New Catalytic Strategies for Metal-Free C-C Bond Formation

过渡金属催化的交叉偶联是形成sp2-sp2和sp2-sp3 C-C键的唯一有效工具。然而，SP3-SP3联轴器固有的挑战在很大程度上阻碍了对该问题的普遍适用解决方案的开发。此外，依赖过渡金属催化剂来建立烷基-烷基键可能会导致药物开发环境中的问题，因为这些催化剂容易被类药物分子中常见的基本官能团中毒。此外，微量金属污染在制药中是一个严重的问题。由于这些原因，一种无金属的C(SP3)-C(SP3)键形成方法在有机合成中可能被证明是变革性的。在这个项目中，我们将探索一些在不依赖于金属催化的情况下形成无金属C(SP3)-C(SP3)键的方法，利用可见光催化产生自由基中间体。我们最初的目标是开发一种新的一锅法烷基羧酸的同系化工艺，将脂肪链延长一个碳。这样的进程将是综合强大的，但目前无法以直接方式实现。

Transition metal-catalysed cross-coupling is a uniquely powerful tool for the formation of sp2-sp2 and sp2-sp3 C-C linkages. However, challenges inherent in sp3-sp3 couplings have largely impeded the development of generally applicable solutions to this problem. Moreover, a reliance on transition metal catalysts to forge alkyl-alkyl linkages can lead to problems in a drug development setting, as these catalysts are prone to poisoning by the basic functionalities commonly encountered in drug-like molecules. Additionally, trace metal contamination is a serious concern in a pharmaceutical manufacture. For these reasons, a metal-free approach to C(sp3)-C(sp3) bond formation could prove transformative in organic synthesis. In this project, we will explore a number of approaches to metal-free C(sp3)-C(sp3) bond formation without reliance on metal catalysis, using visible-light photocatalysis to generate radical intermediates. Our initial objective is to develop a novel, one-pot homologation process for alkyl carboxylic acids, extending an aliphatic chain by a single carbon. Such a process would be synthetically powerful, but is currently unachievable in a direct fashion.