通过一内吉希交叉合方法合成α-Aryl和α-Heteroaryl4-Silyloxy Piperidines
Matthew T Gill1, Lucy A Tomczyk1, Andres R Gomez-Angel1
1Department of Chemistry, University of York, York, YO10 5DD, U.K.
一种新方法使得使用单Negishi交叉合,可直接对受保护的4-基利丁进行alpha-arylation. 这种方法为药物相关化合物提供了高产量和多重选择性.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 合成方法论 合成方法论
背景情况:
- 皮皮里丁支架在经批准的药品中普遍存在.
- 功能化的piperidines的高效合成对于药物发现至关重要.
- 直接的阿尔法功能化方法非常受欢迎.
研究的目的:
- 为受保护的4-基利素开发一种直接和二元选择性α-arylation方法.
- 为了建立Negishi交叉合反应的单程序.
- 为制药相关的皮佩里丁衍生物提供一个多功能途径.
主要方法:
- 一尼吉希交叉合反应. 一尼吉希交叉合反应.
- 化/转金属化/交叉合的序列.
- 在整个过程中使用单一的溶剂 (烯).
主要成果:
- 成功地实现了受保护的4-基利的直接α-arylation.
- 报告了与各种 heteroaryl 化物进行高产的交叉合.
- 在反应中表现出高的2,4-cis-diastereoselectivity.
- 展示了20个示例,展示了该方法的范围.
结论:
- 开发的方法提供了一个直接的, diastereoselective 路径到功能化的 piperidines.
- 一的Negishi交叉合是高效的,并使用单一的溶剂.
- 这种方法很容易适用于制药行业的药物开发.
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