Synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation catalyzed by 2-methyl-5-phenylbenzoxazolium perchlorate

Article abstract of DOI:10.1016/j.tet.2014.03.013

Several acidic azolium salts prepared from oxazole, thiazole, and imidazole derivatives were investigated as catalysts in N-glycosylation reaction using a silylated modified pyrimidine and an acylated ribose or glucose to afford the corresponding pyrimidine nucleoside. Among the salts, 2-methyl-5- phenylbenzoxazolium perchlorate showed the highest catalytic activity. This salt is a nonhygroscopic crystalline compound that shows higher activity than the frequently used trimethylsilyl triflate. Reactions with this salt can be conducted in gram scales.

Full text of DOI:10.1016/j.tet.2014.03.013

Tetrahedron 70 (2014) 3635e3639
Contents lists available at ScienceDirect
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€
Synthesis of modified pyrimidine nucleosides via Vorbruggen-type
N-glycosylation catalyzed by 2-methyl-5-phenylbenzoxazolium
perchlorate
*
Hiroshi Shirouzu, Hiroki Morita, Masaki Tsukamoto
Graduate School of Information Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 January 2014
Received in revised form 28 February 2014
Accepted 4 March 2014
Available online 18 March 2014
Several acidic azolium salts prepared from oxazole, thiazole, and imidazole derivatives were investigated
as catalysts in N-glycosylation reaction using a silylated modified pyrimidine and an acylated ribose or
glucose to afford the corresponding pyrimidine nucleoside. Among the salts, 2-methyl-5-
phenylbenzoxazolium perchlorate showed the highest catalytic activity. This salt is a nonhygroscopic
crystalline compound that shows higher activity than the frequently used trimethylsilyl triflate. Re-
actions with this salt can be conducted in gram scales.
Keywords:
Ó 2014 Elsevier Ltd. All rights reserved.
N-Glycosylation
Pyrimidine nucleoside
Brønsted acid
Oxazolium perchlorate
Catalysis
1. Introduction
activity, a stoichiometric amount of TMSOTf is usually used.
Moreover, this reagent is a hygroscopic liquid and must be handled
Modified pyrimidine nucleosides are an important class of
compounds as antiviral and anticancer agents,1 and are constitu-
ents in various tools for biotechnology.2 These nucleosides are
carefully. To overcome this problem, Jamison et al. utilized the
acidic pyridinium salt 5a (Fig. 1) as a glycosylation catalyst and
demonstrated the potential of this Brønsted acid. However, due to
poor reactivity, the reaction proceeded at elevated temperature
(100e150 ꢀC) under microwave irradiation.6 Another approach was
the use of glycosyl donors with different leaving groups, such as
trifluoroacetimidates7 and ortho-alkynyl benzoates8 coupled with
suitable catalysts, TMSOTf and a gold(I) complex, respectively.
These donors require one or two steps to prepare precursors for the
leaving groups. Moreover, glycosyl trifluoroacetimidates are rela-
tively unstable.
€
mostly synthesized by a Vorbruggen-type N-glycosylation re-
action3,4 initiated by Hilbert and Johnson,5 utilizing sugar acetates,
such as 1 and silylated pyrimidines 2 in the presence of trime-
thylsilyl triflate (TMSOTf) (cf. Scheme 1). Because of its low re-
The use of sugar acetates as glycosyl donors is advantageous
because they are chemically stable and commercially available. We
therefore design more active catalysts in N-glycosylation using
Scheme 1. Standard N-glycosylation reactions using 1-O-acetyl-2,3,5-tri-O-benzoyl-
b-
D-ribofuranose (1) and silylated 5-substituted uracils 2.
* Corresponding author. Tel./fax: þ81 52 789 4779; e-mail address: tsukamoto@
Fig. 1. Acidic azolium and pyridinium salts 4e7 investigated as catalysts for N-glyco-
sylation reactions.
is.nagoya-u.ac.jp (M. Tsukamoto).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.03.013

3636
H. Shirouzu et al. / Tetrahedron 70 (2014) 3635e3639
sugar acetates. In the presence of a Brønsted acid such as pyr-
idinium salt 5a,6 a reaction might be initiated by protonation at the
anomeric acetate of the glycosyl donor 1 to form a sugar cation3
with the liberation of acetic acid, suggesting that Brønsted acids
with higher acidity would enhance catalytic activity. It is well
known that basicity decreases in the order of imidazole, pyridine,
thiazole, and oxazole and that the acidity of the corresponding
protonated salts (i.e., acidic azolium or pyridinium salts) increases
in that order.9,10 In addition, several salts are nonhygroscopic and
easy to handle. Despite their favorable properties, as far as we
know, acidic azolium salts have not been examined as glycosylation
catalysts. Consequently, we investigated the utility of acidic azo-
lium salts as catalysts in N-glycosylation reactions and found that
salts derived from the oxazole derivative were effective catalysts as
described below.
showed higher activity than the corresponding triflates: 7b was
more active than 7a (entries 7 and 8), and the pyridinium triflate
5a6 showed no activity (entry 3). Although 7b was the most active,
a trace amount of N1,N3-bis-N-glycoside 8 was formed (entry 8),
which would lower the isolated yields due to separation difficulty.
This was also the case in reactions using other catalysts, such as 5b,
6a, 6b, and 7a (entries 4e7).
To prevent the formation of N1,N3-bis-N-glycoside 8, we
screened solvents in reaction using oxazolium perchlorate 7b. The
screening revealed that the reaction in acetone gave the best result
without forming by-product 8 (entry 9). Yields of reactions in THF
and 1,2-dichloroethane in the presence of 7b were less than 70%
(entries 10 and 11), though a trace amount of 8 was also detected. In
toluene, no product was obtained (entry 12). The catalytic activity
of 7b (entries 8 and 9) was superior to those of Lewis acids, such as
TMSOTf (entries 13 and 14) and tin(IV) chloride (entries 15 and 16)
in either acetonitrile or acetone. In addition, perchloric acid showed
no catalytic activity (entries 17 and 18), indicating that azoles play
an essential role in controlling the acidity of the catalytic active
species.
2. Results and discussion
Acidic azolium salts 4,11 6,12,13 and 7,14 as well as pyridinium salts
56 shown in Fig. 1 were prepared by mixing the nitrogen hetero-
cycles and acids according to the method reported by Hayakawa
et al.11 Nitrogen heterocycles include 1-methylbenzimidazole, 2,6-
di-tert-butyl-4-methylpyridine, benzothiazole, and 2-methyl-5-
phenylbenzoxazole, while acids include triflic acid6 and
perchloric acid.15 All of the salts were nonhygroscopic crystalline
compounds. 2-Methyl-5-phenylbenzoxazole was selected because
benzoxazolium triflate was hygroscopic. The substituents on the
benzoxazole are important in order to keep the salts
nonhygroscopic.
Catalytic activities of acidic salts 4e7 (Fig. 1) were evaluated in
the reaction of 1-O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranose (1)
To investigate the validity of oxazolium perchlorate 7b, we
conducted reactions with various silylated pyrimidines 2 on
a 0.3 mmol scale. As shown in Table 2, reactions with the silylated
pyrimidines 2ae2f were completed in 6 h, producing the corre-
sponding nucleosides 3ae3f in 84e94% yields without formation of
the undesired N1,N3-bis-N-glycosides. The target compounds were
isolated by recrystallization (entries 1e4) or column chromatog-
raphy (entries 5 and 6). One of the effects of acetone as solvent
could be the low solubility of the silylated N1-glycosylated prod-
ucts, which precipitated in the course of the reactions. This situa-
tion might suppress the formation of N1,N3-bis-N-glycosides.
and silylated 5-fluorouracil 2a in acetonitrile under refluxing
(Scheme 1). The catalyst loading was set at 5 mol %. After 2 h, the
aliquot of the reaction was quenched and the yield of the N-gly-
cosylated product 3a was determined by 1H NMR (Table 1). Re-
activity depended strongly on the parent nitrogen heterocycles and
counter anions of the salts. Among the catalysts, 2-methyl-5-
phenylbenzoxazolium perchlorate (7b) showed the highest activ-
ity, giving 3a in 80% yield (entry 8). When the perchlorates were
employed, the reactivities dropped as the parent nitrogen hetero-
cycle was changed from the oxazole, thiazole, pyridine, and imid-
azole derivatives (entries 2, 4, 6, and 8). Moreover, the perchlorates
Table 2
Synthesis of pyrimidine ribosides 3 from 1-O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribo-
furanose (1) and silylated 5-substituted urasils 2 by using oxazolium perchlorate 7b
(Scheme 1)a
Table 1
Catalyst screening in reaction of 1-O-acetyl-2,3,5-tri-O-benzoyl-
b-D-ribofuranose
(1) and silylated 5-fluorouracil 2a (Scheme 1)a
Entry
Silylated base
Nucleoside
Isolated yield, %
1
2
3
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
88
84
90
94
92
84
Entry
Catalyst
Solvent
Yield of 3ab, %
1
2
3
4
5
6
7
8
4a
4b
5a
5b
6a
6b
7a
7b
7b
7b
7b
7b
TMSOTf
TMSOTf
SnCl4
SnCl4
HClO4
HClO4
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
Acetone
THF
ClCH2CH2Cl
Toluene
MeCN
Acetone
MeCN
Acetone
MeCN
<5
<5
<5
52c
58c
64c
55c
80c
81
48c
70c
0
50
60
46
0
0
0
4
5b
6
a
Unless otherwise stated, the reaction was conducted on a 0.30 mmol scale under
the following conditions: [1]¼100 mM, [2]¼130 mM, [7b]¼5 mM, acetone, reflux,
6 h.
b
[2e]¼120 mM.
9
10
11
12
13
14
15
16
17
18
Under the above-optimized conditions in acetone with 7b, the
reaction of sugar acetate 1 (0.10 mmol) and a silylated purine base
derived from N6-benzoyladenine or N2-isobutyrylguanine ended
with the recovery of the starting acetate 1 and the acylated purine
base. Reactions in acetonitrile also did not proceed, for reasons that
are unclear.
Acetone
Tetra-O-acetyl-b-D-ribofuranose (9) can also be employed as
a glycosyl donor. As shown in Scheme 2, the tri-acetylated nucle-
osides 10d and 10e were obtained in 96e98% yields by the use of
a
Reaction was conducted on a 0.10 mmol scale of 1.
Estimated by 1H NMR spectrum of the crude product.
A trace amount (<5%) of by-product 8 was also obtained.
b
c

H. Shirouzu et al. / Tetrahedron 70 (2014) 3635e3639
3637
4. Experimental section
4.1. General
N-Glycosylation reactions were carried out by using the usual
Schlenk technique on a dual manifold vacuumeargon system. Thin-
layer chromatography (TLC) analysis was conducted by using silica
gel 60 F254 (Merck No. 5715, thickness 0.25 mm). Normal-phase
medium-pressure liquid chromatography (MPLC) was conducted
using a Purif-Pack SI-60 column (size 60, 120) on a Purif-compact
(Moritex, Japan).
Scheme 2. N-Glycosylation reaction using 1,2,3,5-tetra-O-acetyl-
and silylated 5-substituted uracils 2d and 2e in 0.30 mmol scale.
b-D-ribofuranose (9)
Melting points were determined by using a Yanaco MP-500V
instrument and were uncorrected. Elemental analyses were
conducted on a Yanaco MT-6 instrument. HRMS measurements
were performed on a JEOL JMS-700 (FAB) instrument. Specific
rotations of nucleosides were measured on a JASCO DIP-140
digital polarimeter using a sodium lamp in a 3.5 mmꢁ10 cm
cell. Infrared (IR) spectra were recorded on a JASCO FT/IR-460
spectrometer. Nuclear magnetic resonance (NMR) spectra were
measured on a JEOL JNM-ECP500 instrument. The chemical shifts
of 1H NMR in CDCl3, CD3CN, and DMSO-d6 are expressed in parts
acetonitrile as a solvent.16 In the case of 2e, the reaction was
completed in 30 min. Due to its high reactivity, 1.2 equiv of 2e
relative to 9 was used.
Oxazolium perchlorate 7b was also effective as a catalyst in re-
actions of pentaacetyl-b-D-glucose (11) and silylated 5-substituted
uracils 2 as shown in Table 3.4,17,18 Optimization of the conditions
revealed that the reaction proceeded smoothly in acetonitrile with
a catalyst loading of 10 mol % because the glycosyl donor 11 was less
reactive than ribofuranose 1. Within 24 h, the corresponding nu-
cleosides 12 were obtained in 91e99% yields. Excellent reactivity of
2e was also observed.
per million (ppm) relative to
relative to 77.0, 1.3, and 39.5]. Signal patterns are indicated as
d
7.26, 1.94, and 2.50 [In 13C NMR,
d
follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet;
br, broad signal.
The above-optimized conditions using the glycosyl donors 1, 9,
and 11 were safely applied to gram-scale reactions for the synthesis
of 3a (91% yield), 10d (95%), 10e (97%), 12a (91%), and 12b (93%),
while maintaining the yields.
4.2. Materials
The dehydrated solvents were commercially supplied and
stored in 1 L Schlenk tubes: pyridine (Wako), acetonitrile (Wako),
toluene (Wako), and 1,2-dichloroethane (Tokyo Kasei).
Table 3
1-O-Acetyl-2,3,5-tri-O-benzoyl-
pared according to the reported procedure.19 1 is also commercially
available from Tokyo Kasei. Tetra-O-acetyl- -ribofuranose (9),
b-D-ribofuranose (1) was pre-
N-Glycosylation reactions using pentaacetyl-b-D-glucose (11) and silylated 5-
substituted uracils 2 catalyzed by 2-methyl-5-phenylbenzoxazolium perchlorate
(7b) in 0.30 mmol scale
b-D
pentaacetyl-b-D-glucose (11), all the 5-substituted pyrimidine
nucleobases (Tokyo Kasei) and N6-benzoyladenine (Nacalai) were
commercially supplied. N2-Isobutyrylguanine was prepared
according to the reported procedure.20
The azoles and pyridine derivative were commercially supplied:
1-methylbenzimidazole (Aldrich), 2,6-di-tert-butyl-4-methylpyri
dine (Aldrich), benzothiazole (Tokyo Kasei), benzoxazole (Tokyo
Kasei), and 2-methyl-5-phenylbenzoxazole (Aldrich).
The following reagents were commercially supplied: tri-
fluoromethanesulfonic acid (Kishida), 70% aqueous perchloric acid
(SigmaeAldrich), hexamethyldisilazane (HMDS) (Chisso), TMSOTf
(Tokyo Kasei), tin(IV) chloride (Kanto), and 0.1 mol/L dioxane so-
lution of perchloric acid (Kishida).
Silylated base
[2], mM
Time, h
Nucleoside
Isolated yield, %
2a
2b
2c
2d
2e
130
130
130
130
120
24
24
24
24
2
12a
12b
12c
12d
12e
91
93
99
95
98
4.3. Preparation of acidic azolium and pyridinium salts
Acidic azolium and pyridinium salts, 4e7, were prepared
according to the reported procedure.6,11e14 The general procedure
was exemplified in the case of 7a together with spectroscopic data
of 4b, 5b, and 7b.
3. Conclusion
4.3.1. 2-Methyl-5-phenylbenzoxazolium triflate (7a). 2-Methyl-5-
phenylbenzoxazole (3.06 g, 14.6 mmol) was dissolved in CH2Cl2
(10 mL), and to this was added CF3SO3H (1.3 mL, 15 mmol) at 0 ꢀC.
After the temperature was raised to room temperature (rt), CH2Cl2
(5 mL) was added and the mixture was stirred for another 3 h. To
this, Et2O (20 mL) was added and the white powder was collected
by filtration and washed with Et2O (ca. 200 mL) followed by drying
under vacuum to give the titled compound (4.60 g, 87% yield) as
a pale white crystal: mp 161e163 ꢀC; [found: C, 50.36; H, 3.28; N,
3.71. C15H12NO4F3S requires C, 50.14; H, 3.37; N, 3.90.]; IR (KBr)
On the basis of general trends in the acidities of acidic azolium
salts, it was revealed that 2-methyl-5-phenylbenzoxazolium per-
chlorate was effective as a catalyst for the synthesis of modified
pyrimidine nucleosides via N-glycosylation reaction. The catalytic
activity was higher than that of TMSOTf. Both pyrimidine ribosides
and glucosides were obtained in good to excellent yields from
commercially available acylated ribose or glucose. Reactions can be
scaled up to the gram level. Because the catalyst is a non-
hygroscopic crystalline compound, it is easier to handle than fre-
quently used trimethylsilyl triflate.
2547, 1634, 1613, 1459, 1302, 1240, 1218 cmꢂ1 1H NMR (500 MHz,
;

3638
H. Shirouzu et al. / Tetrahedron 70 (2014) 3635e3639
DMSO-d6)
d
2.63 (s, 3H), 7.37 (tt, J¼7.3 and 1.4 Hz, 1H), 7.47 (m, 2H),
4.5. General procedure for gram-scale N-glycosylation
7.62 (dd, J¼8.5 and 2.0 Hz, 1H), 7.68e7.74 (m, 3H), 7.91 (d, J¼1.5 Hz,
1H); 13C NMR (125 MHz, DMSO-d6)
d
14.2, 110.6, 116.9, 117.1, 120.7
A mixture of 5-fluorouracil (339.1 mg, 2.6 mmol), pyridine
(2.0 mL), and HMDS (4.0 mL) in an 80-mL Schlenk tube was
refluxed for ca. 30 min to give a clear solution of 2a. Then, all the
volatiles were removed under reduced pressure (ca. 1 mmHg) to
give a clear syrup, which was dissolved in acetone (20 mL). To this
were added 1 (1.02 g, 2.0 mmol) and 7b (30.5 mg, 0.10 mmol,
5 mol %) and the mixture was stirred under refluxing for 6 h. After
the mixture was cooled to 0 ꢀC, EtOAc (15 mL) and MeOH (2.0 mL)
were added, while stirring at 0 ꢀC for 15 min. The solvent was
evaporated to less than 10 mL, and the residue was diluted with
EtOAc (300 mL) and washed with a saturated NaHCO3 aq (100 mL).
After the organic phase was separated, it was washed with a sat-
urated NaHCO3 aq (100 mLꢁ2) and brine (100 mL) then dried with
Na2SO4. Evaporation of the solvent afforded the crude product,
which was purified by recrystallization from EtOAc (ca. 31 mL) and
hexane (ca. 30 mL) to give 20,30,50-tri-O-benzoyl-5-fluorouridine
(3a) (1.05 g, 91%) as a white powder. Spectral data were consistent
(CF3, q, J¼321 Hz), 123.7, 127.1, 127.3, 129.0, 137.0, 140.2, 142.0, 150.4,
164.7.
4.3.2. 1-Methylbenzimidazolium perchlorate (4b). Compound 4b
(2.86 g, 91%) was obtained under the following conditions: 1-
methylbenzimidazole (1.78 g, 14 mmol), 70% aqueous perchloric
acid (1.16 mL, 14 mmol), CH2Cl2 (5.0 mL), Et2O (280 mL). Mp
120e121 ꢀC; [found: C, 41.14; H, 3.89; N,12.00. C8H9ClN2O4 requires
C, 41.31; H, 3.90; N, 12.04.]; IR (KBr) 3161, 1992, 1614, 1564, 1454,
1361, 1272 cmꢂ1; 1H NMR (500 MHz, DMSO-d6)
(m, 2H), 7.87 (m, 1H), 7.99 (m, 1H), 9.54 (s, 1H); 13C NMR (125 MHz,
DMSO-d6) 33.0, 113.2, 114.8, 126.0, 126.4, 130.8, 131.8, 142.1.
d 4.08 (s, 3H), 7.64
d
4.3.3. 2,6-Di-tert-butyl-4-methylpyridinium
perchlorate
(5b). Compound 5b (2.28 g, 89%) was obtained under the following
conditions: 2,6-di-tert-butyl-4-methylpyridine (1.71 g, 8.3 mmol),
70% aqueous perchloric acid (0.72 mL, 8.3 mmol), CH2Cl2 (2.0 mL),
Et2O (190 mL). Mp 253.0e255.3 ꢀC; [found: C, 54.82; H, 7.95; N,
4.57. C14H24ClNO4 requires C, 54.99; H, 7.91; N, 4.58.]; IR (KBr) 3391,
2971, 2874, 1637, 1620, 1482, 1375, 1253 cmꢂ1; 1H NMR (500 MHz,
with the reported ones.6 Found: C, 62.65; H, 4.06; N, 4.82.
22
C
30H23FN2O9 requires C, 62.72; H, 4.04; N, 4.88. [
a
]
D
ꢂ63.3ꢃ1.2 (c
0.100, CHCl3)21 1H NMR (500 MHz, DMSO-d6)
;
d
4.67 (dd, J¼11.8
and 5.5 Hz, 1H), 4.70e4.79 (m, 2H), 5.88e5.94 (m, 2H), 6.17 (d,
J¼3.5 Hz, 1H), 7.41e7.47 (m, 4H), 7.50 (dd, J¼8.0 and 7.5 Hz, 2H),
7.65 (m, 3H), 7.88 (dd, J¼8.0 and 1.0 Hz, 4H), 8.01 (dd, J¼8.0 and
1.0 Hz, 2H), 8.21(d, J¼7.0 Hz, 1H), 12.0 (s, 1H); 13C NMR (125 MHz,
CD3CN)
CD3CN)
d
1.50 (s, 18H), 2.60 (s, 3H), 7.73 (s, 2H); 13C NMR (125 MHz,
22.7, 28.9, 37.3, 124.2, 162.9.
d
4.3.4. 2-Methyl-5-phenylbenzoxazolium perchlorate (7b).14 Com
pound 7b (5.77 g, 78%) was obtained under the following condi-
tions: 2-methyl-5-phenylbenzoxazole (5.00 g, 24 mmol), 70%
aqueous perchloric acid (2.06 mL, 25 mmol), CH2Cl2 (40 mL), Et2O
(300 mL). Mp 208e211 ꢀC (lit.14 mp 204 ꢀC); [found: C, 54.19; H,
3.87; N, 4.24. C14H12ClNO5 requires C, 54.29; H, 3.91; N, 4.52.]; IR
DMSO-d6)
d
63.7, 70.3, 73.1, 78.9, 88.9, 126.1 (C-6, JCeF¼34 Hz),
128.4, 128.5, 128.7, 128.8, 129.2, 129.30, 129.31, 129.4, 133.6, 133.9,
134.0, 140.2 (C-5, JCeF¼230 Hz), 149.0, 157.1 (C-4, JCeF¼25 Hz),
164.6, 165.5.
Acknowledgements
(KBr) 3037, 1634, 1614, 1457, 1430, 1403, 1307 cmꢂ1
(500 MHz, DMSO-d6)
;
1H NMR
2.63 (s, 3H), 7.37 (t, J¼7.5 Hz, 1H), 7.47
d
We are grateful to Dr. Kin-ichi Oyama (Nagoya University) for his
valuable comments on the manuscript and for conducting the el-
emental analyses and the MS measurements. We also thank Pro-
fessors Kumi Yoshida and Tadao Kondo (Nagoya University) for the
helpful discussions. This work was financially supported by Nagoya
University (691445).
(dd, J¼8.0 and 7.5 Hz, 2H), 7.62 (dd, J¼8.5 and 2.0 Hz, 1H), 7.69e7.73
(m, 3H), 7.90 (d, J¼1.5 Hz, 1H); 13C NMR (125 MHz, DMSO-d6)
d
14.2, 110.6, 117.1, 123.7, 127.1, 127.3, 129.0, 137.0, 140.1, 142.0, 150.0,
164.6.
4.4. Catalyst screening
Supplementary data
A mixture of 5-fluorouracil (16.9 mg, 0.13 mmol), pyridine
(0.20 mL), and hexamethyldisilazane (HMDS) (0.40 mL) in a 20-
mL Schlenk tube was refluxed for ca. 30 min to give a clear so-
lution of 2a. Then, all the volatiles were removed under reduced
pressure (ca. 1 mmHg) to give a clear syrup, which was dissolved
in MeCN (1.0 mL). To this were added 1-O-acetyl-2,3,5-tri-O-
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.03.013.
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9. Haake, P.; Bausher, L. P. J. Phys. Chem. 1968, 72, 2213e2217.
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ed.; Macmillan: New York, NY, 1985; p 1017.
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Hirose, M.; Noyori, R. J. Am. Chem. Soc. 2001, 123, 8165e8176.
12. Zhou, X. S.; Liu, J. B.; Luo, W. F.; Zhang, Y. W.; Song, H. J. Serb. Chem. Soc. 2011, 76,
1607e1615.
TMSOTf (27
solution (0.10 mL, 5
1 and 2a in MeCN or acetone (0.90 mL). In the case of the SnCl4-
catalyzed reaction, MeCN or acetone (3.0 mL) solution of SnCl4
m
L, 150
m
mol) was prepared and an aliquot of the
m
mol) was immediately added to a mixture of
(18
(0.10 mL, 5
in MeCN or acetone (0.90 mL). In the case of the HClO4-catalyzed
reaction, 0.1 mol/L dioxane solution (50 L) of HClO4 was added to
the solution (950 L) of 1 and 2a. In a similar manner, reactions
were conducted in different conditions shown in Table 1.
m
L, 150
m
mol) was prepared and an aliquot of the solution
m
mol) was immediately added to a mixture of 1 and 2a
m
13. Dean, R. L.; Wood, J. L. J. Mol. Struct. 1975, 26, 197e213.
14. Bach, G.; Domaschka, G. J. Signal AM. 1980, 8, 137e144.
m
€
15. Vorbruggen, H.; Bennua, B. Chem. Ber. 1981, 114, 1279e1286.

H. Shirouzu et al. / Tetrahedron 70 (2014) 3635e3639
3639
16. In these glycosylations, no N1,N3-bis-N-glycoside was observed.
20. Jenny, T. F.; Schneider, K. C.; Benner, S. A. Nucleosides Nucleotides 1992, 11,
1257e1261.
17. In a previous report, 12aee were synthesized in 70e80% yields in the presence
of a 1.4 equiv of TMSOTf relative to 11 under the microwave irradiation.18
.
21. There are two references on the [
a
]
D value of 3a: [
a
]
25 ꢂ73.4 (c 0.093, CHCl3)22
D
28
18. Kantsadi, A. L.; Hayes, J. M.; Manta, S.; Skamnaki, V. T.; Kiritsis, C.; Psarra, A.-M.
G.; Koutsogiannis, Z.; Dimopoulou, A.; Theofanous, S.; Nikoleousakos, N.;
Zoumpoulakis, P.; Kontou, M.; Papadopoulos, G.; Zographos, S. E.; Komiotis, D.;
Leonidas, D. D. ChemMedChem 2012, 7, 722e732.
and [
a
ꢀ
]
ꢂ33 (c 2, CHCl3).23
D
ꢀ
22. Prystas, M.; Sorm, F. Collect. Czech. Chem. Commun. 1964, 29, 2956e2969.
23. Yung, N. C.; Burchenal, J. H.; Fecher, R.; Duschinsky, R.; Fox, J. J. J. Am. Chem. Soc.
1961, 83, 4060e4065.
19. Ishikawa, F.; Nomura, A.; Ueda, T.; Ikehara, M.; Mizuno, Y. Chem. Pharm. Bull.
1960, 8, 380e384.