Liu Xin, Fu Yue, Chen Zhijie, Liu Peng, Dong Guangbin
Department of Chemistry, University of Chicago, Chicago, IL, USA.
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Nat Chem. 2023 Oct;15(10):1391-1399. doi: 10.1038/s41557-023-01312-z. Epub 2023 Aug 31.
Oxygen-substituted arenes widely exist in biologically important molecules and can serve as versatile handles to install other functional groups. However, direct and site-selective installation of oxygen groups to common aromatic compounds remains challenging, especially when additional arene functionalization is simultaneously required. Current arene C-H oxidation strategies generally require directing groups or precisely prefunctionalized substrates to control site-selectivity. While palladium/norbornene cooperative catalysis is promising for site-specific arene vicinal difunctionalization through simultaneous reactions with an electrophile and a nucleophile, the electrophile scope has been limited to species based on relatively 'soft' elements, such as carbon, nitrogen and sulfur. Here we report the development of an ortho oxygenation reaction with common aryl halides to rapidly deliver diverse aryl ethers. The coupling of the 'hard' oxygen electrophile is enabled by a stable, polarity-reversed, conformationally predistorted N-O reagent and facilitated by a C7-bromo-substituted norbornene mediator. Mechanistic studies reveal a unique S2-type pathway between the N-O reagent as the oxygen electrophile and an electron-rich Pd(II) nucleophile.
氧取代芳烃广泛存在于具有重要生物学意义的分子中，并且可作为安装其他官能团的通用手柄。然而，将氧基团直接且位点选择性地安装到常见的芳香族化合物上仍然具有挑战性，特别是当同时需要额外的芳烃官能化时。目前的芳烃C-H氧化策略通常需要导向基团或精确预官能化的底物来控制位点选择性。虽然钯/降冰片烯协同催化对于通过与亲电试剂和亲核试剂同时反应实现位点特异性芳烃邻位双官能化很有前景，但亲电试剂的范围仅限于基于相对“软”元素（如碳、氮和硫）的物种。在此，我们报告了一种与常见芳基卤化物发生邻位氧合反应以快速生成多种芳基醚的方法。“硬”氧亲电试剂的偶联通过稳定的、极性反转的、构象预扭曲的N-O试剂实现，并由C7-溴取代的降冰片烯介导剂促进。机理研究揭示了作为氧亲电试剂的N-O试剂与富电子Pd(II)亲核试剂之间独特的S2型途径。
