A Palladium(0)‐Catalyzed C4 Site‐Selective C−H Difluoroalkylation of Isoquinolin‐1(2H)‐Ones

Herein, we report a Palladium(0)‐catalyzed C4 site‐selective C−H difluoroalkylation of isoquinolin‐1(2H)‐ones through a radical pathway. The present reaction enables the preparation of 2,2‐difluoro‐2‐(1‐oxo‐1,2‐dihydroisoquinolin‐4‐yl)acetates/acetamides through the direct cross‐coupling reaction of...

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Bibliographic Details
Published in:Advanced synthesis & catalysis 2021-04, Vol.363 (8), p.2170-2176
Main Authors: Zhu, You‐Quan, Hui, Li‐Wen, Zhang, Shi‐Bo
Format: Article
Language:English
Subjects:
Acetates
Coupling (molecular)
Cross coupling
Difluoroalkylation
Ethyl bromodifluoroacetate
Isoquinolin-1(2H)-ones
Palladium
Site-selective
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Summary:Herein, we report a Palladium(0)‐catalyzed C4 site‐selective C−H difluoroalkylation of isoquinolin‐1(2H)‐ones through a radical pathway. The present reaction enables the preparation of 2,2‐difluoro‐2‐(1‐oxo‐1,2‐dihydroisoquinolin‐4‐yl)acetates/acetamides through the direct cross‐coupling reaction of readily available isoquinolin‐1(2H)‐ones with 2‐bromo‐2,2‐difluoroacetates or 2‐bromo‐2,2‐difluoroacetamides. Therefore, this method provides an efficient and convenient approach to install a difluoroacetate or a difluoroacetamide moiety into bioactive molecules. Bioassay results showed that introduction of these difluorinated groups at C4 position was beneficial to improve their antiviral activity and compound 5 ab was found to exhibit similar antiviral activity with commercial Ningnanmycin.
ISSN:1615-4150
1615-4169
DOI:10.1002/adsc.202001614