ChemInform Abstract: The Synthesis of Aracemic 4-Substituted Pyrrolidinones and 3- Substituted Pyrrolidines. An Asymmetric Synthesis of (-)-Rolipram

Conjugate additions of RCuCNLi to the chiral α,β-unsaturated lactam 4 gives almost exclusive exo addition-a reversal in stereochemistry when cuprates were added to chiral lactam 1. The lactams 5 were transformed into 4-substituted pyrrolidinones 8 via a three-step sequence which involved decarbalkoxylation, silane reduction and metal-ammonia benzylamine cleavage. The chemical yields as well as the enantiomeric purity were very high for this process. As an example of the usefulness of this scheme, the antidepressant (-)-Rolipram was prepared in good overall yield