Palladium-catalyzed direct C5-arylation or C4,C5-diarylation of 2-alkylisothiazol-3-ones

Oumaima Mhadhbi (1, 2) , Linhao Liu (3, 1) , Amal Benzai (3) , Besma Mellah (2) , Néji Besbes (2) , Jerome Ollivier (3) , Marie Cordier (3) , Henri Doucet (3)

1 UTM - Université de Tunis El Manar
2 Centre of Biotechnology Bordj Cedria
3 ISCR - Institut des Sciences Chimiques de Rennes

The regioselectivity of the Pd-catalyzed direct arylation of unsubstituted 2-alkylisothiazol-3(2H)-ones was investigated. Conditions for the regioselective palladium-catalyzed direct C5-arylation of 2-alkylisothiazol-3-ones using aryl bromides as the coupling partners are reported. This procedure tolerates a wide variety of substituents such as nitro, nitrile, ester, chloro, fluoro, trifluoromethyl, trifluoromethoxy, difluoromethoxy at para-, meta- and also ortho-positions on the aryl bromide. Both methyl- and octyl-substituents at 2-position of alkylisothiazol-3-ones are tolerated. Moreover, at a more elevated temperature in the presence of a larger excess of the aryl bromide, the access to the C4,C5-diarylated alkylisothiazol-3-ones is also possible, revealing that the C4-position of isothiazol-3(2H)-ones is reactive for direct arylation when the C5-position is blocked. Therefore, this method provides a one pot access to a wide variety of isothiazolinone derivatives allowing to modify easily their biological properties.

Keywords: Homogeneous catalysis; Palladium; C–H bond functionalization; Direct arylation isothiazolinones

Domains: Chemical Sciences

Oumaima Mhadhbi, Linhao Liu, Amal Benzai, Besma Mellah, Néji Besbes, et al.. Palladium-catalyzed direct C5-arylation or C4,C5-diarylation of 2-alkylisothiazol-3-ones. Tetrahedron, 2022, pp.132894. ⟨10.1016/j.tet.2022.132894⟩. ⟨hal-03735535⟩