Himandrine skeleton

The first synthesis of the hexacyclic himandrine skeleton was achieved by L.N. Mander and co-workers. The last six-membered heterocycle was formed via an intramolecular Wacker-type oxidation in which the terminal alkene side-chain reacted with the secondary amine functionality. The oxidation was conducted in anhydrous acetonitrile to insure that the Pd-alkene complex was substituted exclusively by the internal nucleophile. The resulting six-membered enamine was then hydrogenated and the MOM protecting groups removed to give the desired final product. 

Finally, in Wander s synthesis of the hexacyclic himandrin skeleton, amino-alkene 100 was oxidized to its corresponding methyl ketone, which was trapped by nucleophilic addition of the amine.7 Dehydration of the adduct then delivered enamine 100, which possessed all six rings of the himandrine skeleton. 

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