Synthesis of Trifluoromethyl Ketones via Tandem Claisen Condensation and Retro-Claisen C-C Bond-Cleavage Reaction

A highly efficient, operationally simple approach to trifluoromethyl ketones has been developed that builds on the use of a tandem process involving Claisen condensation and retro-Claisen C-C bond cleavage reaction. Enolizable alkyl phenyl ketones were found to react readily with ethyl trifuoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones, which were quite different from the general Claisen condensation products, beta-diketones. This procedure uses readily available starting materials and can be extended to the preparation of perfluoroalkyl ketones in excellent yield.