Scholarlink

<p>The configuration of cyclobutane-based drug molecules plays a critical role in their biological and pharmacological properties. Although substantial progress has been made in the chemoselective and diastereoselective construction of substituted cyclobutanes, achieving efficient diastereodivergent catalysis from the same set of starting materials remains challenging. In this work, an electrochemical cobalt-catalysed method for the reductive coupling of alkynes and cyclobutenes is reported, enabling the synthesis of a range of substituted cyclobutane diastereoisomers. Proton sources are used to generate cobalt–hydride intermediates through a sequence of cathodic reduction and protonation. By modulating the steric and electronic properties of the proton sources, the <i>trans/cis</i> ratio can be altered, offering a different approach for the efficient synthesis of two diastereoisomers of the desired cyclobutane product. Mechanistic studies support a Co(II)–H reaction pathway and suggest that diastereodivergence arises from distinct distortions of the proton source and differential interactions between the cyclobutyl cobalt intermediate and the respective proton sources.</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

Diastereodivergent construction of disubstituted cyclobutanes via electrochemical cobalt-catalysed reductive coupling

  • 期刊论文

  • 发表日期：

    2026年1月5日

查看全文
  • Jie Yang,
  • Hengxu Li,
  • Qiong Wang,
  • Qiang Liu

摘要

The configuration of cyclobutane-based drug molecules plays a critical role in their biological and pharmacological properties. Although substantial progress has been made in the chemoselective and diastereoselective construction of substituted cyclobutanes, achieving efficient diastereodivergent catalysis from the same set of starting materials remains challenging. In this work, an electrochemical cobalt-catalysed method for the reductive coupling of alkynes and cyclobutenes is reported, enabling the synthesis of a range of substituted cyclobutane diastereoisomers. Proton sources are used to generate cobalt–hydride intermediates through a sequence of cathodic reduction and protonation. By modulating the steric and electronic properties of the proton sources, the trans/cis ratio can be altered, offering a different approach for the efficient synthesis of two diastereoisomers of the desired cyclobutane product. Mechanistic studies support a Co(II)–H reaction pathway and suggest that diastereodivergence arises from distinct distortions of the proton source and differential interactions between the cyclobutyl cobalt intermediate and the respective proton sources.