An easy access to protected (4S, 5R)-5-alkyl-4-hydroxy-2-pyrrolidinones and their use as versatile synthetic intermediates

✍ Scribed by Pei Qiang Huang; Shi Li Wang; Jian Liang Ye; Yuan Ping Ruan; You Qing Huang; Hong Zheng; Jing Xing Gao

• Book ID: 104208838
• Publisher: Elsevier Science
• Year: 1998
• Tongue: French
• Weight: 741 KB
• Volume: 54
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(98)00734-0

✦ Synopsis

A versatile approach to enantiopure (4S, 5R)-5-alkyl-4-hydroxy-2-pyrrolidinones is described. The key steps involve a regioselective Grignard reagent addition to (S)-malimides, and diastereoselective reductive dehydroxylation of the resulting hemi-azaketais. The flexibility of this methodology has been demonstrated by the synthesis of (21L 3R)-3-amino-l-benzyl-2methylpyrrolidine, the parent diamine of antipsychotic agent, emonapride, and the unnatural enantiomer of the 13-hydroxy-)'-amino acid residue of hapalosin in lactam form.