A Straightforward One-Step Access to Ticlopidine Derivatives Arylated at the C5-Position of the Thienyl Ring via Pd-Catalyzed Direct Arylations

Dhieb Atoui (1, 2) , Haoran Li (1) , Ridha Ben Salem (2) , Thierry Roisnel (1) , Jean-François Soulé (1) , Henri Doucet (1)

1 ISCR - Institut des Sciences Chimiques de Rennes
2 Université de Sfax - University of Sfax

The reactivity of Ticlopidine, which belongs to the thienopyridine drug family, in Pd-catalyzed C-H bond functionalization was investigated. The use of a palladium-diphosphine catalyst associated to potassium acetate base in N,N-dimethylacetamide was found to promote the regioselective arylation at the C5-position of the Ticlopidine thienyl ring with aryl bromides in high yields. In the course of this reaction, no dechlorination or debenzylation of the 2-chlorobenzyl group of Ticlopidine was observed. A wide variety of substituents on the aryl bromide was tolerated, such as nitro, nitrile, acetyl, propionyl, benzoyl, ester, chloro, fluoro or trifluoromethyl. Bromopyridines and bromoquinolines were also successfully employed. This methodology gives a one-step access to arylated Ticlopidine derivatives from commercially available compounds via a straightforward C-H bond functionalization procedure. Therefore, it provides a very appealing method to build a library of compounds containing a Ticlopidine unit.

Keywords: catalysis; palladium; C-H bond functionalization; Ticlopidine; arylation

Domains: Chemical Sciences

Dhieb Atoui, Haoran Li, Ridha Ben Salem, Thierry Roisnel, Jean-François Soulé, et al.. A Straightforward One-Step Access to Ticlopidine Derivatives Arylated at the C5-Position of the Thienyl Ring via Pd-Catalyzed Direct Arylations. Asian Journal of Organic Chemistry, 2019, 8 (11), pp.2155-2161. ⟨10.1002/ajoc.201900609⟩. ⟨hal-02391908⟩