Total Synthesis of (−)-Rauvomine B via a Strain-Promoted Intramolecular Cyclopropanation

We describe the first total synthesis of the unusual cyclopropane-containing indole alkaloid (−)-rauvomine B via a strategy centered upon intramolecular cyclopropanation of a tetracyclic N-sulfonyltriazole. Preparation of this precursor evolved through two generations of synthesis, with the ultimately successful route involving a palladium-catalyzed stereospecific allylic amination, a cis-selective Pictet–Spengler reaction, and ring-closing metathesis as important bond-forming reactions. The key cyclopropanation step was found to be highly dependent on the structure and conformational strain of the indolo­quinolizidine N-sulfonyltriazole precursor, the origins of which are explored computationally through DFT studies. Overall, our synthesis proceeds in 11 total steps and 2.4% yield from commercial materials.