Catalytic Fluoroalkylation Reactions of Alkoxy‐substituted (Hetero)Arenes

Abstract

Electron‐rich alkoxy‐substituted (hetero)arenes and electrophilic fluoroalkyl moieties represent advantageous partners for substitution reactions due to their electronic match. Fluoroalkylation strategies of alkoxy‐substituted (hetero)arenes are herein presented which depict photocatalytic and thermal methods. Photocatalytic methods rely on the use of diverse photocatalysts such as Ru(bpy)3Cl2, tetrabutylammonium decatungstate TBADT, N‐doped carbon nanodots NCNDs, and vitamin derivatives which can partner with the Langlois reagent NaSO2CF3, CF3CO2H, and perfluoroalkyl iodides RF‐I as fluoroalkylating reagents. Also, electrocatalytic methods that make use of the cathodic reduction of CF3SO2Cl to generate CF3 radicals can achieve trifluoromethylation reactions of alkoxy‐substituted (hetero)arenes. On the other hand, thermal methodologies comprising Pd(OAc)2 catalysis and using CF3Br as trifluoromethylating source have been implemented.

Recent advances in transition metal-mediated trifluoromethylation reactions

“…[12][13][14] Molecules with trifluoromethyl groups represent a unique class of fluorinated compounds that find their utility not only in the academic community but also in their prevalence in a variety of agrochemical and pharmaceutical drugs (Scheme 1). [15][16][17][18] The introduction of a CF 3 group into organic molecules has been quite prominent in the last decade, with some outlining the electronic nature of the recruited reagents, which can be radical, electrophilic or nucleophilic (Scheme 2), while others have focussed on the use of catalysts, the stereoselectivity of reactions, or the type of bonds that are deposited in trifluoromethylation reactions. [19][20][21][22][23][24][25][26][27][28][29][30][31][32] In recent years, numerous reports of trifluoromethylation of hydrocarbons and heteroarenes have appeared using various transition metal complexes.…”

“…12–14 Molecules with trifluoromethyl groups represent a unique class of fluorinated compounds that find their utility not only in the academic community but also in their prevalence in a variety of agrochemical and pharmaceutical drugs (Scheme 1). 15–18…”

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

“…To verify the generation of perfluoroalkyl radicals from compounds 1, we conducted an experiment with perfluorohexyl analogue 1b and 1,1-diphenylethylene (7) as a radical trapping agent (Scheme 4). Gratifyingly we observed the formation of 2-(perfluorohexyl)-1,1-diphenylethylene (8), and propiophenone through GC-MS analysis. Additionally, the presence of free SO 2 gas was confirmed by the reaction of acidic potassium dichromate solution on paper (green coloration of the exposed surface).…”

“…Given their importance, multiple synthetic methodologies for the introduction of long perfluorinated chains into aromatic rings have been developed since the first reports of such transformation by George Tiers in 1960, and McLoughlin and Thrower in 1969 [2,3]. Most approaches have made extensive use of organometallic chemistry, radical initiators, photocatalysis, electrochemistry, and more sophisticated platforms such as metal nanoparticles, all of which have been reviewed thoroughly in the literature [4][5][6][7][8].…”

Fluoroalkyl Iodides in Fluoroalkylative Difunctionalization of C−C Multiple Bonds

“…[20][21][22] In 2012, Buck et al updated this summarizing progress from 2000 to 2010. [23] In more recent accounts, [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] fluoroalkyl iodides appear only in the context of other fluorinating agents and/or type of transformation under review. Furthermore, in 2022, use of perfluoroalkyl halides for photo-induced perfluoroalkylation was reviewed.…”