CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

用于对映选择性合成的手性催化剂

• 批准号: 3305946
• 负责人: Michael PATRICK Doyle
• 金额: $ 8.72万
• 依托单位: TRINITY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3305946
• 关键词: amides; boranes; carbene; catalyst; chemical addition; chemical reaction; chemical substitution; chemical synthesis; cyclization; cyclopropanes; diazo compound; intermolecular interaction; lactams; lactones; ligands; metal complex; organometallic compounds; rhodium; stereochemistry; stereoisomer; ylide

The long term objectives of this project are to design and construct chiral dirhodium(II) tetrakis(carboxamides) whose catalytic applications will provide convenient and effective asymmetric syntheses of molecules having biomedical importance. These catalysts have a unique geometry in which four chiral carboxamide ligands are oriented so that each rhodium possesses two adjacent Rh-N bonds. As a result, reactive substrates have relatively unimpeded access to rhodium, and the resulting reaction intermediates are advantageously arranged for enantioselective intermolecular transformations and, especially, intramolecular cyclizations. As indicated by results obtained with intramolecular cyclopropanation reactions for which enantiomeric excesses of > 94% have been achieved, chiral rhodium(II) carboxamides are particularly suitable for highly selective catalytic metal carbene processes involving diazo compounds. Furthermore, the design of these catalysts allows placement of a polar substituent at the asymmetric center of the ligand over the carbene center to provide electronic stabilization to the rhodium-bound carbene, orientation of carbene substituents into an electronically and sterically preferred configuration, and control over the direction of approach by nucleophiles to the carbene center. Focus will be placed on chiral dirhodium(II) catalyst applications to carbenoid transformation including cyclopropanation, aromatic cycloaddition, carbon-hydrogen insertion, and metal-stabilized ylide reactions. Based on preliminary investigations, exceptional enantiocontrol is expected from intramolecular cyclopropanation and aromatic cycloaddition processes resulting in lactones, lactams, and cyclopentanones. Further developments in catalyst design are predicted to advance C-H insertion, cyclopropanation, and ylide transformations to similar high levels of enantioselectivity. Chiral dirhodium(II) catalysts will be designed and developed to achieve high enantioselectives in carbenoid transformations of disubstituted diazomethanes. Addition reactions of organoboranes for which these chiral catalysts are effective will also be investigated. The advantages of chiral dirhodium(II) carboxamides, especially those possessing chiral oxazolidinone or 2-pyrrolidone-5-carboxylate ligands, extends to their ease of preparation, their stability, and the convenience of synthetic access to structurally modified ligands.

该项目的长期目标是设计和构建手性 Dirhodium（ii）催化施用的四方（羧酰胺） 提供具有方便有效的不对称合成分子的合成 生物医学重要性。 这些催化剂具有独特的几何形状 四个手性羧酰胺配体是定向的 两个相邻的RH-N键。 结果，反应性底物具有相对的 不受阻碍的进入若im愧，由此产生的反应中间体是 有利地安排了对映选择性分子间变换 尤其是分子内环化。 如结果所示 用分子内环丙谁会获得的反应获得 已经达到了> 94％的对映体超额，手性若im（II） 羧酰胺特别适合高度选择性催化金属 涉及重氮化合物的卡宾工艺。 此外，设计 这些催化剂允许将极性取代基放置在不对称的 在卡宾中心上方配体的中心提供电子 稳定到结合迦中的碳，卡宾的方向 取代基于电子和空间优先的构型， 并控制亲核试剂到卡宾的进近方向 中心。 将重点放在手性dirhodium（II）催化剂应用上 转化卡宾类动物，包括环丙烷，芳香族 环加成，碳 - 氢插入和金属稳定的Ylide 反应。 基于初步研究，卓越的对映射控制 预计会通过分子内环丙者和芳族环加成 导致内酯，乳糖和环戊酮的过程。 更远 预计催化剂设计中的发展将推进C-H插入， 环丙烷化和YLIDE转化为相似的高水平 对映选择性。 手性dirhodium（II）催化剂将被设计和 开发以实现高映选择剂在类carbenoid转化中 脱叠氮杂甲烷。 有机菜的加法反应 这些手性催化剂是有效的。 这 手性dirhodium（II）羧酰胺的优点，尤其是那些 具有手性黄唑啉酮或2-吡咯酮-5-羧酸盐配体， 扩展到他们的准备易度，稳定性和便利性 合成访问结构修饰的配体。