NOVEL MECHANISTIC MODEL FOR THE JACOBSEN EPOXIDATION

雅各布森环氧化的新机理模型

• 批准号: 6179126
• 负责人: Maria White
• 金额: $ 3.24万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6179126
• 关键词: adrenergic agents; alkenes; catalyst; chemical conjugate; chemical models; chemical synthesis; epoxides; free radicals; stereochemistry; stereoisomer

The increased consideration given to the role of absolute stereochemistry in the function of biologically active molecules has intensified the quest for the development of truly useful catalytic processes to effect highly efficient synthesis of optically pure compounds. Because enantiomerically pure epoxides are among the most versatile chiral building blocks in organic synthesis, development of synthetic catalysts that provide practical access to them is highly desirable. The Jacobsen epoxidation, utilizing (salen)Mn-oxo transfer catalysts, has afforded easy access to a variety of valuable enantiomerically pure epoxides from inexpensive conjugated olefin precursors. However, a satisfactory mechanistic explanation for this catalysts' success remains elusive, precluding the rational design of analogous catalysts for specific asymmetric processes. The proposal herein introduces a novel "shifted top-on" cation radical (STO+) mechanistic model for the Jacobsen epoxidation that provides a simple and clear explanation for the high enantioselectivities observed experimentally for a wide range of conjugated olefin classes. The STO+ model is then utilized as a heuristic tool for the design of a new series of catalysts to specifically effect the asymmetric epoxidation of the highly elusive conjugated terminal olefin substrate class. To illustrate the synthetic utility of conjugated terminal epoxides, an efficient, highly general, three-step synthetic route to enantiopure beta-aryl amino alcohol adrenergic agents, important in the treatment of such diverse disorders as hypertension and asthma, is proposed.

更多地考虑绝对的作用 生物活性分子功能中的立体化学 加强了对真正有用的催化材料的开发的探索 高效合成光学纯的方法 化合物。 因为对映体纯的环氧化物是最 有机合成中的多功能手性构件，开发 提供实用途径的合成催化剂非常重要 理想的。 Jacobsen 环氧化，利用 (salen)Mn-oxo 转移 催化剂，可以轻松获得各种有价值的 来自廉价共轭烯烃的对映体纯环氧化物 前体。然而，对此有一个令人满意的机械解释 催化剂的成功仍然难以捉摸，妨碍了合理的设计 用于特定不对称过程的类似催化剂。 提案 本文介绍了一种新型“顶上移动”阳离子自由基（STO+） Jacobsen 环氧化的机理模型提供了一个简单的 以及对观察到的高对映选择性的清晰解释 实验适用于各种共轭烯烃类别。 STO+ 然后将模型用作启发式工具来设计新的 一系列专门影响不对称环氧化反应的催化剂 高度难以捉摸的共轭末端烯烃底物类别。 到 说明共轭末端环氧化物的合成用途， 高效、高度通用、对映体纯的三步合成路线 β-芳基氨基醇肾上腺素能药物，在治疗中很重要 提出了高血压和哮喘等多种疾病的治疗方法。