A palladium-catalyzed, late-stage functionalization of 4-alkyl-1,5-diaryl-1 H-pyrazole-3-carboxylates to achieve acetoxylation or iodination via Csp²−H bond activation with synthetically useful to excellent yields is described. These straightforward transformations feature highly functionalized substrates, excellent site selectivity, rapid reaction, and simple operation. The C−O and C−I bond-forming protocols allow convenient accesses to lots of complex monoacetoxylated and monoiodinated products from pharmaceutically important intermediates. Iodoacetic acid is also used as the iodinating agent in C−H bond activation.

A one-pot synthesis of highly substituted 1H-pyrazole-5-carboxylates 1 has been developed starting from easily available 4-aryl-2,4-diketoesters 2 and arylhydrazine hydrochlorides 3. More active 2-carbonyl group of 2 was blocked with methoxyamine hydrochloride to give 2-methoxy imine intermediates, which were then subjected to condensation cyclization with 3 in situ to provide the desired products 1. In addition, the geometrical configuration of 1aa was unambiguously confirmed by single crystal X-ray crystallography.

The treatment of α-bromoalkyl aryl ketones and 2-(propan-2-ylidene)hydrazine carbothioamide afforded 4-aryl-2-(2-(propan-2-ylidene)hydrazinyl)thiazoles via a Hantzsch-thiazole synthesis, which reacted with 4-aryl-2,4-diketoesters via a sequential Knorr-pyrazole reaction to deliver a variety of aryl-substituted ethyl 1-(thiazol-2-yl)-1H-pyrazole-3-carboxylates in a one-pot fashion with moderate to high yields. The key intermediates 4-aryl-2,4-diketoesters, existing as its enolic lithium salt, were synthesized in situ by a high-yield tert-BuOLi-mediated Claisen condensation of alkylphenones and diethyl oxalate. This class of elegant molecule comprises aryl groups on the two different heterocyclic cores, and the configurations of two representative molecules were determined by single crystal X-ray crystallography.

A one-pot approach to ethyl 1,4,5-triaryl-1H-pyrazole-3-carboxylates has been developed in moderate to high yields. The tert-BuOLi-mediated Claisen condensation of 1,2-diarylethanones and ethyl oxalyl chloride efficiently provided the enolized lithium salts of ethyl 2,4-dioxo-3,4-diarylbutanoates, which in situ reacted with arylhydrazine hydrochlorides via a hydrochloric acid-promoted Knorr reaction to produce the exquisite triarylpyrazole-3-carboxylates. The procedure promises a convenient access to this highly crowded framework for drug discovery.