Synthesis of Chiral Diaryl Methanols via RuPHOX-Ru Catalyzed Asymmetric Hydrogenation

The RuPHOX-Ru catalyzed asymmetric hydrogenation of diaryl ketones has been established, providing the corresponding chiral diaryl methanols in up to 99% yield and 99% ee. The protocol could be performed on a gram-scale with a relatively low catalyst loading (2000 S/C) and the resulting products allow for several useful transformations, in particular for the synthesis of chiral drugs, such as, (S)-Orphenadrine and (S)-Neobenodine. Deuterium labeling and control experiments revealed that the RuPHOX-Ru-catalyzed asymmetric hydrogenation is fully subject to hydrogenation with H-2 as the sole hydrogen source.