Biomimetic macrocycle-forming Diels-Alder reaction of an iminium dienophile: synthetic studies directed toward gymnodimine

The macrocyclic core of gymnodimine has been constructed via an intramolecular Diels-Alder reaction of an alpha,beta-unsaturated iminium dienophile in water. The cycloaddition furnished a single exo-product, along with two endo-products. Through X-ray analysis of a suitable derivative, the stereochemistry of the exo-product was established, thereby demonstrating that its stereochemistry matches that of gymnodimine. In contrast, macrocyclization of an analogous alpha,beta-unsaturated ketone dienophile gave only undesired endo-products. Interestingly, the imine dienophile shows remarkable stability in water. reaction: see text]