Nickel-Catalyzed Asymmetric Synthesis Of Chiral Phosphine Oxides

Amongst phosphorus-containing compounds,chiral phosphine oxides have been applied widely in chiral synthetic chemistry,biomedicine,functional materials,and other fields due to their special structure.In recent decades,various chiral phosphine oxides have been constructed through diverse catalytic asymmetric synthesis strategies,assisting further exploration of such compounds.At present,there are still some problems in the construction of chiral phosphine oxides catalyzed by transition metals,such as single substrate type and catalytic mode,and insufficient product types.Therefore,it is of great research significance to develop new transition metal catalytic systems,which can easily and efficiently synthesize various types of chiral phosphine oxides,and can further expand asymmetric catalytic strategies.In this thesis,the stereoselective synthesis of axial chiral allenylphosphine oxides,phosphinoyl 1,3butadienes,and P-chiral allenylphosphine oxides was achieved by nickel-catalyzed propargyl phosphinoyl substitution reaction,which provides a new method for the efficient construction of phosphorus-containing organic compounds.The development of general catalytic methods for the regio-and stereoselective construction of phosphoryl derivatives from identical substrates remains a formidable challenge in organic synthesis.Enabled by the newly developed chiral bisphosphine ligands,we disclosed a nickel-catalyzed allenylation of phosphine oxides rationally and predictably,allowing the construction of versatile chiral allenylphosphoryl derivatives with high enantiopurity.The reaction strategy has mild conditions and a wide range of substrates.Mechanism studies have shown that the enantioselectivity of this reaction is mainly regulated by the ligand,regardless of the chirality of the substrate;nonlinear effect experiments confirm that the reaction is catalyzed by a single ligand.We obtained various chiral phosphorus-containing compounds through this asymmetric synthesis strategy.1,3-Dienes are of much synthetic value because they can participate in a wide variety of reactions as a general structural unit.Here,we described an efficient nickel-catalyzed regioselective 1,3-dienylation reaction using stable secondary phosphine oxides.Based on this strategy,we achieved a series of phosphinoyl 1,3-butadienes in excellent yield and highly regioselectivity under acidic conditions using an achiral phosphine ligand 1,2-bis(dicyclohexylphosphaneyl)benzene under acidic conditions as well as using a chiral ligand 1,2-bis(2,5-diisopropylphosphine)benzene under the neutral conditions.Further studies revealed that both ligand and pH can modulate the regioselectivity of this reaction.P-stereogenic allenylphosphine oxides possess many unique properties allowing many potential applications in natural product synthesis,pharmaceuticals as well as ligands in asymmetric organometallic catalysis.We developed a nickel-catalyzed stereoselective synthesis of P-chiral allenylphosphine oxides with good enantioselectivity starting from secondary phosphine oxides and propargylic carbonates.Mechanistic studies have found that the racemization process of the secondary phosphine oxide in the reaction system is difficult to occur,and the enantioselective control of the product may be achieved through the kinetic resolution of the substrate by the chiral allenyl nickel intermediate.