Silirane-Mediated Stereoselective Synthesis of Amines

硅烷介导的胺立体选择性合成

• 批准号: 7110639
• 负责人: LAURA L ANDERSON
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-12 至 2009-04-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110639
• 关键词: amines; aminoalcohol; azapurine; chemical structure function; chemical synthesis; method development; oxygenous heterocyclic compound; postdoctoral investigator; silanes; stereochemistry

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.

描述（由申请人提供）：提出了硅杂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Woerpel小组研究的硅烷介导的多氧化合物合成的延伸。区域和立体选择性插入亚胺和亚硝酸盐的Si-C键的硅烷将开发形成构象约束的azasilacyclic化合物与三个连续的立体碳中心。这些产物将通过亲核加成和环化反应在结构上进行详细阐述，这些反应将通过氮杂硅烷环的构象偏好进行立体电子控制。Si-N键的水解或酰化将提供相应的胺或脲，Si-C键的氧化将释放非对映体富集的1，3-氨基醇。这个项目在合成上很有吸引力，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，硅烷插入方法的进步将为含氮药物靶标的立体选择性合成提供新的途径。