Non-directed highly para-selective C-H functionalization of TIPS-protected phenols promoted by a carboxylic acid ligand

• Published in: 中国化学快报（英文版） 2023, Vol.34 (3), p.342-346
• Main Authors: Jingyao Geng, Zhang Fang, Guangliang Tu, Yingsheng Zhao
• Format: Article
• Language: English
• ISSN: 1001-8417

Palladium-catalyzed non-directed C-H functionalization provides an efficient approach for direct func-tionalization 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-DMAdCO2H)can affect the site selectivity during the C-H activation step in palladium-catalyzed non-directed C-H functionalization,leading to highly para-selective C-H olefination of TIPS-protected 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 mecha-nism study revealed that the spatial repulsion factor between carboxylic acid ligand and bulky protect-ing 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.