Glycosyl azides of sugar 2-sulfonic acids

Article abstract of DOI:10.1016/j.tetlet.2005.05.112

Phenyl and trityl 2-O-sulfonyl-1-thio-α-d-manno- and β-d-glucopyranosides were reacted with sodium azide to yield 2-S-phenyl or 2-S-trityl-d-gluco- and d-mannopyranosyl azides, respectively. Usually, both anomers were formed in approximately equal amounts

Full text of DOI:10.1016/j.tetlet.2005.05.112

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5191–5194
Glycosyl azides of sugar 2-sulfonic acids
*
´ ´ ´ ´ ´ ´ ´
Ferenc Sajtos, Laszlo Lazar, Aniko Borbas, Istvan Bajza and Andras Liptak
´
´
Research Group for Carbohydrates of the Hungarian Academy of Sciences, H-4010 Debrecen, PO Box 55, Hungary
Received 22 April 2005; revised 18 May 2005; accepted 25 May 2005
Available online 14 June 2005
Abstract—Phenyl and trityl 2-O-sulfonyl-1-thio-a-D-manno- and b-D-glucopyranosides were reacted with sodium azide to yield 2-S-
phenyl or 2-S-trityl-D-gluco- and D-mannopyranosyl azides, respectively. Usually, both anomers were formed in approximately
equal amounts and formation of glycals was also observed in some cases. The product distribution of these reactions depends
on the nature of the aglycone, the applied reagent and also on the solvent. These results can be rationalised by the intermediacy
of episulfonium as well as oxocarbenium ions. Oxidation of the 2-S-trityl-a-D-glucopyranosyl or a-D-mannopyranosyl azides by
OxoneÒ, gave sodium 2-sulfonato-a-D-gluco- and a-D-mannopyranosyl azides, respectively.
Ó 2005 Elsevier Ltd. All rights reserved.
It is generally accepted, that the 1,2-thiomigration (the
L
O
O
migration of thioalkyl or thioaryl aglycone to C-2)
which was first utilised in the synthesis of 2-thio-D-
ribose and 20-thio-adenosine derivatives,1 proceeds
through an episulfonium ion intermediate.1–3 Precondi-
tions for this reaction are (i) an anomeric S-alkyl or S-
aryl group, (ii) a good leaving group at C-2 (O-metha-
nesulfonyl, O-toluenesulfonyl, O-SF2NEt2, etc.), (iii) a
trans orientation of the aforementioned substituents.
The added nucleophile opens the episulfonium interme-
diate producing the ÔnormalÕ 1,2-trans product, however,
formation of the ÔabnormalÕ 1,2-cis products in these
reactions was also reported. Normally, inversion of con-
figuration at C-2 occurs indicating that besides the epi-
sulfonium ion mechanism, another, the oxocarbenium-
ion mechanism, also operates. On the basis of MNDO
semi-empirical4 and high-level ab initio calculations,5 it
was suggested that the oxocarbenium ion is the more
reactive species (Scheme 1).
O
SR
SR
SR
A
B
C
Nu
Nu
Nu
L = leaving group
Nu = nucleophile
O
O
Nu
SR
RS
Nu
D
E
Scheme 1. Proposed mechanism of the formation of 1,2-cis and 1,2-
trans products during the 1,2-thiomigration reaction.
mannopyranosyl derivative was used the yield was only
59% but formation of the a-anomer was not observed.
These and our earlier observations, together with some
sporadic data in the literature suggest that 1,2-thio-
migration strongly depends on reaction conditions: the
bulkiness of the aglycone, the bulkiness and power of
the nucleophile, the nature of the solvent and the
temperature.
We have reported6 1,2-thiomigration of b-D-glucopyr-
anosides in the presence of NaOMe. From p-methoxy-
benzylthio-, tritylthio- and (2-naphthyl)methylthio-b-D-
glucopyranosides,
methyl
2-S-(p-methoxybenzyl),
methyl 2-S-trityl and methyl 2-S-(2-naphthyl)methyl-a-
D-mannopyranosides, respectively, were formed in
excellent yields (>90%). However, when a trityl 1-thio-
In our work on the synthesis of sugar sulfonic acids, one
specific goal is the preparation of sugar sulfonic acids of
glycosyl azides. Here, we report on some 1,2-thiomigra-
tions in the presence of the azide nucleophile. To the
best of our knowledge, synthesis of 2-thioalkyl/aryl
Keywords: Carbohydrate sulfonic acids; Thiomigration; Glycosyl
azides.
*
Corresponding author. Tel.: +36 52512900; fax: +36 52512913;
e-mail: liptaka@puma.unideb.hu
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.112

5192
F. Sajtos et al. / Tetrahedron Letters 46 (2005) 5191–5194
OR
O
Ph
O
Ph
O
O
O
O
BnO
BnO
SPh
OR
SPh
1 R=H
2 R=H
a
a
3 R=Ts, 82%
4 R=Ts, 87%
b
b
38%
35%
33%
35%
SPh
O
SPh
O
O
Ph
O
Ph
Ph
O
O
BnO
Ph
O
O
O
O
O
O
BnO
BnO
N3
BnO
N3
PhS
SPh
N3
N3
7
8
5
6
d
d
c
51%
O
48%
c
43%
50%
SPh
O
Ph
O
Ph
O
O
O
BnO
NHAc
BnO
NHAc
SPh
10
9
Scheme 2. Reagents and conditions: (a) 1.1 equiv TsCl, 5.7 equiv NaOH, 5.2 equiv K2CO3, rt, 4 h; (b) 10 equiv NaN3, DMF, 80 °C, overnight;
(c) H2/Pd(C), 1.5 equiv TEA, THF, rt, 2 h; Ac2O, Py, rt, 2 h; (d) 1.2 equiv PPh3, THF, 35 °C, 5 h; H2O, 35 °C, overnight; Ac2O, Py, rt, 2 h.
glycosyl azides is unprecedented. A few 2-deoxy-2-phen-
ylseleno-glycopyranosyl azides7–9 have been prepared by
free radical or polar addition of phenylselenyl azide on
glycals, however, 1,2-selenomigration in the presence
of azide has not been reported.
of Et3N) was the method of choice. In both cases, both
anomeric azides furnished exclusively the b-products 9
(1JC1,H1 = 159.7 Hz) and 10 (1JC1,H1 = 156.0 Hz) after
acetylation. The appearance of coupling between the
NH protons and the anomeric protons in the spectra of
compounds 9 and 10 proved unambiguously the position
of the azide group in compounds 5–8.
Conventional tosylation of 110,11 and 212,13 gave com-
pounds 3 and 4, respectively (Scheme 2), which were
treated with NaN3 (10 equiv) in N,N-dimethylformam-
ide at 80 °C overnight. From the reaction of 3 with
sodium azide, compounds 5 and 6 were isolated in yields
of 33% and 35%, respectively. Compound 4 also gave
two products, 7 (38%) and 8 (35%). The characteristic
band in the IR spectra of 5–8 at t = 2150 cmꢀ1 con-
firmed the presence of the N3 functionality. In the 13C
NMR spectra, there was a substantial upfield shift of
the signals corresponding to C-2 and a slight downfield
shift of the anomeric signals. Due to signal overlapping,
the proton spectra were unsuitable for the determination
of the anomeric configurations, and the small difference
in the [a]D values also caused uncertainty in this respect.
The tosylates 3 and 4 were also reacted with Me3SiN3
(Scheme 3) to study the effect of the counter-ion on
the reaction. Starting from 4, the ÔnormalÕ product 7
was isolated in a yield of only 28%, and the major prod-
uct was the glycal 11. In contrast, compound 3 gave only
the ÔnormalÕ product 5 in good yield (72%) and no glycal
Ph
O
O
O
a
4
+
BnO
7
28%
SPh
11
1
However, large differences in JC1,H1 couplings left no
55%
doubt about the anomeric configurations: 5 (162.0 Hz)
and 8 (158.0 Hz) were the b-, while 6 (170.3 Hz) and 7
(172.7 Hz) were the a-anomers.14
Ph
O
O
a
O
3
5
72%
+
BnO
For additional structural elucidations, azides 5–8 were
converted into the acetamides 9 and 10.15 In the case of
the 1,2-cis derivatives (6 and 8), PPh3 was used for the
reductions,16 however, under the same conditions, the
1,2-trans compounds (5 and 7) gave complex mixtures,
therefore, catalytic hydrogenation (Pd–C in the presence
PhS
OSiMe3
12
5%
Scheme 3. Reagents and conditions: (a) 10 equiv Me3SiN3, DMF,
80 °C, overnight.

F. Sajtos et al. / Tetrahedron Letters 46 (2005) 5191–5194
5193
OH
OH
OR
O
Ph
Ph
O
Ph
O
O
O
O
O
HO
HO
a
O
d
47%
O
O
+
R'O
BnO
BnO
53%
TrS
STr
N3
STr
STr
13
14 R=R'=H
17 47% (DMSO)
18 8% (DMSO)
b
c
27% (DMF)
15% (DMF)
15 R=H, R '=Bn, 91%
e
76%
16 R=Ms, R'=Bn, quant.
Ph
O
O
O
BnO
NaO3S
N3
19
STr
O
SO3Na
O
Ph
O
O
BnO
Ph
O
O
Ph
O
O
O
d
25%
e
BnO
STr
BnO
79%
OMs
N3
N3
20
21
22
Scheme 4. Reagents and conditions: (a) 1.5 equiv benzaldehyde dimethyl acetal, 0.02 equiv TsOH, DMF, 50 °C, 6 h; (b) 1.3 equiv Bu2SnO, 2 equiv
CsF, toluene, reflux, 3 h; 2 equiv BnBr, DMF, rt, overnight; (c) 2 equiv MsCl, Py, rt, 4 h; (d) 10 equiv NaN3, DMSO or DMF, 80 °C, 24 h;
(e) 2.5 equiv OxoneÒ, 20 equiv KOAc, AcOH, rt, overnight.
D-manno- and b-D-glucopyranosides. In each case, com-
plete inversion of the configuration was observed at C-2.
Using NaOMe, a product with inversion of the ano-
meric configuration was formed exclusively. The ano-
meric selectivity nearly disappeared when NaN3 was
used with phenylthio glycosides, however with Me3SiN3,
formation of the ÔnormalÕ product was observed. Exclu-
sive formation of the ÔabnormalÕ product was found in
the case of the tritylthio D-mannopyranosyl compound,
which is unprecedented in the literature. These observa-
tions suggest that with azide as the nucleophile, besides
the episulfonium intermediate, the oxocarbenium ion
intermediate also plays a substantial role in the determi-
nation of the product distribution. Although there are
many factors governing this transformation, we have
succeeded in developing a new approach for the synthe-
sis of a new class of carbohydrate derivatives, the 2-C-
sulfonyl-glycosyl amines.
formation was observed. (A small amount of the tri-
methylsilyl glycoside 12 was isolated from the reaction
mixture.)17
Having clarified the structure of the products of migra-
tion of the SPh aglycone, we used these reaction condi-
tions for the trityl 1-thio-a-D-mannopyranoside
derivative 15 (Scheme 4). The advantage of the STr
group is that it can be easily and directly oxidised with
OxoneÒ to the corresponding sulfonic acid. Compound
15 was prepared from trityl 1-thio-a-D-mannopyrano-
side6 (13) in a short synthetic sequence. We note here,
that tosylation of 15 was unsuccessful, probably due
to steric reasons, so a mesyl group was used instead.
The 1,2-thiomigration reaction in this case gave 17 in
a yield of 27%, but this could be improved (47%) by
changing the solvent to DMSO. No ÔnormalÕ product
formation was observed. As a by-product, the glycal
18 was isolated in a minor amount (DMF, 15%; DMSO,
8%). By changing the solvent (MeCN, 2-butanone), the
glycal was formed exclusively. Spectroscopic (IR,
NMR) and X-ray diffraction data were used for the
structural elucidation of 17.18
Acknowledgements
The authors thank the National Research Foundation
(OTKA AT48798, OTKA T35128, and OTKA
T38066) for financial support.
Performing the 1,2-thiomigration with compound 20,6
the ÔnormalÕ product 21 was isolated, albeit in a poor yield
(25%) along with an inseparable mixture of by-products.
References and notes
Compounds 17 and 21 were then successfully oxidised
using OxoneÒ to yield sulfonates 19 and 22,
respectively.18
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3. Johnston, B. D.; Pinto, B. M. J. Org. Chem. 2000, 65,
4607–4617.
In conclusion, we have performed 1,2-thiomigration
reactions with phenyl and trityl 2-O-sulfonyl-1-thio-a-

5194
F. Sajtos et al. / Tetrahedron Letters 46 (2005) 5191–5194
4. Jones, D. K.; Liotta, D. C. Tetrahedron Lett. 1993, 34,
7209–7212.
5. Dudley, T. J.; Smoliakova, I. P.; Hoffmann, M. R. J. Org.
Chem. 1999, 64, 1247–1253.
1H NMR (360 MHz, CDCl3): d 5.58 (dd, 1H, 3J1,2 = 1.9 Hz,
3
3JH1,NH = 9.8 Hz, H-1), 3.62 (dd, 1H, J1,2 = 1.9 Hz,
3J2,3 = 2.6 Hz, H-2); 13C NMR (90 MHz, CDCl3): d 77.5
(C-1), 58.4 (C-2). Anal. Calcd for C28H29NO5S (491.60): C,
68.41; H, 5.95; N, 2.85. Found: C, 68.63; H, 5.89; N, 2.87%.
´
´
´
6. Liptak, A.; Sajtos, F.; Janossy, L.; Gehle, D.; Szilagyi, L.
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Org. Lett. 2003, 5, 3671–3674.
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7. Santoyo-Gonzales, F.; Caluo-Flores, F. G.; Garcis-Men-
doza, P.; Hernandez-Mateo, F.; Isac-Garcia, J.; Roblez-
Diaz, R. J. Org. Chem. 1993, 58, 6122–6125.
8. Czernecki, S.; Randriamandinby, D. Tetrahedron Lett.
1993, 34, 7915–7916.
9. Giuliano, R. M.; Davis, R. S.; Boyko, W. J. J. Carbohydr.
Chem. 1994, 13, 1135–1143.
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10. Szurmai, Z.; Balatoni, L.; Liptak, A. Carbohydr. Res.
1994, 254, 301–309.
11. Oshitari, T.; Shibasaki, M.; Yoshizawa, T.; Tomita, M.;
Takao, K.; Kobayashi, S. Tetrahedron 1997, 53, 10993–
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12. Zuurmond, H. M.; van der Klein, P. A. M.; van der
Marel, G. A.; van Boom, J. H. Tetrahedron Lett. 1992, 33,
2063–2066.
13. Zuurmond, H. M.; van der Klein, P. A. M.; van der
Marel, G. A.; van Boom, J. H. Tetrahedron 1993, 49,
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deak, Z. Tetrahedron 2001, 57, 4609–4621.
17. Physical, selected H and 13C NMR data for compounds
1
11 and 12: 11: [a]D +4.0 (c 0.10, CHCl3); 1H NMR
(360 MHz, CDCl3): d 6.85 (s, 1H, H-1); 13C NMR
(90 MHz, CDCl3): d 152.3 (C-1), 108.0 (C-2). Anal. Calcd
for C26H24O4S (432.53): C, 72.20; H, 5.59%. Found: C,
72.03; H, 5.62%. 12: [a]D ꢀ55.0 (c 0.22, CHCl3); 1H NMR
3
(360 MHz, CDCl3): d 5.32 (d, 1H, J1,2 = 2.5 Hz, H-1),
3
3
3.33 (dd, 1H, J1,2 = 2.5 Hz, J2,3 = 10.7 Hz, H-2); 13C
NMR (90 MHz, CDCl3): d 94.9 (C-1), 56.1 (C-2). Anal.
Calcd for C29H34O5SSi (522.19): C, 66.63; H, 6.56%.
Found: C, 66.69; H, 6.52%.
1
18. Physical, selected H and 13C NMR data for compounds
17, 19, 21 and 22: 17: [a]D ꢀ43.2 (c 0.11, CHCl3); 1H NMR
3
(360 MHz, CDCl3): d 2.96 (d, 1H, J1,2 = 4.0 Hz, H-1),
3
3
2.92 (dd, 1H, J1,2 = 4.0 Hz, J2,3 = 10.8 Hz, H-2); 13C
NMR (90 MHz, CDCl3):
d 90.4 (C-1), 50.6 (C-2),
1JC1,H1 = 171.3 Hz. Anal. Calcd for C39H35N3O4S
(641.78): C, 72.99; H, 5.50; N, 6.55%. Found: C, 73.10;
H, 5.54; N, 6.52%. 19: [a]D +74.1 (c 0.10, CHCl3); 1H
NMR (360 MHz, CDCl3): d 5.71 (d, 1H, 3J1,2 = 3.9 Hz, H-
14. Characteristic 13C NMR (90 MHz, CDCl3) data of
compounds 5–8: 5: d 91.4 (C-1), 56.1 (C-2). Anal. Calcd
for C26H25N3O4S (475.56): C, 65.67; H, 5.30; N, 8.84%.
Found: C, 65.90; H, 5.29; N, 8.87%. 6: d 90.9 (C-1), 54.7
(C-2). Anal. Calcd for C26H25N3O4S (475.56): C, 65.67; H,
5.30; N, 8.84%. Found: C, 65.62; H, 5.35; N, 8.90%. 7: d
90.7 (C-1), 54.3 (C-2). Anal. Calcd for C26H25N3O4S
(475.56): C, 65.67; H, 5.30; N, 8.84%. Found: C, 65.81; H,
5.33; N, 8.79%. 8: d 88.2 (C-1), 59.0 (C-2). Anal. Calcd for
C26H25N3O4S (475.56): C, 65.67; H, 5.30; N, 8.84%.
Found: C, 65.74; H, 5.21; N, 8.80%.
3
3
1), 3.38 (dd, 1H, J1,2 = 3.9 Hz, J2,3 = 10.5 Hz, H-2); 13C
NMR (90 MHz, CDCl3): d 88.5 (C-1), 62.8 (C-2). Anal.
Calcd for C20H20N3NaO7S (469.44): C, 51.17; H, 4.29; N,
8.95%. Found: C, 51.06; H, 4.25; N, 8.91%. 21: [a]D +123.9
1
(c 0.73, CHCl3); H NMR (360 MHz, CDCl3): d 3.47 (d,
1H, J1,2 = 1.3 Hz, H-1), 3.06 (dd, 1H, J1,2 = 1.3 Hz,
3
3
3J2,3 = 4.7 Hz, H-2); 13C NMR (90 MHz, CDCl3): d 91.1
(C-1), 50.2 (C-2), JC1,H1 = 172.2 Hz. Anal. Calcd for
1
15. Physical, selected 1H and 13C NMR data for compounds 9–
10: 9: [a]D ꢀ15.9 (c 0.19, CHCl3); 1H NMR (360 MHz,
CDCl3): d 5.30 (t, 1H, 3J1,2 = 3JH1,NH = 10.2 Hz, H-1), 2.97
C39H35N3O4S (641.78): C, 72.99; H, 5.50; N, 6.55%.
Found: C, 73.12; H, 5.44; N, 6.61%. 22: [a]D +55.7 (c 0.13,
CHCl3); 1H NMR (360 MHz, CDCl3): d 6.27 (br s, 1H, H-
3
3
(t, 1H, J1,2 = 3J2,3 = 10.2 Hz, H-2); 13C NMR (90 MHz,
1), 3.62 (br d, 1H, J2,3 = 5.3 Hz, H-2); 13C NMR
CDCl3): d 80.7 (C-1), 56.1 (C-2). Anal. Calcd for
C28H29NO5S (491.60): C, 68.41; H, 5.95; N, 2.85%. Found:
C, 68.66; H, 5.81; N, 2.79%. 10: [a]D ꢀ14.1 (c 0.13, CHCl3);
(90 MHz, CDCl3): d 89.5 (C-1), 61.8 (C-2). Anal. Calcd
for C20H20N3NaO7S (469.44): C, 51.17; H, 4.29; N, 8.95%.
Found: C, 51.09; H, 4.27; N, 8.90%.