AlCl3-mediated Defluorinative Diarylhydroxylation Transformation of CF3: Chemoselective Arylation of CF3 and Chlorocarbonyl Groups Attached to Aromatic Rings

Abstract

The CF3 group in 4-trifluoromethylbenzoyl chloride is efficiently diarylated and converted into a diarylhydroxymethyl group by treatment with AlCl3 in the presence of an excess amount of halobenzene (C6H5X; X = F, Cl, and Br). The diarylation is followed by arylation of the chlorocarbonyl group to afford triarylated products, diarylhydroxymethylated benzophenones. The employment of TfOH in place of AlCl3 promotes the exclusive arylation of the chlorocarbonyl group leaving the CF3 group unchanged to afford selectively 4-trifluoromethylbenzophenones, which then undergo diarylhydroxymethylation with the aid of AlCl3.

Main-Group Lewis Acids for C–F Bond Activation

“…In analogy, aluminum halides have been shown to induce the fluorine–halogen exchange of aliphatic fluorocarbons to afford the corresponding halides. ,, Even prior to the work of Olah, Henne and Newman discovered that benzotrifluoride is converted to benzotrichloride in the presence of an equimolar amount of AlCl 3 . The same reaction employing overstoichiometric amounts of AlCl 3 in the presence of an arene results in Friedel–Crafts-type alkylations. − As an example, clean formation of dichlorodiarylmethane 34 from trifluoromethyl benzene 33 is observed (Scheme ) . The mechanism of this reaction is assumed to proceed via initial F–Cl exchange, followed by AlCl 3 -mediated regioselective Friedel–Crafts alkylation of toluene with the resulting benzotrichloride.…”

Aluminum oxide mediated C–F bond activation in trifluoromethylated arenes

“…Despite the presence of three fluorine atoms at the benzylic position examples of the conversion of respective C-F bonds to C-C bond are rare. These include: the use of low-valent Nb complexes, [7][8][9] reaction with organoaluminium reagents, 10,11 Brønsted acid mediated activation, [12][13][14] electroreductive coupling, 15 lanthanoid induced activation, 16 AlCl 3 mediated arylation, 17 and the usage of Mg-Cu bimetal systems. 18 Recently we have found out that thermally activated g-aluminum oxide is very effective for the activation of C ARYL -F bonds under mild conditions, leading to the effective intramolecular C-C bond formation via cyclodehydrofluorination.…”

A Review on the Halodefluorination of Aliphatic Fluorides

“…Later, in 2010, Yonezawa and co-workers also utilized aluminum-mediated Friedel-Crafts alkylation using the CF 3 group in 4-(trifluoromethyl)benzoyl chloride. 33 However, in this case, disubstitution of the trifluoromethyl group by fluorobenzene was observed, and the remaining chloride was hydrolyzed to a hydroxyl group. Thus, although the reaction likely proceeds via an initial chlorodefluorination, no chloro groups are observed in the product (Scheme 20B).…”