RESUMEN
Novel axially chiral biphenyl diphosphine ligands Enm-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 α-acetamido-1,3-indanediones, providing chiral α-acetamido-ß-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 Enm-BridgePhos-Rh complexes is highly related to the excellent enantioselectivities.
RESUMEN
Rh-catalyzed sequential asymmetric hydrogenations of 3-amino-4-chromones have been achieved for the first time via an unprecedented dynamic kinetic resolution under neutral conditions, providing (S,R)-3-amino-4-chromanols in high yields (up to 98%) with excellent enantio- and diastereoselectivities (up to 99.9% ee and 20:1 dr). The mechanistic studies based on control experiments and density functional theory (DFT) calculations suggest that the dynamic kinetic resolution process for the intermediate enantiomers generated in the first hydrogenation step proceeded via a stereomutation (or called chiral assimilation) pathway from an undesired enantiomer to the desired enantiomer rather than via traditional racemization of the undesired enantiomer. The protocol can be performed on a gram scale with a relatively low catalyst loading and offers a practical and convenient pathway for synthesizing a series of bioactive chromanols and their derivatives.
Asunto(s)
Rodio , Hidrogenación , Cromonas , Estereoisomerismo , CatálisisRESUMEN
The efficient RuPHOX-Ru catalyzed asymmetric hydrogenation of α-substituted tetralones via a dynamic kinetic resolution has been achieved for the synthesis of chiral tetrahydronaphthols. The mechanism study indicated that hydrogenation with H2 gas, rather than transfer hydrogenation with EtOH solvent as the hydrogen source, predominates in the reaction pathway.
RESUMEN
Chiral chromanols and their derivatives have been synthesized via a RuPHOX-Ru catalyzed asymmetric hydrogenation of chromones in high yields, >20 : 1 drs and with up to 99.9% ee. Control experiments show that the reaction undergoes two sequential asymmetric hydrogenation steps of the C[double bond, length as m-dash]C and C[double bond, length as m-dash]O double bonds. The reaction could be performed on a gram-scale with a relatively low catalyst loading (up to 1000 S/C), and the resulting products can be transformed to several biologically active compounds.