Two‐Step Access to 4‐Aryl‐5‐Heteroarylpyrazoles via Palladium‐Catalyzed Sequential Transformations Using Palladium 1,4‐Migration Tool

ABSTRACT Access to pyrazoles (hetero)arylated at both the C4 and C5 positions via palladium‐catalyzed C─H bond activation is generally challenging. This is due to the similar reactivity of these two positions, which often results in the formation of mixtures of C4‐, C5‐ and C4, C5‐(di)functionalized pyrazoles. The present report describes the synthesis of 4‐aryl‐5‐heteroarylpyrazoles through a novel method that involves Suzuki coupling of 1,2‐dihalobenzene with pyrazol‐4‐ylboronic acids, followed by palladium‐catalyzed C─H bond arylation. The key step in this methodology is the Pd 1,4‐migration, which occurs between the aryl and pyrazole rings in the C─H bond arylation catalytic cycle. This step regio‐selectively activates the C─H bond at the C5 position of the pyrazole ring. This pyrazole heteroarylation method exhibits a high level of tolerance to substituents on the benzene ring as well as a variety of heteroarenes. Furthermore, air‐stable catalysts and inexpensive bases were utilized in these reactions.