Scholarlink

<p>Nickel-catalysed enantioconvergent cross-coupling has emerged as a key strategy for constructing stereochemically defined C(<i>sp</i><sup>3</sup>) centres. However, the reliance on nickel(I)/nickel(III) catalytic cycles has limited the range of compatible alkyl electrophiles and nucleophiles. Here we report an aryl-radical-enabled oxidative addition mechanism that connects Ni<sup>II</sup> and formal Ni<sup>IV</sup> oxidation states, enabling the enantioselective difluoromethylation of unactivated alkyl halides. Mechanistic investigations, including X-ray crystallography, electron paramagnetic resonance spectroscopy and density functional theory calculations, support the involvement of a nickel(II/III/IV) cycle via the stepwise oxidative addition of Ni<sup>II</sup> intermediates. The broad substrate scope and compatibility with pharmaceutically relevant molecules highlight the potential of this catalytic platform in asymmetric catalysis.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Enantioselective difluoromethylation of unactivated alkyl halides via a formal nickel(II/IV) cycle

  • 期刊论文

  • 发表日期：

    2026年3月9日

查看全文
  • Xian Zhao,
  • Lingfeng Yin,
  • Chia-Jung Yang,
  • Andrew T. Poore,
  • Xinyu Zhang,
  • Stephen C. Yachuw,
  • Chao Wang,
  • Xiao Wang,
  • Hairong Guan,
  • Jeanette A. Krause,
  • Mu-Jeng Cheng,
  • Shiliang Tian,
  • Wei Liu

摘要

Nickel-catalysed enantioconvergent cross-coupling has emerged as a key strategy for constructing stereochemically defined C(sp3) centres. However, the reliance on nickel(I)/nickel(III) catalytic cycles has limited the range of compatible alkyl electrophiles and nucleophiles. Here we report an aryl-radical-enabled oxidative addition mechanism that connects NiII and formal NiIV oxidation states, enabling the enantioselective difluoromethylation of unactivated alkyl halides. Mechanistic investigations, including X-ray crystallography, electron paramagnetic resonance spectroscopy and density functional theory calculations, support the involvement of a nickel(II/III/IV) cycle via the stepwise oxidative addition of NiII intermediates. The broad substrate scope and compatibility with pharmaceutically relevant molecules highlight the potential of this catalytic platform in asymmetric catalysis.