Silirane-Mediated Stereoselective Synthesis of Amines

描述(申请人提供)：建议将硅烷环丙烷插入反应应用于氨基醇的立体选择性合成。该项目是沃尔佩尔小组研究的硅烷介导的多氧化合物合成的延伸。亚胺和亚硝酸盐在硅烷的Si-C键上的区域和立体选择性插入将被开发成具有三个连续的立体碳中心的构象受限的氮杂硅环化合物。这些产物将通过亲核加成和环化反应在结构上进行细化，这些反应将受到氮杂硅烷环的构象偏好的立体电子控制。然后，Si-N键的水解或酰化反应将提供相应的胺或尿素，而Si-C键的氧化将释放非对映浓缩的1，3-氨基醇。这个项目综合起来很有吸引力，因为它结合了简单的起始材料，利用五元环的构象偏好形成了复杂的产品。氨基醇是生物活性分子中常见的基序，这种硅烷插入方法的进展将为含氮药物靶标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.