Scholarlink

<p>Transition metal-catalysed enantioselective radical transformations have emerged as powerful tools for the synthesis of chiral molecules, and a range of methods have been developed. However, most of these successful reactions are effective for resonance-stabilized radicals; in sharp contrast, achieving precise stereocontrol over highly reactive, unstabilized alkyl radicals remains a major challenge, with very few successful examples. Here we establish a ligand-mediated radical orientation strategy that enables the highly enantioselective cyanation of such transient intermediates via copper catalysis. The chiral Box<sup>OH</sup> ligand engages in dynamic hydrogen bonding with various remote functional groups on the radical species, strategically reshaping the reaction energy landscape and overcoming the inherently barrierless radical coupling process to dictate stereoselectivity. Consequently, this method enables the direct asymmetric cyano-functionalization of unactivated alkenes and inert <i>sp</i><sup>3</sup> C–H bonds, expanding asymmetric radical reactions beyond stabilized intermediates and providing a platform for the enantioselective functionalization of abundant chemical feedstocks.</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

Ligand-mediated radical orientation enables asymmetric cyanation of unstabilized alkyl C-radicals

  • 期刊论文

  • 发表日期：

    2026年7月10日

查看全文
  • Xin Chen,
  • Wenzheng Fan,
  • Junfeng Wang,
  • Pinhong Chen,
  • Guosheng Liu

摘要

Transition metal-catalysed enantioselective radical transformations have emerged as powerful tools for the synthesis of chiral molecules, and a range of methods have been developed. However, most of these successful reactions are effective for resonance-stabilized radicals; in sharp contrast, achieving precise stereocontrol over highly reactive, unstabilized alkyl radicals remains a major challenge, with very few successful examples. Here we establish a ligand-mediated radical orientation strategy that enables the highly enantioselective cyanation of such transient intermediates via copper catalysis. The chiral BoxOH ligand engages in dynamic hydrogen bonding with various remote functional groups on the radical species, strategically reshaping the reaction energy landscape and overcoming the inherently barrierless radical coupling process to dictate stereoselectivity. Consequently, this method enables the direct asymmetric cyano-functionalization of unactivated alkenes and inert sp3 C–H bonds, expanding asymmetric radical reactions beyond stabilized intermediates and providing a platform for the enantioselective functionalization of abundant chemical feedstocks.