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Enantioselective Double Michael Addition/Cyclization with an Oxygen-Centered Nucleophile as the First Step in a Concise Synthesis of Natural (+)-Asteriscanolide

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journal contribution
posted on 11.03.2000, 00:00 by Leo A. Paquette, Jinsung Tae, Mark P. Arrington, Aladin H. Sadoun
The total synthesis of (+)-asteriscanolide (1) starting from 2-bromo-4,4-dimethylcyclopentenone has been accomplished. The synthetic route features two key steps. The first step is an unprecedented Michael−Michael reaction sequence that involves a heteronucleophile and proceeds with complete asymmetric induction. The two five-membered rings of the target molecule are thereby generated enantioselectively in a single laboratory step. The second step is based on utilization of ring-closing metathesis to provide an eight-membered ring in which a conjugated 1,3-diene unit resides. Other features of the synthetic stratagem involve the utilization of singlet oxygen in a regiocontrolled ene reaction, the fully stereocontrolled hydrogenation of a dienone, and a chemoselective ruthenium tetraoxide oxidation.