S. Manabe, J.-i. Yoshida et al.
various temperatures (from À808C to 08C), indicated that 2 was convert-
ed to glycosyl sulfonium ions as a mixture of a- and b-isomers (3a/3b
45:55). The reaction mixture was warmed to room temperature and then
MeOH (2 mL, 0.05 mmol) was added under an argon atmosphere. During
the NMR measurement, which was carried out at room temperature for
1 day, the glycosyl sulfonium ion 3a and 3b was converted to a mixture
of a- and b-isomers of the methyl glycoside (4a/4b 41:59).
(3,4,6-Tri-O-acetyl-2-azido-2-deoxy-a-d-glucopyranosyl)dimethylsulfon-
AHCTUNGTRENNUNG
ium ion (3a): Selected data for 3a (6.5–2.9 ppm for 1H NMR at 08C,
100–55 ppm for 13C NMR at À408C). 1H NMR (CD2Cl2, 600 MHz): d=
6.26 (d, J=4.8 Hz, 1H, H-1), 5.33 (dd, J=8.3, 6.9 Hz, 1H, H-3), 5.04 (dd,
J=7.6, 6.9 Hz, 1H, H-4), 4.62 (dd, J=7.6, 4.8 Hz, 1H, H-2), 4.24–4.21
(m, 1H, H-6), 4.16 (dd, J=12.4, 2.0 Hz, 1H, H-6’), 4.13–4.11 (m, 1H, H-
5), 3.16 (s, 3H, SCH3), 2.94 ppm (s, 3H, SCH3); 13C NMR (CD2Cl2,
150 MHz): d=90.0 (C-1), 73.9 (C-5), 70.5 (C-3), 66.3 (C-4), 61.6 (C-6),
58.5 ppm (C-2).
(3,4,6-Tri-O-acetyl-2-azido-2-deoxy-b-d-glucopyranosyl) dimethylsulfon-
AHCTUNGTRENNUNG
ium ion (3b): Selected data for 3b (6.5–2.9 ppm for 1H NMR at 08C,
100–55 ppm for 13C NMR at À408C). 1H NMR (CD2Cl2, 600 MHz): d=
5.42 (d, J=10.3 Hz, 1H, H-1), 5.38 (pseudo t, J=9.6 Hz, 1H, H-3), 5.12–
5.09 (m, 1H, H-4), 4.24–4.21 (m, 3H), 4.02 (dd, J=10.3, 9.6 Hz, 1H, H-
2), 3.10 (s, 3H, SCH3), 2.96 ppm (s, 3H, SCH3); 13C NMR (CD2Cl2,
150 MHz): d=81.4 (C-1), 76.7 (C-5), 73.9 (C-3), 66.5 (C-4), 60.7 (C-6),
58.6 ppm (C-2); LRMS (CS): m/z: calcd for C14H22N3O7S [M]+, 376.12;
found, 376.19. Further details are given in the Supporting Information.
Figure 4. The time-course 1H NMR spectra of the reaction between the
glycosyl sulfonium ions 3a/3b and MeOH (600 MHz, CD2Cl2, room tem-
perature). The blue peaks indicate H-1, H-2, and H-4 of the a-glycosyl
sulfonium ion 3a. The red peaks indicate H-1, H-2, and H-4 of the b-gly-
cosyl sulfonium ion 3b.
of glycosyl triflate 2 (4a/4b 13:87).[8] On the other hand, the
reaction may proceed by a contact ion pair (CIP) mechanis-
m[11a] or an SN2 like mechanism in the case of the glycosyla-
tion of glycosyl triflate 2, although more data should be ac-
cumulated before the elucidation of a detailed mechanism.
In conclusion, both a- and b-glycosyl sulfonium ions were
successfully produced from an electrochemically generated
glycosyl triflate and were characterized by NMR spectrosco-
py and mass spectrometry. The time-course NMR study for
the reaction with MeOH clearly revealed that the a-glycosyl
sulfonium ion is more reactive than the b-glycosyl sulfonium
ion. The stereochemical outcome indicates that the reaction
does not proceed by a simple SN2 mechanism. Rather, the
reaction seems to proceed via an glycosyl cation intermedi-
ate. We believe that the present observations will make a
significant contribution to mechanistic studies on glycosyla-
tion reactions. Further work aimed at the elucidation of the
stereochemistry and reactivity of various glycosyl sulfonium
ions is currently in progress.
Acknowledgements
This research was partially supported by Grants-in Aid for Scientific Re-
search (Grant No. 19590032, 17205012, and 20245008) from the JSPS, In-
centive Research Grant from RIKEN (S.M.), and a Grant-in-Aid for the
Global COE Program, from the MEXT, Japan. T.N. thanks Meiji Seika
Kaisha, Ltd. for financial support. S.M. thanks Ms. Akemi Takahashi for
her technical assistance.
Keywords: carbohydrates
·
glycosylation
·
NMR
spectroscopy · oxidation · stereochemistry
b) A. R. Vaino, S. S. C. Chan, W. A. Szarek, G. R. J. Thatcher, J.
Batchelor, D. F. Green, B. D. Johnston, B. O. Patrick, B. M. Pinto,
[4] T. Nokami, A. Shibuya, H. Tsuyama, S. Suga, A. A. Bowers, D.
667–690; c) S. Yamago, T. Yamada, T. Maruyama, J. Yoshida,
4198; e) A. Rencurosi, L. Lay, G. Russo, E. Caneva, L. Poletti, Car-
Experimental Section
The anodic oxidation was carried out in an H-type divided cell (4G glass
filter) equipped with a carbon felt anode and a platinum plate cathode.
In the anodic chamber were placed the thioglycoside
1 (43.4 mg,
0.0992 mmol) and 0.1m Bu4NOTf in CD2Cl2 (5.0 mL). In the cathodic
chamber were placed trifluoromethanesulfonic acid (22 mL, 0.25 mmol)
and 0.1m Bu4NOTf in CD2Cl2 (5.0 mL). The constant current electrolysis
(4.0 mA) was carried out at À788C with magnetic stirring. After
1.5 FmolÀ1 of electricity was consumed, the reaction mixture in the
anodic chamber was transferred to a 5 mm NMR tube with a septum cap
under an argon atmosphere at À788C. After the NMR measurement of
triflate 2, dimethyl sulfide (5 mL, 0.05 mmol) was added under an argon
atmosphere at À788C. The NMR measurement, which was carried out at
2254
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2252 – 2255