School of Chemistry, University of Manchester, Manchester, UK.
Nat Chem. 2018 Jul;10(7):724-731. doi: 10.1038/s41557-018-0062-3. Epub 2018 Jun 21.
Biaryls are ubiquitous core structures in drugs, agrochemicals and organic materials that have profoundly improved many aspects of our society. Although traditional cross-couplings have made practical the synthesis of many biaryls, C-H arylation represents a more attractive and cost-effective strategy for building these structural motifs. Furthermore, the ability to install biaryl units in complex molecules via late-stage C-H arylation would allow access to valuable structural diversity, novel chemical space and intellectual property in only one step. However, known C-H arylation protocols are not suitable for substrates decorated with polar and delicate functionalities, which are commonly found in molecules that possess biological activity. Here we introduce a class of ruthenium catalysts that display a unique efficacy towards late-stage arylation of heavily functionalized substrates. The design and development of this class of catalysts was enabled by a mechanistic breakthrough on the Ru(II)-catalysed C-H arylation of N-chelating substrates with aryl (pseudo)halides, which has remained poorly understood for nearly two decades.
联芳烃是药物、农用化学品和有机材料中普遍存在的核心结构，极大地改善了我们社会的许多方面。尽管传统的交叉偶联已经使许多联芳烃的合成成为可能，但 C-H 芳基化代表了构建这些结构基序更具吸引力和成本效益的策略。此外，通过晚期 C-H 芳基化在复杂分子中安装联芳烃单元，可以仅通过一步获得有价值的结构多样性、新的化学空间和知识产权。然而，已知的 C-H 芳基化方案不适用于带有极性和脆弱官能团的底物，这些官能团通常存在于具有生物活性的分子中。在这里，我们介绍了一类钌催化剂，它们对功能化程度高的底物的晚期芳基化具有独特的功效。该类催化剂的设计和开发得益于对近二十年来一直知之甚少的 Ru(II)催化的 N-螯合底物与芳基（假）卤化物的 C-H 芳基化的突破性机制。
