Mild and Rapid Pd-Catalyzed Cross-Coupling with Hydrazine in Continuous Flow: Application to the Synthesis of Functionalized Heterocyeles

摘要

Functionalized arylhydrazines are of widespread importance as intermediates in the syntheses of nitrogen-containing heteroeyeles. In this regard, indoles, arylpyrazoles/pyr-azolones, and aryltriazoles, among others, can be efficiently generated from arylhydrazines. These heterocyclic motifs are prevalent structural elements in numerous compounds of significant biological/medicinal value. Among current strategies to generate arylhydrazines, nucleophilic aromatic substitution to an aryl halide (ArX) or diazotiza-tion of an aniline followed by reduction of the diazonium salt have long been preparative methods of choice [Eq. (1)]. However, the former method typically requires an arene activated by electron-withdrawing groups, while the diazoti-zation/reduction sequence is redox-exhaustive and involves the generation of unstable diazonium intermediates.