An enantioselective approach to the synthesis of non natural (-)-meroq
uinene 1 based on sequential inter- and intramolecular Michael reactio
n between (L)-menthyl N-benzyl-5-amino-2E-pentenoate 3 and 1-acetyloxy
-4-methoxymethyloxy-2-nitrobutane 10b, acting as surrogate of 2-nitro-
1,3-butadiene 4, is described. The heterocyclization process led to th
e formation of the piperidine ring system 12, obtained as an unseparab
le 80:20 mixture of diastereomers at the newly created chiral centres
at C-3 and C-4, which became easily separable by column chromatography
after transformation of the nitrogen protective benzyl group into the
corresponding carbamates 14 and 15. Both compounds, after elaboration
of the chain geminal to the nitro group into a vinyl appendage, under
went regio- and stereo-selective removal of the nitro group by palladi
um-catalyzed displacement with hydride generated by formate to give th
e precursor 19, easily converted by treatment with hydrochloric acid t
o 1,isolated as hydrochloride.