In the context of palladium-catalyzed C–H bond arylation, it has been well-established that pyrazoles, with both C4 and C5 available positions, typically result in the formation of mixtures of C4-, C5-arylated, and also C4, C5-diarylated products. In this study, the reactivity of ethyl 1-methylpyraz...
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Académie des sciences
2025-06-01
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| Series: | Comptes Rendus. Chimie |
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| author | Rahali, Ahlem Le Floch, Norman Allouche, Fatma Doucet, Henri |
| author_facet | Rahali, Ahlem Le Floch, Norman Allouche, Fatma Doucet, Henri |
| author_sort | Rahali, Ahlem |
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| description | In the context of palladium-catalyzed C–H bond arylation, it has been well-established that pyrazoles, with both C4 and C5 available positions, typically result in the formation of mixtures of C4-, C5-arylated, and also C4, C5-diarylated products. In this study, the reactivity of ethyl 1-methylpyrazole-4-carboxylate in palladium-catalyzed C–H arylation was investigated. The objective was to determine the effectiveness of the presence of an ester substituent at the C4 position of the pyrazole as a blocking group in controlling the regioselectivity of such C–H bond arylations. It was observed that the presence of such an ester substituent acted as a convenient blocking group, thereby enabling the control of regioselectivity in the arylation process at the C5 position of the pyrazole. The reaction exhibits a high degree of tolerance to a wide variety of aryl bromides, including a diverse array of functional groups at the para, meta, and ortho positions of the aryl bromides. Heteroarylation is also possible. In the course of these couplings, no decarboxylation of the pyrazole unit was observed, and the reaction requires only 2 mol% of an air-stable phosphine-free palladium catalyst and KOAc as an inexpensive base. Furthermore, the removal of the pyrazole ester substituent was found to be easy, which demonstrates the potential of such an ester substituent as a removable blocking group. |
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| publishDate | 2025-06-01 |
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| spelling | doaj-art-c080369a138d4f7bb8c5c8e5d4fe25252025-08-01T07:30:59ZengAcadémie des sciencesComptes Rendus. Chimie1878-15432025-06-0128G156157110.5802/crchim.40310.5802/crchim.403Rahali, Ahlem0Le Floch, Norman1Allouche, Fatma2Doucet, Henri3https://orcid.org/0000-0002-1410-3663Laboratoire de Chimie Médicinale et Environnementale, Institut Supérieur de Biotechnologie, Route de la Soukra km 4, 3038 Sfax, Tunisia; Univ Rennes, CNRS, ISCR-UMR 6226, F-35000 Rennes, FranceUniv Rennes, CNRS, ISCR-UMR 6226, F-35000 Rennes, FranceLaboratoire de Chimie Médicinale et Environnementale, Institut Supérieur de Biotechnologie, Route de la Soukra km 4, 3038 Sfax, TunisiaUniv Rennes, CNRS, ISCR-UMR 6226, F-35000 Rennes, FranceIn the context of palladium-catalyzed C–H bond arylation, it has been well-established that pyrazoles, with both C4 and C5 available positions, typically result in the formation of mixtures of C4-, C5-arylated, and also C4, C5-diarylated products. In this study, the reactivity of ethyl 1-methylpyrazole-4-carboxylate in palladium-catalyzed C–H arylation was investigated. The objective was to determine the effectiveness of the presence of an ester substituent at the C4 position of the pyrazole as a blocking group in controlling the regioselectivity of such C–H bond arylations. It was observed that the presence of such an ester substituent acted as a convenient blocking group, thereby enabling the control of regioselectivity in the arylation process at the C5 position of the pyrazole. The reaction exhibits a high degree of tolerance to a wide variety of aryl bromides, including a diverse array of functional groups at the para, meta, and ortho positions of the aryl bromides. Heteroarylation is also possible. In the course of these couplings, no decarboxylation of the pyrazole unit was observed, and the reaction requires only 2 mol% of an air-stable phosphine-free palladium catalyst and KOAc as an inexpensive base. Furthermore, the removal of the pyrazole ester substituent was found to be easy, which demonstrates the potential of such an ester substituent as a removable blocking group.https://comptes-rendus.academie-sciences.fr/chimie/articles/10.5802/crchim.403/C–H bond functionalizationDirect arylationHomogeneous catalysisPalladiumPyrazoles |
| spellingShingle | Rahali, Ahlem Le Floch, Norman Allouche, Fatma Doucet, Henri Comptes Rendus. Chimie C–H bond functionalization Direct arylation Homogeneous catalysis Palladium Pyrazoles |
| topic | C–H bond functionalization Direct arylation Homogeneous catalysis Palladium Pyrazoles |
| url | https://comptes-rendus.academie-sciences.fr/chimie/articles/10.5802/crchim.403/ |