Study on Development and Application of Kinetic Resolution in Asymmetric Olefination

碳-碳键形成反应对于构建复杂的功能化合物包括药物具有重要意义。Wittig反应及相关反应已被广泛应用于这一目的，然而，在该反应中没有中心手性形成。这类反应在不对称合成中的应用包括对映（非对映）羰基或其π-面的识别，以及外消旋羰基化合物的动力学拆分。特别是，后者的方法具有显着的适用性，光学活性化合物的合成，如果动态版本是成功开发。在膦酸酯部分带有轴向手性BINOL的光学活性HWE（Homer-Wadsworth-Emmons）试剂已被证明是基于羰基或其面的分化的不对称烯烃化的有效手性诱导剂。本研究对这些手性HWE试剂的阴离子动力学拆分进行了研究，以开发新的拆分方法 ...更多信息 产生光学活性的感兴趣的化合物或手性化合物。首次对不对称烯化反应及相关反应的最佳反应条件进行了探索，发现二乙基锌作为碱是有效的。虽然环己酮衍生物的动力学拆分结果令人失望，但当使用一些二醛的金属络合物作为外消旋底物时，获得了令人满意的化学和光学产率以及回收的起始物质。此外，该方法已成功应用于非天然异常氨基酸的产生。因此，来自外消旋氨基酸的氨基醛被检查作为可能的动力学拆分的底物，并给出有趣的氨基酸衍生物的光学活性形式。此外，对反应物的结构与对映选择性之间的关系进行了研究，并对产物的立体化学进行了预测。最后，将该方法应用于代表性药物萘普生的不对称合成。诚然，仍然有一些空间进行进一步的研究，如动态动力学拆分，但本研究可能提供一种新的方法，创造有趣的光学活性化合物，包括药物。少

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