Stereoselective Syntheses of cis-2-Alkyl-6-methylpiperidines

Article abstract of DOI:10.1021/jo00228a022

Syntheses in the pine alkaloid family, the fire ant venom series, and continued studies in the Poranthera species are presented.Reaction of 5-lithio-2-pentanone-2,2-dimethylpropylene ketal or the corresponding dialkylcuprate compound with carboxylic acid derivatives gives selectively protected 1,5-dicarbonyl compounds.After reductive amination of the newly formed ketone function, acidic hydrolysis of the cyclic ketal gives 6-alkyl-2-methyl-3,4,5,6-tetrahydropyridines.Stereoselective reduction of the imine function affords cis-2,6-disubstituted piperidines.Examplesof this approach include syntheses of dihydropinidine from Pinus sabiniana and the fire ant venoms cis-2-methyl-6-undecylpiperidine and 2-methyl-6-undecyl-3,4,5,6-tetrahydropyridine from Solenopis geminata and S. xyloni.A preliminary report on an approach to porantherilidine, from Poranthera corymbosa, is described.