alkene and the resulting alkyl radical affords the hydro‐aryldifluoromethylated product via hydrogen abstraction from N‐methylpyrrolidone (NMP).
Zhu and coworkers also developed a photocatalytic fluoroalkylation of alkenes bearing benzaldehyde or propenal functionalities on the side chain with fluorinated carboxylic acids by using the combination of Ir‐catalyst and the oxidant PhI(OAc)2 (Scheme 2.29) [60]. Cyclic ketones bearing fluoroalkyl groups, such as CF2Ar, CF2H, and CF2Me groups, were obtained up to 90% yield.
Scheme 2.28 Ir‐photocatalyzed aryldifluoromethylation.
Scheme 2.29 Carbo and heterocyclic ketone synthesis by Ir‐photocatalyzed carbo‐fluoroalkylation of alkenyl aldehydes.
Recently, Gouverneur and coworkers developed a photocatalyst‐free hydro‐difluoromethylation [61a] as well as ‐chlorofluoromethylation [61b] of simple alkenes under blue LED irradiation (Scheme 2.30); the reactions were accomplished by the use of a combination of fluorine‐containing carboxylic acid and iodobenzene diacetate.
Scheme 2.30 Metal‐free photochemical hydro‐fluoroalkylations.
2.2.5 Other Methods
2.2.5.1 Hydro‐Trifluoromethylation of Fullerene
A few exceptional reactions that do not fall into the categories described above (2.1–2.4) have been reported recently and are introduced herein. In fullerene trifluoromethylation reactions, silver trifluoroacetate was reported to show high reactivity for installing multiple trifluoromethyl groups (see Section 2.2.3) [45-48]. Very recently, Garyunkov and coworkers achieved hydro‐trifluoromethylation of C60 (Scheme 2.31) [62]. In this work, C60 reacted readily with potassium or cesium trifluoroacetate in o‐dichlorobenzene/benzonitrile at c.180 °C in the presence of a crown ether, affording a [C60–CF3]M (M = K or Cs) intermediate. Treatment of the intermediate with acid gave the hydro‐trifluoromethylation product.
Scheme 2.31 Hydro‐trifluoromethylation of fullerene.
2.2.5.2 Metal‐Free Aryldifluoromethylation Using S2O82−
Persulfate (S2O82−) salts were reported to promote metal‐free aryldifluoromethylations using aryldifluoroacetic acids (Scheme 2.32); in 2016, Wu and coworkers reported an aryldifluoromethylation of ethynyl benziodoloxolone with aryldifluoroacetic acids by using potassium persulfate in acetonitrile/H2O cosolvent (Scheme 2.32a) [63]; in contrast to Hashmi's conditions using silver catalyst (Scheme 2.25d) [56], Wu's conditions did not require any transition metal catalyst. Zhang and coworkers developed an aryldifluoromethylation of quinoxaline‐2(1H)‐ones with aryldifluoroacetic acid in dimethylsulfoxide (DMSO) (Scheme 2.32b) [64]. In both studies, persulfate salts were considered to oxidize the carboxylic acids and to generate the corresponding reactive difluorobenzyl radical via oxidative decarboxylation.
Scheme 2.32 Metal‐free aryldifluoromethylation using S2O82− as an oxidant.
2.3 Perfluoroalkylation with Perfluorocarboxylic Anhydride
Perfluorocarboxylic anhydrides are readily available and widely used perfluoroalkyl sources for organic syntheses, like the carboxylic acids. However, it was initially not easy to use the anhydrides directly as perfluoroalkyl sources, although a few secondary reagents prepared from them were reported [2]. Recently, several methods that are synthetically highly useful have been developed.
2.3.1 Reactions Using Perfluorocarboxylic Anhydride/Urea·H2O2
Bräse and coworkers reported a radical perfluoroalkylation of aromatic compounds by using a combination of perfluorocarboxylic anhydrides and urea‐hydrogen peroxide; a mixture of 10 equiv of urea‐hydrogen peroxide (urea·H2O2) and 20 equiv of the carboxylic anhydrides generated diacyl peroxide in situ, and this reacted with arene substrates (Scheme 2.33) [65]. In that work, 15 perfluoroalkylated compounds were synthesized in up to 50% yield.
Scheme 2.33 Aromatic perfluoroalkylation using perfluorocarboxylic anhydride/urea·H2O2.
The group of Sodeoka and Kawamura independently developed perfluoroalkylations using diacyl peroxide generated in situ from anhydrides/urea·H2O2, and described various transformations, in particular bifunctionalization‐type perfluoroalkylations of alkenes (Schemes Scheme 2.34 and Scheme 2.35) [66, 67]. Although the reactive perfluoroalkyl radical could be generated via thermal fragmentation of the diacyl peroxide, heating of a mixture of alkene and in situ‐generated diacyl peroxide gave a complex mixture. They hypothesized that reactivity control of the alkyl radical formed by the reaction of alkene with perfluoroalkyl radical would be the key to a successful reaction [68a–c]. First, catalytic control using copper catalyst was demonstrated; when a catalytic amount of [Cu(CH3CN)4]PF6] was added to a mixture of substrate and the peroxide, not only the selectivity but also the conversion was dramatically improved, affording allylic perfluoroalkylation products in up to 95% yield (Scheme 2.34a) [68a].
Scheme 2.34 Cu‐catalyzed perfluoroalkylations of alkenes. DBU, 1,8‐diazabicyclo[5.4.0]undec‐7ene; AIBN, 2,2′‐azobis(isobutyronitrile).
