Tungstate-catalyzed Biomimetic Oxidative Halogenation Of (Hetero) Arenes And Its Application In Drug Molecule Synthesis

(Hetero)aryl halide is among molecules of significant value in functional material,agrochemistry and organic synthesis.Especially in public health,(hetero)aryl halide is a key structural motif in drug design frequently encountered in small molecule drugs,such as chlorpromazine,benzbromarone(treatment of gout),and amiodarone(antiarrhythmia).Its preparation,in most cases,still heavily relies on traditional electrophilic halogenation(utilizing reagents like bromine,chlorine,etc.),unavoidably producing one equivalent of byproduct,which is not atomeconomic,environment-and operation-friendly.In the past decade,transition-metal(TM)-,photo-and electrocatalyzed halogenation of(hetero)arenes provide useful solutions to these problems,but they suffer from either harsh condition,or limited substrate scope(directing group required for TM-catalyzed halogenation).Therefore,it is of great significance to develop an economic approach for halogenation of(hetero)arene with broad substrate scope.The halogenase-catalyzed halogenation is highly specific under mild condition,but its activity and stability are quite sensitive to environment and substrate scope is unique,which limit its further application.The biomimetic halogenation based on halogenase,however,can both merge advantages(eg.,mild condition)and overcome disadvantages(e.g.,poor stability)of halogenase,serving as an useful alternative to the above halogenation approaches.In this paper,we have developed a tungstate-catalyzed biomimetic halogenation based on vanadium haloperoxidases.Within the established tungstate/hydrogen condition,this reaction showed operation-,condition-and amplification-friendly with broad substrate scope.In addition,synthesis of some drug molecules bearing(hetero)aryl halide has been investigated.