ASYMMETRIC CONJUGATE ADDITIONS TO CHIRAL BICYCLIC LACTAMS - SYNTHESIS OF ARACEMIC TRANS-2,3-DISUBSTITUTED PYRROLIDINES

The trans-2,3-disubstituted pyrrolidine moiety, found in the pyrrolizidine alkaloids as well as other natural products, has been accessed from the alpha,beta-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 diastereoselectivity. Other cuprates were investigated and resulted in diminished or opposite stereoselectivities. Further transformation of the beta-substituted lactams provided the title compounds in good overall yield and high enantiomeric excess.