Aryl halide (Br, Cl, I) is among the most important compounds in pharmaceutical industry, material science, and agrochemistry, broadly utilized in diverse transformations. Tremendous approaches have been established to prepare this scaffold; however, many of them suffer from atom economy, harsh condition, inability to be scaled up, or cost-unfriendly reagents and catalysts. Inspired by vanadium haloperoxidases herein we presented a biomimetic approach for halogenation (Br, Cl, I) of (hetero)arene catalyzed by tungstate under mild pH in a costefficient and environment-and operation-friendly manner. Broad substrates, diverse functional group tolerance, and good chemo-and regioselectivities were observed, even in late-stage halogenation of complex molecules. Moreover, this approach can be scaled up to over 100 g without time-consuming and costly column purification. Several drugs and key precursors for drugs bearing aryl halides (Br, Cl, I) have been conveniently prepared based on our approach.

Phenolic acids (PAs) can be derived from lignin, and their value-added transformations provide a good renewable source for arenes. The halogenase-catalyzed decarboxylative halogenation of PAs is a key step in the biosynthesis of many halogenated natural products. Inspired by halogenase, herein we present a synthetically useful tungstate-catalyzed decarboxylative halogenation of electron-deficient (hetero)phenolic acids under mild conditions, based on which the antibiotic bromophene and its analogues were prepared concisely. Mechanism studies support the halogenation−decarboxylation procedure, but the decarboxylation−halogenation pathway cannot be excluded. Additionally, the chloride can reverse the selectivity between bromination and iodination in this reaction, somehow providing a useful perspective for the halide selectivity in vanadiumdependent haloperoxidase in seawater.

The concise construction of diene scaffolds is quite useful in the synthesis of polyenes. Many diene building blocks have been developed based on Suzuki, Still and Hiyama couplings. Herein, the commercially available and environmentally friendly compound dienedioic acid is used as a diene building block. Broad substrate scope, good functional group tolerance, and late-stage derivatization of complex drug molecules are achieved. Different moieties can be conveniently introduced to both sides. Piperine and the methyl ester of azoxymycin C are each prepared in three steps. Additionally, one product shows promising anticancer activities in leukemia K562 and MV-4-11 cells. Mechanistic studies indicate that the reaction proceeds through a Heck-decarboxylate coupling procedure, and the carboxylic group acts as a directing group to promote the reaction and control regioselectivity. Our research suggests that dienedioic acid can serve as a good alternative for diene preparation via a directed Heckdecarboxylate coupling.