Catalyst-free nucleophilic substitution of hydrogen in quinoline rings by acylethynylpyrroles: stereoselective synthesis of 2-(E-2-acylethenylpyrrolyl)quinolines

Abstract

Catalyst-free nucleophilic substitution of hydrogen in quinolines under the action of available acylethynylpyrroles occurs at 80–110 °C in MeCN or toluene to stereoselectively afford 2-(E-2-acylethenylpyrrolyl)quinolines with a yield up to 78%. This unexpected cross-coupling proceeds apparently via the redox ring-opening of the intermediate quinoline/acylethynylpyrrole cycloadduct. Thus, we produced the first example of intramolecular S_N^H substitution of hydrogen in quinoline using the pyrrole nucleophile with 1,2-transfer of the acylethenyl substituent in the intermediate [2 + 3]-cycloadduct. This intermediate was isolated in the case of 1-methylisoquinoline wherein the [2 + 3]-cycloadduct was found to be stable. In general, the reaction mechanism was also supported using a high-level correlation electron pair approximation approach LPNO-CEPA/1/CBS utilizing M06-2X/Def2-TZVPP geometry.