ENANTIOSELECTIVE SYNTHESES OF 2-ALKYLPIPERIDINES, 2,6-DIALKYLPIPERIDINES AND INDOLIZIDINE ALKALOIDS THROUGH DIASTEREOSELECTIVE MANNICH-MICHAEL REACTIONS

Aldimines of 2,3,4,6-tetra-O-pivaloyl-beta-D-galactosylamine react wit h 1-methoxy-3-trimethylsilyloxybuta-1,3-diene in a Mannich-Michael con densation reaction sequence to give 2-substituted N-galactosyl-5,6-deh ydropiperidin-4-ones 3 with high diastereoselectivity. The X-ray analy sis of the 2-propyl derivative 3a proved (R)-configuration of the majo r diastereomer and led to the correction of our earlier assignment of configuration for (-)-coniine hydrochloride 9a obtained from this inte rmediate. Despite their low reactivity, these enaminones 3 can be conv erted into chiral 2,6-cis-disubstituted piperidinones 12 with high ste reoselectivity by reaction with ogano-cuprates in combination with har d electrophiles. Enantiomerically pure alkaloids such as (-)-dihydropi nidine and gephyrotoxine 167B have been synthesized according to this methodology.