德国明斯特大学Armido Studer小组宣布他们实现了自由基和离子途径的吡啶、喹啉和异喹啉间位C-H官能化。2022年11月18日，国际知名学术期刊《科学》发表了这一成果。

研究组通过氧化还原中性的去芳香化-芳香化过程，实现了一种高区域选择性的吡啶类间位C-H三氟甲基化、全氟烷基化、氯化、溴化、碘化、硝化、磺化和硒化。该研究引入的去芳香化活化模式，为吡啶和其他氮杂芳烃的间位选择性反应提供了多样化平台，并可通过自由基或离子途径反应。这些不需催化剂的反应的广泛范围和高选择性使其适用于药物的后期功能化。

研究人员表示，吡啶的碳-氢官能化是快速构建和衍生化许多农药、药品和材料的有力工具。由于吡啶固有的电子性质，选择性间位碳-氢功能化具有挑战性。

附：英文原文

Title: Radical and ionic meta-C–H functionalization of pyridines, quinolines, and isoquinolines

Author: Hui Cao, Qiang Cheng, Armido Studer

Issue&Volume: 2022-11-18

Abstract: Carbon-hydrogen (CH) functionalization of pyridines is a powerful tool for the rapid construction and derivatization of many agrochemicals, pharmaceuticals, and materials. Because of the inherent electronic properties of pyridines, selective meta-CH functionalization is challenging. Here, we present a protocol for highly regioselective meta-CH trifluoromethylation, perfluoroalkylation, chlorination, bromination, iodination, nitration, sulfanylation, and selenylation of pyridines through a redox-neutral dearomatization-rearomatization process. The introduced dearomative activation mode provides a diversification platform for meta-selective reactions on pyridines and other azaarenes through radical as well as ionic pathways. The broad scope and high selectivity of these catalyst-free reactions render these processes applicable for late-stage functionalization of drugs.

DOI: ade6029

Source: https://www.science.org/doi/10.1126/science.ade6029