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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

A route to the titled compounds in >99% ee was achieved from sequential diastereoselective alkylations of chiral, nonracemic bicyclic lactams 6 and 15. An intramolecular addition of the organolithium species derived from 17a-c and 28a-d gave, after hydrolysis, diketones 25a-c and 30a-d, which were cyclized to the titled compounds 4a-c and 31a-d. As an example of the versatility of this method, the ABC ring system of the triterpene stelliferin A, isolated from marine organisms, was prepared in high enantiomeric excess

The trans-2,3-disubstituted pyrrolidine moiety, found in the pyrrolizidine alkaloids as well as other natural product, has been accessed from the α,β-unsaturated bicyclic lactams 1d and 10. Conjugate addition of lower order cyanocuprates to lactams 1d and 10 resulted in endo entry of the cuprate with high diasterelectivity. Other cuprates were investigated and resulted in diminished or opposite stereoselectivities. Further transformation of the β-subtituted lactams provided the title compounds in good overall yield and high enantiomeric excess