Organic Chemistry

A General Approach to 2,2-Disubstituted Indoxyls: Total Synthesis of Brevianamide A and Trigonoliimine C

Myles Smith UT Southwestern Medical Center

Abstract

The indoxyl unit is a common structural motif in alkaloid natural products and bioactive compounds. Here, we report a general method that transforms readily available 2-substituted indoles into 2,2-disubstituted indoxyls via nucleophile coupling with a 2-alkoxyindoxyl intermediate and showcase its utility in short total syntheses of the alkaloids brevianamide A (7 steps) and trigonoliimine C (6 steps). The developed method is operationally simple and demonstrates broad scope in terms of nucleophile identity and indole substitution, tolerating 2-alkyl substituents and free indole N–H groups, elements beyond the scope of most prior approaches. Spirocyclic indoxyl products are also accessible via intramolecular nucleophilic trapping.

Content

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Supplementary material

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Indoxyl SI