Synthesis of (2S,4S,5S)-5-hydroxy-4-methylpipecolic acid via amide methylenation of 5-hydroxy-4-methyl-2-piperidinone with dimethyltitanocene

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