Organic Synthesis Reagents on Transition Metals

描述（由申请人提供）：复杂分子的合成，如药物中使用的分子，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，烯烃复分解已成为这一过程的关键工具。烯烃复分解已广泛应用于药物发现，现在正进入过程化学。许多通过复分解反应产生的药物制剂已经通过了第二阶段的试验，还有一些正在进入第三阶段。尽管人们对烯烃复分解反应的认识已经有几十年了，但直到发现了高活性和稳定的催化剂，这些催化剂对大多数官能团都有耐受性，并且很容易被有机化学家使用，它才在有机合成中发挥了作用。钌基复分解配合物上配体的修饰导致了高效催化剂的广泛应用，从药物合成到高端复合材料的构建。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。催化剂设计的最后一个缺陷是缺乏对双键几何形状的控制。在大多数情况下，反应产生大多数更稳定的E几何异构体。在上一个资助期内，在从简单末端烯烃高产出z -烯烃的催化剂设计方面取得了重大突破。这些催化剂开辟了许多新的应用。在下一个授予期间，将努力提高其效率和选择性，并开发利用其能力的应用程序。在发现z选择性催化剂的基础上，将设计新的系统，专注于纯e -烯烃的合成。下一个授权期的研究结果将进一步提高强力烯烃复分解反应在新药和生物活性分子合成中的应用。

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.