Vicinal Bis(methylene) Heterocyclic Diene in Natural Product Synthesis: A Convergent Biomimetic Total Synthesis of Prunolactone A

The first total syntheses
of the natural isocoumarin
prunolactone
A with a 6/6/6/6/6 spiropentacyclic skeleton and its unnatural (3′R)-epimer in 10 and 8 steps, respectively, are reported.
The syntheses feature in situ generation of a reactive
3,4-bis­(methylene)­isocoumarin intermediate, its biomimetic Diels–Alder
reactions with the shikimic-acid-derived scytolide and (8R)-scytolide, and a Mitsunobu reaction allowing access to scytolide
in a stereochemically pure form. Computational support for the selectivity
of the Diels–Alder reaction is provided.