Synthesis of α‐Fluoroketones from Carboxylic Acids via Decarboxylation of Fluorinated Malonates

Abstract

Listen

Translate article

α‐Fluoroketones are versatile intermediates in the synthesis of fluorinated heterocycles and other fluorine‐containing building blocks. We have recently disclosed a novel route to such an α‐fluoroketone using the corresponding benzoic acid as a starting material. The reaction sequence started with the CDI‐activation of the carboxylic acid and its acylation with diethyl malonate, fluorination of the resulting acyl malonate with Selectfluor, and finally a double‐decarboxylation to provide the desired α‐fluoroketone in 73% yield over three telescoped steps. We were interested in the generality of this approach to access α‐fluoroketones from readily available carboxylic acids. In this article, we disclose the crucial modifications of the reaction conditions that were needed to make them broadly applicable to a diverse array of carboxylic acids. Under the optimized conditions, a wide range of α‐fluoroketones were isolated in good to excellent yields and in high purity.