Copper-Catalyzed Asymmetric Propargylic Substitution of 2,2,2-Trifluoroethyl-isoxazoles with Propargylic Alcohol Derivatives.

Abstract

The trifluoromethyl group is one of the most functional and widely used fluoroalkyl groups in medicinal chemistry and drug discovery. However, few methodologies have been reported for the asymmetric introduction of the trifluoromethyl group into organic molecules. In this study, a diastereo- and enantioselective propargylic substitution reaction was performed between propargylic carbonates and 2,2,2-trifluoroethyl-substituted nitroisoxazoles catalyzed by a Cu-pybox complex. This method enables the preparation of a series of propargylation products with two contiguous stereogenic centers, one of which is a chiral trifluoromethyl-bearing carbon. In most cases, the desired products were produced in high yields with good to excellent diastereo- and enantioselectivities.