Palladium-catalyzed selective C5 H bond arylation of pyrazole using hydroxymethyl substituent as blocking group

• Synthesis of 5-arylpyrazoles using an unprotected hydroxymethyl group at C4 of pyrazoles. • The hydroxymethyl function on pyrazole was not affected. • No need of protection deprotection sequence of pyrazole hydroxymethyl function. • A wide range of functionalized aryl bromides as the coupling partners was tolerated. • The reaction employs an air-stable Pd catalyst and KOPiv as an inexpensive base. In this study, we investigated the reactivity of two unprotected hydroxymethyl-substituted pyrazoles in palladium-catalyzed C H arylation. The conditions for the regioselective C5-arylation of (1-methylpyrazol-4-yl)methanol, while leaving the hydroxymethyl function intact, have been established. The reaction demonstrates broad substrate compatibility, accommodating a diverse array of electron-deficient and electron-excessive aryl bromides, including those bearing substituents in the para -, meta - and ortho -positions and is compatible with heteroaryl bromides. Furthermore, the reaction uses only 2 mol% of an air-stable palladium catalyst and KOPiv as an inexpensive base. This method enables the synthesis of a diverse range of pyrazole derivatives in a single step, thus facilitating the straightforward modification of their biological properties.