Work

Evaluation of C3-substituents on pyrazoles as remote directing groups in palladium-catalyzed direct arylation

Year: 2025

Type: article

Abstract: The palladium-catalyzed C–H bond functionalization of pyrazoles frequently presents significant challenges in terms of control of the selectivity of the reaction. This is due to the similar reactivity of their C4 and C5 positions, which frequently leads to the formation of mixtures of C4- and C5-mono-arylated pyrazoles , as well as C4,C5-di-arylated pyrazoles. This study demonstrates that the incorporation of suitable substituents at the C3-position of pyrazoles, such as trifluoromethyl or formyl, can result in the regioselective formation of the C5-arylated pyrazoles. These reactions demonstrate a high degree of tolerance for a variety of substituents on the aryl bromide. Moreover, our procedure utilizes an air-stable palladium catalyst that is readily available and a cost-effective base . In contrast, the presence of nitrile or bromo substituents at the C3-position of pyrazoles resulted in the formation of mixtures of products.

Source: Tetrahedron

DOI: 10.1016/j.tet.2025.134783

Authors: Besma Saoudi, Norman Le Floch, Henri Doucet

Institutions: University Frères Mentouri Constantine 1, Centre National de la Recherche Scientifique, Institut des Sciences Chimiques de Rennes, Université de Rennes

Language: English

Topic: Catalytic C–H Functionalization Methods

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $3,680

Funder: Centre National de la Recherche Scientifique