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.