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

Article abstract of DOI:10.1021/jo010439p

A general route to enantiopure spirocarbocycles is described. The use of various chiral bicyclic lactams 1 that have been doubly alkylated with olefinic halides gives good yields of α,α-disubstituted chiral lactams 2 which were cyclized to spiro-olefins using ring closure metathesis methodology (Grubbs' catalyst). These spirolactams 3, formed in generally excellent yields, were shown to be smoothly transformed into spirocyclopentenone 6, spirocyclohexenone, 7, and spirolactams 8. Further demonstration of this spirocyclization methodology was featured in a formal synthesis of zizaene, by preparing in enantiomeric form the Coates' intermediate 21. This synthetic effort provided additional examples of the synthetic versatility of chiral bicyclic lactams 2a,b.