Qiong Chai, Fengming Zhang, Minghang Wang, Meiqi Li, Yong Jian Zhang
An efficient micellar palladium-catalyzed aqueous Buchwald-Hartwig amination has been developed, enabled by the self-assembly of amphiphilic copolymer polyethylene glycol-polyvinylethylene glycol (PEG-PVEG). Using 0.5 mol % BrettPhos-Pd-G3 as a catalyst, the aqueous amination showed broad a substrate scope, including aryl bromides, aryl chlorides, sterically hindered reaction partners, and amides. The practical utility of this micellar system was demonstrated by the gram-scale synthesis of a key pharmaceutical API intermediate and catalyst recycling.