Protecting-group-free O-glysosidation using p-toluenesulfonohydrazide and glycosyl chloride donors

Article abstract of DOI:10.1016/j.carres.2013.08.019

A range of N′-glycosylsulfonohydrazides (GSHs) display good reactivity but poor stereoselectivity in protecting-group-free O-glycosidations when a moderate excess of the model acceptor n-decanol is employed. This stable, readily-accessed class of donor may be more tractable for the glycosylation of non-volatile acceptors than Fischer's glycosidation conditions. It is possible to generate unprotected glycosyl chlorides from GSHs in situ. In an effort to find conditions to improve glycosidation stereoselectivity, methanolysis of unprotected glucosyl chloride under halide-ion exchange conditions was examined. Relative to its tetra-O-benzyl analogue, this donor displays moderate, inverted stereoselectivity and a significantly faster reaction rate.

Full text of DOI:10.1016/j.carres.2013.08.019

Carbohydrate Research 386 (2014) 73–77
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Protecting-group-free O-glysosidation using
p-toluenesulfonohydrazide and glycosyl chloride donors
⇑
Rohan J. Williams, Caroline E. Paul, Mark Nitz
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada
a r t i c l e i n f o
a b s t r a c t
A range of N0-glycosylsulfonohydrazides (GSHs) display good reactivity but poor stereoselectivity in pro-
tecting-group-free O-glycosidations when a moderate excess of the model acceptor n-decanol is
employed. This stable, readily-accessed class of donor may be more tractable for the glycosylation of
non-volatile acceptors than Fischer’s glycosidation conditions. It is possible to generate unprotected gly-
cosyl chlorides from GSHs in situ. In an effort to find conditions to improve glycosidation stereoselectiv-
ity, methanolysis of unprotected glucosyl chloride under halide-ion exchange conditions was examined.
Relative to its tetra-O-benzyl analogue, this donor displays moderate, inverted stereoselectivity and a sig-
nificantly faster reaction rate.
Article history:
Received 15 July 2013
Received in revised form 15 August 2013
Accepted 16 August 2013
Available online 27 August 2013
Keywords:
Protecting-group-free glycosidation
Protecting-group-free glycosylation
N0-Glycosylsulfonohydrazides
Glycosyl chlorides
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
MOP donors requires multistep protecting-group chemistry. Davis
et al. have employed an unprotected 4-bromobutyl mannoside do-
First reported in 1893, the Fischer glycosidation remains the
preferred method to synthesize many simple glycosides.1 How-
ever, despite modifications to Fischer’s protocol the general utility
of the reaction is curtailed by the requirement for strong acid catal-
ysis, the formation of primarily the thermodynamic product and
typically the requirement for a large excess of acceptor.2–6 Re-
cently, we have introduced N0-glycosylsulfonohydrazides (GSHs)
as glycosyl donors in protecting-group-free glycosidation reactions
(Fig. 1a).7 These donors have been employed to rapidly generate
nor to generate glycosides in moderate yields, even in the absence
of an activator (Fig. 1c).10 However, this donor could only be gen-
erated in low yield and the performance of other glycans as analo-
gous donors was not examined. Finn and co-workers have
employed unprotected alkynyl donors which upon heating and
activation with AuCl3 afforded O-glycosides in moderate yields
(a)
(b)
O
O
S
O
N
O-glycosides and glycosyl azides of N-acetyl-
NAc) with b-selectivity and also glycosyl 1-phosphates of a variety
of -glycans with
-selectivity.8 In contrast to Fischer’s conditions,
D-glucosamine (Glc-
HO
O
H
N
HO
N
H
O
H3CO
D
a
the glycosylation of these donors required only a moderate excess
of acceptor, suggesting that the use of GSHs could prove to be more
appropriate for the rapid glycosylation of non-volatile or more-
valuable alcohols. This motivated us to explore the selectivity
and reactivity of O-glycosidation of GSHs.
The rapid access to carbohydrate-based compounds afforded by
a protecting-group-free glycosylation strategy has driven the
investigation of several approaches. Hanessian et al. developed do-
nors which operate through remote activation, most notably
employing unprotected 3-methoxy-2-pyridyl (MOP) donors to effi-
ciently afford chiefly 1,2-cis glycosides (Fig. 1b).9 However, unlike
GSHs which can be formed without chromatographic purification
in a single high yielding step from the free sugar, the synthesis of
(c)
(d)
OH
OH
OH
O
O
O
OH
R
HO
O
Br
(e)
Cl
Cl-
N+
N
Figure 1. A brief survey of reagents employed in protecting-group-free glycosyla-
tions developed since the Fischer glycosidation; (a) N0-glycosylsulfonohydrazide
(GSH) donors, (b) 3-methoxy-2-pyridyl (MOP) donors, (c) 4-bromobutyl mannoside
donor, (d) alkynyl donors, (e) 2-chloro-1,3-dimethylimidazolinium chloride (DMC)
as a dehydrative condensing agent.
⇑
Corresponding author. Tel.: +1 416 946 0640.
E-mail address: mnitz@chem.utoronto.ca (M. Nitz).
0008-6215/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2013.08.019

74
R. J. Williams et al. / Carbohydrate Research 386 (2014) 73–77
(Fig. 1d).11 Shoda and co-workers have avoided protecting-group
chemistry in generating glycosyl azides12 and aryl thioglyco-
sides13,14 directly from unprotected sugars using 2-chloro-1,3-
dimethylimidazolinium chloride (DMC) (Fig. 1e). This dehydrative
condensing agent affords product in good yield and with strong
1,2-trans stereoselectivity, however, the generation of O-glycosides
using DMC has yet to be reported.
Herein, we survey the O-glycosylation of various GSH donors
using n-decanol as a model non-volatile acceptor. The behaviour
of protecting-group-free donors is further explored through an
examination of the selectivity of the methanolysis of unprotected
glucosyl chloride under various temperature and solvent condi-
tions and a comparison of the kinetics of methanolysis of unpro-
tected glucosyl chloride and its tetra-O-benzyl analogue.
was further decreased to 25% when employing 5 equiv of acceptor.
Decreases in the yield n-decyl-O-galactoside were accompanied by
an increase in the formation of a complex mixture of products, pre-
sumably resulting from oligomerization.
Although the GSH donors examined displayed adequate reactiv-
ity to n-decanol when 20 equiv of the acceptor were employed,
their stereoselectivity was poor. We were curious whether unpro-
tected glycosyl chlorides, readily generated from GSHs in situ (see
Supplementary data),7 might exhibit enhanced stereoselectivity
under halide-ion exchange conditions. This strategy was pioneered
by Lemieux for the 1,2-cis stereoselective generation of protected
glycosides.15 Although protected glycosyl chlorides have a long
history in carbohydrate synthesis, to our knowledge, the in situ
generation of an unprotected glycosyl chloride from a GSH is the
only case where an unprotected glycosyl chloride has been ob-
served. Although conversion of the GSH 1 to the unprotected glyco-
syl chloride 5 is less than quantitative, inspection of the 1H NMR
spectra indicates that it is the major species formed (see Supple-
mentary data). Employing methanol as a model acceptor, 1H
NMR spectroscopy indicated that the b-methyl glucoside of 6
was formed in moderate excess in all solvents examined (Table 2).
This is in contrast to the 1,2-cis stereoselectivity expected from
Lemieux’s protocol. Although the formation of 6 became more ster-
eoselective at lower temperatures, the reaction rate was slow, with
days required at ꢀ17 °C. Thus, lower temperatures were not inves-
tigated. Due to the moderate stereoselectivity and low reaction
rate at reduced temperatures of the unprotected glucosyl chloride
5 we sought to generate the more reactive unprotected glucosyl
bromide. Efforts to generate this species using tetrabutylammo-
nium bromide as a halide source were not productive, methyl glu-
coside 6 did not form under conditions analogous to the chloride
case and the presence of any unprotected glucosyl bromide could
not be confidently identified by 1H NMR spectroscopy.
2. Results and discussion
In order to examine the feasibility of employing GSHs for the
glycosylation of non-volatile alcohols, conditions to which the
Fischer glycosidation is often poorly-suited, n-decanol was em-
ployed as a model acceptor. As described previously, the GSHs em-
ployed were generated through condensation of the carbohydrate
of interest and p-toluenesulfonohydrazide in the presence of acetic
acid.8 These mild conditions employ cheap, readily-accessible re-
agents without the requirement for chromatographic purification
to obtain GSHs of sufficient purity for subsequent glycosylation
upon activation with a source of electrophilic halogen, typically
N-bromosuccinimide. Initially, variation in the performance of dif-
ferent GSH donors was assessed using conditions previously estab-
lished for the GlcNAc GSH donor.7 Employing 20 equiv of acceptor
afforded the desired glycosides in good yield (Table 1 and 71–79%).
As expected in the absence of a participating group at C2, there was
little stereocontrol except in the manno-case where 1,2-diaxial
interactions provided moderate stereoselectivity. Having demon-
strated that the donors 1–4 afforded their corresponding n-decyl-
O-glycosides in similar yields, the tolerance of the protocol for
lower excesses of acceptor was explored using the galactosyl donor
4. Reducing the equivalents of acceptor employed relative to the
donor resulted in a corresponding decrease in yield and did not af-
fect stereoselectivity. Employing 10 equiv of n-decanol relative to
donor 4 generated n-decyl-O-galactoside in 43% yield and which
Having observed that the stereoselectivity of the methanolysis
of the unprotected glycosyl chloride 5 differed markedly from what
would be expected for a protected glycosyl chloride under halide-
ion exchange conditions, we sought to gain further insight into the
reaction through examining its kinetics. In order to examine their
relative reactivity, freshly generated unprotected glucosyl chloride
5 and its tetra-O-benzyl analogue 7 were transferred to an NMR
tube and the methanolysis of both donors was monitored by 1H
Table 1
Investigation of the performance of GSH donors 1–4 utilizing the acceptor n-decanol.
Donor
Equivalents of n-decanol
Yield (%)
74
a/b Ratio
HO
O
S
O
HO
H
N
HO
20
1.4/1
N
H
HO
O
1
HO
OH
O
O
S
HO
H
N
HO
20
20
79
77
2.9/1
0.7/1
N
H
2
O
O
S
O
H
N
HO
HO
N
H
HO
O
3
20
10
5
71
43
25
1/1
1/1
1/1
OH
HO
HO
O
S
O
H
N
N
H
HO
O
4
Reaction conditions: GSH donor (0.718 mmol), dimethylformamide (5.0 mL), n-decanol, N-bromosuccinimide (2.4 equiv), 4 Å mol sieves, rt, 30 min.

R. J. Williams et al. / Carbohydrate Research 386 (2014) 73–77
75
Table 2
Investigation of the solvent and temperature dependence of the anomeric ratio of methyl glucoside 6 produced from the glucosyl chloride 5 (generated in situ from the GSH donor
1, see Supplementary data), as determined by 1H NMR spectroscopy after 18 h reaction time
HO
HO
HO
HO
HO
HO
O
S
O
O
O
H
N
(a)
(b)
HO
HO
HO
N
H
HO
OMe
HO
HO
O
Cl
1
5
6
Temp (°C)
a/b Ratio of methyl glucoside formed from 5 in various solvents
Dimethylformamide
Acetonitrile
Acetone
Dichloromethane
Tetrahydrofuran
ꢀ17
+3
Rt
1/2.4
1/2.3
1/2.5
1/4
1/3.5
1/2.8
1/8
1/4.3
1/3.8
1/4.2
1/3.7
1/2.7
1/2
1/2
1/3.9
Reaction conditions: (a) desired solvent, N-bromosuccinimide (2.4 equiv), tetrabutylammonium chloride (5 equiv); (b) desired temperature, methanol (20 equiv).
Figure 2. Excerpt of stacked 1H NMR spectra comparing the relative methanolysis of tetra-O-benzylglucopyranosyl chloride 7 (6.38 ppm) and unprotected glucopyranosyl
chloride 5 (6.16 ppm) in d3-acetonitrile at 0 °C. Tetrachloroethane 8 (6.48 ppm) is present as an internal standard.
NMR spectroscopy using tetrachloroethane 8 as an internal stan-
dard. At room temperature methanolysis of the unprotected gluco-
syl chloride 5 was complete within 7 min whereas the reaction
with the protected derivative 7 took approximately 23 h. Cooling
the experiment to 0 °C permitted detailed analysis, allowing acqui-
sition of a sufficient number of 1H NMR spectra before the methan-
olysis of 5 was complete (Fig. 2).
At 0 °C the half-life of methyl glucoside formation from 5 was
calculated to be approximately 200 times greater than that of the
protected derivative with a half life of approximately 27 min for
5 compared to approximately 100 h for the tetra-O-benzyl ana-
logue 7 (see Supplementary data). This difference in reactivity is
significantly greater than the 40-fold increase in reactivity Bols
and co-workers observed upon exchange of acyl groups (disarmed)
to benzyl groups (armed) on an aryl thioglucoside.16 Likewise, a
tert-butyldimethylsilyl protected (super-armed) aryl 6-deoxythi-
oglucoside was found to have only 20 times greater reactivity than
the benzyl protected thioglucoside.
More rigorous examination is required before one can confi-
dently rationalize the behaviour of the unprotected glucosyl donor
5 under halide-ion exchange conditions. The stereoselecive 1,2-cis
glycosidation of protected glycosyl chloride donors such as 7 relies
on the reaction proceeding solely through the more reactive b-
chloride or related close-contact ion-pairs. However, given the
increased methanolysis rate and moderate yet inverted stereose-
lectivity of 5 compared to the protected analogue 7 one can
speculate that the unprotected
a-glycosyl chloride or related
unprotected close-contact ion-pairs may be far more reactive than
analogous species in protected cases. Alternatively, the b-glycosyl
chloride may be captured by the 2-OH to afford an a-1,2-anhydro

76
R. J. Williams et al. / Carbohydrate Research 386 (2014) 73–77
intermediate which is opened by methanol to afford the b-linked
product.
73.62, 75.12, 75.13, 77.90, 78.13, 100.08, 104.36. The spectral data
were in agreement with those reported.18
In conclusion, although they react non-stereoselectively, unpro-
tected GSH donors offer extremely rapid and high yielding access
to simple O-glycosides. These donors may provide a useful alterna-
tive to the Fischer glycosidation in conditions where a vast excess
of acceptor is not tractable. Glycosidation of unprotected glucosyl
chloride gave moderate b-selectivity at reduced temperatures but
the slow reaction rate and non-absolute stereocontrol experienced
at these temperatures was judged to be impractical. Comparison of
the reactivity of an unprotected glucosyl chloride and its tetra-O-
benzyl analogue showed that methanolysis proceeded 200-times
faster for the unprotected compound, demonstrating the differ-
ences in reactivity that may be expected in protected versus
unprotected glycosyl donors.
3.2.2. n-Decyl-
According to the general procedure, donor 2 and n-decanol
(2.74 mL, 14.36 mmol) afforded n-decyl- -mannopyranoside
(0.183 g, 79%, /b: 2.9/1) as a colourless oil; dH (400 MHz, CD3OD)
0.86–0.90 (m), 1.27–1.38 (m), 1.53–1.63 (m), 3.15–3.20 (m), 3.36–
3.91 (m), 4.47 (1H, d, J1,2 1.0, H1-b), 4.70 (1H, d, J1,2 1.7, H1- ); dC
(100 MHz, CD3OD) 14.43, 27.73, 27.37, 30.46, 30.58, 30.63, 30.70,
30.71, 30.74, 30.75, 33.06, 62.88, 62.93, 68.58, 68.63, 70.63,
72.30, 72.59, 72.68, 74.56, 75.39, 78.24, 101.54, 101.74. The spec-
tral data were in agreement with those reported (spectral data
for the b-anomer previously reported in CDCl3).19,20
D-mannopyranoside
D
a
a
3.2.3. n-Decyl-
According to the general procedure, donor 3 and n-decanol
(2.74 mL, 14.36 mmol) afforded n-decyl- -xylopyranoside
(0.161 g, 77%, /b: 0.7/1) as a colourless oil; dH (400 MHz, CD3OD)
0.89–0.92 (m), 1.25–1.43 (m), 1.58–1.68 (m), 3.13–3.88 (m), 4.18
(1H, d, J1,2 7.6, H1-b), 4.70 (1H, d, J1,2 3.7, H1- ); dC (100 MHz, CD3-
OD) 14.43, 23.74, 27.10, 27.35, 30.46, 30.47, 30.56, 30.62, 30.67,
30.70, 30.73, 30.75, 30.82, 33.06, 63.01, 66.93, 69.27, 70.90,
71.24, 71.59, 73.64, 74.94, 75.22, 77.90, 100.37, 105.12. The spec-
tral data were in agreement with those reported (only b-anomer
previously reported).21
D-xylopyranoside
3. Experimental section
D
a
3.1. General methods
a
Reactions were monitored by TLC analysis (pre-coated Silica Gel
60 F254 plates, 250 lm layer thickness on aluminium) and visual-
ized by 254 nm UV light and staining with ethanolic H2SO4 (10%
v/v). Reagents were obtained from Sigma Aldrich or Acros Organics
and were used without further purification. 1H NMR spectra were
obtained on a Varian instrument at 400 MHz at 25 °C unless other-
wise stated. Chemical shifts are reported in parts per million with
the residual solvent peak used as an internal standard. 1H NMR
spectra were referenced to the d4-methanol peak at d 3.34 ppm
or the d3-acetonitrile peak at d 1.94 ppm. 13C NMR spectra were
measured at 25 °C on a Varian instrument at 100 MHz and were
referenced to the d4-methanol peak at d 49.0 ppm. NMR spectra
are tabulated as follows: chemical shift, multiplicity (s = singlet,
d = doublet, m = multiplet), number of protons, and coupling con-
stant(s). J values are given in Hz. Flash chromatography was per-
formed according to the method of Still et al. with Silica-P Flash
3.2.4. n-Decyl-
According to the general procedure, donor 4 and n-decanol
(2.74 mL, 14.36 mmol) afforded n-decyl- -galactopyranoside
(0.164 g, 71%, /b: 1/1) as a colourless oil that crystallized upon
D-galactopyranoside
D
a
standing; dH (400 MHz, CD3OD) 0.86–0.89 (m), 1.24–1.38 (m),
1.56–1.65 (m), 3.28–3.30 (m), 3.39–3.54 (m), 3.66–3.89 (m), 4.17
(1H, d, J1,2 7.4, H1-b), 4.77 (1H, d, J1,2 3.2, H1-a); dC (100 MHz, CD3-
OD) 14.43, 23.73, 27.13, 27.35, 30.47, 30.61, 30.62, 30.64, 30.71,
30.72, 30.75, 30.76, 30.85, 33.07, 62.45, 62.73, 69.23, 70.30,
70.85, 71.09, 71.57, 72.33, 72.57, 75.05, 76.58, 100.32, 104.99.
The spectral data were in agreement with those reported.19,22
According to the general procedure, donor 4 and n-decanol
Silica Gel 60 (40–63 l
m particle size, Silicycle).17 Solvents were
evaporated under reduced pressure using a rotary evaporator at
less than 50 °C.
(1.37 mL, 7.18 mmol) afforded n-decyl-D-galactopyranoside
(0.098 g, 43%,
standing.
a/b: 1/1) as a colourless oil that crystallized upon
3.2. General procedure for the formation of n-decyl-O-
glycosides
According to the general procedure, donor 4 and n-decanol
(0.68 mL, 3.59 mmol) afforded n-decyl- -galactopyranoside
/b: 1/1) as a colourless oil that crystallized upon
D
A mixture of GSH (0.718 mmol), dimethylformamide (5.0 mL),
n-decanol (5, 10 or 20 equiv relative to GSH) and freshly-acti-
vated 4 Å molecular sieves was allowed to stir for 1 h under N2
before the addition of N-bromosuccinimide (0.307 g, 1.72 mmol).
The reaction was stirred for 30 min when TLC analysis (20:80
MeOH/CH2Cl2) indicated that the starting material had been con-
sumed. Sufficient Amberlite IRA-67 free base resin was added to
quench the reaction, as judged by its loss of yellow colouration.
The mixture was filtered and the solvent removed under reduced
pressure. The residue was purified by flash chromatography (8–
15% MeOH in CH2Cl2 with 1% Et3N) to afford the target n-decyl-
O-glycosides.
(0.057 g, 25%,
standing.
a
3.3. Representative procedure for the methanolysis of
-glucopyranosyl chloride under varying temperature and
a-D
solvent conditions
N-Bromosuccinimide (0.061 g, 0.346 mmol) was added to a
solution of glucosyl donor 1 (0.500 g, 0.144 mmol) and tetrabutyl-
ammonium chloride (0.199 g, 0.718 mmol) in the solvent of inter-
est (3 mL). After gas evolution had subsided (30 s) the solution
was, if necessary, cooled to the appropriate temperature before
the addition of methanol (0.117 mL, 2.88 mmol). After 18 h cyclo-
hexene (0.073 mL, 0.718 mmol) and water (0.5 mL) were added
and the solvent was removed under reduced pressure. The ano-
meric ratio of the methyl glucoside in the lyophilized residue
was assessed using 1H NMR spectroscopy in d3-MeCN. The
procedure previously reported for the generation of unprotected
glycosyl chlorides employed 2,6-lutidine.7 Further investigation
of this protocol determined that the addition of 2,6-lutidine to
the reaction mixture is redundant, with indistinguishable results
obtained in its presence or absence.
3.2.1. n-Decyl-
According to the general procedure, donor 1 and n-decanol
(2.74 mL, 14.36 mmol) afforded n-decyl- -glucopyranoside
(0.170 g, 74%, /b: 1.4/1) as a colourless oil that crystallized upon
D-glucopyranoside
D
a
standing; dH (400 MHz, CD3OD) 0.88–0.92 (m), 1.26–1.42 (m),
1.58–1.66 (m), 3.15–3.93 (m), 4.24 (1H, d, J1,2 7.4, H1-b), 4.77
(1H, d, J1,2 3.8, H1-a); dC (100 MHz, CD3OD) 14.44, 23.73, 27.12,
27.34, 30.47, 30.48, 30.63, 30.64, 30.64, 30.71, 30.73, 30.76,
30.81, 33.06, 62.69, 62.78, 69.14, 70.90, 71.66, 71.83, 73.60,

R. J. Williams et al. / Carbohydrate Research 386 (2014) 73–77
77
3.4. Comparison of the rate of methanolysis of a-D-
References
glucopyranosyl chloride and 2,3,4,6-tetra-O-benzyl-a-D-
glucopyranosyl chloride
1. Fischer, E. BER 1893, 26, 2400.
2. Park, T. J.; Weiwer, M.; Yuan, X. J.; Baytas, S. N.; Munoz, E. M.; Murugesan, S.;
Linhardt, R. J. Carbohydr. Res. 2007, 342, 614–620.
3. Rauter, A. P.; Almeida, T.; Xavier, N. M.; Siopa, F.; Vicente, A. I.; Lucas, S. D.; Marques, J.
P.; Ribeiro, F. R.; Guisnet, M.; Ferreira, M. J. J. Mol. Catal. A: Chem. 2007, 275, 206–213.
4. Bornaghi, L. F.; Poulsen, S. A. Tetrahedron Lett. 2005, 46, 3485–3488.
5. Roy, B.; Mukhopadhyay, B. Tetrahedron Lett. 2007, 48, 3783–3787.
6. Wessel, H. P. J. Carbohydr. Chem. 1988, 7, 263–269.
N-Bromosuccinimide (0.078 g, 0.437 mmol) followed by
2,3,4,6-tetra-O-benzyl-
a
-
D
-glucosyl
chloride
7
(0.085 g,
0.152 mmol)23 were added to a solution of glucosyl donor 1
(0.063 g, 0.182 mmol), tetrabutylammonium chloride (0.152 g,
7. Gudmundsdottir, A.; Nitz, M. Org. Lett. 2008, 10(16), 3461–3463.
8. Edgar, L.; Dasgupta, S.; Nitz, M. Org. Lett. 2012, 14(16), 4226–4229.
9. Hanessian, S.; Lou, B. Chem. Rev. 2000, 100, 4443–4463.
10. Davis, B. G.; Wood, S. D.; Maughan, M. A. T. Can. J. Chem. 2002, 80, 555–558.
11. Mamidyala, S. K.; Finn, M. G. J. Org. Chem. 2009, 74, 8417–8420.
12. Tanaka, T.; Nagai, H.; Noguchi, M.; Kobayashi, A.; Shoda, S.-I. Chem. Commun.
2009, 3378–3379.
13. Tanaka, T.; Matsumoto, T.; Noguchi, M.; Kobayashi, A.; Shoda, S. Chem. Lett.
2009, 38, 458–459.
14. Yoshida, N.; Noguchi, M.; Tanaka, T.; Matsumoto, T.; Aida, N.; Ishihara, M.;
Kobayashi, A.; Shoda, S. Chem. Asian J. 2011, 6, 1876–1885.
15. Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; James, K. J. Am. Chem. Soc. 1975, 97,
4056–4062.
0.546 mmol) and 1,1,2,2-tetrachloroethane (1.9 lL, 0.018 mmol)
in d3-acetonitrile (0.60 mL). After gas evolution had subsided
(30 s), the mixture was transferred to an NMR-tube and cooled to
0 °C. A 1H NMR spectrum was obtained within 6 min of the addi-
tion of N-bromosuccinimide. Methanol (0.113 mL, 3.64 mmol)
was added and 1H NMR spectra were subsequently acquired at reg-
ular intervals at 0 °C.
Acknowledgements
16. Pedersen, C. M.; Marinescu, L. G.; Bols, M. Chem. Commun. 2008, 2465–2467.
17. Still, W. C.; Kahn, M.; Mitra, A. M. J. Org. Chem. 1978, 43, 2923–2985.
18. Adasch, V.; Hoffman, B.; Milius, W.; Platz, G.; Voss, G. Carbohydr. Res. 1998, 314,
177–187.
We thank the Natural Science and Engineering Research Council
of Canada for financial support.
19. Limousin, C.; Cleophax, J.; Petit, A.; Loupy, A.; Lukacs, G. J. Carbohydr. Chem.
1997, 16, 327–342.
Supplementary data
20. Bonar-Law, R. P.; Sanders, J. K. M. J. Am. Chem. Soc. 1995, 117.
21. Xu, W.; Osei-Prempeh, G.; Lema, C.; Oldham, E. D.; Aguilera, R. J.; Parkin, S.;
Rankin, S. E.; Knutson, B. L.; Lehmler, H.-J. Carbohydr. Res. 2012, 349, 12–23.
22. Okahata, Y.; Mori, T. J. Chem. Soc., Perkin Trans. 1 1996, 23, 2861–2866.
23. Encinas, L.; Chiara, J. L. J. Comb. Chem. 2008, 10, 361–363.
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the online version, at http://dx.doi.org/10.1016/j.carres.2013.
08.019.