Effect of acid catalysis on the direct electrophilic fluorination of ketones, ketals, and enamides using Selectfluor™

The fluorination of ketones, ketals, and enamides has been achieved using the electrophilic fluorinating reagent Selectfluor™ (F-TEDA-BF4). For the reactions of ketones and ketals the use of sulfuric acid (0.1 equiv) as an additive was found to facilitate the reaction leading to more rapid product formation. This behavior is analogous to the known effects of acid catalysis on the bromination of ketones. The reactions were generally quite selective leading to the formation of monofluorinated products, and could be accomplished on reaction scales up to 85 mmol using N-protected piperidone based substrates. Reactions in the presence of MeOH led to the formation of the corresponding fluoroketones or fluoroketals depending upon the substrate. The formation of the fluoroketals in this manner, as well as the fluorination of cyclic enamides are examples of multi-component coupling reactions.