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DOI: 10.1055/s-2002-25770
An Improved and Stereoselective Route to All-cis-2,6-Disubstituted 4-Hydroxypiperidines from Accessible 4-Substituted 4-N-Benzylaminobut-1-enes
Publication History
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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References
The detailed results from these studies will be published elsewhere.
35The exact composition of the formed stereoisomeric mixtures has not been studied.
37The reaction conditions used (20 °C) allow the oxidation of the homoallylamines.