Chemoselective Palladium-Catalyzed Direct C–H Arylation of 5-Carboxyimidazoles: Unparalleled Access to Fused Imidazole-Based Tricycles Containing Six-, Seven- or Eight-Membered Rings

Jérémy Thireau (1) , Cédric Schneider (1) , Christine Baudequin (1) , Sandrine Gaurrand , Patrick Angibaud , Lieven Meerpoel , Vincent Levacher (1) , Olivier Querolle , Christophe Hoarau (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

The right way and size! The chemoselective Pd0‐catalyzed inter‐ and intramolecular direct C–H arylation of methyl imidazole‐5‐carboxyxlates with or without CuI assistance is described in the sparsely employed low‐polarity 1,4‐dioxane solvent. This protocol is applicable to the synthesis of fused imidazole‐based tricyclic systems incorporating medium‐sized rings. An extensive study of the chemoselective Pd‐catalyzed inter‐ and intramolecular direct C–H arylation of N‐benzylated 5‐carboxyimidazoles with halides with and without CuI assistance in 1,4‐dioxane as a low‐polarity solvent was explored. The method was suitable for the synthesis of fused imidazole‐based tricyclic systems incorporating medium‐sized rings, including, for the first time, eight‐membered rings, which are valuable in modern drug design.

Domains: Chemical Sciences

Jérémy Thireau, Cédric Schneider, Christine Baudequin, Sandrine Gaurrand, Patrick Angibaud, et al.. Chemoselective Palladium-Catalyzed Direct C–H Arylation of 5-Carboxyimidazoles: Unparalleled Access to Fused Imidazole-Based Tricycles Containing Six-, Seven- or Eight-Membered Rings. European Journal of Organic Chemistry, 2017, 2017 (17), pp.2491-2494. ⟨10.1002/ejoc.201700297⟩. ⟨hal-02046311⟩