The Castle Synthesis of - -Acutumine

A central step in the synthesis of 3 was the spirocychzation of 7 to 8. Initially, iodine atom abstraction generated the aryl radical. The diastereoselectivity of the radical addition to the 

Oxidative cleavage to the aldehyde followed by reductive amination gave 10, that looks as though it could be poised for intramolecular displacement of the secondary chloride. Nonetheless, Lewis acid mediated ionization followed by cyclization proceeded smoothly, to establish the fourth ring of the natural product. Oxidation state adjustment then completed the synthesis of (-)-Acutumine 3. 

The face selective enone allylation followed by oxy-Cope rearrangement (1 — 2), a highlight of the approach presented here, will have many applications in target-directed synthesis. 

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