S.-S. P. Chou, C.-W. Ho / Tetrahedron Letters 46 (2005) 8551–8554
SPh
8553
H
H
(path a)
N
H
N
CH3
SPh
SPh
N
H
a
b
h
t
a
n
p
10a, n = 1 (cis
)
10b, n = 2 (cis
)
CH3
n
O
SPh
p
a
t
h
(path b)
H
n
H
CH3
5a, n = 1
5b, n = 2
5A, n = 1
5B, n = 2
N
H
n
trans (not obtained)
Scheme 1. Preferred pathway for the diastereoselective formation of cis-10a–b from 5a–b.
shows a Bohlmann band at 2783 cmꢀ1, indicating the
presence of one or more a-hydrogens oriented trans-
biaxially to the nitrogen lone pair.40,41 Likewise, for
compound 10b, the proton at C-9a (d 2.12–2.28) has
cross signals with the proton at C-6 (d 2.73–2.86) and
the Hb at C-4 (d1.79, t, J = 11.3 Hz), indicating the cis
relationship of the hydrogens at C-9a and C-6. The IR
spectrum of 10b also shows a Bohlmann band at
3. Boger, D. L.; Weinreb, S. M. Hetero Diels–Alder Meth-
odology in Organic Synthesis; Academic Press: Orlando,
1987.
4. Bailey, P. D.; Millwood, P. A.; Smith, P. D. Chem.
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5. Laschat, S.; Dickner, T. Synthesis 2000, 1781–1813.
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3588.
7. Buonora, P.; Olsen, J.-C.; Oh, T. Tetrahedron 2001, 57,
6099–6138.
2788 cmꢀ1
.
8. Chou, S. S. P.; Hung, C. C. Synth. Commun. 2001, 31,
1097–1104.
9. Chou, S. S. P.; Hung, C. C. Synth. Commun. 2002, 32,
3119–3126.
10. Chou, S. S. P.; Chen, K. W. Synth. Commun. 2004, 34,
4573–4582.
11. Gompper, R.; Heinemann, U. Angew. Chem., Int. Ed.
Engl. 1980, 19, 216–217.
To explain the stereospecific formation of cis-10a and
cis-10b, we postulated that the iminium ions 5A and
5B were first formed as the intermediate. The hydride
ion would then prefer to attack from the axial direction
due to the stereoelectronic effect (Scheme 1).42,43 In
addition, approach of the hydride from the b-face lead-
ing to a chair conformation is favored over that from the
a-face, because the latter will lead to a less stable boat
conformation.
12. Barluenga, J.; Aznar, F.; Fernandez, M. Tetrahedron Lett.
1995, 36, 6551–6554.
13. For the reaction of an aza-diene with the C@N bond of
tosyl isocyanate, see: Saito, T.; Kimura, H.; Soda, T.;
Karakasa, T. Chem. Commun. 1997, 1013–1014.
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476.
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Chem. 1978, 43, 402–405.
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8323–8326.
In summary, we have synthesized 6-substituted 2-pipe-
ridinones 3a–b from the aza-Diels–Alder reactions of 3-
sulfolenes 1a–b with p-toluenesulfonyl isocyanate, and
have successfully converted them to indolizidine 5a and
quinolizidine 5b. We have also carried out some useful
functional transformations of compounds 5a and 5b.
18. Chou, S. S. P.; Hung, C. C. Synthesis 2001, 2450–
2462.
Acknowledgements
19. Chou, S. S. P.; Chiu, H. C.; Hung, C. C. Tetrahedron Lett.
2003, 44, 4653–4655.
20. Daly, J. W.; Spande, T. F. In Alkaloids: Chemical and
Biological Perspectives; Pelletier, S. W., Ed.; Wiley: New
York, 1986; Vol. 3, Chapter 1.
Financial support of this work by the National Science
Council of the Republic of China is gratefully acknowl-
edged (NSC 93-2113-M-030-004).
21. For a recent review, see: Michael, J. P. Nat. Prod.
Rep. 2004, 21, 625–649. For some recent examples on
the synthesis of indolizidines and quinolizidines, see Refs.
22–26.
References and notes
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Preparation, Reactivity andSynthetic Applications of
Piperidine and its Derivatives; Elsevier: Amsterdam, 1991.
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Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,
1991; Vol. 5, pp 401–449.
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23. Back, T. G.; Hamilton, M. D.; Lim, V. J. J.; Parvez, M.
J. Org. Chem. 2005, 70, 967–972.
24. Patil, N. T.; Pahadi, N. K.; Yamamoto, Y. Tetrahedron
Lett. 2005, 46, 2101–2103.