Transition Metal-organocatalyzed Asymmetric Hydrogenation With Thiourea-biphosphine Ligand

The combination of transition-metal catalysis and organocatalysis as a promising strategy,such as cooperative catalysis,sequential/relay catalysis and synergistic catalysis,has drawn extensive attention due to its unique activation pattern.After decades of development and systematic research,this promising strategy has promoted numerous challenging asymmetric reactions.Recently,based on the bifunctional activation strategy,which is assisted by thiourea-biphosphine ligands,our group combined both activation patterns of transition-metal catalysis and organocatalysis into an individual molecule and has reported numbers of corresponding challenging asymmetric hydrogenation reaction.In this dissertation,we extended this strategy to the asymmetric hydrogenation of more types of unsaturated functionalized olefins,while excellent reactivity and enantioselectivity was achieved in the asymmetric hydrogenation of ?-amino nitro-olefins and ?,?-unsaturated N-acylpyrazoles.Moreover,their corresponding products could be transformed into numerous important intermediates in organic synthesis and pharmaceutical.The research contents are as follows.1.The catalytic system of Rh/Zhaophos was successfully extended to the asymmetric hydrogenation of ?-amino nitro-olefins.The reaction has achieved excellent reactivities and enantioselectivities under modified conditions(>99% conversion,up to 96% ee).Furthermore,their corresponding chiral ?-amino nitroalkane products could be efficiently converted into numerous valuable intermediates in pharmaceutical and other biologically active molecules,such as Voseltamivir,GR-205171 A,(+)-CP-99.994 and Asimadoline.2.The catalytic system of Rh/Zhaophos was successfully extended to the asymmetric hydrogenation of ?,?-unsaturated N-acylpyrazoles.The results show that this Rh/Zhaophos catalytic system achieved excellent reactivities and enantioselectivities(up to 97% yield,90-99% ee).Further exploration of controlled experiments verified the importance of hydrogen bonding interaction between substrates and catalyst in the asymmetric hydrogenation of ?,?-unsaturated N-acylpyrazoles.Moreover,the pyrazole group of these hydrogenation products could be easily removed to achieve the corresponding chiral carboxylic acid derivatives,which can be transformed into valuable pharmaceutical intermediates.3.The catalytic system of Rh/Zhaophos was successfully extended to the asymmetric hydrogenation of azepine/oxazepine-type seven-member cyclic imine hydrochlorides.The reaction has achieved excellent reactivities and enantioselectivities under modified conditions(>99% conversion,up to 99% ee).Moreover,control experiment results displayed that the anion-bonding interaction between the chloride ion of the substrate and thiourea motif of the ZhaoPhos played an important role to obtain excellent enantioselectivity.