NOVEL MECHANISTIC MODEL FOR THE JACOBSEN EPOXIDATION

对绝对的作用给予更多的考虑 立体化学在生物活性分子功能中的作用 加强了对开发真正有用的催化剂的探索 实现光学纯化合物高效合成的工艺方法 化合物。因为对映体纯的环氧化物是 在有机合成中的多功能手性构建块，开发 为它们提供实际途径的合成催化剂是高度 令人向往。利用(Salen)锰氧转移的雅各布森环氧化反应 催化剂，提供了方便地获得各种有价值的 从廉价的共轭烯烃中获得对映体纯的环氧化物 先驱物。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，排除了合理的设计 用于特定不对称过程的类似催化剂。这项建议 本文介绍了一种新型的“顶端移位”阳离子自由基(STO+)。 雅各布森环氧化反应的机理模型提供了一个简单的 并清楚地解释了观察到的高对映体选择性 实验上适用于广泛的共轭烯烃类。STO+ 然后利用模型作为启发式工具来设计新的 专用于不对称环氧化反应的系列催化剂 属于高度难以捉摸的共轭末端烯烃底物类别。至 说明共轭末端环氧化物的合成用途，以及 高效、高通用性、三步合成对映体 治疗中重要的β-芳基氨基醇肾上腺素能药 关于高血压和哮喘等多种疾病的研究被提出。

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.