Facile Access to 3,5-Dihalogenated Pyrazoles by Sydnone Cycloaddition and their Versatile Functionalization by Pd-Catalyzed Cross-Coupling Processes

The 1,3-dipolar cycloaddition of diversely N-substituted 4-iodosydnones with 3-halopropiolates produces easily separable mixtures of dihalogenated pyrazolylcarboxylic esters at a preparative scale level, with the 3,5-dihalogenopyrazole regioisomers always predominating. Further decarboxylation of the major isomers provided the corresponding 3,5-dihalogenopyrazoles with a free C-4 position. These were found to be valuable scaffolds for the elaboration of unsymmetrically 1,3,5-trisubstituted pyrazole derivatives by site-selective Pd-catalyzed cross-coupling reactions. Notably, the flexible and site-selective introduction of different (hetero)aryl, vinyl, or alkyl substituents at the C-5 and C-3 positions of the pyrazole core could be achieved through sequential Suzuki-type reactions with various boron compounds. Furthermore, the Suzuki coupling sequence could be amenable to a one-pot procedure that enables rapid generation of the targeted compounds.