Ligand-Promoted Pd(II)-Catalyzed Functionalization of Unactivated C(sp3)–H Bond: Regio- and Stereoselective Synthesis of Arylated Rimantadine Derivatives
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- 作者：Zhoulong Fan ; Shiqi Shu ; Jiabin Ni ; Qizheng Yao ; Ao Zhang
- 刊名：ACS Catalysis
- 出版年：2016
- 出版时间：February 5, 2016
- 年：2016
- 卷：6
- 期：2
- 页码：769-774
- 全文大小：539K
- ISSN：2155-5435
文摘
Stereoselective functionalization of the adamantyl bridge methylene C(sp3)–H bonds is a rather appealing, yet challenging strategy due to the bulky and unactivated nature. Here we present a palladium-catalyzed C(sp3)–H arylation/hetereoarylation of the antivirus drug rimantadine with the picolinamide moiety as the bidentate directing group and a mono-N-protected amino acid (MPAA) as the ligand. Multisubstituted rimantadine substrates and diverse aryl/heteroaryl iodides are well tolerated, and a series of optically pure arylated rimantadine derivatives have been synthesized in high regio- and diastereoselectivity that provides ample compound space for further pharmaceutical research.