Scholarlink

<p>Highly strained rings serve as privileged building blocks for the synthesis of saturated, three-dimensional scaffolds, which are increasingly recognized as critical components in modern drug discovery. Here we disclose a substrate-dependent, divergent strategy to access a broad family of housanes through an intramolecular-energy-transfer-mediated [2 + 2] cycloaddition of 1,4-dienes—a transformation that has long been considered challenging. This method rapidly builds up strain while suppressing the di-<i>π</i>-methane rearrangement, thereby expanding the toolkit for efficient exploration of housane chemical space. Substituent engineering enables switching between single and double energy-transfer pathways to deliver 1,3- and 1,2-disubstituted housanes with excellent stereocontrol and broad functional-group tolerance. Mechanistic studies and density functional theory calculations support an energy-transfer pathway and rationalize the observed selectivity.</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

Divergent housane synthesis via intramolecular [2 + 2] cycloaddition of 1,4-dienes

  • 期刊论文

  • 发表日期：

    2026年2月19日

查看全文
  • Fuhao Zhang,
  • Julius Domack,
  • Niklas Hölter,
  • Constantin G. Daniliuc,
  • Frank Glorius

摘要

Highly strained rings serve as privileged building blocks for the synthesis of saturated, three-dimensional scaffolds, which are increasingly recognized as critical components in modern drug discovery. Here we disclose a substrate-dependent, divergent strategy to access a broad family of housanes through an intramolecular-energy-transfer-mediated [2 + 2] cycloaddition of 1,4-dienes—a transformation that has long been considered challenging. This method rapidly builds up strain while suppressing the di-π-methane rearrangement, thereby expanding the toolkit for efficient exploration of housane chemical space. Substituent engineering enables switching between single and double energy-transfer pathways to deliver 1,3- and 1,2-disubstituted housanes with excellent stereocontrol and broad functional-group tolerance. Mechanistic studies and density functional theory calculations support an energy-transfer pathway and rationalize the observed selectivity.