Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands

Roman O. Iakovenko, Anna N. Kazakova, Vasiliy M. Muzalevskiy, Alexander Yu. Ivanov, Irina A. Boyarskaya, Andrea Chicca, Vanessa Petrucci, Juerg Gertsch, Mikhail Krasavin, Galina L. Starova, Andrey A. Zolotarev, Margarita S. Avdontceva, Valentine G. Nenajdenko, Aleksander V. Vasilyev

Research output

22 Citations (Scopus)

Abstract

4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH=CHCOCF3 (CF3-enones) react with arenes in excess of Bronsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH=CHC(OH+)CF3 and the O, C-diprotonated ArHC+ CH2C(OH+) CF3 species, have been studied by means of H-1, C-13, F-19 NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y c
Original languageEnglish
Pages (from-to)8827-8842
Number of pages16
JournalOrganic and Biomolecular Chemistry
Volume13
Issue number33
DOIs
Publication statusPublished - 2015

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    Iakovenko, R. O., Kazakova, A. N., Muzalevskiy, V. M., Ivanov, A. Y., Boyarskaya, I. A., Chicca, A., Petrucci, V., Gertsch, J., Krasavin, M., Starova, G. L., Zolotarev, A. A., Avdontceva, M. S., Nenajdenko, V. G., & Vasilyev, A. V. (2015). Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands. Organic and Biomolecular Chemistry, 13(33), 8827-8842. https://doi.org/10.1039/c5ob01072a