-2-oxazolines described here
are not just participating group equivalents. Due to their excep-
tional reactivity, the new glycosyl donors can be activated under
conditions that usually leave other types of glycosyl donors intact.
This opens prospects for orthogonal glycosylations, which will be
the subject of our further research.
4.2. General procedure for the reaction of N-alkoxycarbonyl
glycosyl halides (3–6) with silver salts in the presence of
triethylamine
Glycosyl halide (0.7 mmol) was dissolved in dichloromethane
(4 mL) and the solution obtained was concentrated to half its vol-
ume. Powdered molecular sieves (4 Å, 200 mg) were added to the
solution and the mixture was cooled to ꢀ35 °C. A solution of AgOTf
or AgClO4 (obtained by dissolution of AgOTf (234 mg, 1.3 equiv) or
of AgClO4 (189 mg, 1.3 equiv) in benzene (6 mL) and concentration
of the solution to half its volume) and triethylamine (127 lL,
1.3 equiv) were added to the cooled mixture. After 30 min, when
TLC showed the reaction completion, the mixture was filtered
and the precipitate was washed with anhydrous CCl4 (2 ꢃ 2 mL).
The filtrate and washings were collected and concentrated to dry-
ness in vacuo. The products were isolated by chromatography of
the dry residue on a column of neutral alumina using benzene–tri-
ethylamine (100:2, v/v) or diethyl ether–triethylamine (100:2, v/v)
mixtures as the eluents.
4. Experimental
4.1. General methods
Reagents of reagent grade were purchased from standard ven-
dors (Aldrich and Fluka) and used without additional purification
unless otherwise indicated. THF and diethyl ether were boiled un-
der reflux over metallic sodium followed by distillation. CH2Cl2,
CCl4, triethylamine, and benzene were distilled over phosphorus
pentoxide. Molecular sieves (4 Å) were activated under vacuum
at 320 °C for 3 h. sym-Collidinium perchlorate was prepared
according to the known method,44 and stored over P2O5. All reac-
tions were monitored by TLC, which was performed on silica gel
STH-1A-coated aluminum foil (Sorbpolimer, Russian Federation).
Visualization of spots of carbohydrate derivatives was effected by
exposure of TLC plates to chlorosulfonic acid vapor for 5 min at
room temperature followed by heating to ꢂ200 °C. Column chro-
matography was carried out on Silica Gel 60 (Fluka 220–448 mesh)
and on neutral aluminum oxide type 507 C (Fluka 0.05–0.15 mm).
1H NMR spectra were recorded on a Varian Mercury 400 spectrom-
4.3. 2-Isobutoxy-(3,4,6-tri-O-acetyl-1,2-dideoxy-
a-D-
glucopyrano)-[2,1-d]-2-oxazoline (2)
Compound 2 was obtained from 629 in 81% yield as a colorless
20
546
syrup. Analytical data for 2: ½
aꢄ
+11.8 (c 2.3, CCl4); IR (CCl4): m
2962 and 2872 (CH3), 1745 and 1240 (ester), and 1665 cmꢀ1
(C@N); 1H NMR (300.13 MHz, CDCl3): d 6.00 (d, 1H, J1,2 7.0 Hz, H-
1), 5.20 (br t, 1H, J3,2 2.7 Hz, H-3), 4.93 (ddd, 1H, J4,3 2.4 Hz, H-4),
4.22 (dd, 1H, J6a,6b 12.5 Hz, J6a,5 4 Hz, H-6a), 4.19 (dd, 1H, J6b,5
4.6 Hz, H-6b), 4.13 (ddd, 1H, J2,4 1.1 Hz, H-2), 4.07 (dd, 1H, JCHa,CH
6.6 Hz, CHaCH(CH3)2), 3.99 (dd, 1H, JCHb,CHa 10.1 Hz, JCHb,CH
7.0 Hz, CHbCH(CH3)2), 3.80 (br dt, 1H, J5,4 9.0 Hz, H-5), 2.13– 2.00
(m, 1H, CH2CH(CH3)2), 2.09, 2.08, 2.05 (3s, 9H, 3OAc), 0.97 (d, 6H,
JCH3,CH 6.8 Hz, 2CH3); 13C NMR (75.48 MHz, CDCl3): d 170.7,
eter (400.49 MHz) or on
a
Bruker AM300 spectrometer
Bruker
(300.13 MHz). 13C NMR spectra were recorded on
a

S. S. Pertel et al. / Carbohydrate Research 356 (2012) 172–179
177
169.6, 169.3 (CH3CO), 163.2 (NCO), 100.3 (C-1), 77.4
(CH2CH(CH3)2), 71.0 (C-3), 68.0 (C-4), 67.9 (C-5), 63.4 (C-6), 62.9
(C-2), 27.9 (CH(CH3)2), 21.0, 20.9, 20.8 (CH3CO), 19.0 (CH3CH),
18.9 (CH3CH); HRMS (ESI): m/z Calcd for [C17H25 NO9]Na+:
410.1427. Found: 410.1426.
approximately 12 h, when TLC showed the reaction completion,
the mixture was filtered and the precipitate was washed with
CH2Cl2 (3 ꢃ 2 mL). The filtrate and washings were collected and
concentrated to dryness in vacuo. The dry residue was chromato-
graphed on a column of silica gel using CHCl3 ? CHCl3–EtOH,
100:0.5 (v/v) solvent systems followed by crystallization from
4.4. 2-(2,2,2-Trichloroethoxy)-(3,4,6-tri-O-acetyl-1,2-dideoxy-
a-
diethyl ether–hexane mixture to give 9b as white crystals
23
D
-glucopyrano)-[2,1-d]-2-oxazoline (1)
(108 mg, 84%): mp 147.5–148 °C; ½
a
ꢄ
ꢀ26.2 (c 2.5, CHCl3); 1H
546
NMR (400.40 MHz, DMSO-d6): d 7.33-7.22 (m, 5H, Ar-H), 7.17 (d,
1H, JNH,2 9.1 Hz, NH), 5.09 (br t, 1H, J3,2 9.9 Hz, H-3), 4.85 (br t,
1H, J4,3 9.8 Hz, J4,5 9.8 Hz, H-4), 4.81 (d, 1H, JPhCHa,PhCHb 12.2 Hz,
PhCHa), 4.69 (d, 1H, J1,2 8.4 Hz, H-1), 4.57 (d, 1H, PhCHb), 4.21
(dd, 1H, J6a,5 4.7 Hz, J6a,6b 12.2 Hz, H-6a), 4.04 (dd, 1H, J6b,5 1.9 Hz,
H-6b), 3.75 (dd, 1H, JCHa,CH 6.8 Hz, CHaCH(CH3)2), 3.75–3.65 (m,
1H, H-5), 3.70 (dd, 1H, JCHb,CHa 10.7 Hz, JCHb,CH 6.6 Hz,
CHbCH(CH3)2), 3.53 (br q, 1H, H-2), 2.04, 1.97, 1.93 (3s, 9H,
3OAc), 1.84 (br n, 1H, CH2CH(CH3)2), 0.89 (d, 6H, JCH3,CH 6.7 Hz,
2CH3); 13C NMR (75.48 MHz, CDCl3): d 170,8, 170.7, 169.6 (CH3CO),
156.2 (NHCO), 136.9 (C aromatic), 128.6 (2C, CH aromatic), 128.1
(CH aromatic), 128.0 (2C, CH aromatic), 99.9 (C-1), 72.4 (C-3),
72.0 (C-5), 71.5 (CH2CH(CH3)2), 70.9 (PhCH2), 68.9 (C-4), 62.3 (C-
6), 56.2 (C-2), 28.1 (CH3CH), 20.9, 20.8, 20.7 (CH3CO), 19.1, 19.0
(CH3CH); HRMS (ESI): m/z Calcd for [C24H33NO10]Na+: 518.2002.
Found: 518.2006.
Compound 1 was obtained from 528 in 63% yield as a colorless
25
syrup. Analytical data for 1: ½
a
ꢄ
+20.1 (c 1.38, CCl4); IR (CCl4): m
546
1745 and 1230 (ester), and 1665 cmꢀ1 (C@N); 1H NMR
(300.13 MHz, C6D6): d 5.62 (d, 1H, J1,2 7.0 Hz, H-1), 5.48 (br t, 1H,
J3,2 2.7 Hz, H-3), 5.15 (ddd, 1H, J4,3 2.5 Hz, H-4), 4.81 (d, 1H, JCHa,CHb
11.8 Hz, CHaCCl3), 4.57 (d, 1H, CHbCCl3), 4.19 (dd, 1H, J6a,6b 12.3 Hz,
J6a,5 3.6 Hz, H-6a), 4.12 (dd, 1H, J6b,5 4.8 Hz, H-6b), 3.91 (br dt, 1H,
J5,4 9.4 Hz, H-5), 3.82 (ddd, 1H, J2,4 1.1 Hz, H-2), 1.64, 1.62, 1.56 (3s,
9H, 3OAc); 13C NMR (75.48 MHz, C6D6): d 169.9, 169.2, 168.8
(CH3CO), 162.6 (NCO), 102.0 (C-1), 94.7 (CH2CCl3), 79.5 (CH2CCl3),
71.5 (C-3), 68.6 (2C, C-5, C-4), 63.3 (C-2), 63.2 (C-6), 20.3 (CH3CO),
20.2 (2C, CH3CO); HRMS (ESI): m/z Calcd for [C15H18Cl3NO9]K+:
499.9684. Found: 499.9593.
4.5. Benzyl 3,4,6-tri-O-acetyl-2-deoxy-2-
(isobutyloxycarbonylamino)-a-D-glucopyranoside (9a)
4.6.2. Method B
2-Isobutoxy-(3,4,6-tri-O-acetyl-1,2-dideoxy-
[2,1-d]-2-oxazoline 2 (100 mg, 0.258 mmol) and benzyl alcohol
(41.9 L, 1.5 equiv) were dissolved in CH2Cl2 (8 mL) and the solu-
tion was concentrated to half its volume. Powdered molecular
sieves (4 Å, 200 mg) and trifluoromethanesulfonic acid (22 L,
a
-
D
-glucopyrano)-
2-Isobutoxy-(3,4,6-tri-O-acetyl-1,2-dideoxy-
[2,1-d]-2-oxazoline 5 (100 mg, 0.258 mmol) and benzyl alcohol
(41.9 L, 1.5 equiv) were dissolved in anhydrous diethyl ether
(8 mL) and the solution was concentrated to half its volume. Pow-
dered molecular sieves (4 Å, 200 mg) and 0.005 M solution of sym-
a-D-glucopyrano)-
l
l
l
1 equiv) were added to the mixture. After 24 h, when TLC showed
collidinium perchlorate in CH2Cl2 (18 lL) were added to the mix-
the reaction completion, the reaction mixture was neutralized by
addition of triethylamine (39 lL, 1.3 equiv). Then the solution
was concentrated in vacuo and the dry residue was chromato-
graphed on a column of silica gel using CHCl3 ? CHCl3–EtOH,
100:0.5 (v/v) solvent systems followed by crystallization from hex-
ture. After approximately 16 h, when TLC showed the reaction
completion, the mixture was filtered and the precipitate was
washed with CH2Cl2 (3 ꢃ 2 mL). The filtrate and washings were
collected and concentrated to dryness in vacuo. The dry residue
was chromatographed on a column of silica gel using CHCl3
CHCl3–EtOH, 100:0.5 (v/v) solvent systems to afford 9b (102 mg,
80%) and 9 (1.2 mg, 0.9%).
?
ane to give 9a as white crystals (102 mg, 80%): mp 73.5–74 °C;
21
546
½
aꢄ
+108.6 (c 0.8, CHCl3); 1H NMR (300.13 MHz, CDCl3): d 7.42-
a
7.28 (m, 5H, Ar-H), 5.24 (br t, 1H, J3,2 10.4 Hz, J3,4 9.6 Hz, H-3),
5.10 (br t, J4,5 9.7 Hz, 1H, H-4), 4.97 (d, 1H, J1,2 3.6 Hz, H-1), 4.92
(d, 1H, JNH,2 10.0 Hz, NH), 4.73 (d, 1H, JPhCHa,PhCHb 11.8 Hz, PhCHa),
4.56 (d, 1H, PhCHb), 4.25 (dd, 1H, J6a,5 4.0 Hz, J6a,6b 12.0 Hz, H-6a),
4.05 (br dt, 1H, H-2), 4.04 (dd, 1H, H-6b), 3.98 (ddd, 1H, J5,6b 2.3 Hz,
H-5), 3.86 (dd, 1H, JCHa,CH 6.7 Hz, CHaCH(CH3)2), 3.76 (dd, 1H,
JCHb,CHa 10.4 Hz, JCHb,CH 6.8 Hz, CHbCH(CH3)2), 2.10, 2.01, 2.00 (3s,
9H, 3OAc), 1.87 (br n, 1H, JCH,CH3 6.7 Hz, CH2CH(CH3)2), 0.90 (d,
6H, 2CH3); 13C NMR (75.48 MHz, CDCl3): d 171.1, 170.8, 169.5
(CH3CO), 156.3 (NHCO), 136.6 (C aromatic), 128.8 (2C, CH aro-
matic), 128.5 (CH aromatic), 128.3 (2C, CH aromatic), 97.0 (C-1),
71.5 (2C, C-3, CH2CH(CH3)2), 70.3 (PhCH2), 68.5 (C-5), 68.1 (C-4),
62.1 (C-6), 53.8 (C-2), 28.1 (CH3CH), 20.9, 20.8, 20.7 (CH3CO),
19.1 (2C, CH3CH); HRMS (ESI): m/z Calcd for [C24H33NO10]Na+:
518.2002. Found: 518.1997.
4.7. Benzyl 3,4,6-tri-O-acetyl-2-deoxy-2-(2,2,2-
trichloroethoxycarbonylamino)-b-D-glucopyranoside (10)
4.7.1. Method A
2-(2,2,2-Trichloroethoxy)-(3,4,6-tri-O-acetyl-1,2-dideoxy-
-glucopyrano)-[2,1-d]-2-oxazoline 1 (100 mg, 0.216 mmol) and
benzyl alcohol (34.9 L, 1.5 equiv) were dissolved in CH2Cl2
a-
D
l
(8 mL) and the solution was concentrated to half its volume. Pow-
dered molecular sieves (4 Å, 200 mg) and 0.005 M solution of sym-
collidinium perchlorate in CH2Cl2 (18 lL) were added to the mix-
ture. After approximately 12 h, when TLC showed the reaction
completion, the mixture was filtered and the precipitate was
washed with CH2Cl2 (3 ꢃ 2 mL). The filtrate and washings were
collected and concentrated to dryness in vacuo. The dry residue
4.6. Benzyl 3,4,6-tri-O-acetyl-2-deoxy-2-
was chromatographed on a column of silica gel using CHCl3 ?
(isobutyloxycarbonylamino)-b-
D
-glucopyranoside (9b)
CHCl3–EtOH, 100:0.5 (v/v) solvent systems followed by crystalliza-
tion from hexane to give 10 as white crystals (116 mg, 94%): mp
17
546
122–123 °C; ½
aꢄ
–23.9 (c 2.8, CHCl3); 1H NMR (300.13 MHz,
4.6.1. Method A
CDCl3): d 7.42–7.27 (m, 5H, Ar-H), 5.23 (dd, 1H, J3,2 9.4 Hz, J3,4
10.6 Hz, H-3), 5.10 (br d, 1H, JNH,2 9.9 Hz, NH), 5.08 (t, 1H, J4,5
9.7 Hz, H-4), 4.92 (d, 1H, JPhCHa,PhCHb 12.1 Hz, PhCHa), 4.71 (br s,
2H, CH2CCl3), 4.63 (d, 1H, PhCHb), 4.60 (d, 1H, J1,2 8.9 Hz, H-1),
4.30 (dd, 1H, J6a,5 4.8 Hz, H-6a), 4.18 (dd, 1H, J6b,6a 12.2 Hz, J6b,5
2.4 Hz, H-6b), 3.71 (br q, 1H, H-2), 3.67 (ddd, 1H, J5,4 10.5 Hz, H-
5), 2.10, 2.01, 2.00 (3s, 9H, 3OAc); 13C NMR (75.48 MHz, CDCl3): d
2-Isobutoxy-(3,4,6-tri-O-acetyl-1,2-dideoxy-
[2,1-d]-2-oxazoline 2 (100 mg, 0.258 mmol) and benzyl alcohol
(41.9 L, 1.5 equiv) were dissolved in CH2Cl2 (8 mL) and the solu-
a-D-glucopyrano)-
l
tion was concentrated to half its volume. Powdered molecular
sieves (4 Å, 200 mg) and 0.005 M solution of sym-collidinium per-
chlorate in CH2Cl2 (18 lL) were added to the mixture. After

178
S. S. Pertel et al. / Carbohydrate Research 356 (2012) 172–179
170.8, 170.7, 169.6 (CH3CO), 154.1 (NHCO), 136.7 (C aromatic),
128.7 (2C, CH aromatic), 128.3 (CH aromatic), 128.1(2C, CH aro-
matic), 99.4 (C-1), 95.6 (CH2CCl3), 74.7 (CH2CCl3), 72.1 (C-3), 72.0
(C-5), 70.9 (PhCH2), 68.9 (C-4), 62.2 (C-6), 56.4 (C-2), 20.9, 20.8,
20.7 (CH3CO); HRMS (ESI): m/z Calcd for [C22H26Cl3NO10]Na+:
592.0520. Found: 592.0515.
graphed on a column of silica gel using CHCl3 ? CHCl3–EtOH,
100:1 (v/v) solvent systems followed by crystallization from chlo-
roform–diethyl ether mixture to give 15 as white crystals (81 mg,
70%). In addition to the target compound 15, the unreacted allyl
glycoside 12 (15 mg) was isolated from the reaction mixture. Tak-
ing into account the unreacted 12 the yield of 15 was 99%: mp
25
546
208–210 °C; ½
a
ꢄ
+34 (c 1.0, CH3OH); 1H NMR (300.13 MHz,
4.7.2. Method B
CDCl3): d 7.61–7.47 (m, 2H, Ar-H), 7.44–7.32 (m, 3H, Ar-H), 6.25
(d, 1H, JNH,2 7.5 Hz, NHAc), 5.91 (broad decet, 1H, JCH,OCHb 6.0 Hz, Jcis
10.4 Hz, Jtrans 16.7 Hz, OCH2–CH@CH2), 5.61 (t, 1H, J3,4 9.9 Hz, HB-3)
2-(2,2,2-Trichloroethoxy)-(3,4,6-tri-O-acetyl-1,2-dideoxy-
-glucopyrano)-[2,1-d]-2-oxazoline 6 (100 mg, 0.216 mmol) and
benzyl alcohol (34.9 L, 1.5 equiv) were dissolved in anhydrous
a-
D
0
0
l
5.54 (s, 1H, PhCH), 5.33(ddt, 1H, JCHa,CHb 2.9 Hz, J1 ,3 1.5 Hz, OCH2–
0
0
diethyl ether (8 mL) and the solution was concentrated to half its
CH@CHa), 5.24 (ddt, 1H, J1 ,3 1.3 Hz, OCH2–CH@CHb), 5.23 (br d,
1H, J1,2 8.7 Hz, HB-1) 5.16 (br d, 1H, JNH,2 6.8 Hz, NHTroc) 5.00 (d,
1H, J1,2 3.4 Hz, HA-1), 4.98 (t, 1H, J4,5 9.7 Hz, HB-4), 4.67 (d, 1H,
JCHa,CHb 12.1 Hz, CHaCCl3), 4.61 (d, 1H, CHbCCl3), 4.45 (br d, 1H,
J6a,6b 11.9 Hz, HB-6a), 4.28 (dd, 1H, J6a,6b 9.8 Hz, J6a,5 4.2 Hz, HA-
6a), 4.18 (dddd, 1H, JOCHa,CH 5.4 Hz, OCHaCH@CH2), 4.14 (br dt,
1H, HA-2), 4.02 (dddd, 1H, JCHb,CHa 12.8 Hz, OCHbCH@CH2), 4.01
(t, 1H, J3,2 9.5 Hz, HA-3), 3.97 (dd, 1H, J6b,5 2.9 Hz, HB-6b), 3.85 (br
dt, 1H, J5,4 9.1 Hz, HA-5), 3.76 (br t, 1H, J6b,5 9.9 Hz, HA-6b), 3.67
(t, 1H, J4,3 9.2 Hz, HA-4), 3.66 (br dd, 1H, HB-5), 3.09 (ddd, 1H, J2,3
10.0 Hz HB-2), 2.07, 2.03, 2.00, 1.82 (4s, 12H, 3OAc+NAc); 13C
NMR (75.48 MHz, CDCl3): d 171.0, 170.6, 169.9 (CH3CO), 169.8,
153.7, (NHCO), 136.8 (C aromatic), 133.7 (CH@CH2), 129.8 (CH aro-
matic), 128.8 (2C, CH aromatic), 126.5 (2C, CH aromatic), 118.3
(CH@CH2), 102.5 (PhCH), 97.6 (CA-1), 97.0 (CB-1), 95.6 (CH2CCl3),
80.9 (CA-4), 74.4 (CH2CCl3), 72.2 (CB-5), 71.1 (CA-3), 70.5 (CB-3),
69.1 (CA-6), 69.0 (OCH2–CH@CH2), 68.3 (CB-4), 63.4 (CA-5), 61.2
(CB-6), 55.8 (CB-2), 53.0 (CA-2), 23.1, 20.9, 20.8, 20.5 (CH3CO);
HRMS (ESI): m/z Calcd for [C33H41Cl3N2O15]Na+: 833.1470. Found:
833.1465.
volume. Powdered molecular sieves (4 Å, 200 mg) and 0.005 M
solution of sym-collidinium perchlorate in CH2Cl2 (18 lL) were
added to the mixture. After approximately 14 h, when TLC showed
the reaction completion, the mixture was filtered and the precipi-
tate was washed with CH2Cl2 (3 ꢃ 2 mL). The filtrate and washings
were collected and concentrated to dryness in vacuo. The dry res-
idue was chromatographed on a column of silica gel using CHCl3 ?
CHCl3–EtOH, 100:0.5 (v/v) solvent systems to afford 10 (99 mg,
80%).
4.8. 2,2,2-Trichloroethyl 3,4,6-tri-O-acetyl-2-deoxy-2-(2,2,2-
trichloroethoxycarbonylamino)-b-D-glucopyranoside (14)
2-(2,2,2-Trichloroethoxy)-(3,4,6-tri-O-acetyl-1,2-dideoxy-
-glucopyrano)-[2,1-d]-2-oxazoline 1 (100 mg, 0.216 mmol) and
2,2,2-trichloroethanol 11 (41.7 L, 2 equiv) were dissolved in
a-
D
l
CH2Cl2 (8 mL) and the solution was concentrated to half its vol-
ume. Powdered molecular sieves (4 Å, 200 mg) and 0.1 M solution
of sym-collidinium perchlorate in CH2Cl2 (108 lL) were added to
the mixture. After approximately 24 h, when TLC showed the reac-
tion completion, the mixture was filtered and the precipitate was
washed with CH2Cl2 (3 ꢃ 2 mL). The filtrate and washings were
collected and concentrated to dryness in vacuo. The dry residue
4.10. Allyl [3,4,6-tri-O-acetyl-2-deoxy-2-(2,2,2-
trichloroethoxycarbonylamino)-b-D-glucopyranosyl]-(1?4)-2-
acetamido-6-O-benzoyl-3-O-benzyl-2-deoxy-b-D-
was chromatographed on a column of silica gel using CHCl3
?
glucopyranoside (16)
CHCl3–EtOH, 100:0.5 (v/v) solvent systems followed by crystalliza-
tion from diethyl ether to give 14 as white crystals (46 mg, 35%):
Allyl 2-acetamido-6-O-benzoyl-3-O-benzyl-2-deoxy-b-
pyranoside 1311 (50 mg, 0.111 mmol) and 2-(2,2,2-trichloroeth-
oxy)-(3,4,6-tri-O-acetyl-1,2-dideoxy- -glucopyrano)-[2,1-d]-
2-oxazoline 1 (103 mg, 2 equiv) were dissolved in CH2Cl2 (8 mL)
and the solution was concentrated to half its volume. Powdered
molecular sieves (4 Å, 200 mg) and 0.005 M solution of sym-collidi-
D-gluco-
21
mp 123–124 °C;
½
a
ꢄ
ꢀ11.5 (c 0.43, CH3OH); 1H NMR
546
(300.13 MHz, CDCl3) d 5.37 (dd, 1H, J3,2 10.7 Hz, J3,4 9.7 Hz, H-3),
5.26 (br d, 1H, JNH,2 9.3 Hz, NH), 5.11 (t, 1H, J4,5 9.7 Hz, H-4), 5.00
(d, 1H, J1,2 8.3 Hz, H-1), 4.77 (d, 1H, JCHa,CHb 11.9 Hz, CHaCCl3),
4.67 (d, 1H, CHbCCl3), 4.47 (d, 1H, JCHa,CHb 11.9 Hz, OCHaCCl3),
4.31 (dd, 1H, J6a,5 4.6 Hz, J6a,6b 12.4 Hz, H-6a), 4.19 (dd, 1H, J6b,5
2.5 Hz, H-6b), 4.18 (d, 1H, OCHbCCl3), 3.76 (br dt, 1H, H-2), 3.78–
3.72 (m, 1H, H-5), 2.11, 2.05, 2.04 (3s, 9H, 3OAc); HRMS (ESI): m/
z Calcd for [C17H21Cl6NO10]Na+: 631.9194. Found: 631.9190.
a-D
nium perchlorate in CH2Cl2 (18
After 24 h some more 0.005 M solution of sym-collidinium perchlo-
rate in CH2Cl2 (180 L) was added to the reaction mixture. After
lL) were added to the mixture.
l
approximately 48 h, when TLC showed the reaction completion,
the mixture was filtered and the precipitate was washed with
CH2Cl2 (3 ꢃ 2 mL). The filtrate and washings were collected and
concentrated to dryness in vacuo. The dry residue was chromato-
graphed on a column of silica gel using CHCl3 ? CHCl3–EtOH,
100:1 (v/v) solvent systems followed by crystallization from chlo-
roform–carbon tetrachloride mixture to give 16 as white crystals
(58 mg, 57%). In addition to the target compound 16, the unreacted
allyl glycoside 13 (10 mg) was isolated from the reaction mixture.
4.9. Allyl [3,4,6-tri-O-acetyl-2-deoxy-2-(2,2,2-
trichloroethoxycarbonylamino)-b-D-glucopyranosyl]-(1?3)-2-
acetamido-4,6-O-benzylidene-2-deoxy-b-D-glucopyranoside
(15)
Allyl 2-acetamido-4,6-O-benzylidene-2-deoxy-
oside 1243 (50 mg, 0.143 mmol) and 2-(2,2,2-trichloroethoxy)-
(3,4,6-tri-O-acetyl-1,2-dideoxy- -glucopyrano)-[2,1-d]-2-oxazo-
a-D-glucopyran-
a-
D
Taking into account the unreacted 13 the yield of 16 was 72%: mp
23
546
line 1 (100 mg, 0.216 mmol) were dissolved in CH2Cl2 (8 mL) and
the solution was concentrated to half its volume. Powdered molec-
ular sieves (4 Å, 200 mg) and 0.005 M solution of sym-collidinium
193–195 °C (decomp.);
½
aꢄ
ꢀ1 (c 2.0, CH3OH); 1H NMR
(400.45 MHz, CDCl3): d 8.06 (dd, 2H, J 8.4 Hz, J 1.3 Hz, Ar-H), 7.61
(tt, 1H, J 7.4 Hz, Ar-H), 7.48 (br t, 2H, J 7.9 Hz, Ar-H), 7.34–7.28
(m, 5H, Ar-H), 6.16 (br d, 1H, JNH,2 8.3 Hz, NHAc), 5.87 (br o, 1H, Jcis
10.7 Hz, Jtrans 17.0 Hz, OCH2–CH@CH2), 5.56 (d, 1H, JNH,2 9.3 Hz,
perchlorate in CH2Cl2 (18
24 h some more 0.005 M solution of sym-collidinium perchlorate
in CH2Cl2 (180 L) was added to the reaction mixture. After
lL) were added to the mixture. After
0
0
l
NHTroc), 5.26 (br dq, 1H, JCHa,CHb 2.9 Hz, J1 ,3 1.5 Hz, OCH2–
0
0
approximately 48 h, when TLC showed the reaction completion,
the mixture was filtered and the precipitate was washed with
CH2Cl2 (3 ꢃ 2 mL). The filtrate and washings were collected and
concentrated to dryness in vacuo. The dry residue was chromato-
CH@CHa), 5.16 (br dq, 1H, J1 ,3 1.4 Hz, OCH2–CH@CHb), 5.09 (dd,
1H, J3,4 9.6 Hz, HB-3), 5.07 (dd, 1H, J4,5 9.6 Hz, HB-4) 4.76 (s, 2H,
PhCH2), 4.73 (dd, 1H, J6a,5 5.0 Hz, HA-6a), 4.72 (d, 1H, J1,2 9.0 Hz,
HA-1), 4.69 (d, 1H, CHaCCl3), 4.68 (d, 1H, JCHb,CHa 12.0 Hz, CHbCCl3),

S. S. Pertel et al. / Carbohydrate Research 356 (2012) 172–179
179
4.62 (dd, 1H, J6b,6a 11.5 Hz, J6b,5 3.8 Hz, HA-6b), 4.54 (d, 1H, J1,2
8.2 Hz, HB-1), 4.35 (br dd, 1H, JCHa,CHb 13.0 Hz, JCHa,CH 5.0 Hz,
OCHaCH@CH2), 4.22 (dd, 1H, J6a,6b 12.4 Hz, J6a,5 4.4 Hz, HB-6a),
4.04 (br ddt, 1H, JCHb,CH 6.1 Hz, OCHbCH@CH2), 4.01-3.87 (m, 5H,
HB-6b, HA-5, HA-3, HA-4, HA-2), 3.78 (br q, 1H, J2,3 9.5 Hz, HB-2),
3.47 (br dt, 1H, HB-5), 2.03, 2.00, 1.99, 1.94, (4s, 12H, 3OAc+NAc);
13C NMR (150.90 MHz, CDCl3): d 171.0, 170.6, 170.4 (CH3CO),
169.4 (NHCO), 166.5 (PhCO), 154.8 (NHCO), 138.5 (C aromatic),
133.9 (CH@CH2), 133.5 (CH aromatic), 129.9 (C aromatic), 129.8
(2C, CH aromatic), 128.7 (2C, CH aromatic), 128.5 (2C, CH aro-
matic), 127.8 (CH aromatic), 127.7 (2C, CH aromatic), 117.5
(CH@CH2), 100.9 (CB-1), 99.2 (CA-1), 95.4 (CH2CCl3), 77.0 (CA-4),
75.6 (CA-3), 74.8 (CH2CCl3), 73.0 (2C, PhCH2+CA-5), 72.1 (CB-5),
71.9 (CB-3), 69.7 (OCH2–CH@CH2), 68.3 (CB-4), 64.4 (CB-6), 61.8
(CA-6), 56.7 (CB-2), 51.9 (CA-2), 23.4, 20.8, 20.7, 20.6 (CH3CO);
HRMS (ESI): m/z Calcd for [C40H47Cl3N2O16]Na+: 939.1883. Found:
939.1878.
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Supplementary data
Supplementary data (NMR and mass spectra for new
compounds) associated with this article can be found, in the online
version, at http://dx.doi.org/10.1016/j.carres.2012.03.026.
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