在三胺N-CH3组的选择性C-H功能化中进行反热力学原子抽象
Joshua P Barham1,2, Matthew P John2, John A Murphy1
1WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde , 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
Journal of the American Chemical Society
|November 5, 2016
概括
这项研究引入了一种用于选择性地功能化氨基中的N-甲基的新方法. 这种化学转化使复杂分子 (包括药物) 的有效地选择性修饰成为可能.
科学领域:
- 有机化学
- 催化剂
- 合成方法
背景情况:
- 在氨基中选择性功能化C-H键仍然是有机合成的一个重大挑战.
- 现有的方法往往缺乏对其他基替代物的N-甲基所需的选择性.
研究的目的:
- 开发一种高选择性和高效的N-甲基组在N-甲基-N,N-二甲基胺中的功能化方案.
- 在复杂分子的后期功能化中展示该方法的实用性.
主要方法:
- 通过与三盐的氧化利用现场生成的激素DABCO•+ (1,4-diazabicyclo[2.2.2]octane激素) 的单协议.
- 从N-CH3组中选择性C-H抽取,然后与有机金属核友反应.
主要成果:
- 在N-CH2R或N-CHR2组上实现高化学选择性N-CH3功能化.
- 已证明试剂的可扩展性和可回收性.
- 成功地将该方法应用于天然产品和药品的后期功能化.
结论:
- 开发的协议为N-甲基组的认证提供了一种新且高度选择性的途径.
- 这种方法为药物发现和天然产品化学中的快速衍生和SAR研究提供了强大的工具.
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