Electrochemistry of chalcogenoglycosides. Rational design of iterative glycosylation based on reactivity control of glycosyl donors and acceptors by oxidation potentials

Article abstract of DOI:10.1021/jo0261350

Electrochemical properties of various para-substituted phenylthio-, phenylseleno-, and phenyltelluroglucopyranosides bearing acetyl, benzoyl, and benzyl protecting groups have been investigated to estimate the reactivity of chalcogenoglycosides toward electrochemical glycosylations. The oxidation potential of the chalcogenoglycosides shows good correlation with the ionization potential of chalcogen atoms, and decreases in the order thio-, seleno-, and telluroglycosides. It is also affected by the para-substituents, and the substitution effect correlates very well with the HOMO energy of para-substituted benzenechalcogenol and with the Hammett σ_p⁺ value. Electrochemical glycosylation of telluroglycosides has been examined, and it was found that the use of an undivided cell is more effective than the use of a divided cell. Selective activation of the chalcogenoglycosides in bulk electrolysis based on their oxidation potentials has been examined, and the relative reactivity of the telluroglycosides can be estimated from their oxidation potentials. However, the relative reactivity of selenoglycosides in the preparative glycosylation was rather insensitive to the oxidation potential values.

Full text of DOI:10.1021/jo0261350

Electr och em istr y of Ch a lcogen oglycosid es. Ra tion a l Design of
Iter a tive Glycosyla tion Ba sed on Rea ctivity Con tr ol of Glycosyl
Don or s a n d Accep tor s by Oxid a tion P oten tia ls†
Shigeru Yamago,* Koji Kokubo, Osamu Hara, Sadayoshi Masuda, and J un-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering,
Kyoto University, Sakyo-ku, Kyoto 606-8501, J apan
yamago@sbchem.kyoto-u.ac.jp
Received J uly 3, 2002
Electrochemical properties of various para-substituted phenylthio-, phenylseleno-, and phenyltel-
luroglucopyranosides bearing acetyl, benzoyl, and benzyl protecting groups have been investigated
to estimate the reactivity of chalcogenoglycosides toward electrochemical glycosylations. The
oxidation potential of the chalcogenoglycosides shows good correlation with the ionization potential
of chalcogen atoms, and decreases in the order thio-, seleno-, and telluroglycosides. It is also affected
by the para-substituents, and the substitution effect correlates very well with the HOMO energy
+
of para-substituted benzenechalcogenol and with the Hammett σp value. Electrochemical glyco-
sylation of telluroglycosides has been examined, and it was found that the use of an undivided cell
is more effective than the use of a divided cell. Selective activation of the chalcogenoglycosides in
bulk electrolysis based on their oxidation potentials has been examined, and the relative reactivity
of the telluroglycosides can be estimated from their oxidation potentials. However, the relative
reactivity of selenoglycosides in the preparative glycosylation was rather insensitive to the oxidation
potential values.
Intensive efforts have been recently aimed at the
synthesis of oligosaccharides because of their numerous
important biological functions.1,2 Since oligosaccharides
consist of several anomeric C-O bond linked monosac-
charides, the synthesis would necessarily require itera-
tive glycosylation. Therefore, the reactivity control of the
anomeric substituents is one of the major challenges of
a generalized oligosaccharide synthesis.3 To achieve
efficient and high-throughput synthesis, several glyco-
sylation strategies have recently been developed, includ-
ing a two-stage activation method,4 the armed-disarmed
glycosylation,5 a one-pot synthesis,6 an orthogonal method,7
enzymatic glycosylation,8 a programmable one-pot strat-
egy,9 and solid-phase synthesis.10,11 Despite these recent
developments, the rational design of the oligosaccharide
synthesis still remains unachieved, primarily due to the
(5) (a) Green, L. G.; Ley, S. V. In Carbohydrates in Chemistry and
Biology; Ernst, B., Hart, G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim,
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Udodong, U.; Fraser-Reid, B. J . Am. Chem. Soc. 1988, 110, 5583. (c)
Zuurmond, H. M.; van der Meer, P. H.; van der Klein, P. A. M.; van
der Marel, G. A.; van Boom, J . H. J . Carbohydr. Chem. 1993, 12, 1091.
(d) Hashimoto, S.; Sakamoto, H.; Honda, T.; Abe, H.; Nakamura, S.;
Ikegami, S. Tetrahedron Lett. 1997, 38, 8969.
(6) (a) Raghavan, S.; Kahne, D. J . Am. Chem. Soc. 1993, 115, 1580.
(b) Yamada, H.; Harada, T.; Takahashi, T. J . Am. Chem. Soc. 1994,
116, 7917. Takahashi, T.; Adachi, M.; Matsuda, A.; Doi, T. Tetrahedron
Lett. 2000, 41, 2599. (c) Douglas, N. L.; Ley, S. V.; Lu¨cking, U.;
Warriner, S. J . Chem. Soc., Perkin Trans. 1 1998, 51. (d) Tsukida, T.;
Yoshida, M.; Kurokawa, K.; Nakai, T.; Achiha, T.; Kiyoi, T.; Kondo,
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Biology; Ernst, B., Hart, G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim,
Germany, 2000; Vol. 2, pp 723-844. Wong, C.-H.; Halcomb, R. L.;
Ichikawa, Y.; Kajimoto, T. Angew. Chem., Int. Ed. Engl. 1995, 34, 521.
Takayama, S.; McGarvey, G. J .; Wong, C.-H. Chem. Soc. Rev. 1997,
26, 407.
* To whom correspondence should be addressed. Fax: +81-75-753-
5911. Email: (J .-i. Y.) yoshida@sbchem.kyoto-u.ac.jp.
† This paper is dedicated to Professor Hans J . Schafer on the
occasion of his 65th birthday.
(1) (a) Carbohydrates in Chemistry and Biology; Ernst, B., Hart, G.
W., Sinay, P., Eds.; Wiley-VCH: Weinheim, Germany, 2000; Vol. 1.
(b) Varki, A. Glycobiology 1993, 3, 97.
(2) For recent review articles on oligosaccharide synthesis, see: (a)
Preparative Carbohydrate Chemistry; Hanessian, S., Ed.; Marcel
Dekker, Inc.: New York, 1997. (b) Sears, P.; Wong, C.-H. Science 2001,
291, 2344. (c) Seeberger, P. H.; Haase, W.-C. Chem. Rev. 2000, 100,
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10.1021/jo0261350 CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/08/2002
8584
J . Org. Chem. 2002, 67, 8584-8592

Electrochemistry of Chalcogenoglycosides
SCHEME 1
SCHEME 2
ing sugar derivatives would also possess different oxida-
tion potentials. We also expected that the para-substit-
uent of the aryl group would finely tune the reactivity of
the glycosides. In addition, since the C-2 protecting group
is known to affect glycosidic reactivity,5 we also examined
the effect of the protecting group on the oxidation
potential. Since telluroglycosides possess the lowest
oxidation potential of any chalcogenglycoside, they would
be expected to be the most reactive. However, there had
been no report on the O-glycosylation of telluroglycosides
until our preliminary results appeared.19 We report here
(1) the electrochemical study of various chalcogenogly-
cosides in terms of the electrochemical activation of
chalcogenoglycosides, (2) the O-glycosylation of telluro-
glycosides, and (3) several attempts at the chemoselective
activation of chalcogenoglycosides by the electrochemical
method.20
difficulty in predicting the reactivities of sugar deriva-
tives, which are strongly affected by structures, protect-
ing groups, and reaction conditions, e.g., activating
reagents and solvents. Given these considerations, the
programmable one-pot strategy seems to be the most
effective, because one can design a combination glycosyl
donor/acceptor strategy using an empirical database.
However, prediction of the reactivity of new glycosides
is, unfortunately, rather difficult. An alternative, and
potentially more general, strategy to overcoming this
problem is the use of a single anomeric substituent under
single reaction conditions. However, this type of strategy
has been limited to only the glycal assembly method,12
and two new methods have recently appeared from Gin
et al.13 and from our own laboratory.14
Resu lts a n d Discu ssion
Oxid a tion P oten tia ls of Ch a lcogen oglycosid es.
Various para-substituted phenylthio-, phenylseleno-, and
phenyltelluroglucopyranosides bearing acetyl, benzoyl,
and benzyl protecting groups (2-11) were prepared, and
We report here an alternative approach for the rational
design and prediction of the reactivity of glycosyl accep-
tors and donors by an electrochemical reaction.15,16
Because oxidation potentials directly give us reactivity
indices of sugar derivatives, we would be able to estimate
their reactivity. Therefore, if we could synthesize several
sugar derivatives possessing different oxidation poten-
tials and reactivities, we would be able to repeat glyco-
sylation iteratively, changing only the electronic voltage
(Scheme 1).
We focused on chalcogenoglycosides 1 (X ) S, Se, Te),
because glycosides bearing oxygen, sulfur, and selenium
atoms can be activated under electrochemical oxidation
(Scheme 2).17,18 Since the ionization potential of the
chalcogen atom is considerably different, the correspond-
(17) (a) Noyori, R.; Kurimoto, I. J . Org. Chem. 1986, 51, 4322. (b)
Amatore, C.; J utand, A.; Mallet, J .-M.; Meyer, G.; Sinay, P. J . Chem.
Soc., Chem. Commun. 1990, 718. Mallet, J .-M.; Meyer, G.; Yvelin, F.;
J utand, A.; Amatore, C.; Sinay, P. Carbohydr. Res. 1993, 244, 237. (c)
Balavoine, G.; Gref, A.; Fischer, J .-C.; J ubineau, A. Tetrahedron. Lett.
1990, 31, 5764. Balavoine, G.; Berteina, S.; Gref, A.; Fischer, J .-C.;
Lubineau, A. J . Carbohydr. Chem. 1995, 14, 1217. Balavoine, G.;
Berteina, S.; Gref, A.; Fischer, J .-C.; Lubineau, A. J . Carbohydr. Chem.
1995, 14, 1237. (d) Nokami, J .; Osafune, M.; Ito, Y.; Miyake, F.;
Sumida, S.; Torii, S. Chem. Lett. 1999, 1053.
(18) Yoshida, J .; Sugawara, M.; Kise, N. Tetrahedron Lett. 1996,
37, 3157. Yoshida, J .; Sugawara, M.; Tatsumi, M.; Kise, N. J . Org.
Chem. 1998, 63, 5950.
(19) Yamago, S.; Kokubo, K.; Yoshida, J . Chem. Lett. 1997, 111,
Yamago, S.; Kokubo, K.; Murakami, H.; Mino, Y.; Hara, O.; Yoshida,
J . Tetrahedron Lett. 1998, 39, 7905.
(12) Williams, L. J .; Garbaccio, R. M.; Danishefsky, S. J . In
Carbohydrates in Chemistry and Biology; Ernst, B., Hart, G. W., Sinay,
P., Eds.; Wiley-VCH: Weinheim, Germany, 2000; Vol. 1, pp 61-92.
(13) Nguyen, H. M.; Poole, J . L.; Gin, D. Y. Angew. Chem., Int. Ed.
2001, 40, 414.
(14) Yamago, S.; Yamada, T.; Hara, O.; Ito, H.; Mino, Y.; Yoshida,
J . Org. Lett. 2001, 3, 3867.
(15) Organic Electrochemistry, 4th ed., revised and expanded; Lund,
H., Hammerich, O., Eds.; Marcel Dekker: New York, 2001.
(16) For other papers on our study of electrochemical synthesis,
see: Yoshida, J .; Suga, S.; Suzuki, S.; Kinomura, N.; Yamamoto, A.;
Fujiwara, K. J . Am. Chem. Soc. 1999, 121, 9546. Suga, S.; Suzuki, S.;
Yamamoto, A.; Yoshida, J . J . Am. Chem. Soc. 2000, 122, 10244. Suga,
S.; Suzuki, S.; Yoshida, J . J . Am. Chem. Soc. 2002, 124, 30.
(20) For other papers on our study of C-glycoside synthesis, see:
Yamago, S.; Miyazoe, H.; Yoshida, J . Tetrahedron Lett. 1999, 40, 2339.
Yamago, S.; Miyazoe, H.; Yoshida, J . Tetrahedron Lett. 1999, 40, 2343.
Yamago, S.; Miyazoe, H.; Goto, R.; Yoshida, J . Tetrahedron Lett. 1999,
40, 2347. Yamago, S.; Miyazoe, H.; Goto, R.; Hashidume, M.; Sawazaki,
T.; Yoshida, J . J . Am. Chem. Soc. 2001, 123, 3697. Yamago, S.;
Hashidume, M.; Yoshida, J . Tetrahedron 2002, 58, 6805.
J . Org. Chem, Vol. 67, No. 24, 2002 8585

Yamago et al.
TABLE 1. Oxid a tion P oten tia l of
1-Ar ylch a lcogen oglycosid es
a
a
glycoside
Eox
1.65
glycoside
Eox
2a
2b
3a
3b
3c
4a
4b
5a
5b
5c
5d
6a
6b
6c
7a
7b
8a
8b
8c
8d
1.31 (1.36)
1.18 (1.21)
1.18 (1.16)
0.95
0.98 (0.92)
0.90 (0.94)
0.97 (0.90)
0.91 (0.86)
0.59 (0.62)
(1.43)
1.46 (1.50)
1.52
1.47 (1.43)
1.22
1.24
1.25 (1.28)
1.31
1.25 (1.25)
1.15
9b
10b
11b
0.69
(1.21)
F IGURE 2. Correlation between the calculated IP of para-
substituted benzenethiols and the Eox of 2 and 3.
0.76 (0.82)
a
Decomposition potentials (V vs Ag/AgCl) were measured in a
0.1 M CH3CN solution of LiClO4 at room temperature using linear
sweep voltammetry equipped with a rotating disk electrode. Peak
potentials (V vs Ag/AgCl) measured by Osteryoung square wave
voltammetry are shown in parentheses.
F IGURE 3. Correlation between the calculated IP of para-
substituted benzeneselenols and the Eox of 4-6.
group. The observed tendency is consistent with the
armed-disarmed glycoside chemistry, in which glyco-
sides bearing 2-alkyl protecting groups are more reactive
than those bearing 2-acyl protecting groups.5
F IGURE 1. Correlation between the IP of the chalcogen atom
and the Eox of 2-8 and 11.
Ab initio molecular orbital calculations of various para-
substituted benzenechalcogenols (p-RC6H4XH; R ) H,
Me, OMe, NMe2; X ) S, Se, Te) at the HF/LANL2DZ level
were performed to delve more deeply into the differences
in the oxidation potentials.22 The calculations indicate
that the ionization potential (IP) thus obtained correlated
nicely with the oxidation potential of the chalcogenogly-
cosides (Figures 2-4). Molecular orbital analyses of
PhXH (X ) S, Se, Te) suggest that the magnitude of the
orbital coefficient of the HOMO is largest at the n-orbital
of the chalcogen atom, which is further conjugated with
the aromatic p-orbitals. The interaction of the n-orbital
and the p-orbitals is strongest when X ) S, slightly
weaker when X ) Se, and even weaker when X ) Te.
Electron-donating para-substituents further increase the
HOMO energy level (R ) Me, OMe, NMe2), and the
n-orbital of the nitrogen atom possesses the largest
orbital coefficients for the HOMO orbital of the dimethy-
lamino-substituted benzenethiol and benzeneselenol (X
) S and Se).
their electrochemical properties were measured by cyclic
voltammetry (CV), linear sweep voltammetry (LSV), or
Osteryoung square wave voltammetry (OSW).21 An ir-
reversible and single-electron oxidation was observed by
CV analysis. The data on the oxidation potential of 2-11
by LSV (decomposition potential) or OSW (peak poten-
tial) are presented in Table 1. Due to the inherent
baseline deviation near the decomposition potential in
LSV, especially in the measurement of telluroglycosides,
the oxidation potentials obtained by OSW may be more
reliable than those obtained by LSV.
The oxidation potential is strongly affected by the
chalcogen atom, as we expected, and the potential
decreases in the order thio- (X ) S), seleno- (X ) Se),
and telluroglycosides (X ) Te) among the chalcogenogly-
cosides with the same protecting group P and the same
para-substituent R. The oxidation potential of 1 and the
ionization potential of the chalcogen atoms show good
linear correlation with r > 0.99 (Figure 1). This result
can be explained by the fact that the single-electron
oxidation takes place from the n-orbital (lone pair) of the
chalcogen atom, which is the HOMO of the chalco-
genoglycosides (see below). It is also worth noting that
the benzyl-protected glycosides (P ) Bn) possess lower
oxidation potential than the acetyl-protected (P ) Ac) and
benzoyl-protected (P ) Bz) ones, presumably because acyl
groups are electron-withdrawing compared to the benzyl
The correlation between the oxidation potentials and
the Hammett σp value of the para-substituents is shown
in Figure 5. While several σp values have been reported,
(22) Gaussian 94, Revision E.2: Frisch, M. J .; Trucks, G. W.;
Schlegel, H. B.; Gill, P. M. W.; J ohnson, B. G.; Robb, M. A.; Cheeseman,
J . R.; Keith, T.; Petersson, G. A.; Montgomery, J . A.; Raghavachari,
K.; Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.;
Cioslowski, J .; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.;
Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.;
Replogle, E. S.; Gomperts, R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.;
Defrees, D. J .; Baker, J .; Stewart, J . P.; Head-Gordon, M.; Gonzalez,
C.; Pople, J . A., Gaussian, Inc., Pittsburgh, PA, 1995.
(21) Osteryoung, J .; O’Dea, J . J . In Electroanalytical Chemistry;
Bard, A. J ., Ed.; Dekker: New York, 1986; Vol. 14.
8586 J . Org. Chem., Vol. 67, No. 24, 2002

Electrochemistry of Chalcogenoglycosides
SCHEME 3
theoretical calculations of the arylchalcogenols, and the
formation of the ditelluride in the glycosylation reaction
shown below, we proposed the following reaction mech-
anism (Scheme 3): A single-electron oxidation of the
telluroglycoside takes place at the n-orbital of the tel-
lurium moiety to generate the short-lived radical cation
intermediate, which spontaneously dissociates to the
aryltelluro radical and the oxycarbenium ion. The radical
dimerizes to the ditelluride, and the oxycarbenium ion
reacts with an alcohol to give the O-glycoside.
F IGURE 4. Correlation between the calculated IP of para-
substituted benzenetellurols and the Eox of 8.
Electr och em ica l Glycosyla tion of Tellu r oglyco-
sid es in a Divid ed Cell. The glycosylation of 8 and
3-phenylpropanol was carried out using constant-poten-
tial electrolysis at 1.1 V in a LiClO4 solution of MeCN in
an H-type divided cell using a carbon fiber anode and a
Pt foil cathode. The reaction mainly afforded a mixture
of the O-glycoside 12, the ortho ester 13, and the diaryl
ditelluride (eq 1). The ortho ester 13 was converted to
F IGURE 5. Correlation between the Hammett substituent
constant (σp+) and the Eox of 3, 6, and 8.
the σp+ value shows a better linear correlation (r ) 0.95-
0.96) than the σp value (r ) 0.88-0.89).23 Because the
o
+
σp value expresses enhanced resonance properties and
fits well when the reaction involves a vacant orbital
adjacent to the aryl ring, it is consistent with the
hypothesis that the single electron oxidation takes place
at the chalcogen n-orbital to generate the cation radical
species. Figure 5 also indicates that the oxidation poten-
tials of the telluroglycosides are less affected by the para-
substituents than those of the thio- and selenoglycosides.
This is due to the weaker interaction of the n-orbital of
the Te atom with the aryl group than that of the S and
Se atoms, as suggested by the theoretical calculations.
The effect of the C-6 substituents is negligible, and the
C-6-modified chalcogenoglycosides 9 and 10 showed
oxidation potentials virtually identical with those of the
corresponding C-6-protected glycosides 3 and 6, respec-
tively.
Mech a n ism of th e Activa tion of Ch a lcogen ogly-
cosid es. The CV and OSV analyses of the telluroglyco-
sides 7, 8, and 11 were investigated in more detail in
conjunction with the mechanism of the glycosylation of
telluroglycosides as shown below. The CV of 7, 8, and 11
in a LiClO4 solution of MeCN only showed an irreversible
single-electron oxidation wave. The corresponding reverse
reduction wave could not be observed at the scan speed
of 100-1000 mV/s. The OSV of 7b also showed an
irreversible oxidation wave at a frequency of 500 Hz,
indicating the lifetime of the intermediate is less than 2
ms. From the results of the electrochemical analyses, the
12 in quantitative yield by treatment with Me3SiOTf. The
yield of 12 is reported in Table 2 (entries 1-8) together
with the anomeric stereoselectivity. The selective forma-
tion of â-12 is due to the well-known intramolecular
participation of the 2-acyl protecting group.
The efficiency of the glycosylation was slightly affected
by the para-substituent R of the aryl group as well as
the protecting group. The glycosylation of 8a -c (R ) H,
Me, OMe) resulted in virtually identical results within
experimental errors, though the reaction of 8d (R )
NMe2), which has the lowest oxidation potential among
the telluroglycosides examined in this study, showed very
low current efficiency (entries 1-8). The benzyl-protected
telluroglycoside 11b also reacted smoothly with various
glycosyl acceptors, including 3-phenylpropanol, cyclohex-
anol, and the 6-hydroxy glycoside 14 to give the corre-
sponding O-glycosides 15 and 16C in good yields with
moderate â-selectivities (entries 9-11).
While the telluroglycosides are activated under elec-
trochemical oxidation and serve as reactive glycosyl
donors, the reaction in a divided cell usually requires a
long reaction time due to the high ohmic resistance of
the solution and the low electric current. Under these
conditions, the effects of water that might come from
(23) Isaacs, N. S. Physical Organic Chemistry, Longman Scientific
& Technical: Essex, U.K., 1987; p 129.
J . Org. Chem, Vol. 67, No. 24, 2002 8587

Yamago et al.
TABLE 2. Electr och em ica l O-Glycosyla tion of Tellu r oglycosid es
electricity
(F/mol)
major
product
yieldc
(%)
entry
donora
acceptorb
electrolyte/solvent
R:âd
1
2
3
4
5
6
7
8
9
10
11
12
13
8b
HO(CH2)3Ph
LiClO4/MeCN
3.2
2.5
3.5
2.6
3.5
3.7
3.9
3.0
3.6
1.8
2.9
4.0
7.0
12
76 (90)e
54 (59)
53 (59)e
68
54
50
5:>95
5:>95
5:>95
5:>95
5:>95
5:>95
5:>95
5:>95
34:76
20:80
29:71
5:>95
5:>95
n-Bu4NClO4/MeCN
n-Bu4NBF4/MeCN
n-Bu4NBF4/EtCN
n-Bu4NBF4/EtNO2
n-Bu4NBF4/MeCN
n-Bu4NBF4/MeCN
LiClO4/MeCN
n-Bu4NBF4/MeCN
LiClO4/MeCN
LiClO4/MeCN
8a
8c
8d
11b
11b
11b
8b
HO(CH2)3Ph
HO(CH2)3Ph
HO(CH2)3Ph
HO(CH2)3Ph
c-C6H11OH
14
65
18 (56)e
70
15A
15B
16C
16D
16D
68
63
14
14
LiClO4/MeCN
LiClO4/MeCN
36
8b
90f
a
b
The telluroglycosides were the single â-anomers (>95%), except for 11b, which consisted of a 70:30 mixture of R- and â-anomers.
A
1 equiv sample of alcohol was used. c Isolated yield. Determined by 1H NMR and/or HPLC. e Yield based on reacted telluroglycoside.
d
f The reaction was carried out in an undivided cell. See the text.
TABLE 3. Effect of Ad d itives on Electr och em ica l
outside the cell cannot be negligible. For example, the
desired disaccharide was obtained in only 36% yield due
to the competitive reaction with water in the glycosyla-
Glycosyla tion of 8b in a n Un d ivid ed Cell
yield (%)
tion of 8b with 14 (entry 12). To overcome this limitation,
we next examined the glycosylation in an undivided cell,
in which the electrodes are located in close proximity.
entry
additive (equiv)
12
17
1
2
3
4
5
none
66
80
75
77
89
32
10
17
16
7
PhCO2H (1.0)
2,6-Me2C6H3OH (1.0)
2,4,6-(t-Bu)3C6H2OH (1.0)
2,6-Me2C6H3OH (5.0)
decreased the formation of 17 from 32% to 10% and
increased the formation of the O-glycoside 12 from 66%
to 80%, but a small portion of benzoic acid reacted with
8b to form 1,2,3,4,6-penta-O-benzoylglucopyranoside (en-
try 1). Sterically bulky 2,6-dimethylphenol was found to
be inert to the glycosylation reaction and also diminished
the formation of 17, but the use of the bulkier 2,4,6-tri-
tert-butylphenol showed only a small effect (entries 3 and
4). The use of 5 equiv of 2,6-dimethylphenol almost
suppressed the formation of 17 and furnished 14 in 89%
yield (entry 5).
Using optimal conditions, we examined the disaccha-
ride synthesis. The glycosylation of 8b and 14 was carried
out in the presence of 5 equiv of 2,6-dimethylphenol in
an undivided cell. While the previous synthesis in a
divided cell afforded the disaccharide 16D in 36% yield,
the reaction in an undivided cell afforded the same
disaccharide in 90% yield (Table 2, entry 13).
Selective Activa tion of Ch a lcogen oglycosid es. We
next examined the selective activation of the chalco-
genoglycosides on the basis of their oxidation potentials
(eq 2). First, we compared the reactivity of the telluro-
Electr och em ica l Glycosyla tion in a n Un d ivid ed
Cell. The glycosylation of 8b and 3-phenylpropanol in
an undivided cell was carried out under the same
conditions as in a divided cell except for the cell design.
While the reaction afforded the desired O-glycoside 12
in 66% yield, the formation of 3-phenylpropyl benzoate
(17) in 32% yield was also observed. Among several minor
side products, we could also isolate the 3,4-dihydroxy-O-
glucopyranoside 18 in 2% yield. Since the cathodic
reduction of organic compounds sometimes generate
bases,24 the formation of 17 and 18 could be attributed
to the base-mediated reaction of the alcohol and 8b.
We found that addition of an organic acid was effective
in decreasing the formation of the benzoate 17 (Table 3).
For example, the addition of 1 equiv of benzoic acid
glycosides on the basis of the armed-disarmed glycosy-
lation strategy. Intermolecular competition of the 2-ben-
zoyl- and 2-benzyl-protected telluroglycosides 8b and 11b
(24) Kashimura, S. J . Synth. Org. Chem., J pn. 1985, 43, 549.
Niyazymbetov, M. E.; Evans, D. H. J . Org. Chem. 1993, 58, 779.
8588 J . Org. Chem., Vol. 67, No. 24, 2002

Electrochemistry of Chalcogenoglycosides
TABLE 4. Selective Activa tion of Ch a lcogen oglycosid es
6c reacted only about 2 times faster than 6a (entry 6).
Unfortunately, the activation of the telluroglycoside 8b
and the selenoglycoside 5b was found to be nonselective
despite the large differences in the oxidation potentials
(entry 7).
With the results of the intermolecular competition in
hand, we next examined the disaccharide synthesis based
on selective activation. Since chemical transformations
of the telluroglycosides are problematic at the present
time, we examined the competition between the telluro-
glycoside and the thio- and selenoglycosides. Electrolysis
of the telluroglycoside 8b in the presence of the thiogly-
coside 9b was carried out in a divided cell, and the
desired disaccharide 19 was obtained in 42% yield
together with 46% of the unreacted 9b (eq 3). The same
recoveryc (%)
b
∆Eox
(V)
∆Gq
(kJ /mol)
entry
I
II conditionsa
I
II
1
2
3
4
5
6
7
11b 8b
11b 8b
8b 8a
8b 8a
6b 5b
6c 6a
8b 5b
i
ii
i
ii
i
0.08
0.08
0.04
0.04
0.02
0.20
0.35
7.7
7.7
3.9
3.9
2.1
21
16
20
28
34
51
38
9
>95
>95
81
98
49
i
ii
62
41
33
a
(i) A mixture of I (1 equiv), II (1 equiv), and 3-phenylpropanol
(1 equiv) was electrolyzed in a divided cell with 3.0 F/mol of
electricity at a constant potential of 1.1 V. (ii) A mixture of I (1
equiv), II (1 equiv), and 3-phenylpropanol (2 equiv) in the presence
of 2,6-dimethylphenol (10 equiv) was electrolyzed in an undivided
cell at a constant potential of 1.1 V. In all cases, the corresponding
O-glycosides were obtained. b ∆Eox ) Eox(II) - Eox(I). c Determined
by 1H NMR and/or HPLC of the crude mixture.
in the presence of 3-phenylpropanol (1 equiv each) was
carried out by a constant-potential electrolysis (1.1 V vs
Ag/AgCl) in a divided cell at room temperature. After 3.0
F/mol of electricity was applied, the crude reaction
mixture was analyzed by 1H NMR and HPLC, which
revealed that all the O-glycoside came from 11b and that
8b was recovered quantitatively (Table 4, entry 1). The
competition in an undivided cell also gave the same
results (entry 2). The difference in the oxidation potential
was 0.08 V, which corresponds to the difference of the
Gibbs free energy of 7.7 kJ /mol. This energy difference
nicely accounts for the observed experimental results.
We next examined the competition between the tel-
luroglycosides bearing different para-substituents R of
the aryl group. A constant-potential electrolysis (1.1 V
vs Ag/AgCl) of phenyl- and p-methylphenyl-substituted
telluroglycosides 8a and 8b in the presence of 3-phenyl-
propanol (1 equiv each) in a divided cell resulted in the
formation of the O-glycoside 12 in 72% yield, together
with the recovery of 8a and 8b in 81% and 28% yield,
respectively (entry 3). The competition in an undivided
cell also gave virtually identical results (entry 4), indicat-
ing that 8b reacted at least 4 times faster than 8a . The
difference in the oxidation potential of 8a and 8b was
0.04 V, a value corresponding to the difference in the
Gibbs free energy of 3.9 kJ /mol. This energy difference
is also consistent with the observed reactivity difference.
Both experiments demonstrated that the telluroglyco-
sides were selectively and predictably activated, depend-
ing on the difference of the oxidation potentials.
reaction in an undivided cell in the presence of 5 equiv
of 2,6-dimethylphenol resulted in the formation of 19 in
72% together with 25% of the unchanged 9b. In both
cases, no oxidized products derived from 9b could be
detected. The results indicated that complete selectivity
was achieved between the telluroglycoside and the thiogly-
coside. The disaccharide 19 would be used for the
following glycosylation reactions.
The synthesis of the disaccharide with the tellurogly-
coside and the selenoglycoside revealed that the sele-
noglycosides were less selective than the thioglycosides
(eq 4). When a mixture of 8b and 6-hydroxyselenoglyco-
side 10a was subjected to electrolysis, the desired dis-
accharide 20 formed in only 30% yield. Among the several
side products, the anhydroglycoside 21 derived from 10a
was isolated in 20% yield. Gel permeation chromatogra-
phy analyses also indicated the formation of a small
amount of trisaccharides, which arose from further
activation of 20 under the reaction conditions.
We next examined the selective activation of the
selenoglycosides on the basis of the C-2 protecting groups
and the p-substituent. However, in sharp contrast to the
telluroglycosides, we found that the selenoglycosides
showed only modest selectivity. The difference in the
oxidation potential of the 2-benzoyl- and 2-benzyl-
Su m m a r y
protected selenoglycosides 5b and 6b was small (∆Eox
)
0.02 V, ∆Gq ) 2.1 kJ /mol), but the latter is known to be
selectively activated over the former by chemical re-
agents.10 However, the competition experiments revealed
no preferential activation, and a 1:1 mixture of the
corresponding O-glycosides was obtained together with
an equal amount of recovered 6b and 7b (entry 5).
Although the difference in the oxidation potential of the
phenyl- and p-methoxyphenyl-substituted selenoglyco-
sides 6a and 6c was 0.20 V, the competition revealed that
We found that telluroglycosides serve as reactive
glycosyl donors under electrochemical oxidation. We
examined both divided and undivided cells, and observed
that undivided cells were better for practical glycoside
syntheses. Since electrochemical glycosylation proceeds
under neutral conditions and does not require the use of
expensive, explosive, or harmful heavy metal chemicals,
it would be suitable for large-scale preparation. We also
demonstrated that the precise tuning of the oxidation
J . Org. Chem, Vol. 67, No. 24, 2002 8589

Yamago et al.
(dt, J ) 9.6, 6.3 Hz, 1H), 4.15 (ddd, J ) 9.6, 5.1, 3.3 Hz, 1H),
4.51 (dd, J ) 12.3, 5.1 Hz, 1H), 4.65 (dd, J ) 12.3, 3.3 Hz,
1H), 4.84 (d, J ) 7.8 Hz, 1H), 5.58 (dd, J ) 9.6, 7.8 Hz, 1H),
5.70 (dd, J ) 9.6 Hz, 1H), 5.93 (dd, J ) 9.6 Hz, 1H),6.97-8.03
(m, 25H); 13C NMR (75 MHz, CDCl3) 30.83 (CH2), 31.58 (CH2),
63.11 (CH2), 68.95 (CH2), 69.74 (CH), 71.90 (CH), 72.11 (CH),
72.87 (CH), 101.28 (CH), 125.75, 128.25, 128.34, 128.41,
128.45, 128.86, 129.36, 129.64, 129.77, 129.80, 129.83, 129.86,
133.17, 133.29, 133.48, 141.48, 165.21(CdO), 165.31(CdO),
165.97(CdO), 166.27 (CdO); HRMS (FAB) m/z calcd for
potential of chalcogenoglycosides is feasible by rational
molecular design, and that the relative reactivity of
telluroglycosides can be easily predicted, in many cases,
from their oxidation potential. We believe that the
current method provides a new idea for the rational
design not only for the synthesis of oligosaccharides but
also for various iterative synthetic transformations.
Exp er im en ta l Section
C
43H384O10 (M + H)+ 715.2543, found 715.2543.
1H (300 and 400 MHz) and 13C (75 and 100 MHz) NMR
spectra were recorded in CDCl3 as solvent. The chemical shifts
are reported in parts per million (δ) with reference to TMS
Da ta for 13: IR (KBr) 1725, 1266, 1104, 1091, 1071, 1026,
710; 1H NMR (300 MHz, CDCl3) 1.79-1.88 (m, 2H), 2.63 (t, J
) 7.8 Hz, 2H), 3.28-3.42 (m, 2H), 4.11-4.16 (m, 1H), 4.37 (dd,
J ) 12.0, 4.8 Hz, 1H), 4.52 (dd, J ) 12.0, 3.0 Hz, 1H), 4.72-
4.75 (ddd, J ) 5.4, 3.0, 1.2 Hz, 1H), 5.50 (dt, J ) 8.7, 1.2 Hz,
1H), 5.77 (dd, J ) 3.3, 1.2 Hz, 1H), 6.02 (d, J ) 5.4 Hz, 1H),
7.10-8.11 (m, 25H); 13C NMR (75 MHz, CDCl3) 30.88 (CH2),
32.18 (CH2), 63.31 (CH2), 63.94 (CH2), 67.43 (CH), 68.48 (CH),
69.18 (CH), 72.16 (CH), 97.53 (CH), 121.41(C), 125.86-141.68
(aromatic), 164.74 (CdO), 165.31 (CdO), 166.12 (CdO); HRMS
(FAB) m/z calcd for C43H38O10 (M + H)+ 715.2543, found
715.2543.
1
(for H) and to solvent (for 13C) as internal standards. Infrared
(FTIR) spectra were recorded in KBr and are reported in cm-1
.
FAB mass spectra were obtained using nitorobenzyl alcohol
as matrix. The oxidation potential was measured in a 0.1 M
MeCN solution of LiClO4 at room temperature by CV, LSV,
or OSW. Glassy carbon working electrodes (7.0 mm diameter
for LSV and 3.0 mm diameter for CV and OSW) and a Pt wire
auxiliary electrode (1.0 mm diameter) were used. IR compen-
sation was employed throughout.
Thioglycosides were prepared as reported.17c,25 The sele-
noglycosides 4a , 5a , 5c, and 6a were prepared as reported.17c,26
Other selenoglycosides were prepared by analogous procedures
(see the Supporting Information). Preparations of tellurogly-
cosides are provided in the Supporting Information.27 Prepara-
tion and characterization of glycosides 14,28 15B,29 and 2130
have already been reported.
Da ta for 1-O-(3-p h en ylp r op yl)-6-O-a cetyl-2,3,4-tr i-O-
ben zyl-r-D-glycop yr a n osid e (r-15A): IR (neat) 1744, 1456,
1237, 1090, 1072, 1028, 739, 698; 1H NMR (400 MHz, CDCl3)
1.92-2.05 (m, 2 H), 1.98 (s, 3 H), 2.64-2.77 (m, 2 H), 3.39-
3.51 (m, 2 H), 3.54 (dd, J ) 9.6, 3.6 Hz, 1 H), 3.64 (dt, J ) 9.9,
6.9 Hz, 1 H), 3.84 (ddd, J ) 9.9, 4.5, 2.4 Hz, 1 H), 4.04 (t, J )
9.3 Hz, 1 H), 4.19 (dd, J ) 12.0, 2.4 Hz, 1 H), 4.26 (dd, J )
12.0, 4.5 Hz, 1 H), 4.56 (d, J ) 10.8 Hz, 1 H), 4.66 (d, J ) 12.0
Hz, 1 H), 4.72 (d, J ) 3.3 Hz, 1 H), 4.79 (d, J ) 12.0 Hz, 1 H),
4.84 (d, J ) 10.5 Hz, 1 H), 4.89 (d, J ) 10.8 Hz, 1 H), 5.03 (d,
J ) 10.8 Hz, 1 H), 7.19-7.36 (m, 20 H); 13C NMR (100 MHz,
CDCl3) 20.80, 30.87, 32.33, 63.15, 67.59, 68.75, 73.22, 75.08,
75.74, 77.51, 80.24, 82.03, 96.97, 125.90, 127.66, 127.90,
127.93, 127.97, 127.98, 128.13, 128.38, 128.42, 128.44, 128.45,
128.50, 137.92, 138.27, 138.74, 141.58, 170.71; HRMS (FAB)
m/z calcd for C38H42O7 (M + H)+ 611.3009, found 611.3007.
Gen er a l P r oced u r e for th e Electr och em ica l Glycosy-
la tion in a Divid ed Cell. Syn th esis of 1-(3-P h en ylp r op yl)-
2,3,4,6-tetr a -O-ben zoyl-â-D-glu cop yr a n osid e (12). An H-
type cell separated by a sintered glass diaphragm (no. 4, pore
size in the range 5-10 µm) was fitted with a platinum plate
cathode (6 cm2), a carbon felt cathode (10 mm × 5 mm × 3
mm), and a platinum wire reference electrode which was
connected to a saturated calomel electrode (SCE). To both the
anodic and cathodic sides of the cell containing activated
molecular sieves 3A (100 mg) was added a 0.1 M LiClO4
solution of MeCN (2 mL each) under an Ar atmosphere. To
the cathodic side were added 1-p-methylphenyltelluro-2,3,4,6-
tetra-O-benzoyl-â-D-glucopyranoside (8b) (160.2 mg, 0.20 mmol)
and 3-phenylpropanol (27.5 mg, 0.20 mmol), and the resulting
mixture was electrolyzed at a constant potential of 1.1 V (vs
SCE) with gentle stirring. After 3.2 F/mol of electricity was
applied, 8b disappeared on TLC. The reaction mixture was
filtered through a short cotton plug, and the resulting solution
was partitioned between water and ethyl acetate. After the
usual workup (extraction with ethyl acetate, washing with
aqueous saturated sodium chloride solution, drying over
magnesium sulfate, and evacuation under reduced pressure),
purification of the crude mixture by flash column chromatog-
raphy (elution with 17% ethyl acetate in hexane) afforded the
title compound (108.6 mg, 76%) and 3,4,6-tri-O-benzoyl-1,2-
O-(1-exo-(3-phenylpropoxy)benzylidene)-R-D-glucopyranoside (13)
(22.9 mg, 16%). The latter compound could be quantitatively
converted to the former upon treatment by a catalytic amount
of TMSOTf.
Da ta for 1-O-(3-p h en ylp r op yl)-6-O-a cetyl-2,3,4-tr i-O-
ben zyl-â-D-glycop yr a n osid e (â-15A): IR (neat) 1744, 1455,
1
1366, 1237, 1154, 1092, 1070, 1030, 749, 698; H NMR (300
MHz, CDCl3) 1.92-2.05 (m, 2 H), 2.02 (s, 3 H), 2.73 (dt, J )
7.5, 3.3 Hz, 2 H), 3.42-3.60 (m, 4 H), 3.68 (t, J ) 8.7 Hz, 1 H),
3.95 (dt, J ) 9.6, 6.3 Hz, 1 H), 4.23 (dd, J ) 11.7, 4.5 Hz, 1 H),
4.32 (dd, J ) 12.0, 2.1 Hz, 1 H), 4.40 (d, J ) 8.1 Hz, 1 H), 4.56
(d, J ) 10.8 Hz, 1 H), 4.76 (d, J ) 11.1 Hz, 1 H), 4.80 (d, J )
11.1 Hz, 1 H), 4.86 (d, J ) 10.8 Hz, 1 H), 4.96 (d, J ) 7.5 Hz,
1 H), 4.99 (d, J ) 7.8 Hz, 1 H), 7.16-7.34 (m, 20 H); 13C NMR
(75 MHz, CDCl3) 20.87, 31.34, 32.26, 63.15, 69.35, 72.75, 74.87,
75.01, 75.73, 77.38, 82.15, 84.64, 103.65, 125.84, 127.68,
127.71, 127.86, 127.97, 128.08, 128.11, 128.34, 128.40, 128.43,
128.49, 137.67, 138.28, 138.34, 141.64, 170.80; HRMS (FAB)
m/z calcd for C38H42O7 (M + H)+ 611.3009, found 611.3003.
Da ta for 1-O-(cycloh exyl)-6-O-a cetyl-2,3,4-tr i-O-ben zyl-
r-D-glycop yr a n osid e (r-15B): IR (neat) 1744, 1454, 1237,
1
1072, 1028; H NMR (300 MHz, CDCl3) 1.17-1.94 (m, 10H),
2.02 (s, 3 H), 3.44-3.55 (m, 3 H), 3.95 (ddd, J ) 10.2, 3.9, 2.7
Hz, 1 H), 4.03 (t, J ) 9.3 Hz, 1 H), 4.23 (dd, J ) 12.0, 2.7 Hz,
1 H), 4.28 (dd, J ) 12.0, 3.9 Hz, 1 H), 4.56 (d, J ) 10.8 Hz, 1
H), 4.65 (d, J ) 11.7 Hz, 1 H), 4.74 (d, J ) 11.7 Hz, 1 H), 4.82
(d, J ) 10.8 Hz, 1 H), 4.88 (d, J ) 10.8 Hz, 1 H), 4.92 (d, J )
3.6 Hz, 1 H), 5.02 (d, J ) 10.8 Hz, 1 H), 7.26-7.36 (m, 15 H);
13C NMR (75 MHz, CDCl3) 21.08, 24.40, 24.70, 25.78, 31.69,
33.51, 63.38, 68.78, 73.20, 75.34, 75.96 (2C), 77.69, 80.17,
82.25, 94.90, 127.89, 128.13, 128.22, 128.33, 128.45, 128.68,
128.74, 138.06, 138.38, 138.97, 171.02; HRMS (FAB) m/z calcd
for C35H42O7 (M + H)+ 575.3009, found 575.3001.
Da ta for 12: IR (KBr) 1732, 1267, 1107, 1093, 1068, 1026,
710; 1H NMR (300 MHz, CDCl3) 1.74-1.96 (m, 2H), 2.46-2.63
(m, 2H), 3.48-3.56 (ddd, J ) 9.6, 7.2, 5.7 Hz, 1H), 3.90-3.98
(25) Nicolaou, K. C.; Randall, J . L.; Furst, G. T. J . Am. Chem. Soc.
1985, 107, 5556.
(26) Benhaddou, R.; Czernecki, S.; Randriamandimby, D. Synlett
1992, 967. Mehta, S.; Pinto, B. M. J . Org. Chem. 1993, 58, 3269.
(27) Yamago, S.; Kokubo, K.; Masuda, S.; Yoshida, J . Synlett 1996,
929.
(28) Gan, L. X.; Whistler, R. L. Carbohydr. Res. 1990, 206, 65.
(29) Koto, S.; Morishima, N.; Kihara, Y.; Suzuki, H.; Kosugi, S.; Zen,
S. Bull. Chem. Soc. J pn. 1983, 56, 188.
(30) Bourke, D. G.; Collins, D. J .; Hibberd, A. I.; McLeod, M. D. Aust.
J . Chem. 1996, 49, 425.
Da ta for 1-O-(cycloh exyl)-6-O-a cetyl-2,3,4-tr i-O-ben zyl-
â-D-glycop yr a n osid e (â-15B): IR (neat) 1742, 1231, 1117,
1
1084, 1067, 1030; H NMR (300 MHz, CDCl3) 1.23-1.94 (m,
10 H), 2.03 (s, 3 H), 3.44 (dd, J ) 9.0, 7.8 Hz, 1 H), 3.49-3.55
8590 J . Org. Chem., Vol. 67, No. 24, 2002

Electrochemistry of Chalcogenoglycosides
(m, 2 H), 3.62-3.72 (m, 2 H), 4.22 (dd, J ) 12.0, 4.8 Hz, 1 H),
4.31 (dd, J ) 11.7, 2.1 Hz, 1 H), 4.50 (d, J ) 8.1 Hz, 1 H), 4.55
(d, J ) 11.1 Hz, 1 H), 4.71 (d, J ) 11.1 Hz, 1 H), 4.78 (d, J )
11.1 Hz, 1 H), 4.85 (d, J ) 10.8 Hz, 1 H), 4.95 (d, J ) 11.1 Hz,
1 H), 4.99 (d, J ) 10.8 Hz, 1 H), 7.28-7.34 (m, 15 H); 13C NMR
(75 MHz, CDCl3) 20.88, 23.98, 24.06, 25.54, 32.01, 33.65, 63.26,
72.63, 74.84, 75.00, 75.69, 77.50, 78.20, 82.13, 84.77, 101.99,
127.64, 127.68, 127.88, 127.95, 128.14, 128.20, 128.38, 128.47,
137.73, 138.37, 138.48, 170.82; HRMS (FAB) m/z calcd for
C35H42O7 (M + H)+ 575.3009, found 575.3008.
Da t a for m et h yl 6-O-(6-O-a cet yl-2,3,4-t r i-O-b en zyl-r-
D-glu cop yr a n osyl)-2,3,4-t r i-O-b en zoyl-r-D-glu cop yr a n o-
sid e (r-16C): IR (KBr) 1734, 1280, 1262, 1108, 1095, 1070,
1028, 710; 1H NMR (300 MHz, CDCl3) 1.98 (s, 3 H), 3.43 (t, J
) 9.0 Hz, 1 H), 3.46 (s, 3 H), 3.51 (dd, J ) 9.6, 3.3 Hz, 1 H),
3.57 (dd, J ) 11.0, 2.0 Hz, 1 H), 3.83 (dd, J ) 10.8, 6.6 Hz, 1
H), 3.93 (dt, J ) 10.2, 3.5 Hz, 1 H), 4.01 (t, J ) 12.2 Hz, 1 H),
4.13 (br d, J ) 12.6 Hz, 1 H), 4.14 (br d, J ) 12.6 Hz, 1 H),
4.32 (ddd, J ) 10.2, 3.9, 1.8 Hz, 1 H, 4.55 (d, J ) 10.8 Hz, 1
H), 4.63 (d, J ) 12.0 Hz, 1 H), 4.70 (d, J ) 3.6 Hz, 1 H), 4.77
(d, J ) 12.0 Hz, 1 H), 4.79 (d, J ) 10.8 Hz, 1 H), 4.87 (d, J )
10.8 Hz, 1 H), 4.96 (d, J ) 10.8 Hz, 1 H), 5.20-5.26 (m, 2 H),
5.49 (t, J ) 9.9 Hz, 1 H), 6.11-6.20 (m, 1 H), 7.16-7.56 (m,
24 H), 7.84-7.90 (m, 2 H), 7.92-8.02 (m, 4 H); 13C NMR (75
Hz, CDCl3) 20.79, 55.59, 62.97, 66.68, 68.53, 68.71, 69.48,
70.50, 72.16, 73.08, 74.75, 75.60, 77.18, 79.99, 81.62, 96.75,
97.00, 127.62, 127.74, 127.83, 127.91, 128.02, 128.24, 128.38,
128.91, 129.05, 129.20, 129.66, 129.88, 129.91, 133.06, 133.33,
133.41, 138.05, 138.22, 138.61, 165.22, 165.79, 170.67; HRMS
(FAB) m/z calcd for C57H56O15 (M + H)+ 981.3697, found
981.3697.
Da ta for m eth yl 6-O-(6-O-a cetyl-2,3,4-tr i-O-ben zyl-â-D-
glu cop yr a n osyl)-2,3,4-t r i-O-b e n zoyl-r-D-glu cop yr a n o-
sid e (â-16C): IR (neat) 1732, 1280, 1263, 1108, 1094, 1069,
1028, 710; 1H NMR (400 MHz, CDCl3) 1.92 (s, 3 H), 3.39 (s, 3
H), 3.42-3.52 (m, 3 H), 3.62-3.70 (m, 1 H), 3.82 (dd, J ) 11.1,
7.5 Hz, 1 H), 4.07 (dd, J ) 11.2, 1.8 Hz, 1 H), 4.13-4.20 (m, 1
H), 4.24 (dd, J ) 11.0, 1.5 Hz, 1 H), 4.38 (ddd, J ) 9.9, 7.5, 2.2
Hz, 1 H), 4.47 (d, J ) 7.5 Hz, 1 H), 4.53 (d, J ) 11,1 Hz, 1H),
4.69 (d, J ) 10.8 Hz, 1 H), 4.77 (d, J ) 11.1 Hz, 1 H), 4.85 (d,
J ) 11.1 Hz, 1 H), 4.95 (d, J ) 10.8 Hz, 1 H), 5.07 (d, J ) 11.1
Hz, 1 H), 5.21 (d, J ) 3.6 Hz, 1 H), 5.25 (dd, J ) 10.2, 3.6 Hz,
1 H), 5.46 (t, J ) 9.9 Hz, 1 H), 6.16 (t, J ) 9.8 Hz, 1 H), 7.20-
7.56 (m, 24 H), 7.82-7.87 (m, 2 H), 7.92-8.00 (m, 4 H); 13C
NMR (75 Hz, CDCl3) 20.68, 55.59, 63.28, 69.00, 69.14, 69.96,
70.48, 72.12, 72.87, 74.84, 75.00, 75.71, 77.54, 82.26, 84.56,
96.90, 104.08, 127.67, 127.74, 127.88, 127.97, 128.09, 128.22,
128.27, 128.40, 128.42, 128.43, 128.46, 128.50, 128.93, 129.12,
129.29, 129.67, 129.88, 129.94, 133.07, 133.35, 133.49, 137.75,
138.39, 138.48, 165.51, 165.77, 165.85, 170.71; HRMS (FAB)
m/z calcd for C57H56O15 (M + H)+ 981.3697, found 981.3702.
Gen er a l P r oced u r e for th e Electr och em ica l Glycosy-
la tion in a n Un d ivid ed Cell. Syn th esis of Meth yl 6-O-
(2,3,4,6-Tetr a -O-ben zoyl-â-D-glu cop yr a n osyl)-2,3,4-tr i-O-
ben zoyl-r-D-glu cop yr a n osid e (16D). A cylindrical reaction
vessel was fitted with a cylindrical platinum cathode (6 cm2),
a carbon felt anode (10 mm × 5 mm × 3 mm), and a platinum
wire reference electrode, which was connected with a standard
calomel electrode. The cathode and the anode were in close
proximity but were separated by a Teflon fiber. To the
undivided cell containing activated molecular sieves 3A (200
mg) were added 8b (570.9 mg, 0.72 mmol), 2,3,4-tri-O-benzoyl-
1-methyl-O-R-D-glucopyranoside (14; 242.8 mg, 0.48 mmol),
2,6-dimethylphenol (291.6 mg, 2.4 mmol), and a 0.2 M LiClO4
solution of MeCN (5 mL) under an argon atmosphere. The
resulting mixture was electrolyzed at a constant potential of
1.1 V (vs SCE) with gentle stirring. After 7.0 F/mol of
electricity was applied, 8b disappeared on TLC. TMSOTf (11.5
mg, 0.05 mmol) was added, and the resulting mixture was
stirred for 30 min. The reaction mixture was filtered through
a short cotton plug, and the resulting solution was partitioned
between water and ethyl acetate. The usual workup, followed
by purification of the crude mixture by flash column chroma-
tography (elution with 17% ethyl acetate in hexane), afforded
the â-anomer of the desired disaccharide (467.4 mg, 90%): IR
(KBr) 1728, 1266, 708; 1H NMR (300 MHz, CDCl3) 3.10 (s, 3H),
3.79 (dd, J ) 7.8, 11.4 Hz, 1H), 4.08-4.25 (m, 3H), 4.45 (dd, J
) 5.1, 12.0 Hz, 1H), 4.61 (dd, J ) 3.0,12.3 Hz, 1H), 4.94 (d, J
) 3.6 Hz, 1H), 4.98 (d, J ) 7.8 Hz, 1H), 5.09 (dd, J ) 3.6, 10.2
Hz, 1H), 5.32 (t, J ) 10.2 Hz, 1H), 5.57 (dd, J ) 8.1, 9.9 Hz,
1H), 5.66 (t, J ) 9.9 Hz, 1H), 5.92 (t, J ) 9.6 Hz, 1H), 6.07 (t,
J ) 9.9 Hz, 1H), 7.26-7.49 (m, 20H), 7.77-8.01 (m, 15H); 13
C
NMR (75 MHz, CDCl3) 54.97 (CH3), 62.96 (CH2), 68.71 (CH),
68.89 (CH2), 69.64 (CH, 2C), 70.29 (CH), 71.82 (CH), 71.96
(CH), 72.25 (CH), 72.79 (CH), 96.45 (CH), 101.78 (CH), 128.28,
128.36, 128.39, 128.47, 128.86, 129.12, 129.29, 129.42, 129.64,
129.70, 129.82, 129.92, 133.10 (C), 133.19 (C), 133.29 (C, 2C),
133.39 (C), 133.51 (C, 2C), 165.30 (CdO, 2C), 165.57 (CdO),
165.78 (CdO), 165.84 (CdO), 165.94 (CdO), 166.24 (CdO);
FABMS (matrix NBA) m/z 1085 (M + H)+. Anal. Calcd for
C
62H52O18: C, 68.63; H, 4.83. Found: C, 68.35; H, 4.67.
1-p -Meth ylp h en ylth io-6-O-(2,3,4,6-tetr a -O-ben zoyl-â-D-
glu cop yr a n osyl)-2,3,4-t r i-O-b e n zyl-â-D-glu cop yr a n o-
sid e (19). To an undivided cell containing activated molecular
sieves 3A (200 mg) were added 8b (223.5 mg, 0.40 mmol), 1-p-
methylphenylthio-2,3,4-tri-O-benzoyl-â-D-glucopyranoside (9b;
478.9 mg, 0.60 mmol), 2,6-dimethylphenol (246.6 mg, 2.0
mmol), and a 0.2 M LiClO4 solution of MeCN (4.0 mL) under
an argon atmosphere. The resulting mixture was electrolyzed
at a constant potential of 1.1 V (vs SCE) with gentle stirring
until 8b dissappeared by TLC analysis. Electricity (7.0 F/mol)
was applied, the reaction mixture was filtered through a short
cotton plug, and the resulting solution was partitioned between
water and ethyl acetate. The usual workup, followed by
purification of the crude mixture by flash column chromatog-
raphy (elution with 17% ethyl acetate in hexane), afforded the
title compound in 72% yield (327.0 mg) The analytical sample
was crystallized from hexane-ethyl acetate: mp 174-178 °C;
IR (KBr) 3030, 1742, 1734, 1713, 1283 (br), 1121 (br), 1090,
1049, 708; 1H NMR (300 MHz, CDCl3) 2.34 (s, 3H), 3.33-3.47
(m, 3H), 3.58 (dd, J ) 8.7, 8.1 Hz, 1H), 3.85 (dd, J ) 11.4, 4.2
Hz, 1H), 4.02-4.08 (m, 1H), 4.13 (d, J ) 11.1 Hz, 1H), 4.40-
4.87 (m, 9H), 4.94 (d, J ) 7.8 Hz, 1H), 5. 57 (dd, J ) 9.6, 7.8
Hz, 1H), 5.68 (t, J ) 9.6 Hz, 1H), 5.85 (t, J ) 9.6 Hz, 1H),
7.09-7.12 (m, 2H), 7.17-7.51 (m, 29H), 7.83-7.93 (m, 6H),
8.00-8.03 (m, 2H); 13C NMR (75 MHz, CDCl3) 21.03 (CH3),
63.08 (CH2), 67.92 (CH2), 69.74 (CH), 71.90 (CH), 72.16 (CH),
73.02 (CH), 74.81 (CH2), 75.28 (CH2), 75.56 (CH2), 77.46 (CH),
78.79 (CH), 80.54 (CH), 86.55 (CH), 87.61 (CH), 101.00 (CH),
127.68 (CH), 127.75 (CH), 127.83 (CH), 127.87 (CH), 128.27
(CH), 128.42 (CH), 128.45 (CH), 128.95 (C), 129.32 (C), 129.68
(C), 129.82 (CH), 129.86 (CH), 129.92 (CH), 132.88 (CH),
133.13 (CH), 133.26 (CH), 133.46 (CH), 137.96 (C), 138.06 (C),
138.18 (C), 138.47 (C), 165.12 (CdO), 165.33 (CdO), 165.92
(CdO), 166.24 (CdO); FABMS (matrix NBA) m/z 1136 (M +
H)+, 1135 (M+). Anal. Calcd for C68H62O14S: C, 71.94; H, 5.50.
Found: C, 71.64; H, 5.38.
1-p-Meth ylp h en ylselen o-6-O-(2,3,4,6-tetr a -O-ben zoyl-
â-D-glu cop yr a n osyl)-2,3,4-tr i-O-ben zyl-â-D-glu cop yr a n o-
sid e (20). To an undivided cell containing activated molecular
sieves 3A (200 mg) were added 8b (479.9 mg, 0.60 mmol), 1-p-
methylphenylseleno-2,3,4-tri-O-benzyl-â-D-glucopyranoside (10b;
241.3 mg, 0.40 mmol), 2,6-dimethylphenol (246.6 mg, 2.0
mmol), and a 0.2 M LiClO4 solution of MeCN (4.0 mL) under
an argon atmosphere. The resulting mixture was electrolyzed
at a constant potential of 1.1 V (vs SCE) with gentle stirring
until 8b disappeared by TLC analysis. Electricity (7.0 F/mol)
was applied, the reaction mixture was filtered through a short
cotton plug, and the resulting solution was partitioned between
water and ethyl acetate. The usual workup, followed by
purification of the crude mixture by flash column chromatog-
raphy (elution with 17% ethyl acetate in hexane), afforded the
title compound in 14% yield (66.9 mg), together with 20% of
the 1,6-anhydro-2,3,4-tri-O-benzyl-D-glucopyranoside (21) (34.5
J . Org. Chem, Vol. 67, No. 24, 2002 8591

Yamago et al.
mg). An analytically pure sample of 20 was obtained by
crystallization from hexane/ethyl acetate.
Da ta for 21: IR (KBr) 2895, 1497, 1454, 1102 (br), 1075
(br), 737, 698; H NMR (300 MHz, C6D6) 3.16 (d, J ) 3.9 Hz,
1
Da ta for 20: IR (KBr) 1725, 1601, 1491, 1451, 1277 (br),
1069, 1026, 710; 1H NMR (400 MHz, CDCl3) 2.04 (s, 3H), 2.34
(s, 3H), 3.36-3.43 (m, 3H), 3.54 (dd, J ) 8.8 Hz, 1H), 3.84
(dd, J ) 11.2, 4.3 Hz, 1H), 4.06 (ddd, J ) 9.7, 5.0, 3.3 Hz, 1H),
4.11-4.15 (m, 1H), 4.40 (d, J ) 11.0 Hz), 4.49 (dd, J ) 12.1,
5.0 Hz, 1H), 4.57 (d, J ) 11.0 Hz, 1H), 4.61-4.66 (m, 2H), 4.70
(d, J ) 9.7 Hz, 1H), 4.71 (d, J ) 11.0 Hz, 1H), 4.79 (d, J ) 9.5
Hz, 1H), 4.82 (d, J ) 10.1 Hz, 1H), 4.94 (d, J ) 7.9 Hz, 1H),
5.57 (dd, J ) 9.7, 7.9 Hz, 1H), 5.68 (dd, J ) 9.7 Hz, 1H), 5.86
(dd, J ) 9.7 Hz, 1H), 7.07-8.03 (m, 34H); 13C NMR (100 MHz,
CDCl3) 14.20 (CH3), 21.20 (CH3), 63.15 (CH2), 67.98 (CH2),
69.80 (CH2), 71.93 (CH), 72.20 (CH), 73.06 (CH), 74.85 (CH2),
75.12 (CH2), 75.58 (CH2), 77.50 (CH), 79.76 (CH), 81.10 (CH),
82.70 (CH), 86.64 (CH), 101.05 (CH), 124.44, 127.51, 127.57,
127.64, 127.70, 127.75, 127.82, 127.91, 127.94, 128.12, 128.14,
128.24, 128.30, 128.35, 128.38, 128.39, 128.48, 128.81, 128.88,
128.89, 129.25, 129.62, 129.73, 129.77, 129.80, 129.83, 129.99,
133.06, 133.11, 133.20, 133.40, 135.01, 137.89, 138.06, 138.10,
138.34, 164.99 (CdO), 165.21 (CdO), 165.81 (CdO), 166.13
(CdO); HRMS (FAB) m/z calcd for C68H59O16Se (M + H)+
1211.2968, found 1211.2959. Anal. Calcd for C68H62O14Se: C,
69.29; H, 5.29. Found: C, 68.72; H, 5.33.
1H), 3.34 (dd, J ) 6.9, 6.0 Hz, 1H), 3.41 (d, J ) 3.3 Hz, 1H),
3.48 (d, J ) 6.6 Hz, 1H), 3.79 (m, 1H), 4.24-4.36 (m, 5H), 4.41
(d, J ) 11.7 Hz, 1H), 4.80 (d, J ) 12.0 Hz, 1H), 5.60 (s, 1H),
7.01-7.25 (m, 15H); 13C NMR (75 MHz, C6D6) 66.21 (CH2),
71.08 (CH2), 71.52 (CH2), 72.65 (CH2), 74.91 (CH), 78.89 (CH),
79.52 (CH), 79.89 (CH), 101.36 (CH), 127.76 (CH), 127.82 (CH),
127.89 (CH), 128.52 (CH), 128.58 (CH), 138.70 (C), 138.87 (C),
139.05 (C); FABMS (matrix NBA) m/z 433 (M + 1)+.
Ack n ow led gm en t. This work was partly supported
by the Nissan Foundation and a Grant-in-Aid for
Scientific Research from the J apan Society for the
Promotion of Science. The experimental assistance of
Tomokazu Maruyama is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Preparation and
characterization of chalcogenoglycosides. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O0261350
8592 J . Org. Chem., Vol. 67, No. 24, 2002