SYNTHESIS OF (2S,4S,5S)-5-HYDROXY-4-METHYLPIPECOLIC ACID VIA AMIDE METHYLENATION OF 5-HYDROXY-4-METHYL-2-PIPERIDINONE WITH DIMETHYLTITANOCENE

(4S,5S)-5-hydroxy-4-methylpiperidine-2-one 4, readily available from S -glutamic acid, serves as a starting material for the synthesis of (2S ,4S,SS)-5-hydroxy-4-methylpipecolic acid 12. The key step of this reac tion sequence is the chemoselective methylenation of the amide carbony l group of 6 with dimethyltitanocene to the exocyclic enecarbamate 7. Hydroboration/oxidation of the double bond resulted in the formation o f all-cis alcohol 8 which was transformed via aldehyde to 12. (C) 1997 Elsevier Science Ltd.