Palladium-catalyzed non-directed C-H functionalization provides an efficient approach for direct functionalization of arenes, but it usually suffers from poor site selectivity, limiting its wide application.Herein, it...Palladium-catalyzed non-directed C-H functionalization provides an efficient approach for direct functionalization of arenes, but it usually suffers from poor site selectivity, limiting its wide application.Herein, it is reported for the first time that the carboxylic acid ligand of 3,5-dimethyladamantane-1-carboxylic acid(1-DMAd CO_(2)H) can affect the site selectivity during the C-H activation step in palladiumcatalyzed non-directed C-H functionalization, leading to highly para-selective C-H olefination of TIPSprotected phenols. This transformation displayed good generality in realizing various other para-selective C-H functionalization reactions such as halogenation, and allylation reactions. A wide variety of phenol derivatives including bioactive molecules of triclosan, thymol, and propofol, were compatible substrates,leading to the corresponding para-selective products in moderate to good yields. A preliminary mechanism study revealed that the spatial repulsion factor between carboxylic acid ligand and bulky protecting group resulted in the selective C-H activation at the less sterically hindered para-position. This new model non-directed para-selective C-H functionalization can provide a straightforward route for remote site-selective C-H activations.展开更多
基金supported by the National Natural Science Foundation of China(No.21772139)the Jiangsu Province Natural Science Found for Distinguished Young Scholars(No.BK20180041)+1 种基金the PAPD Projectsupported by the Open Research Fund of the School of Chemistry and Chemical Engineering,Henan Normal University。
文摘Palladium-catalyzed non-directed C-H functionalization provides an efficient approach for direct functionalization of arenes, but it usually suffers from poor site selectivity, limiting its wide application.Herein, it is reported for the first time that the carboxylic acid ligand of 3,5-dimethyladamantane-1-carboxylic acid(1-DMAd CO_(2)H) can affect the site selectivity during the C-H activation step in palladiumcatalyzed non-directed C-H functionalization, leading to highly para-selective C-H olefination of TIPSprotected phenols. This transformation displayed good generality in realizing various other para-selective C-H functionalization reactions such as halogenation, and allylation reactions. A wide variety of phenol derivatives including bioactive molecules of triclosan, thymol, and propofol, were compatible substrates,leading to the corresponding para-selective products in moderate to good yields. A preliminary mechanism study revealed that the spatial repulsion factor between carboxylic acid ligand and bulky protecting group resulted in the selective C-H activation at the less sterically hindered para-position. This new model non-directed para-selective C-H functionalization can provide a straightforward route for remote site-selective C-H activations.
