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

Abstract

AbstractThis 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.