Synthesis of 1-Vinylpyrrole-imidazole Alkaloids

• Published in: Synthesis (Stuttgart) 2011-09, Vol.2011 (17), p.2843-2847
• Main Authors: Belyaeva, Kseniya V., Andriyankova, Ludmila V., Nikitina, Lina P., Ivanov, Andrei V., Afonin, Andrei V., Ushakov, Igor’ A., Mal’kina, Anastasiya G., Mikhaleva, Al’bina I., Trofimov, Boris A.
• Format: Article
• Language: English
• ISSN: 0039-7881; 1437-210X
• DOI: 10.1055/s-0030-1260134

Abstract The reaction between 1-methylimidazole, cyano(phen­yl)acetylene, and 1-vinylpyrrole-2-carbaldehydes (MeCN, 20-25 ˚C) stereoselectively gives 1-vinylpyrrole-imidazole ensembles with a (Z,Z)-bis(2-cyano-1-phenylvinyl)oxy function in up to 45% yield. Unlike recently reported three-component reaction between imidazoles, electron-deficient acetylenes, and aldehydes affording 1:1:1 adducts, in this case two molecules of acetylene are involved to deliver 1:2:1 adducts thus representing a novel functionalizaton of the pyrrole-imidazole alkaloid scaffold. The initial zwitterion generated from imidazole and cyano(phenyl)acetylene is thought to be transformed into a carbene, which reacts with pyrrole-2-carbaldehyde. Two subsequent rearrangements of the 1:1:1 adduct furnish the intermediate pyrrole-imidazole ensemble, which in its enol form adds to second molecule of cyano(phenyl)acetylene to yield the final products, functionalized pyrrole-imidazole alkaloids.