The synthesis of a C31–C47 model of spirastrellolide A is reported. Key steps include an iron catalyzed cross coupling reaction to incorporate the linear side chain as a single unit, and the carbonyl ene reaction of an exocyclic enol ether to prepare the 5,6-spiroketal. A trans-ketalization from 5,6- to 6,6-spiroketal frameworks is used to facilitate stereochemical assignment.

The carbonyl ene reaction of 2-methylenetetrahydropyrans provides a rapid, high yielding route for the preparation of β-hydroxydihydropyrans under mild conditions. This process provides a new entry for the synthesis of 2-substituted tetrahydropyrans and for the direct introduction of oxygen heterocycles into molecular frameworks.

Three component coupling of a 2-methylenetetrahydropyran, an activated aldehyde or ketone and a secondary nucleophile provides an efficient preparation of tetrahydropyranyl ketides, a unit common to many complex natural products.