(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,5S)-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.

中文翻译：

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5-羟基-4-甲基-2-哌啶酮与二甲基噻吩的酰胺甲基化反应合成（2 S，4 S，5 S）-5-羟基-4-甲基哌酸

易于从S-谷氨酸获得的（4S，5S）-5-羟基-4-甲基哌啶-2-酮4用作合成（2 S，4 S，5 S）-5-羟基的原料-4-甲基哌酸12。该反应顺序的关键步骤是将6的酰胺羰基与二甲基噻吩并茂进行化学选择性的亚甲基化，生成环外的氨基甲酸酯7。双键的硼氢化/氧化导致形成全顺式醇8，其通过醛转化为12。