Synthesis Of Bisphosphine Ligands And Their Applications In Ru-Catalyzed Asymmetric Hydrogenation Ofα,β,γ,δ-Unsaturated Ketones

In this thesis,several biaryl-based chiral bisphosphine ligands,namely the Sun Phos series ligands,were synthesized with an adjusted route,which were applied to ruthenium(Ru)-catalyzed carbonyl-selective asymmetric hydrogenation of α,β,γ,δ-unsaturated ketones.The asymmetric hydrogenation was achieved with good catalytic efficiency,high chemical selectivity and good enantioselectivity.1.Axial chiral Sun Phos series bisphosphine ligands with different substituents were synthesized through the route of biaryl phosphate as an intermediate: using aromatic ring bromo,nickel(Ni)catalyzed carbon phosphine bond construction,LDA coupling under the action of lithiation and ferric chloride to construct a biphenyl type skeleton,dichlorosulfoxide chlorination and aryl Grignard reagents to establish carbon phosphine bonds,resolution of tartaric acid derivatives to obtain chiral phosphine ligand oxides and trichlorosilyl hydrogen reduction,Sun Phos series chiral bisphosphine ligands were synthesized,which has good synthetic convenience with good separation yield and made certain basis for asymmetric hydrogenation reactions.2.Asymmetric hydrogenation of a series of α,β,γ,δ-unsaturated ketones with high chemical selectivity and high enantioselectivity: The asymmetric hydrogenation of some α,β,γ,δ-unsaturated alkyl ketones have been achieved with high chemical selectivity and high enantioselectivity by the screening of the Sun Phos bisphosphine ligands,temperature,hydrogen pressure,alkali and other conditions.In such asymmetric hydrogenation the ee values can be 98%,the TON can reach 1000 and gram scale preparation experiments can also proceed.At the same time,some exploratory studies have been carried out on the enantioselective hydrogenation of α,β,γ,δ-unsaturated aryl ketone substrates.The screening of bisphosphine ligands,solvents,temperature,hydrogen pressure,alkali and other conditions could not obtain good results.Screening of bisamine ligands in bisphosphinebisamines gave certain results,but it is still difficult to obtian a good solution with both high activity and high enantioselective hydrogenation.However,inspired by the ortho-steric effect,the ortho-chlorine atom was added to the aromatic ring leaving with expected hydrogenation results.Given that the halogen can be removed,such α,β,γ,δ-saturation asymmetric hydrogenation of aryl ketones has provided a preliminary solution.