CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

本项目的长期目标是设计和构建手性 二铑（II）四（羧酰胺），其催化应用将 提供了方便和有效的分子的不对称合成， 生物医学的重要性 这些催化剂具有独特的几何形状，其中 四个手性羧酰胺配体被定向，使得每个铑具有 两个相邻的Rh-N键。 因此，反应性基材具有相对低的粘度。 不受阻碍地接触铑，并且得到的反应中间体是 有利地设置用于对映选择性分子间转化 尤其是分子内环化。 如结果所示 通过分子内环丙烷化反应获得， 已实现> 94%的对映体过量，手性铑（II） 羧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方法。 此外，设计 这些催化剂允许极性取代基在不对称 配体中心在卡宾中心之上以提供电子 铑结合卡宾的稳定化，卡宾的取向 取代基转变成电子和空间上优选的构型， 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）催化剂的应用 到类卡宾的转化，包括环丙烷化、芳族化、 环加成、碳氢插入和金属稳定叶立德 反应. 根据初步调查， 预计分子内环丙烷化和芳环加成 产生内酯、内酰胺和环戊酮的过程。 进一步 预计催化剂设计的发展将促进C-H插入， 环丙烷化和叶立德转化为类似的高水平的 对映选择性 将设计手性铑（II）催化剂， 开发用于在类卡宾转化中实现高对映选择性， 二取代的重氮甲烷。 有机硼烷的加成反应， 这些手性催化剂是有效的也将被研究。 的 手性二铑（II）甲酰胺的优点，尤其是那些 具有手性恶唑烷酮或2-吡咯烷酮-5-羧酸酯配体， 扩展到它们的制备容易性、稳定性和方便性， 结构修饰配体的合成途径。

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.