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Studies toward the Total Synthesis of Dumsin. 2. A Second Generation Approach Resulting in Enantioselective Construction of a Functionalized ABC Subunit of the Tetranortriterpenoid Insect Antifeedant

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posted on 05.01.2007 by Leo A. Paquette, Yang Hu, Andreas Luxenburger, Raynauld L. Bishop
A synthesis of the ABC framework of dumsin is described. The optically active intermediate 9b, which is expeditiously assembled from 5-oxobornyl pivalate by the sequential implementation of an oxy-Cope rearrangement and an intramolecular ene reaction, proved to be suitably functionalized for ultimate conversion to 5. The synthesis plan relies on two approaches to this targeted intermediate. In the first, the exocyclic double bond introduced during EtAlCl2-promoted closure of aldehyde 10b is cleaved to leave a carbonyl group that is amenable to hydride reduction and elimination of water. Cleavage of the resulting double bond with ruthenium tetroxide provided the seco ketoacid. The same advanced intermediate was obtained by initially positioning the double bond internal to the five-membered ring in advance of transient ring expansion via diketone formation and intramolecular aldolization. Both of these approaches bypass the complications arising from the substantial steric congestion prevailing in these structural networks. The task of covalently positioning an oxygen atom adjacent to the gem-dimethyl-substituted carbon in 5 was properly realized by oxidative decarboxylation. The stereochemical assignments to many of the intermediates were confirmed by an X-ray crystallographic analysis of 43.