Organic Synthesis Reagents on Transition Metals

描述(由申请人提供)：复杂分子的合成，如那些用于制药的分子，在很大程度上依赖于快速有效地构建碳-碳键的能力。在过去的几十年里，烯烃化合反应已经成为这一过程的关键工具。烯烃复分解反应在药物开发中得到了广泛的应用，目前正在向过程化学发展。一些通过歧化反应而成为可能的药物制剂已经进行了第二阶段的试验，一些正在进入第三阶段。尽管烯烃歧化反应已经知道了几十年，但它只是在发现了对大多数官能团都有容忍性的、易于有机化学家使用的高活性和稳定的催化剂后才在有机合成中有用的。通过对基本Ru基复分解络合物的配体修饰，得到了高效的催化剂，从药物合成到高端复合材料的构建都有广泛的应用。催化剂效率和选择性的每一次进步都开辟了各种新的应用领域。催化剂设计的最后缺陷之一是缺乏对双键几何结构的控制。在大多数情况下，这些反应会产生更稳定的E几何异构体。在上一次授权期内，在催化剂的设计方面取得了重大突破，该催化剂将从简单的末端烯烃高产率地生产Z-烯烃。这些催化剂开辟了许多新的应用领域。在下一个授权期内，将努力提高它们的效率和选择性，并开发利用它们能力的应用程序。在发现Z-选择性催化剂的经验教训的基础上，将设计出专注于纯E-烯烃合成的新系统。下一个授权期的结果将进一步加强强烯烃歧化反应在合成新药物和生物活性分子中的应用。

DESCRIPTION (provided by applicant): The synthesis of complex molecules such as those used in pharmaceuticals depends heavily on the ability to rapidly and efficiently construct carbon-carbon bonds. Over the past decades, olefin metathesis has become a key tool for such a process. Olefin metathesis has been used widely in drug discovery and is now moving into process chemistry. A number of pharmaceutical agents that are made possible by the metathesis reaction have proceeded through Phase II trials and a number are now entering into Phase III. Although the olefin metathesis reaction has been known for a number of decades, it has only become useful in organic synthesis with the discovery of highly active and stable catalysts that are tolerant of most functional groups and are easily used by organic chemists. The modification of ligands on the basic ruthenium-based metathesis complexes has resulted in highly efficient catalysts that are used in a wide array of applications, from pharmaceutical synthesis to the construction of high end composites. Each advance in catalyst efficiency and selectivity has opened a variety of new applications. One of the final deficiencies in catalyst design has been the lack of control of double bond geometry. In most cases, the reactions produce a majority of the more stable E geometric isomer. During the last granting period, major breakthroughs have been made in the design of catalyst that will produce Z-olefins in high yields from simple terminal olefins. These catalysts open many new applications. During the next granting period, efforts will be made to increase their efficiency and selectivity, and to develop applications that exploit their capabilities. Building on the lessons from the discovery of a Z-selective catalyst, new systems will be designed that will be focused on the synthesis of purely E-olefins. The results from the next granting period will further enhance the utility of the powerfl olefin metathesis reaction in the synthesis of new pharmaceuticals and bioactive molecules.