Asymmetric synthesis of 6-alkyl- and 6-arylpiperidin-2-ones. Enantioselective synthesis of (S)-(+)-coniine.
A variety of diolefinic hydrazides (1) have been assembled in a highly diastereoselective manner by addition of allyllithium to chiral SAMP hydrazones followed by N-acylation with acryloyl chloride. Substrates 1 undergo ring-closing metathesis to give the cyclic enehydrazides (5) which can be easily converted into virtually enantiopure 6-alkyl- or 6-arylpiperidin-2-ones (7). The versatility of this hydrazone addition-RCM protocol has been further exemplified by the conversion of the unsaturated heterocycle 5b into the piperidine alkaloid (S)-(+)-coniine.
Lebrun
Stéphane
S
UMR 8009 Chimie Organique et Macromoléculaire, Laboratoire de Chimie Organique Physique, Bâtiment C3(2), Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France.
Couture
Axel
A
Deniau
Eric
E
Grandclaudon
Pierre
P