Highly Enantio‐ and Diastereoselective Hydrogenation of Cyclic Tetra‐Substituted β‐Enamido Phosphorus Derivatives

Catalytic asymmetric hydrogenation of enamido phosphorus derivatives is one of the most efficient methods for the construction of chiral amino phosphorus products, among which the congested tetra‐substituted substrates remains an unaddressed challenge. In this study, we utilize a commercially available Rh‐Josiphos system for the efficient and stereoselective hydrogenation of a wide set of tetra‐substituted cyclic β‐enamido phosphonates/phosphine oxides, thus enabling access to chiral β‐amino phosphorus compounds featuring two vicinal stereocenters. This protocol was broadly applicable to different ring systems possessing various phosphonate/phosphine oxide groups and further applied in the preparation of amino‐phosphine ligands. DFT mechanistic explorations indicate that the C=C migratory insertion into RhIII−H bond could be the rate‐ and stereo‐determining step. The origins of stereoselectivity are revealed through distortion/interaction analysis, which is primarily regulated by distinguished dispersion interactions and steric repulsions. A highly enantio‐ and diastereoselective hydrogenation of congested tetra‐substituted β‐enamido phosphorus derivatives was developed by employing commercially available Rh‐Josiphos as the catalyst. This protocol offers a straightforward entry to a broad variety of previously difficult‐to‐access chiral β‐amino phosphonates/phosphine oxides bearing two vicinal stereocenters embedded in various ring structures.