Liu Wen-Deng, Gao Jiyuan, Mo Jia-Nan, Zhou Yuqiao, Zhao Jiannan
School of Chemistry, Dalian University of Technology, Dalian, 116024, P. R. China.
Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, P. R. China.
Chemistry. 2024 Oct 1;30(55):e202402288. doi: 10.1002/chem.202402288. Epub 2024 Sep 13.
Tetrahydropyridazines constitute an important structural motif found in numerous natural products and pharmaceutical compounds. Herein, we report an aminoacylation reaction of alkenes that enables the synthesis of 1,4,5,6-tetrahydropyridazines through cooperative N-heterocyclic carbene (NHC) and photoredox catalysis. This approach involves the 6-endo-trig cyclization of N-centered hydrazonyl radicals, generated via single-electron oxidation of hydrazones, followed by a radical-radical coupling step. The mild process tolerates a wide range of common functional groups and affords a variety of tetrahydropyridazines in moderate to high yields. Preliminary investigations using chiral NHC catalysts demonstrate the potential of this protocol for asymmetric radical reactions.
四氢哒嗪是许多天然产物和药物化合物中存在的重要结构基序。在此，我们报道了一种烯烃的氨酰化反应，该反应能够通过协同的N-杂环卡宾（NHC）和光氧化还原催化作用合成1,4,5,6-四氢哒嗪。这种方法涉及通过腙的单电子氧化生成的N-中心肼基自由基的6-内型-三氟环化反应，随后是自由基-自由基偶联步骤。该温和的过程耐受多种常见官能团，并以中等到高的产率提供多种四氢哒嗪。使用手性NHC催化剂的初步研究证明了该方案用于不对称自由基反应的潜力。
