近日，美国明尼苏达大学Roberts, Courtney C.团队研究了羧酸衍生的大量苯胺衍生物。2025年11月5日出版的《自然》杂志发表了这项成果。

高取代芳环在药物和农用化学品中广泛存在。在芳环构建领域，芳炔中间体具有媲美大多数官能团的合成潜力：既能与亲核试剂快速反应，又可参与周环反应，还能激活惰性σ键。尽管潜力巨大，目前芳炔仅被特定研究群体主要用于小众领域。其应用范围受限的根源在于现有生成方法存在明显缺陷。

研究组报道了一种能突破此限制的芳炔前体设计策略：将易得的羧酸经一步衍生化制备前体，再通过蓝光照射或加热激活。基于该方法，成功制备了数十种前所未有的胺化芳炔（包括吡啶炔），为基于芳炔中间体的药物研发开辟了新途径。研究组预见该前体平台的后续发展有望实现更复杂结构芳炔的制备，进一步拓展芳炔化学的应用边界。

附：英文原文

Title: Myriad Aryne Derivatives from Carboxylic Acids

Author: Seong, Chris M., Kargbo, Sallu S., Yu, Chia-Ling, Gibney, Daniel, Boyn, Jan-Niklas, Roberts, Courtney C.

Issue&Volume: 2025-11-05

Abstract: Densely substituted aromatic rings are ubiquitous in pharmaceuticals and agrochemicals1. For making aromatic molecules, aryne intermediates have synthetic potential that rivals most functional groups2. They readily react with nucleophiles, participate in pericyclic reactions, and activate inert σ-bonds. Despite their potential, arynes are currently used by a specialized community for mainly niche applications. The lack of widespread adoption of arynes is due to the undesirable means to generate them. Here, we report the design of an aryne precursor to overcome this prohibitive barrier. Readily available carboxylic acids are derivatized in a single step to a make a precursor which is then activated by blue light or by heat. Dozens of previously unknown aminated arynes, including pyridynes, are generated in this work, opening the door to drug discovery using aryne intermediates. We envision that future development of this precursor platform will allow even more decorated arynes to be accessed, further expanding the reach of aryne chemistry.

DOI: 10.1038/s41586-025-09830-1

Source: https://www.nature.com/articles/s41586-025-09830-1