TY - JOUR

T1 - Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands

AU - Iakovenko, Roman O.

AU - Kazakova, Anna N.

AU - Muzalevskiy, Vasiliy M.

AU - Ivanov, Alexander Yu.

AU - Boyarskaya, Irina A.

AU - Chicca, Andrea

AU - Petrucci, Vanessa

AU - Gertsch, Juerg

AU - Krasavin, Mikhail

AU - Starova, Galina L.

AU - Zolotarev, Andrey A.

AU - Avdontceva, Margarita S.

AU - Nenajdenko, Valentine G.

AU - Vasilyev, Aleksander V.

PY - 2015

Y1 - 2015

N2 - 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

AB - 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

U2 - 10.1039/c5ob01072a

DO - 10.1039/c5ob01072a

M3 - Article

VL - 13

SP - 8827

EP - 8842

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 33

ER -