C-H Bond Arylation of Pyrazoles at the β-Position: General Conditions and Computational Elucidation for a High Regioselectivity - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Chemistry - A European Journal Année : 2021

C-H Bond Arylation of Pyrazoles at the β-Position: General Conditions and Computational Elucidation for a High Regioselectivity

Marie Cordier

Résumé

Direct arylation of most five-membered ring heterocycles are generally easily accessible and strongly favored at the α-position using classical palladium-catalysis. Conversely, regioselective functionalization of such heterocycles at the concurrent β-position remains currently very challenging. Herein, we report general conditions for regioselective direct arylation at the β-position of pyrazoles, while C-H α-position is free. By using aryl bromides as the aryl source and a judicious choice of solvent, the arylation reaction of variously N-substituted pyrazoles simply proceeds via β-C-H bond functionalization. The β-regioselectivity is promoted by a ligand-free palladium catalyst and a simple base without oxidant or further additive, and tolerates a variety of substituents on the bromoarene. DFT calculations revealed that a protic solvent such as 2-ethoxyethan-1-ol significantly enhances the acidity of the proton at β-position of the pyrazoles and thus favors this direct β-C-H bond arylation. This selective pyrazoles β-C-H bond arylation was successfully applied for the straightforward building of π-extended poly(hetero)aromatic structures via further Pd-catalyzed combined α-C-H intermolecular and intramolecular C-H bond arylation in an overall highly atom-economical process.
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Dates et versions

hal-03157416 , version 1 (15-06-2021)

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Citer

Xinzhe Shi, E Daiann Sosa Carrizo, Marie Cordier, Julien Roger, Nadine Pirio, et al.. C-H Bond Arylation of Pyrazoles at the β-Position: General Conditions and Computational Elucidation for a High Regioselectivity. Chemistry - A European Journal, 2021, 27 (17), pp.5546-5554. ⟨10.1002/chem.202100031⟩. ⟨hal-03157416⟩
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