# Direct Fluoroformylation of the C3‐Position of Indoles with 2,4‐Dinitro(trifluoromethoxy)benzene as Fluorocarbonyl Source

## TL;DR

A new metal-free method for adding a fluorocarbonyl group to indoles and similar compounds is developed, avoiding toxic reagents and high pressures.

## Contribution

A metal-free, rapid fluoroformylation method using DNTFB as a fluorocarbonyl source is introduced for C3-position of indoles.

## Key findings

- Fluoroformylation of indoles is achieved without metal catalysts or carboxylic acids.
- The method uses 2,4-dinitro(trifluoromethoxy)benzene (DNTFB) to generate fluorophosgene in situ.
- The process can be combined with amidification in a one-pot reaction.

## Abstract

We herein report the direct fluoroformylation of indoles and other heteroaromatic cycles. Acyl fluorides are very useful moieties in coupling reactions with or without metal. However, they are usually obtained from the corresponding carboxylic acids or from aryl halides in pallado‐catalyzed carbonylation/fluorination reactions. Our method uses fluorophosgene generated in situ from 2,4‐dinitro(trifluoromethoxy)benzene (DNTFB) as a fluoroformylating agent without any metal and from carboxylic acid‐free heteroaromatic rings. Moreover, our method can be telescoped with amidification reactions in a one‐pot process.

Indoles bearing acyl fluoride moieties are generally obtained by dehydroxyfluorination of carboxylic acids or by fluoroformylation mediated by palladium catalysts with the disadvantage of requiring toxic reagents or very high pressures. We describe herein the direct, metal‐free, and rapid C3‐fluoroformylation of electro‐enriched indoles using fluorophosgene generated in situ by the degradation of trifluoromethoxide anion obtained from 2,4‐dinitro‐1‐(trifluoromethoxy)benzene (DNTFB).© 2026 WILEY‐VCH GmbH