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

The reaction between allylmagnesium bromide and imines 5a-l leads to the corresponding 4-substituted 4- N-benzy- laminobut-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-substi- tuted 6-exo-phenyl-1-aza-7-oxabicyclo(2.2.1)heptanes 8a-j. Re- ductive 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 den- drobatid frog alkaloid 241D.