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镍催化的恶唑和苯并恶唑的 C-H 芳基化反应,使用具有药物相关性的芳基氯代物和溴代物。

Ni-Catalyzed C-H Arylation of Oxazoles and Benzoxazoles Using Pharmaceutically Relevant Aryl Chlorides and Bromides.

机构信息

Department of Chemistry , St. Olaf College , 1520 St. Olaf Avenue , Northfield , Minnesota 55057 , United States.

Process Research and Development , Merck & Co., Inc. , Rahway , New Jersey 07065 , United States.

出版信息

J Org Chem. 2019 Oct 18;84(20):13092-13103. doi: 10.1021/acs.joc.9b02094. Epub 2019 Sep 24.

Abstract

This manuscript details the development of the nickel-catalyzed arylation of oxazoles and benzoxazoles with aryl halides. A series of aryl, heteroaryl, and druglike electrophiles relevant to pharmaceutical applications were surveyed. The desired arylated products were obtained in synthetically useful yields using electronically and structurally varied aryl halides. The use of microscale high-throughput experimentation was essential for both the rapid identification of optimal reaction parameters and the investigation of the aryl halide scope.

摘要

这篇手稿详细介绍了镍催化的恶唑和苯并恶唑与芳基卤化物的芳基化反应的发展。考察了一系列与药物应用相关的芳基、杂芳基和药物样电子亲合物。使用电子和结构变化的芳基卤化物,以合成有用的产率获得了所需的芳基化产物。微量高通量实验的使用对于快速确定最佳反应参数和调查芳基卤化物范围都是至关重要的。

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