Scholarlink

<p>Despite cross-coupling strategies that enable the functionalization of aromatic heterocycles, the enantioselective C(<i>sp</i><sup>3</sup>)–H alkylation of readily available saturated hydrocarbons to construct C(<i>sp</i><sup>3</sup>)–C(<i>sp</i><sup>3</sup>) bonds remains a formidable challenge. Here we describe a nickel-catalysed enantioselective C(<i>sp</i><sup>3</sup>)–H alkylation of saturated heterocycles using olefins, providing an efficient strategy for the stereoselective construction of C(<i>sp</i><sup>3</sup>)–C(<i>sp</i><sup>3</sup>) bonds. Using readily available and stable olefins and simple saturated nitrogen and oxygen heterocycles as prochiral nucleophiles, the coupling reactions proceed under mild conditions and exhibit broad scope and high functional group tolerance. Furthermore, the enantio- and diastereoselective C(<i>sp</i><sup>3</sup>)–H alkylation of saturated hydrocarbons with alkenyl boronates has been achieved, enabling the synthesis of versatile alkyl boronates containing 1,2-adjacent C(<i>sp</i><sup>3</sup>) stereocentres. Application of this approach to the late-stage modification of natural products and drugs, as well as to the enantioselective synthesis of a range of chiral building blocks and natural products, is demonstrated.</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

Direct stereoselective C(sp3)–H alkylation of saturated heterocycles using olefins

  • 期刊论文

  • 发表日期：

    2025年2月28日

查看全文
  • Zhijun Zhou,
  • Yang Ke,
  • Rui Miao,
  • Fen Hu,
  • Xiaoqin Wang,
  • Yuanyuan Ping,
  • Sheng Xu,
  • Wangqing Kong

摘要

Despite cross-coupling strategies that enable the functionalization of aromatic heterocycles, the enantioselective C(sp3)–H alkylation of readily available saturated hydrocarbons to construct C(sp3)–C(sp3) bonds remains a formidable challenge. Here we describe a nickel-catalysed enantioselective C(sp3)–H alkylation of saturated heterocycles using olefins, providing an efficient strategy for the stereoselective construction of C(sp3)–C(sp3) bonds. Using readily available and stable olefins and simple saturated nitrogen and oxygen heterocycles as prochiral nucleophiles, the coupling reactions proceed under mild conditions and exhibit broad scope and high functional group tolerance. Furthermore, the enantio- and diastereoselective C(sp3)–H alkylation of saturated hydrocarbons with alkenyl boronates has been achieved, enabling the synthesis of versatile alkyl boronates containing 1,2-adjacent C(sp3) stereocentres. Application of this approach to the late-stage modification of natural products and drugs, as well as to the enantioselective synthesis of a range of chiral building blocks and natural products, is demonstrated.