NOVEL MECHANISTIC MODEL FOR THE JACOBSEN EPOXIDATION

更多地考虑到绝对的作用， 立体化学在生物活性分子的功能中具有 加强了对开发真正有用的催化剂的探索， 高效合成光学纯的 化合物. 因为对映体纯的环氧化物是最常见的 有机合成中的多功能手性结构单元， 合成催化剂，提供实际访问他们是高度 令人向往 利用（salen）Mn-氧代转移的Jacobsen环氧化反应 催化剂，提供了方便地获得各种有价值的 由廉价共轭烯烃制备对映体纯的环氧化物 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，排除了合理的设计， 用于特定不对称方法的类似催化剂。 该提案 本文介绍了一种新的“移位的顶部”阳离子自由基（STO+）， Jacobsen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 实验上用于宽范围的共轭烯烃类。 关于STO+ 模型，然后利用作为一种启发式工具的设计，一个新的 一系列催化剂，以具体实现不对称环氧化 高度难以捉摸的共轭末端烯烃底物类。 到 举例说明共轭末端环氧化物的合成效用， 高效、高度通用的三步合成路线， β-芳基氨基醇肾上腺素能药物，在治疗中的重要作用 高血压和哮喘等多种疾病的研究。

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.