Mechanism of anomerization of permethylated methyl D-glycopyranosides by trimethylsilyl trifluoromethanesulfonate

Article abstract of DOI:10.1016/S0008-6215(98)00132-3

Anomerization of permethylated methyl D-glycopyranosides catalyzed by trimethylsilyl trifluoromethanesulfonate was examined by NMR spectroscopy and gas-liquid chromatography. The initial-rate analysis showed that the rates of anomerization of β to α were faster than those of the opposite at various concentrations of the catalyst. The overall rates of disappearance of the substrates were faster than the rates of appearance of the opposite anomers because of the formation of a pyrylium-type of compound. The structure of the latter was proposed based on ¹H and ¹³C NMR spectra, although it was not isolable. Both cyclic and acyclic oxonium ions appear to be intermediates in the anomerization. The former seems to be the key intermediate for the formation of the pyrylium-type of compound as well as the anomerization of α-glycosidic linkages. β-Glycosidic linkages, on the other hand, appear to undergo anomerization mostly via acyclic oxonium ions.

Full text of DOI:10.1016/S0008-6215(98)00132-3

Carbohydrate Research 309 (1998) 243±250
Mechanism of anomerization of permethylated
methyl d-glycopyranosides by trimethylsilyl
tri¯uoromethanesulfonate
Chang Kiu Leea,*, Eun Ju Kima, In-Sook Han Leeb
a Department of Chemistry, Kangweon National University, Chuncheon 200-701, Korea
b Department of Science Education, Kangweon National University, Chuncheon 200-701, Korea
Received 27 February 1996; accepted 30 April 1998
Abstract
Anomerization of permethylated methyl d-glycopyranosides catalyzed by trimethylsilyl tri-
¯uoromethanesulfonate was examined by NMR spectroscopy and gas±liquid chromatography.
The initial-rate analysis showed that the rates of anomerization of ꢀ to ꢁ were faster than those of
the opposite at various concentrations of the catalyst. The overall rates of disappearance of the
substrates were faster than the rates of appearance of the opposite anomers because of the for-
1
mation of a pyrylium-type of compound. The structure of the latter was proposed based on H
and 13C NMR spectra, although it was not isolable. Both cyclic and acyclic oxonium ions appear
to be intermediates in the anomerization. The former seems to be the key intermediate for the
formation of the pyrylium-type of compound as well as the anomerization of ꢁ-glycosidic linkages.
ꢀ-Glycosidic linkages, on the other hand, appear to undergo anomerization mostly via acyclic
oxonium ions. # 1998 Elsevier Science Ltd. All rights reserved
Keywords: Anomerization; Transglycosylation; Cyclic oxonium ion
1. Introduction
catalyzed by methanesulfonic acid. Based on an
NMR study, an acyclic oxonium intermediate such
as II was ruled out in the report. Lemieux and
Shyluk [3] investigated the anomerization of acety-
lated alkyl glycopyranosides in chloroform satu-
rated with boron tri¯uoride at room temperature
or at 61 ꢀC in the presence of titanium tetra-
chloride, and suggested an intermediate ion-pair
such as III. The intermediate III may be considered
to be a modi®cation of I in the sense that both
contain a cyclic oxonium ion, but the outcome is
quite di€erent in that collapse of III to the ꢁ
anomer will result in no incorporation of externally
The anomerization of methyl glycopyranosides
has been the subject of extensive investigation. The
mechanism of the reaction is important because any
intermediate involved is relevant to understanding
the reactions taking place at the glycoside linkage, i.e.
hydrolysis, transglycosylation, reductive cleavage, etc.
Capon [1,2] suggested a cyclic oxonium ion such
as I as the intermediate in the anomerization ꢀof
methyl ꢀ-d-glucopyranoside in methanol at 70 C
* Corresponding author.
0008-6215/98/$Ðsee front matter # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00132-3

244
Chang Kiu Lee et al./Carbohydrate Research 309 (1998) 243±250
added CD3OD. In fact, the process involving III
was called ``intramolecular'', and the outcome is
thus similar to the process in which II is involved.
Furthermore, the molar ratio employed in the
reaction was 5 or 10 equivalents. Therefore, one
can conclude that attachment of cationic species to
merely one or both of the oxygen atoms which
form the acetal functionality may not be enough to
cause anomerization or transglycosylation. There-
fore, we examined the e€ect of the Lewis acids by
examining the 13C NMR chemical shift of per-
methylated methyl d-glycosides.
Complete assignments of the 13C NMR spectra
of methyl 2,3,4,6-tetra-O-methyl-ꢁ- and ꢀ-d-gluco-
pyranosides (1ꢁ and 1ꢀ) in acetonitrile have been
reported [6]. The 13C NMR spectrum of methyl
2,3,4,6-tetra-O-methyl-ꢀ-d-galactopyranoside (3ꢀ)
in D2O has also been reported [7]. The chemical-
shift values of the 13C signals of C-1±C-6 of 1ꢁ in
dichloromethane were shifted slightly to higher
®eld (0.5±0.7 ppm) than the reported values, which
were obtained in acetonitrile. The signals corre-
sponding to methyl carbons were also shifted to
higher ®eld (0.1±0.2 ppm) except that of C-2±
OCH3 which showed a down®eld shift by 0.2 ppm.
Considering the di€erence in polarity of acetoni-
trile ("=35.94) and dichloromethane ("=8.93) the
up®eld shift is understandable [8].
Jansson and Lindberg [4] carried out the anom-
erization of isopropyl tetra-O-methyl-ꢀ-d-glucopyr-
anoside in 10:3 acetic anhydride±acetic acid catalyzed
by H2SO4 and suggested that both cyclic and acyclic
oxonium ions may be possible as intermediates and
one or the other may predominate depending on
the substrates and conditions of reaction.
In the course of our study on the reductive-clea-
vage reaction of permethylated methyl d-glycopyr-
anosides we observed anomerization of the
glycosidic linkage in the presence of trimethylsilyl
tri¯uoromethanesulfonate (Me3SiOTf), boron tri-
¯uoride etherate (BF3.OEt2), and trimethylsilyl
.
methanesulfonate (Me3SiOMs)±BF3 OEt2 (5:1
mol/mol) in dichloromethane [5]. Based on the
analysis of the product compositions of the reac-
tion mixtures of anomerization and transglycosy-
lation in the presence of ethanol we proposed
reaction pathways for ꢀ-glycosides in which both
cyclic and acyclic intermediates compete and for ꢁ-
glycosides in which a cyclic oxonium ion is the sole
intermediate. Here we report the results of our
extensive investigation on the mechanism of
anomerization by NMR spectroscopy.
We understand that H+ and (CH3)3Si+ prob-
ably do not exist as free ions in these solutions, but
donors of these species do exist, and it is frequently
unclear which donor is at work. In this paper we
have often followed the practice of writing the free
ions into equations and schemes, because any
alternative was unreasonably complicated, but it
should be understood that these ions are always
bound to something.
In a comprehensive review it has been reported
that solvent-induced shifts are usually less than
1 ppm and the choice of solvent does not have a
large e€ect on proton-decoupled 13C NMR spec-
tra, except in the case of basic or acidic carbohy-
drates [9]. However, our observation with the ꢀ-
glucopyranoside (1ꢀ) is quite contrary to the gen-
eral statement. As shown in Table 1 the chemical
shift values of C-1±C-6 were signi®cantly changed
(0.7±5.4 ppm) to the up®eld region while those of
methyl carbons varied to a lesser extent (ca.
0.6 ppm). Other notable phenomena were the slight
up®eld shifts (Áꢂ<1 ppm) of 13C signals in the
presence of Me3SiOTf.
2. Results and discussion
R1
R01 R2
OMe H
OMe OMe H
R02
R3
R03
ꢁ-Glc (1ꢁ)
ꢀ-Glc (1ꢀ)
ꢁ-Man (2ꢁ)
ꢁ-Gal (3ꢁ)
ꢀ-Gal (3ꢀ)
OMe H
OMe H
OMe H
At ®rst we were interested in the fate of
Me3SiOTf in the course of anomerization. The
term such as ``catalyst'' is somewhat misleading
because none of it was recovered after the reaction.
H
OMe H
OMe H
H
OMe OMe H
OMe H
H
H
OMe
H
H
OMe OMe H

Chang Kiu Lee et al./Carbohydrate Research 309 (1998) 243±250
245
Table 1
13C Chemical-shift values of methyl 2,3,4,6-tetra-O-methyl-d-glycopyranosides
C±1
C±2
C±3
C±4
C±5
C±6
1-Me
2-Me
3-Me
4-Me
6-Me
1ꢁ
1ꢀ
A
B
C
A
B
C
A
B
A
B
A
B
D
97.7
97.5
98.2
104.7
104.3
105.0
98.6
98.5
98.2
82.0
81.8
82.6
80.8
80.6
84.6
77.4
77.4
76.5
76.0
80.9
81.0
79.8
83.7
83.6
84.3
84.2
83.7
87.2
76.5
76.4
80.5
80.0
84.3
84.1
85.2
79.9
79.6
80.6
75.1
74.9
80.5
71.9
71.0
78.2
78.0
75.2
75.3
73.1
70.3
70.3
71.0
73.2
72.8
75.4
81.7
81.7
69.2
68.7
71.2
71.3
74.9
71.7
71.8
72.4
71.1
70.9
72.4
71.5
72.0
71.6
71.3
73.3
73.2
71.0
55.1
55.0
55.3
56.7
56.5
57.0
54.9
55.2
55.3
55.0
56.8
56.8
57.1
58.6
58.5
58.4
59.1
59.0
60.5
60.6
60.7
61.3
61.0
61.2
60.7
60.9
60.7
61.0
60.7
61.2
60.9
60.8
59.2
59.5
59.2
59.0
60.7
60.0
60.2
60.4
58.9
60.5
60.6
60.4
60.6
59.1
59.2
58.7
58.6
59.3
59.0
58.5
59.1
57.7
59.2
58.1
57.9
59.3
57.6
57.9
58.1
57.7
58.2
58.3
57.1
2ꢁ
3ꢁ
3ꢀ
97.6
104.8
104.7
103.4
A: In dichloromethane-d2.
B: In dichloromethane-d2 with 5 equiv of Me3SiOTf added.
C: In acetonitrile-d3 and from ref. [6].
D: In D2O and from ref. [7].
The up®eld shift does not seem to be the result
of the change in polarity of the solvent by the pres-
ence of Me3SiOTf. Polarity would be increased by
Me3SiOTf and, if that were the case, the shift
should be in the down®eld direction. Complexation
of the lone-pair electrons on the oxygen atom of
the alcohol with a proton derived from tri-
¯uoroacetic acid was known to cause an up®eld
shift of the signals of all carbon atoms in 1-butanol
except the ꢁ carbon [10]. Complexation of a methyl
ether with Me3SiOTf may be visualized either as IV
or as V. Once trimethylsilyl cation is attached to an
oxygen atom forming an oxonium ion of type IV,
C±O bond cleavage may take place. The cleavage
would be facilitated if lone-pair electrons in a
neighboring oxygen atom could assist the depar-
ture of methoxytrimethylsilane. On the other hand,
the complexation of type V may not cause any
bond cleavage but it would be enough to cause a
change in chemical shift of attached carbon atoms.
The observed shift may be the result of such asso-
ciation.
copy, anomerization of 1ꢁ to 1ꢀ was observed.
However, another component was noticable after
3 h. The yield of the component reached about 20±
25% (by NMR) after 48 h. Although we were not
able to isolate the component by employing var-
ious work-up procedures, the NMR spectrum of
the reaction mixture leads us to propose a structure
1
of the component as 4. The H NMR spectrum of
the mixture showed, besides the peaks correspond-
ing to 1ꢁ and 1ꢀ, peaks at ꢂ 3.65 (s, 3H), 4.17 (s,
3H), 4.94 (s, 2H), 8.30 (d, 1H, J=9.0 Hz), 8.68 (dd,
1H, J=3.0 and 9.0 Hz), and 9.27 (d, 1H,
J=9.0 Hz) while the 13C NMR spectrum showed
peaks at 52.5, 58.8, 70.3, 120.5, 124.7, 145.9, 153.3,
1
and 175.8 ppm. The H chemical-shift values of
pyrylium perchlorate were reported to be ꢂ 9.70,
9.36, and 8.53 for ꢁ-, ꢃ-, and ꢀ-protons, respec-
tively, in tri¯uoroacetic acid [11]. The 13C chemical
shift values were also reported as 169.3, 127.7, and
161.2 ppm for ꢁ-, ꢃ-, and ꢀ-carbons, respectively
[12]. Therefore, the values observed in the present
investigation seem to be consistent with the pro-
posed structure 4. Formation of 4 was observed
from all the glycosides (1±3) although their relative
abundance and rate of formation were di€erent.
.
When a mixture of Me3SiOMs±BF3 OEt2 (5:1 mol/
mol) was used the anomerization reaction took
place but the formation of pyrylium ion 4 was not
observed even after 48 h. Similary, BF3.OEt2 alone
did not give 4 even after 4 days. Apparently, the
presence of Me3Si+ ion seems to be essential to
cause breaking the C±O bond which may lead to
formation of 4.
When a solution of 1ꢁ and Me3SiOTf (1:5 by
mole) in CD2Cl2 was monitored by NMR spectros-

246
Chang Kiu Lee et al./Carbohydrate Research 309 (1998) 243±250
rate constants for the formation of 4 were deter-
mined from the build-up of its peak at ꢂ 4.94,
which obeyed the ®rst-order rate law through at
least 24 h. This rate constant is k0. All of these rate
constants depend on the initial solution composi-
tion, and are pseudo ®rst-order rate constants.
We measured the rate of anomerization at dif-
ferent concentrations of the catalyst for the ®rst
®ve minutes by gas±liquid chromatography (GLC),
in which the rates of the reverse reaction and for-
mation of 4 were almost negligible. The results are
listed in Table 4.
The disappearance of permethylated methyl d-
glycosides was monitored by proton NMR spec-
troscopy. The ratio of the anomeric proton of the
reactant to the protons of CH2Cl2, which was pre-
sent in the solvent, was measured, and designated
At. At reached a constant value, designated A , in
1
about 1 h. Plots of ln (At A ) against time were
The rate constants in the Table 4 are larger than
those in the Table 3, but the same isomer is favored
in each case. The di€erence is due to the fact that
the equilibrium constants in the case of Table 4 are
pretty much independent of the catalyst con-
centration, even though the individual rate con-
stants are not.
Although it is dicult to derive a rate equation
which is consistent with the results in Table 4, it
seems apparent that the rate does not increase lin-
early as the concentration of Me3SiOTf increases.
This and the observed down®eld shift of the meth-
oxy proton peaks (Table 2) may be consistent with
the complexation of undissociated Me3SiOTf with
the oxygen atoms in the substrate.
The anomerization of 1ꢀ and 3ꢀ appeared to
reach equilibrium within 30 min and the ratios of
the ꢁ and ꢀ anomers were about 4:1 and 5:1,
respectively, based upon integration of the anome-
ric protons. However, the total amounts of ꢁ and ꢀ
anomers gradually decreased with time because of
the formation of 4.
As illustrated in Scheme 1, a cyclic oxonium
intermediate VI would be formed as a sole inter-
mediate in the formation of 4. Sequential elimina-
tion of methoxy groups from VI would then give
rise to 4. The formation of 4 may be explained as
shown in Scheme 2. Three methoxy groups have to
be eliminated from a substrate in order to form 4.
1
linear, and their slopes gave kobs, which is the sum
of k1 and k . After reaction had proceeded for
1
about 1 h and a constant value of At had been
reached the ratio of the product to the reactant
anomeric proton was measured, and taken as the
anomerization equilibrium constant, K. K is the
ratio, k1=k . From these ratios and sums the
1
individual rate constants could be calculated, and
they are tabulated in Table 3. The formation of 4
could not be detected during the ®rst hour of reac-
tion, but began to appear after longer times. The
Table 2
1H Chemical-shift values of methyl 2,3,4,6-tetra-O-methyl-d-
glycopyranosides
H-1 (J, Hz)
OCH3
1ꢁ
1ꢀ
2ꢁ
3ꢁ
3ꢀ
A
B
A
B
A
B
A
B
A
B
4.74 d (3.6)
4.85 d (3.5)
4.09 d (6.3)
4.15 d (6.5)
4.69 d (1.7)
4.75 d (1.7)
4.79 d (3.3)
4.87 d (3.9)
4.09 d (7.4)
4.14 d (7.0)
3.34, 3.35, 3.43, 3.48, 3.55
3.38, 3.42, 3.50, 3.52, 3.53
3.36, 3.46, 3.46, 3.47, 3.50
3.39, 3.43, 3.44, 3.51, 3.59
3.32, 3.36, 3.43, 3.43, 3.45
3.35, 3.46, 3.49, 3.51, 3.75
3.34, 3.35, 3.42, 3.45, 3.49
3.39, 3.44, 3.52, 3.53, 3.55
3.36, 3.46, 3.47, 3.50, 3.50
3.42, 3.50, 3.52, 3.53, 3.56
A: In dichloromethane-d2.
B: In dichloromethane-d2 with 5 equiv of Me3SiOTf added.
Table 4
Rates of anomerization of methyl 2,3,4,6-tetra-O-methyl-d-
glycopyranosides in the presence of various molar equivalents
Table 3
Rate constants for the anomerization (k1) of methyl 2,3,4,6-
tetra-O-methyl-d-glycopyranosides ꢀand the formation (k0) of 4
in the presence of Me3SiOTf at 25 C in CH2Cl2
ꢀ
of Me3SiOTf and docosane at 25 C
1
Glycoside
k1, min (Â102)
k0, min
k1=k0
1
1
Glycoside
k1, min
0.1
0.5
1.0
2.0
5.0
2
2
4
2
1
4
4
4
3
4
1ꢁ
1ꢀ
2ꢁ
3ꢁ
3ꢀ
1.0(‹0.5)Â10
4.3(‹0.5)Â10
1.1(‹0.5)Â10
3.8(‹0.5)Â10
1.4(‹0.5)Â10
1.3(‹0.5)Â10
1.0(‹0.5)Â10
1.0(‹0.5)Â10
1.2(‹0.5)Â10
3.5(‹0.5)Â10
76.9
430.0
1.1
31.6
400.0
1ꢁ
1ꢀ
3ꢁ
3ꢀ
0.9
8.1
2.9
11.8
1.6
10.3
5.0
2.3
11.6
7.5
2.6
17.4
9.0
2.8
26.7
9.9
15.3
27.5
49.5
59.3

Chang Kiu Lee et al./Carbohydrate Research 309 (1998) 243±250
247
Scheme 1.
Scheme 2.
They seem to form methoxytrimethylsilane, and in
fact, the formation of 4 was not observed at all in
the presence of externally added methoxy-
trimethylsilane (5 equiv).
that leads to anomerization by reducing the e€ec-
tive concentration of the catalyst. Added methox-
ytrimethylsilane may also inhibit the formation of
4 by forcing the reversible step in Scheme 2 toward
the reverse direction.
Formation of MeOSiMe3 could be detected by
NMR spectroscopy. The NMR spectra of the
reaction mixtures clearly showed a peak at ꢂ 3.43
which was proved to correspond to the methoxy
group of MeOSiMe3 in the presence of Me3SiOTf.
The chemical shift values of CH3O and Si(CH3)3 of
methoxytrimethylsilane in CD2Cl2 are ꢂ 3.38 and ꢂ
0.09, respectively, but they are shifted to ꢂ 3.43 and
ꢂ 0.32, respectively, in the presence of Me3SiOTf.
The shift may be the result of formation of a com-
plex in fast equilibrium as follows:
A mixture of 1ꢀ, CD3OSi(CH3)3, and Me3SiOTf
(1:5:5 mol/mol/mol) in CD2Cl2 was examined by
NMR, and it was found that the anomerization
took place much more slowly; about 25% of the ꢀ
anomer was converted to the ꢁ anomer in 24 h.
Without the presence of the silane the anomeriza-
tion reached equilibrium in 30 min in which about
80% of the ꢁ anomer was present. Although the
formation of both CH3OSi(CH3)3 and the methyl-
d3 glucopyranosides were con®rmed by the experi-
ment it was not possible to make a quantitative
assessment because of the diculty in integrating
the individual CH3O resonances. Furthermore, the
GLC retention times of the permethylated methyl
glycosides and the corresponding deuterated com-
pounds were identical on a DB-5 column, and sev-
eral variations in GLC conditions failed to
separate the components.
Such complexation may decrease the possibility
of formation of the substrate±Me3SiOTf complex
Table 5
Composition (mol %) of the mixture of permethylated methyl d-glucopyranosides, ethoxytrimethylsilane, and Me3SiOTf (1:5:5 by
ꢀ
molar equiv) at 25 Ca
Glycoside
1ꢁ
1ꢀ
1 h
12 h
24 hb
48 h
72 h
1 h
12 h
24 hb
48 h
72 h
ꢁ-OMe
ꢀ-OMe
ꢁ-OEt
ꢀ-OEt
100
0
0
92.0
0
5.6
2.4
72.1 (11.9)
0.8 (2.4)
17.9 (67.4)
9.2 (18.3)
68.9
0.9
20.1
10.0
48.0
1.8
35.8
14.4
0
100
0
16.2
80.0
2.0
12.5 (13.4)
65.4 (2.7)
12.1 (65.7)
10.0 (18.1)
4.3
26.0
44.3
25.4
7.3
7.5
61.0
24.2
0
0
1.8
a
The analysis was carried out by GLC.
Values in parentheses are the results of transglycosylation with ethanol (10 equiv) and Me3SiOTf (10 equiv) from ref. [5].
b

248
Chang Kiu Lee et al./Carbohydrate Research 309 (1998) 243±250
The transglycosylation of 1ꢁ and 1ꢀ were inves-
and acyclic oxonium ions. As illustrated in struc-
ture X, the most stable conformation of the ꢀ-gly-
coside appears to be the arrangement in which C-2
and the CH3 at O-1 are anti. One of the lone-pair
orbitals of the O-1 atom therefore becomes syn
with a lone-pair orbital of the ring oxygen atom.
The two syn orbitals may thus form a complex
with Me3Si+, such as X, and in this complex, the
other lone-pair orbital of O-1, which is anti to the
O±C-1 bond, would facilitate O±C-1 bond break-
ing to form acyclic oxonium intermediate VII.
The anti arrangement (XI) of C-2 and the CH3
at O-1 along C-1±O-1 bond in the ꢁ-glycoside
prohibits a syn arrangement of either of the lone-
pair orbitals of O-1 and those of the ring oxygen
atom as shown in XI. Therefore, complexation of
Me3Si+ between O-1 and O-5 should be unlikely.
On the other hand, complexation of Me3Si+
between O-2 and O-1 becomes favorable because
the lone-pair orbitals of the two oxygen atoms are
arranged so that a ®ve-membered ring is readily
formed. In this complex (XI), the lone-pair orbital
of the ring oxygen atom, which is anti to the C-1±O
bond, will assist the C-1±O-1 bond breaking to give
the cyclic oxonium ion VI.
tigated further with ethoxytrimethylsilane and the
results are summarized in Table 5. Although it was
not surprising that the anomerization and trans-
glycosylation of both substrates were retarded sig-
ni®cantly, a few important observations were
made. First, the ratio of ꢁ-OEt and ꢀ-OEt in the
reaction of 1ꢀ was about 1.2:1 after 24 h. Con-
sidering that the ratio of ꢁ and ꢀ isomers of a
solution of 1ꢀ and Me3SiOTf in CH2Cl2 after the
same period is 4.26:1 [5], the observed ratio is dif-
®cult to be explained by a pathway in which a
cyclic oxonium ion is involved. If the ethoxysilane
attacks the cyclic oxonium ion, the ꢁ anomer
should be preferably formed. This may be evidence
for the presence of an acyclic oxonium ion inter-
mediate. We propose an alternative pathway for
the transglycosylation of 1ꢀ in the presence of
ethoxytrimethylsilane as shown in Scheme 3. The
key step may be the formation of an acetal VIII
which can be transformed to IX. Ring closure of
VIII and IX may not have any signi®cant pre-
ference and both the ꢁ-OEt and ꢀ-OEt compounds
could be formed in equal amounts at this stage.
The ethyl ꢀ-Glc may then undergo anomerization
so that the ethyl ꢁ-Glc exists as the major product
when equilibrium is reached.
In the case of 1ꢁ, transglycosylation via the cyc-
lic oxonium ion intermediate should favor the for-
mation of the Et ꢁ-Glc and, in fact, the ꢁ : ꢀ ratio
was about 2:1 after 24 and 48 h and 2.5:1 after 72 h.
A molecular model study using PCMODEL
gave results consistent with the formation of cyclic
The observed rate of anomerization of the
galacto isomer (3ꢀ) was the fastest while the for-
mation of 4 from it was not. We propose (Scheme 4)
that a complex (XIII) is formed with Me3Si+ in
which the oxygen atom at C-4 and the ring oxygen
atom form a 5-membered ring.
Formation of XIII will facilitate the ring open-
ing and will result an acyclic intermediate XIV.
The rate of disappearance of 3ꢀ is about 4 times
faster than that of 3ꢁ. On the other hand, the rate
of formation of 4 from 3ꢀ is about 0.3 times faster
than from 3ꢁ. The reverse in the ratios of rate may
be explained by di€erent fates of XIII and XVI
formed from 3ꢀ and 3ꢁ, respectively. As shown in
Scheme 4, one of the lone-pair orbitals on the
oxygen atom of the anomeric equatorial methoxy
group in XIII may undergo e€ective overlapping
Scheme 3.

Chang Kiu Lee et al./Carbohydrate Research 309 (1998) 243±250
249
with an sp3 orbital of C-1, resulting in cleavage of
the ring. On the other hand, similar overlapping is
not e€ectively taking place with the axial methoxy
group in XVI. Therefore, recomplexing of Me3Si+
with 3ꢁ will take place to form XV, which can
subsequently undergo elimination of the ꢁ-OCH3
group, resulting in a cyclic oxonium ion. Once the
latter forms, anomerization and formation of 4 will
compete. For all ꢁ-glycosides, complexation of
Me3Si+ involving oxygen atoms in the ring and the
axial methoxy group (XII) appears to be unfavor-
able.
lapping. Instead, a cyclic oxonium ion may be
derived from an intermediate such as XVII. The
observed rate of disappearance of 2ꢁ was the
slowest among all the substrates examined. It
seems probable that catalysis of anomerization by
Me3Si+ may arise via formation of a cyclic com-
plex (such as XV; Scheme 4) involving two vicinal
oxygen atoms. Such kind of complexation is not
feasible in 2ꢁ.
3. Experimental
Permethylated methyl ꢁ-d-mannopyranoside
(2ꢁ) did not undergo anomerization in the presence
of Me3SiOTf as previously reported [5], but it also
gave 4. The rate of disappearance of 2ꢁ was essen-
tially identical to the rate of formation of 4. As in
the case of 3ꢁ, formation of a 5-membered ring
complex (XVIII) in 2ꢁ involving the oxygen atoms
in the ring and the axial methoxy group at C-2 is
expected, as illustrated in Scheme 5.
Starting materials.ÐMethyl ꢁ- and ꢀ-d-gluco-
pyranosides, methyl ꢁ-d-mannopyranoside, methyl
ꢁ- and ꢀ-galactopyranosides, and ethoxy-
trimethylsilane were all commercial products. Per-
methylated methyl d-glycopyranosides (1ꢁ, 1ꢀ, 2ꢁ,
3ꢁ, 3ꢀ) were prepared as described previously [5].
Trideuteriomethoxytrimethylsilane was prepared
by re¯uxing chlorotrimethylsilane (8.9 mL, 0.07mol)
and CD3ONa±CD3OD (prepared from 5 mL of
CD3OD and 1.61 g of freshly cut Na) for 3 h and
subsequent distillation. The purity of the product
However, the axial methoxy group at C-1 cannot
transform the complex to either a cyclic or an
acyclic intermediate because of unfavorable over-
1
was con®rmed to be >99% by H and 13C NMR
spectroscopy as well as by GLC. Commercial tri-
methylsilyl tri¯uoromethanesulfonate (Me3SiOTf),
trimethylsilyl methanesulfonate (Me3SiOMs), and
.
boron tri¯uoride etherate (BF3 OEt2) were distilled
under mild vacuum prior to use. Dichloromethane
was dried over CaH2 and distilled prior to use.
Analytical methods.Ð1H NMR spectra were
recorded on a Varian 500 VXR-FT NMR spectrom-
eter in CD2Cl2 containing tetramethylsilane (Me4Si)
as an internal standard. A Hewlett±Packard 5890
Plus gas±liquid chromatograph equipped with a
capillary column (HP-5, 25 m, 0.53 mÂ1.0 ꢄm) and
a ¯ame-ionization detector was used for analysis.
ꢀ
The column was held at 120 C for 2 mꢀin after
ꢀ
injection then programmed to 250 C at 6 C/min.
Nitrogen was used as the carrier gas at a ¯ow rate
of 1 mL/min.
Scheme 4.
Determination of rate constants.ÐStock solu-
tions of each glycoside were prepared in a 1 mL
volumetric ¯ask by dissolving 36.5 mg of the sub-
strate in CD2Cl2 so that the concentration was
0.146 M. A solution of Me3SiOTf was prepared by
dissolving 0.200 mL in CD2Cl2 in a 2 mL volu-
metric ¯ask so that the concentration was 0.517 M.
The solution of glycoside (0.2 mL) was taken with
a gas-tight syringe (0.25 mL) and placed in an
NMR tube (5 mm diameter) and the solution of
Scheme 5.

250
Chang Kiu Lee et al./Carbohydrate Research 309 (1998) 243±250
Me3SiOTf (0.29 mL) was introduced by a gas-tight
syringe (0.50 mL). The ®nal concentration of gly-
coside was 0.06 M and the ®nal concentration of
(Ro Rt) versus time, where Ro is the ratio of the
substrate to docosane immediately after the mixing
and Rt was that at time t.
Transglycosylation in the presence of alkoxy-
trimethylsilane. An illustrative procedure
5
1
Me3SiOTf was 0.30 M. H NMR spectra of the
solution were obtained at predetermined intervals
using a kinetics program. The spectra were
retrieved and the peaks corresponding to H-1 at
around ꢂ 4.1 and 4.8 for ꢀ and ꢁ anomers, respec-
tively, and CH2Cl2 at around ꢂ 5.2 were integrated.
The pseudo-®rst order rate constants (kobs) were
calculated from the slope of a plot of time versus
ln‰ꢁAo A †=ꢁAt A †Š [13] for the period of 1 h
A solution (5 mL) of 1ꢁ (4Â10
M), EtO-
4
4
Si(CH3)3 (2Â10 M), and Me3SiOTf (2Â10 M)
in CH2Cl2 was prepared. The solution was divided
into ®ve Wheaten v-vials and stirred at 25 ꢀC. After
the pre-determined period the solution was treated
with satd NaHCO3 solution and the organic layer
was examined with GLC.
1
1
after which equilibrium of ꢁ and ꢀ anomers is
reached. The rate constant k1 for the forward
reaction was calculated by the following equations:
Acknowledgements
We thank Professors Gary R. Gray and Maurice
M. Kreevoy of the University of Minnesota for
helpful discussion. This research was supported by
the grant from the Research Center for New Bio-
materials in Agriculture-KOSEF.
kobs ˆ k1 ‡ k ˆ k1ꢀ1 ‡ 1=K†
1
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``At'' values were calculated from the ratio of the
integrations of the anomeric proton and CH2Cl2
which was present in the solvent. The value of Ao
was the one obtained from the ®rst spectra of each
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1
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