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

Abstract

α-Fluoroketones are versatile intermediates for 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 reaction 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.