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<p><i>N</i>-Aryl morpholines are valuable heterocyclic scaffolds with significant applications in medicinal and materials chemistry. The efficient construction of the C-N bond between morpholine and aryl units remains a central challenge in organic synthesis. Transition metal-based catalysis, often supported with ligands, allows the selective and efficient production of <i>N</i>-aryl bonds. In parallel, metal-free strategies including microwave-assisted synthesis, quantum dot-mediated reactions, Lewis acid catalysis, and photo-catalysis offer sustainable alternatives. These reactions are discussed in light of their substrate scopes, mechanistic profiles, and reaction efficiencies, highlighting the continuous evolution and optimization essential for further research. Collectively, this review aims to provide a state-of-the-art perspective on the synthesis of <i>N</i>-arylation of morpholine reported in 2021–2025.</p> Graphical Abstract <p></p>

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An insight into the synthetic routes for N-arylation of morpholine using metal-catalyzed and metal-free methods

  • 期刊论文

  • 发表日期：

    2025年8月8日

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  • Saeeda Mubashra,
  • Matloob Ahmad,
  • Sana Aslam

摘要

N-Aryl morpholines are valuable heterocyclic scaffolds with significant applications in medicinal and materials chemistry. The efficient construction of the C-N bond between morpholine and aryl units remains a central challenge in organic synthesis. Transition metal-based catalysis, often supported with ligands, allows the selective and efficient production of N-aryl bonds. In parallel, metal-free strategies including microwave-assisted synthesis, quantum dot-mediated reactions, Lewis acid catalysis, and photo-catalysis offer sustainable alternatives. These reactions are discussed in light of their substrate scopes, mechanistic profiles, and reaction efficiencies, highlighting the continuous evolution and optimization essential for further research. Collectively, this review aims to provide a state-of-the-art perspective on the synthesis of N-arylation of morpholine reported in 2021–2025.

Graphical Abstract