A novel cis-selective cyclohexanone annulation as the key step of a total synthesis of the sesquiterpene isoacanthodoral.

Isoacanthodoral (1) is a structurally unique sesquiterpene in that it is a bicyclo[4.4.0]dec-1-ene with a cis- rather than the common trans-junction between the constituting rings. An efficient construction of this motif has been accomplished by a novel cis-selective cyclohexanone annulation, combining the lithium enolate of ester 8, the alpha,beta-unsaturated ester 6, and vinylmagnesium bromide in a single synthetic operation. For completing the total synthesis of 1, a Shapiro-olefination/hydrogenation sequence and a reductive cyanation were employed.