Total Synthesis of Mycophenolic Acid by a Palladium‐Catalyzed Decarboxylative Allylation and Biomimetic Aromatization Sequence

This paper describes the total synthesis of the fungal natural product mycophenolic acid through palladium-catalyzed allylation, biomimetic cyclization, and aromatization. Methyl (4E)-6-hydroxy-4-methylhex-4-enoate, which was converted in four steps into the key diketo ester dioxinone via two selective C-acylation reactions, was transformed into a resorcylate. Subsequent phenol methylation, lactonization, iodo-ether formation, and halogenation gave a tricyclic intermediate. Palladium-catalyzed cross-coupling with DABCO–(AlMe3)2 and saponification gave mycophenolic acid. An alternative approach with early stage arene methyl incorporation unexpectedly resulted in the formation of a γ-pyrone.