The dimeric oroidin alkaloids, exemplified by palau’amine, axinellamine, and massadine,
remain challenging targets in the context of total synthesis owing to their compact
and heteroatom-rich frameworks. A cycloaddition-rearrangement sequence has been developed
using vinylimidazoles as substrates. The initial Diels–Alder adduct derived from urocanic
acid and N-phenylmaleimide can be transformed into a lactone via a fluoride-induced
ring-opening sequence. A twofold oxidation manifold affords the fully functionalized
cyclopentane moiety present in palau’amine and congeners. Initial explorations to
incorporate a second imidazole moiety are described.
Keywords
Cycloaddition - Oxidation - Alkaloid - Rearrangement - Ring opening
