Stereocontrolled preparation of cis- and trans-2,6-dialkylpiperidines via diastereoselective reaction of 1-aza-4-oxabicyclo[4.3.0]nonane derivatives with Grignard reagents

Article abstract of DOI:10.1016/S0040-4020(98)00863-1

We report here the syntheses of cis- and trans-2,6-disubstituted piperidines using chiral 1-aza-4-oxabicyclo[4.3.0]nonane synthon 1, which shows high reactivity toward nucleophilic attack at its C-5 position. Bicyclic compounds resembling synthon 1 were transformed to cis- and trans- 2,6-disubstituted piperidine derivatives via reactions with various Grignard reagents in a stereospecific manner. Using this methodology, (+)-solenopsin A (2b) and both enantiomers of isosolenopsin A (3a and 3b) were synthesized in an enantioselective manner from a single enantiomeric source.