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.