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<p>The pervasive occurrence of chiral quaternary all-carbon stereocentres has stimulated great efforts towards the construction of such motifs. Among them, transition-metal-catalysed asymmetric radical C(<i>sp</i><sup>3</sup>)–C(<i>sp</i><sup>3</sup>) cross-coupling of racemic tertiary alkyl electrophiles with alkyl-based nucleophiles constitutes an appealing strategy, though it has rarely been reported. The major challenge lies in the sluggish interaction of transition-metal–alkyl species and sterically hindered tertiary alkyl radicals, which complicates both chemo- and enantiocontrol. Here we demonstrate a practical copper-catalysed enantioconvergent C(<i>sp</i><sup>3</sup>)–C(<i>sp</i><sup>3</sup>) cross-coupling of racemic tertiary electrophiles with easily accessed and bench-stable cyclopropanols under mild reaction conditions. Key to success is the rational design of quinine-derived <i>N</i>,<i>N</i>,<i>N</i>-ligands to form coordinatively saturated copper intermediates with low steric congestion around the metal centre to accommodate tertiary alkyl radicals. This protocol provides a highly flexible platform for the rapid synthesis of enantioenriched C(<i>sp</i><sup>3</sup>)-rich building blocks with sterically crowded stereocentres that hold substantial interest in organic synthesis and related disciplines.</p><p></p>

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Copper-catalysed enantioconvergent radical C(sp3)–C(sp3) cross-coupling of tertiary electrophiles with cyclopropanols for quaternary carbon formation

  • 期刊论文

  • 发表日期：

    2026年2月2日

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  • Dong Gao,
  • Long-Zhou Qin,
  • Zhong-Liang Li,
  • Qiang-Shuai Gu,
  • Xin-Yuan Liu

摘要

The pervasive occurrence of chiral quaternary all-carbon stereocentres has stimulated great efforts towards the construction of such motifs. Among them, transition-metal-catalysed asymmetric radical C(sp3)–C(sp3) cross-coupling of racemic tertiary alkyl electrophiles with alkyl-based nucleophiles constitutes an appealing strategy, though it has rarely been reported. The major challenge lies in the sluggish interaction of transition-metal–alkyl species and sterically hindered tertiary alkyl radicals, which complicates both chemo- and enantiocontrol. Here we demonstrate a practical copper-catalysed enantioconvergent C(sp3)–C(sp3) cross-coupling of racemic tertiary electrophiles with easily accessed and bench-stable cyclopropanols under mild reaction conditions. Key to success is the rational design of quinine-derived N,N,N-ligands to form coordinatively saturated copper intermediates with low steric congestion around the metal centre to accommodate tertiary alkyl radicals. This protocol provides a highly flexible platform for the rapid synthesis of enantioenriched C(sp3)-rich building blocks with sterically crowded stereocentres that hold substantial interest in organic synthesis and related disciplines.