Synthesis of 2S,5S- and 2R,5S-5-hydroxypipecolic acid via amide-methylenation of S-5-hydroxy-2-piperidone with dimethyltitanocene

Article abstract of DOI:10.1016/S0957-4166(00)82257-0

A route to 2S,5S-hydroxypipecolic acid is presented, starting with the enantiopure 5S-5-hydroxy-piperidone 7. The key step of this reaction sequence is the chemoselective methylation of the amide carbonyl group of 8 with dimethyltitanocene 9 to 10. The tr