Rh-Catalyzed Enantioselective Desymmetric Hydrogenation of -Acetamido-1,3-indanediones Using Ether-Bridged Biphenyl Diphosphine Ligands

Novel axially chiral biphenyl diphosphine ligands E-n(m)-BridgePhos, bearing an ether chain bridge at the 5,5'-position of the biphenyl backbone, have been developed and successfully applied in the Rh-catalyzed enantioselective desymmetric hydrogenation of alpha-acetamido-1,3-indanediones, providing chiral alpha-acetamido-beta-hydroxybenzocyclic pentones in high yields (up to 97%) and with excellent enantioselectivities (up to 99% ee). The reaction could be carried out on a gram scale, and the corresponding products were used as vital intermediates for the synthesis of analogues of chiral spirobenzylisoquinoline alkaloids. Both the crystal structure analysis and the DFT calculations revealed that the large dihedral angle of the E-n(m)-BridgePhos-Rh complexes is highly related to the excellent enantioselectivities.