在含有胺基的分子中,阿里法性C-H键的远程晚期氧化
Takeshi Nanjo1, Emilio C de Lucca1, M Christina White1
1Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
一种新的酸盐策略使胺具有选择性C-H氧化,这对于制药至关重要. 这种方法克服了以前的N-保护技术的局限性,扩大了药物发现后期功能化的可能性.
科学领域:
- 有机化学
- 医学化学
- 催化剂
背景情况:
- 胺功能在药品和天然产品中普遍存在.
- 由于其电子性质,现有的N-保护策略不适合远程C-H氧化胺.
研究的目的:
- 开发一种新型的保护组策略,使含有胺的分子能够进行远程的选择性C ((sp3) -H氧化.
- 扩大医学相关化合物的后期功能化范围.
主要方法:
- 开发了一种使用甲基三甲硫酸盐的可逆保护策略.
- 在各种胺衍生物上进行了铁催化 (Fe ((PDP) 和Fe ((CF3PDP)) 远程C ((sp3) -H氧化.
- 二级和初级胺被掩盖为N-N胺以促进氧化.
主要成果:
- 在不同类型的氨基酸 (三级氨基酸,化物,二氧化,碳酸盐) 的存在下,化盐的策略成功实现了远程,非定向,选择性C ((sp3) -H氧化.
- 该方法与广泛的功能兼容.
- 掩蔽策略对初级和二级胺有效.
结论:
- 这种新的酸盐策略是首次实现胺的远程C-H氧化.
- 这种方法显著扩大了晚期氧化对药物发现和开发的有用性.
- 该策略有可能产生与自由胺基不相容的其他金属介导反应和C-H氧化.
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