Asymmetric hydrogenation of trifluoromethyl ketones: application in the synthesis of Odanacatib and LX-1031

Abstract

Due to their stereoelectronic properties, trifluoromethyl (or perfluoroalkyl) ketones are challenging substrates in asymmetric (transfer) hydrogenation. We have developed iridium/f-amphol and iridium/f-ampha catalysis systems, which provide a highly efficient method for the synthesis of chiral secondary 2,2,2-trifluoroethanols in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). The practicability of this methodology was demonstrated through the facile preparation of the key intermediates of Odanacatib and LX-1301.