A new approach to (S)-4-hydroxy-2-pyrrolidinone and its 3-substituted analogues

Successive treatment of a phenyl thioether derived from (S)-malic acid with n-BuLi, lithium naphthalenide (LN), and electrophiles led to 4-hydroxy-3-s ubstituted 2-pyrrolidinones in one-pot and in high regio- and diastereosele ctivity at C-3. N-Debenzylation of 1-benzyl-4-hydroxy-2-pyrrolidinone using LN afforded naturally occurring (-)-(S)-4-hydroxy-2-pyrrolidinone. (-)-(3S ,4S)-4-Hydroxy-3-methyl-2-pyrrolidinone, the lactam form of the y-amino aci d residue found in marine natural products, bistramides, was prepared by th e same method. (C) 1999 Elsevier Science Ltd. All rights reserved.