A Combined Rhodium-Photoredox-Catalyzed Approach to Alkene Carbofunctionalization by Carbon-Hydrogen Bond Activation

项目总结 开发新的治疗药物的主要挑战是发现和生产 这些物质。大多数药物中的有效成分是复杂的小分子，可以 规模化合成难度大，成本高。正因为如此，化学合成的新策略 有益于提供从简单、丰富的化学物质到这些分子的替代和有效途径 原料。有机分子中最普遍但又最多样的连接是碳氢键，以及 有机分子也有一个共同的特点，即它们的骨架结构主要由碳组成- 影响与分子受体三维相互作用的碳键 精确的生物活动。因此，利用选择性碳氢键激活事件和 将它们直接应用于受控的碳-碳键形成对这一发现和 实施新的小分子疗法。 这项研究将有机化学中的两个概念结合到一种新的化学合成模式中，即 以立体控制的方式将碳氢键转化为碳碳键。过渡金属， 特别是铑，长期以来一直被认为选择性地断裂未活化的碳-氢键，但通常 在该过程中形成惰性络合物，从而阻碍催化。光催化剂是一种强大的新兴工具 它利用可见光的能量，并利用它来促进过渡金属络合物的反应活性。具体的 这项研究的目的是使用光催化剂来诱导新的反应与活化的罗络合物 碳氢键有三种不同的模式。将这种反应性与丰富的烯烃的使用相结合将 为生物活性复杂骨架的高效合成提供了一种简便的方法 分子。 这项研究的产品将是一种新的合成工具，能够快速发现和生产 具有生物活性的小分子。这最终将通过促进设计和改善公众健康 生产负担得起的药物来诊断、治疗和预防人类疾病。

PROJECT SUMMARY The major challenges in the development of new therapeutic agents are the discovery and production of these substances. The active ingredients in most pharmaceuticals are complex small molecules that can be difficult and expensive to synthesize on scale. Because of this, new strategies for chemical synthesis are beneficial in providing alternative and efficient routes to these molecules from simple, abundant chemical feedstocks. The most ubiquitous yet diverse linkage in organic molecules is the carbon-hydrogen bond, and organic molecules also share the characteristic that their skeletal structure is predominantly composed of carbon- carbon linkages that affect the three-dimensional interactions with molecular receptors responsible for their precise biological activity. Hence, methods that harness selective carbon–hydrogen bond activation events and apply them directly toward controlled carbon–carbon bond-formation are transformative for the discovery and implementation of new small molecule therapeutics. This research combines two concepts in organic chemistry into a new mode of chemical synthesis that converts carbon-hydrogen bonds into carbon-carbon bonds in a stereocontrolled fashion. Transition metals, specifically rhodium, have long been known to selectively cleave unactivated carbon-hydrogen bonds but often form inert complexes in the process, thereby impeding catalysis. Photocatalysts are a powerful emerging tool that harness the energy of visible light and use it to promote reactivity in transition metal complexes. The specific aims of this research are to use photocatalysts to induce new reactivity with rhodium complexes that activate carbon-hydrogen bonds by three distinct modes. Coupling this reactivity with the use of abundant alkenes will provide a convenient method for the efficient synthesis of the complex frameworks of biologically active molecules. The product of this research will be a new synthetic tool that enables the rapid discovery and production of biologically active small molecules. This will ultimately improve public health by facilitating the design and production of affordable medicines to diagnose, treat, and prevent human disease.