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

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-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.

Publisher

American Chemical Society

Publication Date

7-23-2024

Publication Title

Journal of the American Chemical Society

Department

Chemistry and Biochemistry

Document Type

Article

DOI

https://dx.doi.org/10.1021/jacs.4c07669

Keywords

Enantiospecific total-synthesis, Indole alkaloids, Stereoselective-synthesis, Gelsemium alkaloids, General-approach, Rearrangement, Configuration, Construction, Derivatives, Cyclization

Language

English

Format

text

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