Selective Palladium-Catalyzed Direct C-H Arylation of Unsubstituted N-Protected Pyrazoles

A highly selective C-5 arylation of N-dimethylaminosulfamoyl-protected pyrazole with aryl bromides is catalyzed by 2-5mol% palladium in the presence of triphenylphosphine ligand and carboxylic acid additive. Selectivities up to 45:1 (C-5:C-4) can be achieved by running the reaction in non-polar solvents. A thorough study of scope and limitations shows good general tolerance of aryl bromide substitution. However, limitations on tolerance of ortho-subsitution and protic functional groups were established. Together with a telescoped deprotection step this method presents a viable alternative for the synthesis of C-3 arylated pyrazole building blocks.