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A Palladium(0)‐Catalyzed C4 Site‐Selective C−H Difluoroalkylation of Isoquinolin‐1( 2H )‐Ones
Author(s) -
Zhu YouQuan,
Hui LiWen,
Zhang ShiBo
Publication year - 2021
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.202001614
Subject(s) - chemistry , moiety , palladium , catalysis , combinatorial chemistry , molecule , bioassay , coupling reaction , stereochemistry , organic chemistry , biology , genetics
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.