Acid-Promoted Reaction of Trifluoromethylated Allyl Alcohols with Arenes. Stereoselective Synthesis of CF₃-Alkenes and CF₃-Indanes

Abstract

Reaction of 4-aryl-1,1,1-trifluorobut-3-en-2-ols [CF 3 -allyl alcohols, ArCHCHCH(OH)CF 3 ] with arenes under activation with anhydrous FeCl 3 or FSO 3 H was studied. We found that the transformation led to trifluoromethylated alkenes [Ar(Ar′)CHCHCHCF 3 ] or 1-trifluoromethylated indanes (CF 3 -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 3 -allyl alcohols under reaction conditions. Benzene, anisole, veratrole, and ortho-xylene lead exclusively to CF 3 -alkenes with an E-configuration. More π-donating polymethylated arenes (pseudocumene, mesitylene) afford only CF 3 -indanes with a predominantly cis-orientation of substituents at positions 1 and 3 of the indane ring. Meta-and para-xylenes show an intermediate behavior; they may form both CF 3 -alkenes and/or CF 3 -indanes. The mechanisms of the investigated transformations are discussed. ■ INTRODUCTIONFluorinated organic compounds have significant theoretical and practical value in chemistry, biology, medicine, and material science.1,2 Incorporation of a fluorinated moiety into a molecule often changes such important parameters as lipophilicity, metabolic activity, and bioavailability. Trifluoromethylated alkenes (styrenes) are compounds of high practical interest. Some derivatives with such fragments have been widely used for organic light-emitting diodes (OLEDs) and other material chemistry applications.3 Some trifluoromethylated alkenes attract significant attention due to important biological activity and application in medicine. Incorporation of a CF 3 group permits one to design more potent drugs. For example, Tamoxifen (Nolvadex) is the well-known triarylethylene-type antiestrogenic drug, 4 which is used in the therapy of breast cancer and for the treatment of menstrual disorders. 5Panomifene is a trifluoromethylated analogue of Tamoxifen (Figure 1). This drug demonstrated higher anticancer activity; however, quite important is the configuration of the double bond because only one diastereomer can be used.The electron-withdrawing character of fluorinated groups is another advantage, which allows one to control the selectivity of transformations of fluorinated compounds. CF 3 -substituted carbocations are very promising, but still very rare, fluorinated species exhibiting high electrophilicity and selectivity. 6 The present work is a continuation of our investigations on the electrophilic activation of alkenes 7 and alkynes. 8 In a preliminary short communication, 9 we showed that 4-phenyl-1,1,1-trifluorobut-3-en-2-ol 1a alkylated selected aromatics to afford E-4,4-diaryl-1,1,1-trifluorobut-2-enes 2 under action of various Brønsted or Lewis acids. The best results (highest yields of compounds 2) were obtained using 1 equiv of anhydrous iron trichloride FeCl 3 (Scheme 1).Interaction of CF 3 -alcohols 1 with Brønsted or Lewis acids proceeds through intermediate formation of various electrophilic spe...

Effect of catalyst morphology and hydrogen co-feeding on the acid-catalysed transformation of acetone into mesitylene

“…Polymethylbenzenes (PMBs) are a high reactive family of benzene derivatives, being widely used as precursors for the production of more complex chemicals and intermediate species. [1][2][3][4] In general terms, the upgrading processes of PMBs are based on alkylation and acylation reactions using Friedel-Crafts catalysts. 5,6 Several PMBs can be obtained from extracted reformate of nine-carbon compounds by superfractionation (e.g., pseudocumene, mesitylene, hemimellitene, indane, etc.…”

Direct Reduction of Allylic Alcohols Using Isopropanol as Reductant

“…Consequently, substrate 6 i , which had a methoxy‐substituted aryl ring at the α‐position and a nitro‐substituted aryl ring at the γ‐position, gave the best isomeric ratio of 13.3:1 ( 7 i / 7i′ ). In these reactions, the double bonds formed near the electron‐deficient aryl groups except for 7 d / 7d′ . We also examined the direct reduction of an alkyl‐substituted allylic alcohol, but the reaction resulted in the formation of the corresponding diene .…”

“…This mechanism is also in agreement with the selectivity observed in the direct reduction of allylic alcohols bearing two electronically different aryl groups. For example, in the case of 6 i , the nucleophilic attack of hydride to the carbon atom with a greater positive charge preferentially gives alkene 7 i in which the double bond is located near the electron‐deficient aryl group …”

Synthesis of 1-Trifluorometylindanes and Close Structures: A Mini Review

“…Both species D and E (E′↔E″) may take part in interaction with aromatic nucleophiles, whichdepends on substituents in species D and E and the nucleophilicity of arenes (Scheme 11). Thus, the reaction of CF3-allyl alcohols 17 with electron-donating arenes under the action of Lewis acid FeCl3 at room temperature or Brønstedsuperacid FSO3H at -75 o C can be used to obtain monoarylatedtrifluoromethylindanes18a-h (Scheme 12) [28]. Reactions with p-xylene and pseudocumene demonstrate high stereoselectivity, affording only cis-CF3-indanes 18a-h. More striking results are obtained for the reactions with pseudocumene, leading to 50-76% yields of target products.…”