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Synthesis 2002(6): 0771-0783
DOI: 10.1055/s-2002-25770
PAPER
© Georg Thieme Verlag Stuttgart · New York

An Improved and Stereoselective Route to All-cis-2,6-Disubstituted 4-Hydroxypiperidines from Accessible 4-Substituted 4-N-Benzylaminobut-1-enes

Alexey Varlamov*a, Vladimir Kouznetsov*b, Fedor Zubkov*a, Alexey Chernysheva, Olga Shurupovaa, Leonor Y. Vargas Méndezb, Alirio Palma Rodríguezb, Juliette Rivero Castrob, Alfredo J. Rosas-Romeroc
a Department of Organic Chemistry, Russian Peoples Friendship University, 3 Ordzhonikidze St., 117419, Moscow, Russia
Fax: +7(95)9540336; e-Mail: fzubkov@sci.pfu.edu.ru;
b Research Center for Biomolecules, Laboratory of Fine Organic Synthesis, School of Chemistry, Industrial University of Santander, A.A. 678, Bucaramanga, Colombia
Fax: +57(76)349069; e-Mail: kouznet@uis.edu.co;
c Department of Chemistry, Simon Bolivar University, Caracas 1080A,Venezuela
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Received 9 June 2001
Publikationsdatum:
26. April 2002 (online)

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Abstract

The reaction between allylmagnesium bromide and imin­es 5a-l leads to the corresponding 4-substituted 4-N-benzylaminobut-1-enes 6a-l, which were oxidized in a regioselective manner to the alkenylnitrones 7a-l. The intramolecular 1,3-dipolar cycloaddition of these nitrones gave 2-spiroannulated or 2-substituted 6-exo-phenyl-1-aza-7-oxabicyclo[2.2.1]heptanes 8a-j. Reductive cleavage of the N-O bond of the obtained bicycles afforded the diverse substituted 4-hydroxypiperidines 9a-h in good yields. This stereoselective approach allowed the preparation of all-cis-4-hydroxy-6-phenyl-2-nonylpiperidine (9i), a close analogue of dendrobatid frog alkaloid 241D.

Key words

homoallylamines - nitrones - stereoselective intramolecular 1,3-dipolar cycloadditions - 1-aza-7-oxabicyclo[2.2.1]heptanes - 4-hydroxypiperidines - 4-hydroxy-2-spiropiperidines

34

The detailed results from these studies will be published elsewhere.

35

The exact composition of the formed stereoisomeric mixtures has not been studied.

37

The reaction conditions used (20 °C) allow the oxidation of the homoallylamines.