Abstract:
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.
摘要:
四氢吡啶嗪构成了许多天然产物和药物化合物中发现的重要结构基序。在这里,我们报道了烯烃的氨基酰化反应,该反应能够通过协同N-杂环卡宾(NHC)和光氧化还原催化合成1,4,5,6-四氢吡啶嗪。这种方法涉及以N为中心的肼基自由基的6-内-trig环化,通过腙的单电子氧化产生,随后是自由基-自由基偶联步骤。温和的方法容许宽范围的常见官能团,并以中等至高产率提供多种四氢吡啶嗪。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。