Study on Development and Application of Kinetic Resolution in Asymmetric Olefination

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The carbon-carbon bond forming reactions are of most important for construction or complex and functional compounds including medicines. The Wittig and related reactions have been widely used for this purpose, however, no central chirality forms in this reaction. Application of this type of reaction to asymmetric synthesis involves discrimination of enantio (diastereo) topic carbonyl groups or their π-faces and the other is kinetic resolution of racemic carbonyl compounds. Especially, the latter approach has significant applicability to synthesis of optically active compounds, if dynamic version is successfully developed. The optically active HWE (Homer-Wadsworth-Emmons) reagents bearing axially chiral BINOL at the phosphonate moiety have been proven as effective chiral inducer in asymmetric olefination based on differentiation of carbonyl groups or their faces. In this study, the kinetic resolution by the anion of these chiral HWE reagents was examined to develop the novel methodology … More of creation of optically active interesting compounds or chiral synthons. Search of the optimum reaction conditions for asymmetric olefination and related reactions was first carried out and it was found diethyl zinc is effective as a base. Though the kinetic resolution of cyclohexanone derivative was disappointing results, satisfactory chemical and optical yields as well as those of the recovered starting materials were obtained when some metallic complexes of dialdehyde were used as racemic substrates. Furthermore, this methodology was successfully applied to the creation of unnatural abnormal amino acids. Thus, amino aldehydes derived from racemic amino acid was examined as possible substrates for kinetic resolution and to give interesting amino acid derivatives in optical active forms. Furthermore, the relationship between the structure of the reagents and enantioselectivity was investigated and some mechanistic consideration was carried out to predict the stereochemistry of products. Finally, the method was applied to asymmetric synthesis of a representative medicine naproxen. It is true that there are still some rooms for further investigation, such as dynamic kinetic resolution, but the present study might provide a novel method for creation of interesting optically active compounds including medicines. Less