通过可逆原子转移催化剂对三胺的选择性α-C-H功能化
Yangyang Shen1, Ignacio Funez-Ardoiz2, Franziska Schoenebeck2
1Department of Chemistry, Columbia University, New York, New York 10027, United States.
Journal of the American Chemical Society
|November 5, 2021
概括
这项研究引入了一种新方法,用于在硬质阻碍位置选择性地功能化试基胺,克服了用于药物发现的C-H键激活的先前限制.
科学领域:
- 有机化学 有机化学
- 催化剂是一种催化剂.
- 药用化学 医学化学
背景情况:
- 三胺是药品和天然产品中至关重要的构建块.
- 由于硬质障碍,试基胺的选择性功能化具有挑战性.
- 目前的方法有利于较少拥挤的地点,限制合成效用.
研究的目的:
- 开发一种方法,用于选择性α-C(sp3) -H键功能化试基胺在硬质阻碍位置.
- 在试基胺功能化中克服固体控制.
- 为了使药剂的简化合成和后期修改成为可能.
主要方法:
- 利用可逆的原子转移,在α-氨基C(sp3) -H键和一个基之间建立平衡.
- 使用较慢的基因捕捉步骤与缺电子的烯酸.
- 应用Curtin-Hammett原则来引导选择性向更拥挤的α-氨基基基.
主要成果:
- 在更拥挤的α-氨基基位点实现了选择性C(sp3) -C(sp3) 键形成.
- 在多种不同的试基胺中表现出高位点选择性和准备性实用性.
- 建立了一个使用13C NMR转移的地点选择性的定性预测指南.
结论:
- 这种动态系统提供了一种新的战略方法,用于直接C-H功能化.
- 该方法促进了N替代四等碳中心的形成.
- 这种方法具有显著的潜力,可以加速小分子药物发现和简化合成.
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