Trifluoromethyl Ketone Galactose Catalyst for Asymmetric Epoxidation: Experimental and Theoretical Model

Since the introduction of the Shi catalyst, the organocatalytic epoxidation of olefins has become an area of continued research interest. To explore the possibility of enhancing the efficiency and stability of the catalyst, the synthesis of a galactose-derived trifluoromethyl ketone, and its use for stereoselective epoxidation reaction that exploits a transitory dioxirane as active species are herein reported. The trifluoromethyl ketone was built on the C6 of a protected d-galactopyranose. The organocatalyst was obtained smoothly in a few steps, and when utilized for stereoselective epoxidation exhibited excellent stability as no chemical alterations were observed during the reaction. The stereoselectivity, although sometimes moderate, appears surprisingly high considering the conformational freedom of the trifluoromethyl ketone moiety. DFT calculations were performed to investigate the interactions involved in regulating the observed selectivities. Moreover, a new mnemonic model has been developed to serve as a fast-predicting tool for epoxidation of new substrates.