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.

对绝对作用的考虑增加了 立体化学在生物活性分子的功能中具有 加强了对真正有用催化的发展的追求 实现光学纯度高效合成的过程 化合物。 因为在对照层上纯净的环氧化物是最大的 有机合成中的多功能性手性构件，开发 提供实用访问的合成催化剂非常高 理想。 雅各布森环氧化，利用（Salen）Mn-oxo转移 催化剂，可以轻松获得各种有价值的 廉价共轭烯烃的对映体纯环氧化物 前体。但是，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，排除了理性的设计 特定不对称过程的类似催化剂。 提案 此处引入了一个小说的“移动上的”阳离子自由基（sto+） Jacobsen环氧化的机械模型，该模型提供了简单的 并明确对观察到的高对映选择性的解释 实验性地用于广泛的共轭烯烃类。 Sto+ 然后将模型用作设计新的启发式工具 一系列催化剂，以特异性影响不对称的环氧化 高度难以捉摸的共轭末端烯烃底物类。 到 说明了共轭末端环氧化物的合成效用，一种 高效，高度一般，三步的合成途径 β-芳基氨基酒肾上腺素能剂，对治疗很重要 提出了高血压和哮喘等多种疾病。