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

21 May 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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-sulfonyl triazole. 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-sulfonyl triazole 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.

Keywords

rauvomine
indole alkaloid
total synthesis
cyclopropanation
density functional theory

Supplementary materials

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Supporting Information
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Experimental procedures, computational details, copies of NMR spectra.
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