Contrasting reactivity of thioglucoside and selenoglucoside donors towards promoters: implications for glycosylation stereocontrol

Article abstract of DOI:10.1016/j.carres.2006.04.029

The stereochemical outcome of glycosylation reactions with model thioglycosides and selenoglycosides proved to be dependent on the source of promoter iodonium ion, with iodine giving different results to N-iodosuccinimide (NIS) alone or N-iodosuccinimide/

Full text of DOI:10.1016/j.carres.2006.04.029

Carbohydrate Research 341 (2006) 1391–1397
Contrasting reactivity of thioglucoside and selenoglucoside donors
q
towards promoters: implications for glycosylation stereocontrol
Renate M. van Well, Tiina S. K a¨ rkk a¨ inen, K. P. Ravindranathan Kartha and
Robert A. Field*
Centre for Carbohydrate Chemistry, School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK
Received 20 February 2006; received in revised form 12 April 2006; accepted 14 April 2006
Available online 15 May 2006
Abstract—The stereochemical outcome of glycosylation reactions with model thioglycosides and selenoglycosides proved to be
dependent on the source of promoter iodonium ion, with iodine giving different results to N-iodosuccinimide (NIS) alone or N-iodo-
succinimide/trimethylsilyltrifluoromethanesulfonate (NIS/TMSOTf). In contrast to armed thioglycosides, which anomerise, and
disarmed thioglycosides, which do not react, both armed and disarmed selenoglycosides give rise to the corresponding glycosyl iod-
ides when reacted with iodine. Further, whilst the single electron transfer agent DDQ alone is an ineffective promoter, in combina-
tion with iodine it produces better acetonitrile-assisted b-stereoselectivity with both thioglycosides and selenoglycosides than does
tris(4-bromophenyl)aminium hexachloroantimonate (BAHA).
ꢀ
2006 Elsevier Ltd. All rights reserved.
Keywords: Thioglycoside; Selenoglycoside; Glycosylation; Promoter; Mechanism
1
. Introduction
timonate (BAHA) has also been used to promote
8
glycosylation reactions with thioglycosides and seleno-
9
In the past decades there has been an increasing aware-
ness of the importance of carbohydrates in biological
processes and as a consequence, the demand for im-
glycoside donors. This laboratory has a longstanding
interest in the use of molecular iodine and related re-
2
1
agents as promoters for glycosylation chemistry. Iodine
proved synthetic strategies towards oligosaccharides
has grown. Of the many classes of glycosyl donor build-
itself is a mild and effective activator of a variety of
widely used glycosyl donor species, including glycosyl
halides, thioglycosides, selenoglycosides, glycosyl tri-
chloroacetimidates, phosphates and sulfoxides, and
3
ing blocks, thioglycosides have probably received the
most attention due to their inherent shelf stability and
4
10
the ease of chemoselective activation. In the early
pentenyl glycosides. It is generally assumed that io-
4
1
990s, selenoglycosides were demonstrated to be more
dine simply serves as a source of iodonium ion in such
reactions, in much the same way as NIS does. Whilst
iodine alone is able to activate reactive glycosyl donors,
less reactive donors are activated when iodine is used in
conjunction with DDQ, a versatile single electron oxi-
reactive than the corresponding thioglycosides towards
5
a variety of promoter systems; they are also effective
in chemoselective glycosylation reactions employing
6
armed/disarmed strategies. As well as two electron acti-
1
1,12
vation with conventional promoters, such as NIS/TfOH
dising agent.
Activation of thioglycosides with
7
or NIS/TMSOTf, the single electron transfer (SET)
DDQ in the absence of iodine has not proved possible,
demonstrating that the combination of the two re-
activator tris(4-bromophenyl)aminium hexachloroan-
agents (I /DDQ) is key. The mechanism of thioglyco-
2
q
1
sides activation by I2/DDQ is not currently
understood, but the SET properties of DDQ might be
significant.
Iodine: a versatile reagent in carbohydrate chemistry XVIX.
Corresponding author. Tel.: +44 1603 593983; fax: +44 1603
92003; e-mail: r.a.field@uea.ac.uk
*
5
0
008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.04.029

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R. M. van Well et al. / Carbohydrate Research 341 (2006) 1391–1397
Table 1. Model iodonium ion-mediated glycosylation reactions with thioglycoside 1 and selenoglycoside 2
OBn
O
OBn
O
OH
O
BnO
BnO
O
BnO
BnO
BnO
BnO
X-Ph
+
BnO
O
BnO
BnO
BnO
OMe
BnO
1
2
X = S
X = Se
3
4
BnO
OMe
Reagents and conditions
Thioglycoside 1
Selenoglycoside 2
NIS, CH
NIS, CH
NIS, TMSOTf, CH
NIS, TMSOTf, CH
3
CN
Cl
53%, a/b = 1/3
88%, a/b = 1/1
96%, a/b = 1/4.3
97%, a/b = 1.3/1
88%, a/b = 1/2.8
45%, a/b = 1/1.2
64%, a/b = 1/5
32%, a/b = 1/1.2
83%, a/b = 1/5
92%, a/b = 1/1.4
91%, a/b = 1/1.5
52%, a/b = 2/1
2
2
3
CN
Cl
CN
Cl
2
2
I
I
2
(2 equiv), CH
(2 equiv), CH
3
2
2
2
All reactions conducted at room temperature for 30 min. Yields, which are unoptimised, relate to the combined isolated a/b mixture. The stereo-
1
15
chemical outcome of the reaction was determined by integration of the H NMR signals for the methyl aglycones of the anomers of 4.
Herein we report comparison of iodonium ion sources
in the activation of model thioglycosides and selenogly-
cosides, along with studies on the activation of similar
glycosyl donors under single electron transfer condi-
tions. The aim of these studies was to assess the impact
of the source of iodonium ion and SET agent on glyco-
syl donor activation and glycosylation stereocontrol,
and to determine if, consequently, there are differences
in the mechanism of activation of selenoglycosides and
thioglycosides.
polar or charged reaction intermediates) (Table 1).
Broadly the same stereochemical outcomes are evident
for the corresponding reactions with NIS/TMSOTf,
but yields are higher. Whilst iodine gives good yields
in acetonitrile with both donors, b-selectivity with
respect to the corresponding reactions in dichlorometh-
ane is notably poorer than for the corresponding reac-
tions with NIS and NIS/TMSOTf. This may be due to
the generation of glycosyl iodides in situ, arising from
participation of iodide released in the initial S-activation
step. We were therefore drawn to investigate the dimin-
ished ꢁ-selectivity observed in molecular iodine-pro-
moted glycosylation in acetonitrile, and to assess the
likely involvement, or otherwise, of glycosyl iodide
intermediates.
2
. Results and discussion
2
.1. Comparison of NIS, NIS/TMSOTf and iodine
as promoters of model glycosylation reactions with
thioglucoside and selenoglucoside donors
2.2. Investigation of iodine-promoted activation of thio-
1
glucoside and selenoglucoside donors by H NMR
spectroscopy
1
3
Glycosylation reactions with armed thioglycoside 1 or
9
armed selenoglycoside 2 and the primary alcohol accep-
1
4
tor 3 gave the corresponding 1,6-linked disaccharides
The behaviour of both armed thio- and seleno-glycoside
1
5
4
in a manner that was both solvent and promoter-
donors 1 and 2, as well as their disarmed counterparts
1
7
18
dependent (Table 1). One might reasonably expect that
iodonium ion-promoted glycosylation reactions with
both thioglycosides and selenoglycosides would favour
b-glycoside formation more strongly in acetonitrile than
in a non-participating solvent such as dichloromethane.
It is generally accepted that solvent participation by ace-
tonitrile shields the a-face of a glycosyl oxocarbenium
ion by kinetically controlled formation of an a-glycosyl
nitrilium ion, thus favouring the formation of a b-con-
5 and 7, in the presence of iodine was studied directly
1
9
by NMR spectroscopy. In previous studies, we have
shown that reaction of armed, benzyl ether protected
thioglycosides with iodine results in (intermolecular)
thioglycoside epimerisation. We could find no evidence
for glycosyl iodide formation, which may reflect the
reversibility of C–S bond formation, with the equilib-
rium favouring the thioglycosides. Further, disarmed,
ester protected thioglycosides did not react with io-
1
6
19
figured glycosidic linkage.
dine. These earlier observations were borne out by
Comparison of the reaction or donors 1 and 2 in
acetonitrile and dichloromethane with NIS gives the
expected result, with acetonitrile-based reactions favour-
ing b-glycosylation whereas dichloromethane-based
reactions give essentially no stereocontrol and much
slower reaction (a feature typical of reactions involving
the current NMR study of the reaction of thioglycosides
1 and 5 with iodine (Scheme 1), as judged by monitoring
1
19
anomeric proton H NMR signals.
The observation of thioglycoside epimerisation follows on from an
20
earlier work.

R. M. van Well et al. / Carbohydrate Research 341 (2006) 1391–1397
1393
OBn
O
OBn
O
but seems not to be so for selenoglycosides; once the
C–Se bond is cleaved it is not reformed.
I2, CDCl
3
BnO
BnO
BnO
BnO
SPh
24 hr
Glycosyl iodides 6 and 8 might serve as intermediates
in iodine-mediated glycosylation reactions with glyco-
sylselenides 2 and 7, respectively. It is possible that gly-
cosyl iodides formed in situ react directly with acceptor
alcohols, or indeed with further molecular iodine pres-
ent in the reaction mixture. Such processes can, on occa-
sion, give rise to a-glycosylation, even in the presence of
a C-2 participating group, presumably due to the inter-
SPh
BnO
BnO
1α/β
1
OBz
O
I2, CDCl
3
BzO
BzO
no reaction
SPh
24 hr
BzO
5
OBn
O
OBn
O
24
mediacy of a transient b-glycosyl iodide intermediate.
BnO
BnO
I2, CDCl
3
BnO
BnO
SePh
This notion parallels the in situ generation of labile b-
5
min
linked armed glycosyl iodides, which ultimately gives
BnO
2
BnO
I
2
5
6
rise to an a-selective glycosylation process. In addi-
tion, the generation of b-linked armed glycosyl bromides
from selenides has been successfully exploited in itera-
OBz
O
OBz
O
I2, CDCl3
4 days
BzO
BzO
BzO
BzO
26
tive glycosylation chemistry. Bearing in mind the poor
SePh
b-stereocontrol for iodine-promoted reaction of armed
thioglycoside 1 with sugar primary alcohol 3 in acetoni-
trile (Table 1), iodide 6 might also be formed transiently
during the activation of donor 1. Taken together, these
observations suggest that the nucleophilic iodide gener-
ated in iodine-promoted glycosylation reactions may
out-compete the nucleophilicity of acetonitrile solvent,
thus interfering with solvent-mediated stereocontrol of
the glycosylation process (Scheme 2).
BzO
BzO
I
7
8
Scheme 1. Reaction of selenoglycosides and thioglycosides with iodine
under NMR conditions.
In contrast to the reactivity of thioglycosides, armed
selenide donor 2 was transformed within 5 min into
the corresponding a-glycosyl iodide 6,
2
1,22
which decom-
posed at prolonged reaction times. The disarmed donor
selenide 7 reacted much slower with iodine; after four
days it also gave an a-glycosyl iodide product, 8. Known
2.3. Single electron transfer agents as promoters of model
glycosylation reactions with thioglucoside and seleno-
glucoside donors
2
2,23
iodide 8
proved to be reasonably stable and was ob-
tained from the NMR reaction by flash column chroma-
tography in 45% isolated yield. During the reaction of
selenides 2 and 7 with iodine, no anomerisation of the
Looking to promoters with a fundamentally different
mode of action, the single electron transfer agent tris(4-
bromophenyl)aminium hexachloroantimonate (BAHA)
has also been used to promote glycosylation reactions
with thioglycoside and selenoglycoside donors. Litera-
ture reports of the reactions of thioglycoside 1 and
1
b-selenide was detectable by H NMR spectroscopy, in
contrast to the corresponding reaction of armed thiogly-
coside 1. This suggests that the iodine-mediated activa-
tion process is potentially reversible for thioglycosides,
8
9
OP
OP
O
O
PO
PO
PO
I
PO
6
8
P = Bn PO
P = Bz
PO
PhSeI
I
PhSeI
OP
O
OP
O
OP
O
I2
I
R-OH
PO
PO
PO
PO
PO
SePh
PO
SePh
I
PO OR
OP
P = Bn
P = Bz
OP
PhSeSePh
2
7
OP
O
OP
O
PO
PO
PO
PO
I
I
PO
N
PO
C
Me
Scheme 2. Potential intermediates in iodine-promoted activation of selenoglycosides.

1394
R. M. van Well et al. / Carbohydrate Research 341 (2006) 1391–1397
OBn
O
BnO
BnO
OBn
O
OH
O
O
BAHA
MeCN
BnO
BnO
BnO
BnO
BnO
BnO
BnO
4
X-Ph
+
O
BnO
BnO
OMe
BnO
3
From 1α/β = 1/5.2
From 2α/β = 1.7/1
1
2
X = S
X = Se
OMe
8
9
Scheme 3. BAHA-promoted SET-based glycosylation with thioglycoside 1 and selenoglycoside 2.
Table 2. Model SET-based glycosylation reactions with thioglycoside 1 and selenoglycoside 2
OBn
O
OBn
O
OH
O
BnO
BnO
O
BnO
BnO
BnO
BnO
X-Ph
+
BnO
O
BnO
BnO
BnO
OMe
BnO
1
2
X = S
X = Se
3
4
BnO
OMe
Reagents and conditions
Thioglycoside 1
Selenoglycoside 2
BAHA (1.5 equiv), CH
BAHA (1.5 equiv), CH
DDQ (2 equiv), CH CN
3
3
CN
Cl
84%, a/b = 1/4.6
79% a/b = 1.1/1
No disaccharide
87%, a/b = 1/5
32%, a/b = 1/3.4
62%, a/b = 1/2
87% a/b = 1.5/1
No disaccharide
79%, a/b = 1/5
26%, a/b = 1/1.5
2
2
I
I
2
(1.5 equiv), DDQ (1.5 equiv), CH
(1.5 equiv), DDQ (1.5 equiv), CH
3
CN
Cl
2
2
2
All reactions conducted at room temperature for 30 min. Yields, which are unoptimised, relate to the combined isolated a/b mixture. The stereo-
1
15
chemical outcome of the reaction was determined by integration of the H NMR signals for the methyl aglycones of the anomers of 4.
selenoglycoside 2 with acceptor primary alcohol 3 in ace-
tonitrile show a marked donor-dependence in the stereo-
selectivity of the process: reaction with thioglycoside 1
promoted glycosylation in acetonitrile gives rather poor
ꢁ-selectivity (Table 1), addition of DDQ to the iodine-
promoted glycosylation of primary alcohol 3 with either
thioglycoside 1 of selenoglycoside 2 gave the ꢁ-linked
disaccharide 4 in high yield and with greater stereoselec-
tivity than in either the corresponding iodine- or NIS/
1
6
gives pronounced b-selectivity, as expected, but reac-
tion with selenoglycoside 2 gives only a very modest ex-
8
,9
cess of the b-glycoside 4 (Scheme 3). The intriguing
difference in stereoselectivity prompted us to compare
the activation of both classes of glycosyl donor under
single electron transfer (SET) conditions.
à
TMSOTf-mediated processes (Table 2). These results
indicate that activation with I /DDQ follows a different
2
reaction pathway than activation with iodine alone. It
seems unlikely that this particular process involves a sin-
gle electron transfer process; more likely, the DDQ serves
to oxidise iodide, generated in the activation process, to
iodine, so preventing glycosyl iodide and facilitating a-
glycosyl nitrilium ion formation. Interference from nucle-
ophilic counter-ions has previously been noted in glycosyl
sulfoxide activation with ICl, which generates glycosyl
Repetition of the literature BAHA-mediated glycosyl-
ation reactions (Scheme 3) confirmed the previously re-
ported results, that is, good ꢁ-selectivity for reaction
with thioglycoside 1 and poor stereoselectivity when
the selenoglycoside 2 was used (Table 2).
The use of DDQ alone in an attempt to effect SET-
mediated donor activation did not provide any disac-
charide product from reactions with either the thiogly-
coside 1 or selenoglycoside 2 and primary alcohol 3.
However, DDQ-promoted activation of selenoglycoside
2
8
chlorides. Similarly, the activation of thioglycosides
2
9
with dimethyl(methylthio)sulfonium tetrafluoroborate
and the electrochemical activation of chalcoglycosides
in the presence of tetrafluoroborate ions as supporting
2
, but not thioglycoside 1, in the presence of 4 M equiv
of methanol did give rise to anomeric methyl glucosides
27%, a/b = 1/4), as judged by monitoring methyl agly-
3
0
electrolyte both generate glycosyl fluorides. As for io-
(
dine-promoted reactions in dichloromethane, I /DDQ-
2
1
27
cone H NMR signals. The poor yield of methyl glyco-
sides in these reactions is accompanied by substantial
hemiacetal formation.
promoted glycosylation in this solvent is slow.
à
Attempts to activate armed thioglycosides with iodine in the presence
We have previously reported the use of I /DDQ for
2
1
1
of more potent oxidising agents such as CAN did not meet with
successful glycoside synthesis. The nucleophilic nitrate counter-ion
intercepted activated intermediates to give anomeric a-nitrates (P.
Cura and R. A. Field, unpublished observations).
activation of glycosyl halides, and noted the potential
of the same reagent combination for the activation of
1
2
S-p-methoxybenzyl thioglycosides. Although iodine-

R. M. van Well et al. / Carbohydrate Research 341 (2006) 1391–1397
1395
OBn
O
dependent on the source of promoter iodonium ion, with
iodine giving different results to NIS alone or NIS/
TMSOTf. Subsequent comparison of the activation of
thioglycosides and selenoglycosides revealed that they
follow different reaction pathways. In contrast to armed
thioglycosides, which anomerise, and disarmed thiogly-
cosides, which do not react, both armed and disarmed
selenoglycosides give rise to the corresponding glycosyl
iodides on reaction with iodine. Further, whilst DDQ
alone is an ineffective promoter, in combination with
iodine it produces better acetonitrile-assisted b-stereoselec-
tivity with both thioglycosides and selenoglycosides than
does the established single electron transfer agent
BAHA. However, the mechanism of iodine/DDQ action
is likely not a SET process, but instead the DDQ serves
to oxidise released iodide back to iodine, so prevention
in situ glycosyl iodide generation, which may compete
with a-glycosyl nitrilium ion formation (Scheme 5). In
practical terms, use of iodine in conjunction with DDQ
is at least as effective as NIS or NIS/TMSOTf in effecting
acetonitrile-assisted b-glycosylation reactions.
BnO
BnO
SPh
BnO
OBn
O
1
BAHA
MeCN
BnO
BnO
OR
BnO
Cl
(~30%)
OBn
O
9
BnO
BnO
SePh
BnO
2
Scheme 4. Reaction of armed and armed donors with BAHA.
As noted above, we were conscious of the potential
for interference from counter-ions present in glycosyla-
tion reactions. Armed thioglycoside 1 and selenoglyco-
side 2 were therefore reacted with BAHA in the
absence of an acceptor alcohol with a view to evaluate
ꢀ
the impact of the SbCl6 counter-ion present in the
BAHA complex. Activation of thioglycoside 1 or seleno-
glycoside 2 with BAHA in acetonitrile gave a complex
mixture of compounds, the dominant species being the
known a-glycosyl chloride 9 (Scheme 4) accompanied
by hemiacetal and other unidentified degradation
products.
Transient glycosyl chloride formation might therefore
occur in situ during BAHA-promoted glycosylation.
However, if this is the case, the reversibility of C–S bond
formation must, presumably, permit regeneration of
thioglycoside from glycosyl chloride in a manner that
is not evident for the corresponding selenoglycoside.
Overall, it seems likely that, irrespective of the type of
promoter used, the reversibility of C–S and the irrevers-
ibility of C–Se bond cleavage during glycosylation is the
dominant factor that distinguishes the chemistry of thio-
glycosides from that of selenoglycosides. This may well
account for differences in the stereochemical outcome
of reactions employing these classes of glycosyl donor.
3
1
4. Experimental
4.1. Materials and general methods
3
. Summary and conclusions
Reactions were carried out in dry solvents using septa
and syringes for addition of reagents. Dry CH Cl and
2
2
The stereochemical outcome of glycosylation reactions
with model thioglycosides and selenoglycosides is
CH CN were prepared by distillation from CaH ,
3 2
CH OH was distilled from Mg(OCH ) and stored over
3
3 2
OBn
O
OBn
O
BnO
BnO
BnO
BnO
R-OH
X = S, Se;
BnO
I
α/β mixture
N
I2
BnO
I
C
Me
OBn
O
X = S only
BnO
BnO
X-Ph
BnO
X = S, Se;
I2/DDQ
OBn
O
BnO
BnO
I2
R-OH
β-glycoside
I
BnO
N
C
Me
DDQ
Scheme 5. Mechanism to account for differences in iodine and I
2
3
/DDQ-promoted glycosylation in CH CN.

1396
R. M. van Well et al. / Carbohydrate Research 341 (2006) 1391–1397
˚
3
A molecular sieves. TLC was performed on pre-coated
4.2.3. NMR studies on the reaction of glycosyl donors
with I2. Solid I (0.1 mmol) was added to a solution of
aluminium plates (Silica Gel 60 F254, Merck). Spots were
visualised by exposure to UV light or by immersion in
% ethanolic H SO followed by heating to 150 ꢂC.
Solutions of reaction products were dried over MgSO4
and solvents were evaporated under reduced pressure
at 25–40 ꢂC. Column chromatography was performed
on silica gel (40–70 lm, BDH-Merck). Optical rotations
were measured at 25 ꢂC using a Perkin–Elmer 141 polari-
2
thioglycoside or selenoglycoside (0.05 mmol) in CDCl
(0.7 mL). The reaction was followed by H NMR spec-
3
1
5
2
4
troscopy at 400 MHz.
4.2.4. Activation of selenoglycosides with DDQ in
MeCN. Selenoglycoside (0.43 mmol) and DDQ
(0.85 mmol) were dissolved in CH CN (2 mL) and the
3
1
13
meter. H and C NMR spectra were recorded at 24 ꢂC
with a Varian Unity Plus spectrometer at 400 and
resulting mixture was stirred for 16 h. The reaction mix-
ture was diluted with CH Cl (15 mL), washed with
2
2
1
00 MHz, respectively, using TMS as an internal stan-
dard. Accurate electrospray ionisation mass spectra
HR ESI-MS) were obtained using positive ionisation
H O and brine, dried (MgSO ), concentrated and puri-
2 4
fied by column chromatography.
(
mode on a Finnigan MAT 900 XLT mass spectrometer.
The following known compounds were prepared
according to standard literature procedures and/or are
products of the experiments reported herein: phenyl
4.2.5. Activation of selenoglycosides with BAHA in
MeCN. Selenoglycoside (0.16 mmol) and BAHA
(0.32 mmol) were dissolved in CH CN (1 mL) and the
3
resulting mixture was stirred for 8 h. The reaction mix-
1
3
2
,3,4,6-tetra-O-benzyl-1-thio-b-D-glucopyranoside (1);
ture was cooled to 0 ꢂC, neutralised with Et N, filtered
3
phenyl
2,3,4,6-tetra-O-benzyl-1-seleno-b-D-glucopyr-
through Celite, concentrated and purified by column
chromatography.
9
anoside (2); methyl 2,3,4-tri-O-benzyl-a-D-glucopyr-
anoside (3);
1
4
methyl 2,3,4,6-tri-O-benzyl-a/b-1,6-D-
glucopyranosyl-2,3,4-tri-O-benzyl-a-D-glucopyranoside
4.2.6. Glycosylation reactions with BAHA or I2/
DDQ. Donor 1 or 2 (0.40 mmol) and acceptor 3 (0.32
mmol) were dissolved in CH Cl or CH CN (2 mL),
4 A molecular sieves (15 mg) were added and the reaction
mixture was stirred under nitrogen for 30 min. BAHA
1
5
(
4); phenyl 2,3,4,6-tetra-O-benzoyl-1-thio-b-D-gluco-
1
7,32
pyranoside (5);
anosyl iodide (6);
seleno-b-D-glucopyranoside (7);
zoyl-a-D-glucopyranosyl iodide (8);
benzoyl-a-D-glucopyranosyl chloride (9).
2,3,4,6-tetra-O-benzyl-a-D-glucopyr-
phenyl 2,3,4,6-tetra-O-benzoyl-1-
2
2
3
2
1,22
˚
1
8
2,3,4,6-tetra-O-ben-
2
2,23
2,3,4,6-tetra-O-
(1.21 mmol) [or I (0.6 mmol) and DDQ (0.6 mmol)]
2
3
1
was added and the progress of the reaction was followed
by TLC (EtOAc/hexane, 1/4, v/v). When reaction was
complete, the mixture was cooled to 0 ꢂC, neutralised
4
4
.2. General procedures
.2.1. NMR analysis. The stereochemical outcome of
with Et N, filtered through Celite and concentrated.
3
Purification by column chromatography (EtOAc/hexane,
the reactions detailed in Tables 1 and 2 was assessed
by integration of H NMR signals for the methyl agly-
0/1 ! 1/4, v/v) gave an a/b mixture of disaccharides 4.
1
cones of the anomers of disaccharides 4 at 3.32 (b)
1
5
and 3.35 (a) ppm. Epimerisation of thioglycosides
Acknowledgements
1
was judged by monitoring anomeric proton H NMR
signals at 5.39 and 4.58 ppm for a- and b-thioglycosides
We thank the EU (Marie Curie Intra-European fellow-
ship to R. M. van W.), the AICR (studentship to
T.S.K.) and The Weston Foundation for funding. We
are indebted to the EPSRC Mass Spectrometry Service
Centre, Swansea, for invaluable support.
1
9
31
1
, respectively, and 4.85 ppm for thioglycoside 5.
4
.2.2. Glycosylation reactions with NIS/TMSOTf or
iodine. Donor 1 or 2 (0.22 mmol) and acceptor 3
(
(
0.17 mmol) were dissolved in CH Cl2 or CH CN
2 3
1 mL), 4 A molecular sieves (0.10 g) were added and
˚
References
the reaction mixture was stirred under nitrogen for
0 min. NIS (1.1 mmol) and TMSOTf (0.02 mmol) [or
3
1
. For Part XVIII, see: Mukhopadhyay, B.; Cura, P.;
Kartha, K. P. R.; Botting, C. H.; Field, R. A. Org.
Biomol. Chem. 2005, 3468–3470.
solid iodine (0.44 mmol)] were added and the progress
of the reaction was followed by TLC (EtOAc/hexane,
1
/4, v/v). When the reaction was complete, the mixture
was diluted with EtOAc (10 mL), washed with aq NaH-
CO3 solution (2 · 5 mL), aq Na S O solution
2 · 5mL) and brine (5 mL), dried (MgSO ) and concen-
2
. (a) Varki, A. Glycobiology 1993, 3, 97–130; (b) Essentials
of Glycobiology; Varki, A., Cummings, R., Esko, J.,
Freeze, H., Hart, G., Marth, J., Eds.; Cold Spring Harbor
Laboratory Press: Cold Spring Harbor, NY, 1999.
. (a) Paulsen, H. In Modern Methods in Carbohydrate
Synthesis; Khan, S. H., O’Neill, R. A., Eds.; Harwood
Academic: Amsterdam, 1996; pp 1–20; (b) Nicolaou, K.
C.; Mitchell, H. J. Angew. Chem., Int. Ed. 2001, 40, 1576–
2
2
3
(
4
3
trated. Purification by column chromatography
EtOAc/hexane, 0/1 ! 1/4, v/v) gave an a/b mixture
of disaccharides 4.
(

R. M. van Well et al. / Carbohydrate Research 341 (2006) 1391–1397
1397
1
624; (c) Holeman, A.; Seeberger, P. H. Curr. Opin.
18. Zuurmond, H. M.; van der Klein, P. A. M.; de Wildt, J.;
van der Marel, G. A.; van Boom, J. H. J. Carbohydr.
Chem. 1994, 13, 323–339.
Biotechnol. 2004, 15, 615–622.
. (a) Garegg, P. J. Adv. Carbohydr. Chem. Biochem. 1997,
4
5
2, 179–205; (b)Best Synthetic Methods: Carbohydrates;
Osborn, H. M. I., Ed.; Academic Press: Amsterdam, 2003;
c) Oscarson, S. In Glycoscience: Chemistry and Biology I;
19. Kartha, K. P. R.; Cura, P.; Aloui, M.; Readman, S. K.;
Rutherford, T. J.; Field, R. A. Tetrahedron: Asymmetry
2000, 11, 581–593.
(
Fraser-Reid, B., Tatsuta, K., Thiem, J., Eds.; Springer:
Berlin, 2001; pp 643–670.
. Mehta, S.; Pinto, B. M. Tetrahedron Lett. 1991, 32, 4435–
20. Boons, G.-J.; Stauch, T. Synlett 1996, 906–907Veeneman,
G. Ph.D. Thesis, University of Leiden, The Netherlands,
1996.
5
6
4
438.
21. Kronzer, F. J.; Schuerch, C. Carbohydr. Res. 1974, 34, 71–
78.
22. Caputo, R.; Kunz, H.; Mastroianni, D.; Palumbo, G.;
Pedatella, S.; Solla, F. Eur. J. Org. Chem. 1999, 3147–
3150.
. Zuurmond, H. M.; van der Klein, P. A. M.; van der Meer,
P. H.; van der Marel, G. A.; van Boom, J. H. Rec. Trav.
Chim. Pays-Bas 1992, 111, 365–366.
. (a) Veeneman, G. H.; van Leeuwen, S. H.; van Boom,
J. H. Tetrahedron Lett. 1990, 31, 1331–1334; (b) Boons,
G.-J.; Bowers, S.; Coe, D. M. Tetrahedron Lett. 1997,
7
23. Ness, R. K.; Fletcher, H. G.; Hudson, C. S. J. Am. Chem.
Soc. 1950, 72, 2200–2205.
3
8, 3773–3776.
. Marra, A.; Mallet, J.-M.; Amatore, C.; Sina y¨ , P. Synlett
990, 572–574.
. Mehta, S.; Pinto, B. M. Carbohydr. Res. 1998, 310, 43–51.
24. van Well, R. M.; Kartha, K. P. R.; Field, R. A. J.
Carbohydr. Chem. 2005, 24, 463–474.
25. Hadd, M. J.; Gervay, J. Carbohydr. Res. 1999, 320, 61–69,
and references cited therein.
8
1
9
1
1
1
0. Kartha, K. P. R.; K a¨ rkk a¨ inen, T. S.; Marsh, S. J.; Field,
26. (a) Yamago, S.; Yamada, T.; Hara, O.; Ito, H.; Mino, Y.;
Yoshida, J. Org. Lett. 2001, 3, 3867–3870; (b) Yamago, S.;
Yamada, T.; Maruyama, T.; Yoshida, J. Angew. Chem.,
Int. Ed. 2004, 43, 2145–2148; (c) Yamago, S.; Yamada, T.;
Ito, H.; Hara, O.; Mino, Y.; Yoshida, J. Chem. Eur. J.
2005, 11, 6159–6174.
27. Vankayalapati, H.; Singh, G.; Tranoy, I. Tetrahedron:
Asymmetry 2001, 12, 1373–1381.
28. Marsh, S. J.; Kartha, K. P. R.; Field, R. A. Synlett 2003,
1376–1378.
R. A. Synlett 2001, 260–262.
1. Kartha, K. P. R.; Aloui, M.; Field, R. A. Tetrahedron
Lett. 1996, 37, 8807–8810.
2. Kartha, K. P. R.; Aloui, M.; Cura, P.; Marsh, S. J.; Field,
R. A.. In Advances in Sulfur Chemistry; Rayner, C. M.,
Ed.; JAI Press: US, 2000; Vol. 2, pp 37–56.
3. Ferrier, R. J.; Hay, R. W.; Vethaviyasar, N. Carbohydr.
Res. 1973, 27, 55–61.
1
1
1
1
4. Garegg, P. J.; Iversen, T.; Oscarson, S. Carbohydr. Res.
1
976, 50, C12–C14.
5. Garcia, B. A.; Gin, D. Y. J. Am. Chem. Soc. 2000, 122,
269–4279.
6. (a) Ratcliffe, A. J.; Fraser-Reid, B. J. Chem. Soc., Perkin
Trans. 1 1990, 747–750; (b) Braccini, I.; Derouet, C.;
Esnault, J.; Herv e´ du Penhoat, C.; Mallet, J.-M.; Michon,
V.; Sina y¨ , P. Carbohydr. Res. 1993, 246, 23–41.
7. Mallet, A.; Mallet, J.-M.; Sina y¨ , P. Tetrahedron: Asym-
metry 1994, 5, 2593–2608.
29. Blomberg, L.; Norberg, T. J. Carbohydr. Chem. 1992, 11,
751–760.
4
30. France, R. R.; Compton, R. G.; Davis, B. G.; Fairbanks,
A. J.; Rees, N. V.; Wadhawan, J. D. Org. Biomol. Chem.
2004, 2, 2195–2202, and references cited therein.
31. Takeo, K.; Nakagen, M.; Teramoto, Y. Carbohydr. Res.
1990, 201, 261–275.
1
32. Pakulski, Z.; Pierozynski, D.; Zamojski, A. Tetrahedron
1994, 50, 2975–2992.