An asymmetric approach to spirocylic systems: A formal synthesis of zizaene

A general route to enantiopure spirocarbocycles is described. The use of va rious chiral bicyclic lactams 1 that have been doubly alkylated with olefin ic halides gives good yields of alpha,alpha -disubstituted chiral lactams 2 which were cyclized to spiro-olefins using ring closure metathesis methodo logy (Grubbs' catalyst). These spirolactams 3, formed in generally excellen t yields, were shown to be smoothly transformed into spirocyclopentenone 6, spirocyclohexenone, 7, and spirolactams 8. Further demonstration of this s pirocyclization methodology was featured in a formal synthesis of zizaene, by preparing in enantiomeric form the Coates' intermediate 21. This synthet ic effort provided additional examples of the synthetic versatility of chir al bicyclic lactams 2a,b.