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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
Further Information

Publication History

Received 9 June 2001
Publication Date:
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

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The detailed results from these studies will be published elsewhere.

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

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