4-Arylation of 3-alkoxypyrazoles

Sandrine Guillou (1) , Olivier Nesmes (1) , Mikhail S. Ermolenko (2) , Yves L. Janin (1)

1 Chimie Organique
2 ICSN - Institut de Chimie des Substances Naturelles

Following the study of the alkoxypyrazoles nitrogen's reactivity toward arylation or alkylation reactions, we report here our results on the introduction of various aryl groups on carbon 4 position of 3-alkoxy pyrazoles. This was achieved from the corresponding 4-halogeno derivatives via a Suzuki-Miyaura aryl- aryl coupling reaction. The unexpected difficulties (lack of reactivity or unwanted halogen reduction) encountered in the C-4 arylation of NH-free 4-halogenopyrazoles led us to design solutions to this recurrent problem. The cleavage of the 3-alkoxy group was also investigated using hydrogen bromide in acetic acid or boron tribromide in dichloromethane. This led, in one case, to the observation of a remarkable neighboring group-assisted electrophilic aryl boronylation. This second part of our work paves the way to the synthesis of many original chemical libraries featuring 3-alkoxy 1,4-diaryl pyrazoles as well as the corresponding 1,4-diaryl pyrazol-3-ones

Domains: Organic chemistry

Sandrine Guillou, Olivier Nesmes, Mikhail S. Ermolenko, Yves L. Janin. 4-Arylation of 3-alkoxypyrazoles. Tetrahedron, 2009, 65 (17), pp.3529-3535. ⟨10.1016/j.tet.2009.01.109⟩. ⟨pasteur-00370362⟩