克服了对异循环的定向C-H功能化的局限性
Yue-Jin Liu1, Hui Xu1, Wei-Jun Kong1
1State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Nature
|November 11, 2014
概括
这项研究引入了一种针对异环体的C-H激活的新方法,克服了由和硫原子引起的催化剂中毒. N-甲胺组使选择性功能化成为可能,促进了药物发现应用.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 催化剂是一种催化剂.
背景情况:
- 定向的C-H激活对于药物发现至关重要,但受到异环基质基质中异原子协调的阻碍.
- 异环中的和硫原子可以毒害金属催化剂或将功能化直接转移到不需要的位置.
研究的目的:
- 开发一种强大的方法,用于C-H功能化异环,克服了协调异环原子所造成的局限性.
- 为了使C-H激活在基于异环的药物发现中的应用.
主要方法:
- 使用一个N-甲胺基组作为指导组和阳离子连接体.
- 使用空气作为氧化剂,在现场从Pd(0) 源生成一个活性PdX2物种.
- 将催化剂定位在目标C-H键附近,以避免基质异原子的干扰.
主要成果:
- 在异环环上成功实现了C-H功能化,绕过了和硫原子的干扰.
- 展示了一种方法,它取代了由异原子决定的常规定位选择性模式.
- 开发了一种操作上简单的有氧反应,用于定向的C-H激活.
结论:
- N-甲胺的策略有效地克服了用于药物化学的定向C-H激活的基本局限性.
- 这种方法扩大了用于药物发现的复杂异环分子合成中C-H激活的范围.
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