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Bourgouin, A. Chem. Lett. 1974, 109, and Tetrahedron
1975, 31, 1047.
5. (a) Corey, E. J.; Nicolaou, K. C.; Melvin, L. S., Jr. J. Am.
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Ind. (London) 1956, 1526.
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2163; (b) Swarbrick, M. E.; Gosselin, F.; Lubell, W. D. J.
Org. Chem. 1999, 64, 1993; (c) Gosselin, F.; Lubell, W. D.
J. Org. Chem. 1998, 63, 7463.
ꢀ
7. (a) Gryko, D.; Urbanczyk-Lipkowska, Z.; Jurczak, J.
Tetrahedron: Asymmetry 1997, 8, 4059; (b) Reetz, M. T.;
tendency towards self-metathesis of 11 is based on the
high steric demand of the bulky TMS-group. Using
5 mol % of [Ru], the mixed CM product 19 could be
obtained in good yield. TMS-ether 11 was employed in a
slight excess of 1.2 equiv in order to suppress homo-
dimerization of 18, which occurred to a small extent as
the major side reaction in this CM. Subsequent treat-
ment of the crude product with TBAF furnished alcohol
20 in diastereomerically pure form.20 Treatment of 20
with Pd/C under a hydrogen atmosphere afforded (+)-
carpamic acid methyl ester 21 quantitatively and with
complete stereoselectivity. Subsequent saponification
furnished (+)-carpamic acid 2. Spectral and analytical
data were consistent with those reported in the litera-
ture.4c;f
€
Rofling, K.; Griebenow, N. Tetrahedron Lett. 1994, 35,
1969; (c) Thompson, W. J.; Tucker, T. J.; Schwering, J. E.;
Barnes, J. L. Tetrahedron Lett. 1990, 31, 6819; (d) Ibuka,
T.; Habashita, H.; Otaka, A.; Fuji, N. J. Org. Chem. 1989,
54, 5409; (e) Hanson, G. J.; Lindberg, T. J. Org. Chem.
1985, 50, 5399.
8. syn/anti-Nomenclature according to Masamune: (a) Masa-
mune, S.; Ali, S. A.; Snitman, D. L.; Garvey, D. S. Angew.
Chem., Int. Ed. Engl. 1980, 19, 557; (b) Masamune, S.;
Kaiho, T.; Garvey, D. S. J. Am. Chem. Soc. 1982, 104,
5521.
9. Ibuka, T.; Habashita, H.; Otaka, A.; Fujii, N.; Oguchi, Y.;
Uyehara, T.; Yamamoto, Y. J. Org. Chem. 1991, 56, 4370.
10. Angle et al. reported the same diastereoselectivity of syn/
anti 8:1. They speculated that the source of the Grignard
reagent may be responsible for this: Angle, S. R.;
Breitenbucher, J. G.; Arnaiz, D. O. J. Org. Chem. 1992,
57, 5947.
In summary, we have described a concise and highly
efficient total synthesis of (+)-carpamic acid. The key
steps of our convergent synthesis were the highly dia-
stereoselective vinylation of aldehyde 9, a selective CM
reaction and the reductive cyclization of aminoketone
20. Given the high functional group tolerance of the Ru
metathesis catalysts, our concept of CM in combination
with a subsequent cyclizing reductive amination in
general opens up a facile entry into the class of cis-2,6-
disubstituted piperidines. Further syntheses based on
this strategy are currently underway in our laboratories
and will be reported in due course.
11. Franciotti, M.; Mann, A.; Taddei, M. Tetrahedron Lett.
1991, 32, 6783.
12. (a) Seyferth, D.; Wursthorn, K. R.; Mammarella, R. E.
J. Org. Chem. 1977, 42, 3104; (b) Seyferth, D.; Wursthorn,
K. R.; Lim, T. F. O.; Sepelak, D. J. J. Organomet. Chem.
1979, 181, 293; (c) Fleming, I.; Paterson, I. Synthesis 1979,
446.
Acknowledgements
Financial support from the ÔFonds der chemischen
IndustrieÕ is gratefully acknowledged. S.R. thanks the
Graduiertenkolleg ÔSynthetische, mechanistische und
reaktionstechnische Aspekte von MetallkatalysatorenÕ
for a stipend.
13. Reactions of this type had previously been reported by
Tokoroyama et al.: (a) Tsukamoto, M.; Iio, H.; Tokoro-
yama, T. Tetrahedron Lett. 1985, 26, 4471; (b) Iio, H.;
Mizobuchi, T.; Tsukamoto, M.; Tokoroyama, T. Tetra-
hedron Lett. 1986, 27, 6373; (c) Tsukamoto, M.; Iio, H.;
Tokoroyama, T. Tetrahedron Lett. 1987, 28, 4561.
14. Desilylation of a mixture of isomers 11 syn/anti 4:1, which
was obtained via column chromatography, afforded 12 as
a mixture of syn/anti 18:1. Since after the reaction, the
anti-isomer 11 was no longer detected in the reaction
mixture, the change in ratio of the diastereomers is not
based on kinetic reasons. The product(s) formed from
anti-11 could not be determined.
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