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Research on the Highly Enantioselective 1,4-Addition of Diethyl Phosphite to Enones Using a Dinuclear Zn Catalyst

Author: YuanYe
Tutor: WangRui
School: Lanzhou University
Course: Biochemistry and Molecular Biology
Keywords: enones imine asymmetric catalysis Michael addition chiral Br(?)nsted acid Pudovik reaction chiral phosphinamide ligand
CLC: O643.32
Type: PhD thesis
Year: 2009
Downloads: 24
Quote: 0
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Abstract


Catalytic asymmetric reactions are among the most important organic reactions, which create good fortunes to enantiomerically pure chiral drugs and other materials, and continue to be one of the most studied and important areas in organic chemistry.The conjugate addition of nucleophiles to acceptor-substituted double and triple bonds （usually referred to as Michael addition） belongs to the classical carbon-carbon bond forming reactions. Since this reaction often leads to the formation of a stereogenic center, considerable effort has been devoted to the development of efficient stereoselective methods.Chiral phosphonates and their phosphonic acid derivatives have been the object of intense interest in recent years due to their potential biological activity. The asymmetric conjugate addition of phosphites to electron deficient olefins provides a convenient and direct route toward functionalized chiral phosphonates.However, to the best of our knowledge, study on the catalytic asymmetric phospha-Michael addition of enones has never been presented so far, despite the powerful synthetic potential of the phosphorus adducts. Our research team is seeking for the further research in this field and hoping they can meet the high standard of modern synthetic methods.Herein, we would like to report the first example of catalytic asymmetric 1,4-addition of diethyl phosphite to enones based on a dinuclear zinc catalyst. We have demonstrated the first example of asymmetric 1,4-addition reaction of diethyl phosphite with simple enones catalyzed by a dinuclear zinc complex. Theγ-oxo phos-phonates could be obtained in a straightforward procedure in high yields with excellent enantioselectivities （up to 99% ee）.The absolute configuration of compound was determined by chemical correlation with a known compound as follows. The Baeyer-Villiger oxidation of product with CF3CO3H afforded corresponding triester without erosion in enantioselectivity （99% ee）. Then compound triester was hydrolyzed to give 3-phenyl-3-phosphonopropanoic acid of known absolute configuration. By comparison of the optical rotation, the absolute configuration of compound was determined to be S.By comparison of the optical Further-more, this new catalytic phospha-Michael addition reaction was screened effectively for a broad range of enones bearing both aryl and alkylβ-substituents. The strategy makes the asymmetric synthesis of biologically active phosphonates and derivatives there of more accessible.The hydrophosphonylation of aldehydes and imines （Pudovik reaction） is the most general, straightforward and widely applied method for the construction of P-C bonds. For the further studuy of this reaction, our research team synthesized a series of chiral Br（?）nsted acids based on TADDOL and applied in the enantioselective addition of diethyl phosphite to imines. The methodology affordedα-amino phosphonates in moderate enantioselectivity（23%～43%ee） but in high yields（79%～88%）.Optically active propargyl alcohols are important and versatile building blocks for the synthesis of a wide range of pharmaceuticals and natural products. The enantioselective alkynylzinc addition to carbonyl compounds is very useful for the synthesis of chiral propargyl alcohols. From commercially available natural L-phenylalanine, chiral phosphinamide ligands L1～9 were easily prepared in three simple steps and applied in the enantioselective addition of alkynylzinc reagents to aldehydes. Ligand L7 was found to be an outstanding ligand for this reaction. High enantioselectivity with an ee value up to 95% was achieved under very mild conditions.

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CLC: > Mathematical sciences and chemical > Chemistry > Physical Chemistry ( theoretical chemistry ),chemical physics > Chemical kinetics,catalysis > Catalytic > Catalytic reaction
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