Silirane-Mediated Stereoselective Synthesis of Amines

描述（由申请人提供）：提出了硅环丙烷插入反应性在氨基醇立体选择性合成中的应用。该项目是由Woerpel小组研究的硅烷介导的多氧化合物合成的延伸。亚胺和亚硝酸盐的区域和立体选择性插入硅烷的Si-C键将被开发成具有三个连续立体碳中心的构象约束的氮杂环化合物。这些产物将通过亲核加成和环化反应在结构上得到详细阐述，这些反应将由氮杂硅烷环的构象偏好立体电子控制。Si-N键的水解或酰化会得到相应的胺或尿素，Si-C键的氧化会释放出非对映富集的1,3-氨基醇。该项目具有综合吸引力，因为它利用五元环的构象偏好将简单的起始材料偶联以形成复杂的产物。氨基醇是生物活性分子中常见的基序，硅烷插入方法的这一进展将为含氮药物靶点的立体选择性合成提供新的途径。

DESCRIPTION (provided by applicant): The application of silacyclopropane insertion reactivity to the stereoselective synthesis of aminoalcohols is proposed. This project is an extension of the silirane-mediated syntheses of polyoxygenated compounds investigated by the Woerpel group. Regio- and stereoselective insertions of imines and nitrites into the Si-C bonds of siliranes will be developed to form conformationally constrained azasilacyclic compounds with three contiguous stereogenic carbon centers. These products will be elaborated structurally through nucleophilic addition and cyclization reactions that will be controlled stereoelectronically by the conformational preferences of the azasilane ring. Hydroylsis or acylation of the Si-N bond will then provide the corresponding amine or carbamide, and oxidation of the Si-C bond will release diastereoenriched 1,3- aminoalcohols. This project is synthetically appealing because it couples simple starting materials to form complicated products using the conformational preferences of a five-membered ring. Aminoalcohols are common motifs in biologically active molecules and this advancement of silirane insertion methodology will provide new approaches for the stereoselective syntheses of nitrogen-containing pharmaceutical targets.