Enantioselective Synthesis Of P-Chiral Phosphine Oxides Via Cu(I)-Catalyzed Azide-Alkyne Cycloaddition And Their Applications

This thesis aims at catalytic enantioselective construction of P-chiral phosphine oxides via enantioselective Cu(I)-catalyzed azide-alkyne cycloaddition(CuAAC).By utilizing newly developed chiral Pybox ligand bearing a bulky C4 shielding group,we realized a highly enantioselective synthesis of P-chiral phosphine oxides featuring an ethynyl group via desymmetric CuAAC of prochiral diethynylphosphine oxides and kinetic resolution of monoethylphosphine oxides.This protocol allows the facile access of chiral ethynylphosphine oxides that are versatile P-chiral synthons,capable of undergoing a number of diversifying reactions to deliver P-chiral phosphine ligands or organocatalysts.The detailed research works are introduced as follows:1)Chiral Pybox ligand bearing a bulky C4 shielding group played an important role in achieving excellent enantioselectivity while suppressing side bis-triazoles formation in desymmetric CuAAC of prochiral diethynylphosphine oxides.The mechanistic studies suggested that the reaction was a synergic combination of a desymmetrization and a kinetic resolution.Meanwhile,the newly developed ligand could adjust the chiral environment around the copper center and improve the enantioselective control of the reaction.Furthermore,it could inhibit the conversion of chiral mono-triazole to achiral bis-triazole,to achieve high ratio of mono-to bis-triazole.This finding contributed to a highly enantioselective kinetic resolution of racemic ethynylphosphine oxides.Our ligands achieved a better enantioselectivity than unmodified Pybox ligand in both the desymmetrization and the kinetic resolution steps.Those reactions proceed smoothly affording P-chiral phosphine oxides with enantioselectivities up to 99% ee,which are versatile P-chiral synthons that could be readily elaborated.2)The thus obtained P-chiral phosphine oxides featuring an ethynyl group are useful for the diverse synthesis of P-chiral phosphine derivatives.For example,A Sonogashira reaction followed by a reduction readily converted P-chiral phosphine oxides to tertiary phosphines without erosion of ee value.The capacity of these phosphines was evaluated in the [3+2] cycloaddition of chalcone and ethyl buta-2,3-dienoate,with a moderate enantioselective for product being obtained.Furthermore,P-chiral monoethynylphosphine oxides could undergo sequential Glaser coupling and reduction to give 4-bis((R)-dialkynylphosphine)butane,which could form a digold Au(I)complex,the structure of which was confirmed by X-ray analysis.In addition,the P-chiral phosphine-amines synthons were expediently obtained via transformation of P-chiral phosphine oxides,which were prepared to develop P-chiral phosphine-phosphoramide bifunctional organocatalysts.The synthesis of P-chiral phosphine oxide-oxazoline ligand were also realized from P-chiral phosphine oxides.