Extensive Re-Investigations of Pressure Effects in Rhodium- Catalyzed Asymmetric Hydrogenations

Abstract

The catalytic hydrogenation of three pro-chiral substrates methyl Z-α-acetamidocinnamate (MAC), methyl 2-acetamidoacrylate (M-Acrylate) and ethyl 4-methyl-3-acetamido-2-propanoate (E-EMAP) with rhodium precursors complexed with chiral diphosphines is reported at 1–30 bar hydrogen pressure. A library of 56 chiral diphosphines, including 23 BINAP derivatives, 7 JOSIPHOS, 5 BIPHEP, 3 DUPHOS derivatives, and 18 other ligands, was used. While it was generally accepted that high hydrogen pressure would result in lower ees, it is now demonstrated on a statistical basis that an equivalent distribution between beneficial and detrimental pressure effects on ee prevails and that the hydrogen pressure effect on enantioslectivity is not an isolated phenomenon since more than 33% of the reaction systems studied are strongly affected. In some case, the enantioselectivity can be improved up to 97% just by applying a higher hydrogen pressure. Extension of these conclusions to other non-chiral reagents is proposed.