Lewis Acid Mediated Addition of Indoles and Alcohols to Tetronic Acid and Tetramic Acids

Abstract

The electrophilic substitution of indoles with tetronic acid and N-acetyltetramic acid mediated by BF 3 •OEt 2 was investigated. This strategy allowed for the preparation of nine indole-substituted furan-2ones (indolyl-γ-lactones) and 3-pyrrolin-2-ones (indolyl-γ-lactams) and is more straightforward than previously reported synthetic methods. During the course of our investigation, we also discovered a facile synthesis of tetronates and a tetramate via a BF 3 -mediated addition of alcohols to tetronic acid and N-acetyltetramic acid, respectively.

Synthesis of β-Arylbutenolides Mediated by BF3·OMe2

“…The reaction occurs by the attack of the doubly activated position ( ortho to the OH group and para to another electron-donating group) of the aromatic ring at the tetronic acid carbonyl (ketone function). These results differ from the results obtained by Meija et al (2017), 19 who used similar experimental conditions, but the reaction occurs by the attack of oxygen from the hydroxyl of phenol to the carbonyl of tetronic acid, providing a new ether bond. In our work, the reaction proceeds through an aromatic electrophilic substitution reaction of phenol or ether aryl (with electron-donating groups) with the formation of a single product in yields ranging from 85–95%.…”

Synthesis and evaluation of the anti-proliferative activity of diaryl-3-pyrrolin-2-ones and fused analogs

“…Analogs with indole substitution at C4, 11e 28 and 17ce, were inactive, as defined as an IC 50 > 100 M. Two of the analogs with indole substitution at C3, 17ec (10 μM ± 2) and 17ed (38 μM ± 9), showed activity.…”