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

Abstract

AbstractPyrazoles 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.