Earth abundant catalysts as an enabling tool for organic synthesis

项目摘要 过渡金属催化的反应使化学合成发生了革命性的变化 生物活性分子和药物化合物的制备，但需要新的方法来开辟新的 分子空间，克服了目前方法产生的结构偏差。地球富饶 过渡金属，由于它们在金属-碳键中的离子性增加和更高的密度 与最先进的贵金属催化剂相比，它们具有明显的反应性。这项建议 描述了一种新的选择性C-H官能化反应的方法，该方法利用独特的 铁、钴和锰的性质，以可预测地区分性质中的细微差异 C-H键，以实现对现有方法的互补选择性。通过建立和 这些方法阐明了这种方法的一般原则，将使逆向综合分析成为可能 这将转化为对当前金属催化的新分子之外的新分子的合理设计 反应。具体地说，提出了芳烃的亚选择性功能化方法 用于选择性精制在先导化合物中常见的杂环的新路线。在……里面 此外，还提出了合成具有重要结构价值的1，3，5-三取代芳烃衍生物的方法 在药物发现活动中历来未被充分发掘的类型。的方法。 在C(Sp2)-H位存在的情况下，C(Sp3)-H键的化学选择性官能化也被 提出依赖于第一排过渡金属独特的电子性质，很容易得到支持 制备的和模式化的氧化还原活性配体。

Project Summary Transition metal-catalyzed reactions have revolutionized chemical synthesis as applied to the preparation of bioactive molecules and drug compounds, yet new methods are needed to open new molecular space and overcome the structural biases that arise from current methods. Earth-abundant transition metals, by virtue of their increased ionicity in metal–carbon bonding and higher density of states, offer distinct reactivity as compared to state-of-the-art precious metal catalysts. This proposal describes a new approach to site selective C–H functionalization reactions that leverages the unique properties of iron, cobalt and manganese to predictably distinguish subtle differences in the properties of C–H bonds to achieve complementary selectivity to existing methods. By establishing and articulating the general principles of this approach, these methods will enable retrosynthetic analyses that will translate to rational design of new molecules outside the reach of current metal-catalyzed reactions. Specifically, methods for the meta-selective functionalization of arenes are proposed as are new routes for the selective elaboration of heterocycles that are commonly found in lead compounds. In addition, methods are proposed to synthesize 1,3,5-trisubstiuted arene derivatives, a valuable structural type that is been historically underexplored in drug discovery campaigns. Methods for the chemoselective functionalization of C(sp3)–H bonds in the presence of C(sp2)–H sites are also proposed that rely on the unique electronic properties of first-row transition metals supported by readily prepared and modular redox-active ligands.