LETTER
A New Route to Iminosugars via Cyclic Sulfates
1361
(16) Jaeger, V.; Mueller, I.; Paulus, E. F. Tetrahedron Lett. 1985,
26, 2997.
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1995, 60, 6302.
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Asymmetry 1995, 6, 1035.
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314, 25.
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Chem., Int. Ed. Engl. 1994, 33, 1295.
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H.; Bolte, J. J. Org. Chem. 2001, 66, 2296.
The sulfate group of piperidine 15 was removed with con-
centrated H2SO4 and water in dioxane28 (Scheme 3). The
piperidine 17 was isolated in 82% yield. The piperidine
( )-4 was obtained in 38% yield (not optimized) after
hydrogenolysis of the benzyl protecting group over Pd/C
in the presence of acetic acid.29 Analytical data were
identical to those described for compound 4.11 Following
the same procedure, the zwitterionic piperidine 18 was
isolated in 90% yield. All piperidines were characterized
and their analytical data are in agreement with the pro-
posed structures.30
(23) Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82,
5339.
(24) Kantorowski, E. J.; Brown, S. P.; Kurth, M. J. J. Org. Chem.
1998, 63, 5272.
(25) Byun, H. S.; He, L. L.; Bittman, R. Tetrahedron 2000, 56,
7051.
(26) Gao, Y.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110,
7538.
(27) Typical Procedure for Preparation of 15. A solution of 13
(1.08 g, 3.45 mmol) in anhyd MeOH (50 mL) was stirred
under H2 in the presence of 10% Pd/C (500 mg) and anhyd
Na2CO3 (183 mg, 1.73 mmol) for 6 h. The solids were
removed by filtration through a membrane filter (0.2 m)
and the filtrate concentrated under vacuum. The residue was
neutralized with HCl 1N, then purified over an acidic resin
(Dowex 50WX8, 200-400 mesh) using water as eluent.
Compound 15 was isolated as a white solid in 82% yield
(892 mg).
In conclusion, we have opened a new route to trihydroxy-
lated piperidines with access to various configurations;
four new analogs of natural compounds such as DNJ and
DMJ were isolated. Our approach, with a highly stereo-
and regioselective key step, offers simple procedures and
acceptable chemical yields. As no racemization steps can
occur in our methodology, this should lead easily to enan-
tiomerically pure compounds starting from the already de-
scribed isoxazolines 9 and 10.22 Preparation of such
compounds and their evaluation as glycosidase inhibitors
are under investigation. We plan to extend this methodol-
ogy to chiral alkenes and other nitro compounds to have
access to chiral piperidines and other functionalities (R
group shown in structure A, Scheme 1).
Acknowledgement
(28) Barco, A.; Benetti, S.; De Risi, C.; Marchetti, P.; Pollini, G.
P.; Zanirato, V. Tetrahedron 1999, 55, 5923.
(29) Ghavami, A.; Johnston, B. D.; Pinto, B. M. J. Org. Chem.
2001, 66, 2312.
We thank the Centre National de la Recherche Scientifique (CN-
RS), France, for the award of a research fellowship (EG) and the
Université Blaise Pascal for financial support.
(30) All new compounds reported here were racemic and gave
satisfactory spectral data (1H and 13C NMR, IR, mass).
Selected spectral data (1H and 13C), 15: 1H NMR (300 MHz,
D2O): = 1.78 (ddd, 1 H, J = 13 Hz), 1.96 (ddd, 1 H, J = 13,
3.5, 3.5 Hz), 3.24 (dd, 1 H, J = 14, 1 Hz), 3.52 (m, 1 H), 3.63
(dd, 1 H, J = 11, 8 Hz), 3.71 (dd, 1 H, J = 11, 8 Hz), 3.81
(dd, 1 H, J = 14, 3 Hz), 4.03 (ddd, 1 H, J = 13, 3.5, 3.5 Hz),
4.61 (s, 2 H), 4.75 (m, 1 H), 7.43 (m, 5 H). 13C NMR (100
MHz, D2O): = 30.3 (C4), 48.6 (C1), 57.8 (C5), 66.9 (C3),
71.8 (C6 or C7), 75.7 (C2), 75.9 (C7 or C6), 131.3–131.6
(C9-10-11), 139.8 (C8). 17: 1H NMR (300 MHz, D2O): = 1.86
(AB, 1 H, J = 13 Hz), 1.91 (AB, 1 H), 3.21 (dd, 1 H, J = 14,
1 Hz), 3.46 (dd, 1 H, J = 14, 3 Hz), 3.53 (m, 1 H), 3.66 (dd,
1 H, J = 11, 8 Hz), 3.75 (dd, 1 H, J = 11, 4 Hz), 3.99 (m, 1
H), 4.17 (m, 1 H), 4.65 (s, 2 H), 7.46 (m, 5 H). 13C NMR (75
MHz, D2O): = 29.8 (C4), 50.9 (C1), 57.9 (C5), 67.6 (C3),
69.6 (C2), 72.0 (C6 or C7), 76.0 (C6 or C7), 131.4–131.7
(C9-10-11), 140.0 (C8). 18: 1H NMR (300 MHz, D2O): = 1.80
(ddd, 1 H, J = 13 Hz), 2.00 (ddd, 1 H, J = 13, 3.5, 3.5 Hz),
3.28 (dd, 1 H, J = 14, 1 Hz), 3.42 (dddd, 1 H, J = 13, 8, 4, 3.5
Hz), 3.68 (dd, 1 H, J = 12.5, 8 Hz), 3.81 (dd, 1 H, J = 12.5,
4 Hz), 3.86 (dd, 1 H, J = 14, 3 Hz), 4.08 (ddd, 1 H, J = 13,
References
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4.5, 3.5 Hz), 4.79 (m, 1 H). 13C NMR (75 MHz, D2O):
30.1 (C4), 48.5 (C1), 59.7 (C5), 64.0 (C6), 68.5 (C3), 75.6
=
(C2). 16: 1H NMR (400 MHz, (CD3)2SO): = 1.42 (ddd, 1
H, J = 13, 13, 13 Hz), 2.00 (ddd, 1 H, J = 13, 4.5, 4.5 Hz),
2.81 (dd, 1 H, J = 13, 11 Hz), 3.40 (m, 1 H), 3.50 (m, 1 H),
3.56–3.80 (m, 3 H), 4.12 (m, 1 H), 4.55 (AB, 2 H, J = 12 Hz),
7.36 (m, 5 H). 13C NMR (100 MHz, D2O): = 32.2 (C4), 44.7
(C1), 53.7 (C5), 68.1 (C3), 69.6 (C6), 72.6 (C7), 74.4 (C2),
127.9–128.6 (C9-10-11), 137.9 (C8).
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Synlett 2002, No. 8, 1359–1361 ISSN 0936-5214 © Thieme Stuttgart · New York