Shah Jagrut A, Banerjee Arghya, Mukherjee Upasana, Ngai Ming-Yu
Department of Chemistry, State University of New York, Stony Brook, New York, 11794, United States.
Department of Chemistry, Purdue University, West Lafayette, Indiana, 47907, United States.
Chem. 2024 Feb 8;10(2):686-697. doi: 10.1016/j.chempr.2023.11.005. Epub 2023 Dec 11.
Nitro(hetero)arene derivatives are essential commodity chemicals used in various products, such as drugs, polymers, and agrochemicals. In this study, we leverage the excited-state reactivities of copper catalysts and nitro(hetero)arenes, and the Umpolung reactivity of acyl radicals to convert readily available nitro(hetero)arenes directly to valuable 2-aminophenol derivatives, which are important scaffolds in many top-selling pharmaceuticals. This reaction is applicable to a variety of nitro(hetero)arenes, acyl chlorides, and late-stage modifications of complex molecules, making it a useful tool for the discovery of new functional molecules. Mechanistic studies, including radical trapping experiments, Stern Volmer quenching studies, light ON/OFF experiments, and O-labeling studies, suggest a reaction mechanism involving photoexcitation of a copper complex, diradical couplings, and an in-cage contact ion pair (CIP) migration. Our findings offer a streamlined protocol for synthesizing essential pharmacophores from nitro(hetero)arenes while simultaneously advancing knowledge in excited-state and radical chemistry and stimulating new reaction design and development.
硝基（杂）芳烃衍生物是用于各种产品（如药物、聚合物和农用化学品）的重要商品化学品。在本研究中，我们利用铜催化剂和硝基（杂）芳烃的激发态反应性，以及酰基自由基的极性翻转反应性，将容易获得的硝基（杂）芳烃直接转化为有价值的2-氨基酚衍生物，这些衍生物是许多畅销药物中的重要骨架。该反应适用于多种硝基（杂）芳烃、酰氯以及复杂分子的后期修饰，使其成为发现新功能分子的有用工具。机理研究，包括自由基捕获实验、斯特恩-沃尔默猝灭研究、光开/关实验和O标记研究，表明反应机理涉及铜配合物的光激发、双自由基偶联和笼内接触离子对（CIP）迁移。我们的研究结果提供了一种简化的方案，用于从硝基（杂）芳烃合成必需的药效基团，同时推进激发态和自由基化学的知识，并刺激新反应的设计和开发。
