ChemInform Abstract: Formyl Substituent at C‐4 of Pyrazoles: A Temporary Protecting Group for Regioselective Palladium‐Catalyzed Direct Arylation at C‐5.

Abstract

Pyrazoles with an aldehyde function at C-4 underwent a palladium-catalyzed direct arylation reaction to provide a regioselective approach to 5-aryl-substituted pyrazoles. The reaction proceeds in moderate to high yields with a variety of aryl bromides in the presence of 2 mol-% of Pd(OAc)2 as the catalyst. The use of an aldehyde function at C-4 of the pyrazoles presents several advantages: (1) 4-formylpyrazoles are easily prepared from hydrazine derivatives, ketones, and N,N-dimethylformamide (DMF), (2) the control of the regioselectivity of the arylation at C-5 of the pyrazole, (3) the aldehyde substituent can easily be transformed into a wide variety of other substituents, and (4) the formyl group can be considered a temporary protecting group, as it can be removed by a straightforward reaction.