5 research outputs found
Acid-Promoted Reaction of Trifluoromethylated Allyl Alcohols with Arenes. Stereoselective Synthesis of CF<sub>3</sub>‑Alkenes and CF<sub>3</sub>‑Indanes
Reaction
of 4-aryl-1,1,1-trifluorobut-3-en-2-ols [CF<sub>3</sub>-allyl alcohols,
ArCHCHCH(OH)CF<sub>3</sub>] with arenes
under activation with anhydrous FeCl<sub>3</sub> or FSO<sub>3</sub>H was studied. We found that the transformation led to trifluoromethylated
alkenes [Ar(Ar′)CHCHCHCF<sub>3</sub>] or 1-trifluoromethylated
indanes (CF<sub>3</sub>-indanes). The formation of these two types
of reaction products strongly depends on the nucleophilicity of the
starting arene and the electrophilicity of cationic intermediates
generated from CF<sub>3</sub>-allyl alcohols under reaction conditions.
Benzene, anisole, veratrole, and <i>ortho-</i>xylene lead
exclusively to CF<sub>3</sub>-alkenes with an <i>E-</i>configuration.
More π-donating polymethylated arenes (pseudocumene, mesitylene)
afford only CF<sub>3</sub>-indanes with a predominantly <i>cis-</i>orientation of substituents at positions 1 and 3 of the indane ring. <i>Meta-</i> and <i>para-</i>xylenes show an intermediate
behavior; they may form both CF<sub>3</sub>-alkenes and/or CF<sub>3</sub>-indanes. The mechanisms of the investigated transformations
are discussed
Synthesis of various arylated trifluoromethyl substituted indanes and indenes, and study of their biological activity
Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands
4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F 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 cells