CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

用于对映选择性合成的手性催化剂

• 批准号: 3305944
• 负责人: Michael PATRICK Doyle
• 金额: $ 9.02万
• 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/3305944
• 关键词: amides; boranes; carbene; catalyst; chemical addition; chemical reaction; 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 二铑(II)四（甲酰胺）其催化应用将 提供方便有效的分子不对称合成 生物医学的重要性。 这些催化剂具有独特的几何形状，其中 四个手性甲酰胺配体定向排列，使得每个铑都具有 两个相邻的 Rh-N 键。 因此，反应性底物具有相对 不受阻碍地获取铑，所得反应中间体为 有利地安排用于对映选择性分子间转化 特别是分子内环化。 结果表明 通过分子内环丙烷化反应获得，其中 对映体过量已达到 > 94%，手性铑(II) 甲酰胺特别适用于高选择性催化金属 涉及重氮化合物的卡宾过程。 此外，设计 这些催化剂允许在不对称位置放置极性取代基 配体中心位于卡宾中心上方以提供电子 铑结合卡宾的稳定化，卡宾的取向 取代基形成电子和空间优选构型， 并控制亲核试剂接近卡宾的方向 中心。 重点将放在手性二铑(II)催化剂应用上 类胡萝卜素转化，包括环丙烷化、芳香化 环加成、碳氢插入和金属稳定叶立德 反应。 根据初步调查，特殊的对映体控制 预计来自分子内环丙烷化和芳香族环加成 产生内酯、内酰胺和环戊酮的过程。 更远 催化剂设计的发展预计将促进 C-H 插入， 环丙烷化和叶立德转化为类似的高水平 对映选择性。 手性二铑(II)催化剂的设计和 开发用于在类胡萝卜素转化中实现高对映选择性 二取代重氮甲烷。 有机硼烷的加成反应 这些手性催化剂是否有效也将得到研究。 这 手性二铑(II)甲酰胺的优点，特别是那些 具有手性恶唑烷酮或2-吡咯烷酮-5-羧酸酯配体， 延伸到它们的易于准备、稳定性和便利性 合成获得结构修饰配体的方法。