Visible-Light Photoredox Catalysis for the Synthesis of Fluorinated Aromatic Compounds

: Fluorine-containing functional groups are important motifs inﬂuencing physical and biological properties of organic compounds. Visible-light photoredox catalysis as a powerful strategy for the activation of small molecules contributed signiﬁcantly to the rapid progress of new synthetic procedures allowing introduction of ﬂuorine atoms into organic substrates. In this review, we highlight the distinct strategies for transition metal- and organic-photocatalytic ﬂuorination of arenes and heteroarenes by a broad range of ﬂuorinating compounds. The presented procedures are divided into two groups. The ﬁrst group involves the reactions enabling a direct attachment of CF 3 -, C n F m -, F-, CF 3 O-, CF 3 S-, and SO 2 F- substituents to various aromatic compounds. The second group presents the tandem reactions where the formation of the aromatic system occurs after installation of the ﬂuorine-containing group on the non-aromatic fragment of the molecule.


Introduction
Fluorination reactions have gained a prominent role among late-stage synthetic strategies due to the influence of fluorine atom substitution on organic compounds. Introduction of fluoroalkyl groups into organic substrates is an important transformation on account of the changes that these groups bring to molecules, such as an increase in lipophilicity, resistance to oxidation, bioavailability, increase in bioactivity, water repellent properties, metabolic stability, etc. [1][2][3][4][5][6][7][8][9]. Utilization of perfluoroalkylated molecules in material and catalytic chemistry is unprecedented [10][11][12][13][14]. Visible-light photoredox catalysis has become a prominent sector of synthetic methodology in the last several years due to its mild nature, its high functional group compatibility, and the unique mechanistic approaches it enables [15][16][17][18][19][20][21][22]. This method has become an important approach toward the catalytic fluorination of organic molecules. Some reviews support the utility and versatility of the photocatalytic reactions in the synthesis of complex fluorinated compounds [23][24][25][26][27][28][29]. Recently, the study of the introduction of fluorine-containing groups into aromatic or heteroaromatic substrates has accelerated, as evidenced by the large volume of papers published in recent years [30][31][32][33]. Remarkably, there is no current review available dedicated solely to photoinduced fluorination of aromatic compounds. This review will encompass the reactions involving the use of various fluorine-containing reactants in photocatalytic formation of fluorinated aromatic compounds in the timeframe of 2011-2022. The emphasis will be put on both synthetic outcome and reaction mechanism. This review is divided into two parts. In the first part, the photocatalytic reactions are presented involving the installation of the fluorine-containing moiety directly onto the aromatic ring. The second section involves formation of the aromatic ring after photocatalytic installation of the fluorine-containing group onto the molecule. This review does not involve photocatalytic difluoroalkylation of aromatic compounds as it has already been included in another paper [34].

CF3SO2Cl as the Fluorinating Reactant
The CF3 group enjoys a privileged role in the realm of medicinal chemistry because it can influence chemical and metabolic stability, lipophilicity, and binding selectivity [35,36]. Although common pharmacophores often bear CF3 motifs in an aromatic system, access to such analogues typically requires the incorporation of the CF3 group at the start of a multi-step synthetic sequence. Thus, there has been considerable interest in development of new methodologies for highly efficient and selective incorporation of a CF3 group into aromatic molecules. The first efficient protocol for the photocatalytic trifluoromethylation of arenes was developed by the MacMillan group (Scheme 1) [37].   The reaction requires the use of luminescent Co(III) complexes 6 or 7 as photocatalysts which are powerful photo-oxidants E[*A/A −1 ] = (2.26 V and 2.75 V vs. SCE). A plausible reaction mechanism involves excitation of pyrene to its triplet state 8 by means of energy transfer from the excited photocatalyst 6*. Oxidative quenching via singleelectron transfer of CF3SO2Cl affords •CF3 with concomitant formation of the pyrenyl radical cation 9. The electron-deficient •CF3 is added to the most electron-rich position of pyrene. The resultant CF3-pyrenyl radical 10 then undergoes oxidation by the excited photocatalyst 6*, to generate the CF3-pyrenyl cation 11. The two photocatalytic cycles are closed via a single electron transfer where 9 is reduced to pyrene and the reduced photocatalyst [ML2] 2+ is oxidized to 6. Finally, facile deprotonation of 11 with K2HPO4 affords the desired CF3-pyrene. A new photoredox system in which a photoreductive Scheme 2. Visible-light-driven Co-catalyzed trifluoromethylation of polycyclic aromatic hydrocarbons with CF 3 SO 2 Cl.
The reaction requires the use of luminescent Co(III) complexes 6 or 7 as photocatalysts which are powerful photo-oxidants E[*A/A −1 ] = (2.26 V and 2.75 V vs. SCE). A plausible reaction mechanism involves excitation of pyrene to its triplet state 8 by means of energy transfer from the excited photocatalyst 6*. Oxidative quenching via single-electron transfer of CF 3 SO 2 Cl affords •CF 3 with concomitant formation of the pyrenyl radical cation 9. The electron-deficient •CF 3 is added to the most electron-rich position of pyrene. The resultant CF 3 -pyrenyl radical 10 then undergoes oxidation by the excited photocatalyst 6*, to generate the CF 3 -pyrenyl cation 11. The two photocatalytic cycles are closed via a single electron transfer where 9 is reduced to pyrene and the reduced photocatalyst [ML 2 ] 2+ is oxidized to 6. Finally, facile deprotonation of 11 with K 2 HPO 4 affords the desired CF 3 -pyrene. A new photoredox system in which a photoreductive activation of CF 3 SO 2 Cl was achieved has been developed by Blechert and coworkers (Scheme 3) [39]. In this work, heterogeneous, mesoporous graphitic carbon nitride (mpg-CN), a metal-free solid-state organocatalyst with an oxidation potential E[A/A −1 ] = (1.3 V and 1.4 V vs. SHE, pH 7), was able to reduce CF 3 SO 2 Cl, affording •CF 3 . With the developed method, it was possible to trifluoromethylate benzene and a great variety of heteroaromatic compounds such as pyrroles, oxazoles, furanes, thiophenes, indoles, and pyrazines in moderate to excellent yields. A variety of functional groups were tolerated, including aldehydes, esters, halides, and amides. However, the reaction suffers from double trifluoromethylation and formation of chlorinated side products.
atalysts 2023, 13,94 activation of CF3SO2Cl was achieved has been developed by Blechert a (Scheme 3) [39]. In this work, heterogeneous, mesoporous graphitic carbon CN), a metal-free solid-state organocatalyst with an oxidation potential E[A and 1.4 V vs. SHE, pH 7), was able to reduce CF3SO2Cl, affording • developed method, it was possible to trifluoromethylate benzene and a g heteroaromatic compounds such as pyrroles, oxazoles, furanes, thiophene pyrazines in moderate to excellent yields. A variety of functional groups w including aldehydes, esters, halides, and amides. However, the reaction double trifluoromethylation and formation of chlorinated side products. Diaz and coworkers revealed that trifluoromethylation reactions can b carried out in gel media under aerobic conditions, affording the desire comparable yields to those obtained in homogeneous solution (Scheme 4) [ electron-rich 5-membered heteroarenes and electron-deficient 6-membered were trifluoromethylated in the presence of Ir(Fppy)3 or Ru(phe)3Cl2 as the CF3SO2Cl as the fluorinating reactant, and gelator under aerated conditio were comparable to those obtained in solution under an inert atmospher study revealed that, when the same reaction proceeded in solution in th gelator at a concentration marginally below the critical gelation concentrat final obtained product yields were ∼10−15% lower compared to the reacti in gel phase at a concentration above the CGC. This effect was explained o the oxygen-blocking efficiency achieved with the gel network. The authors media seem to be a promising candidate to facilitate photochemical re aerobic conditions, outcompeting the MacMillan procedure requiring Scheme 3. Photocatalytic generation of alkyl radicals for trifluoromethylation of arenes using CF 3 SO 2 Cl and mpg-CN.
Diaz and coworkers revealed that trifluoromethylation reactions can be successfully carried out in gel media under aerobic conditions, affording the desired products in comparable yields to those obtained in homogeneous solution (Scheme 4) [40]. A series of electron-rich 5-membered heteroarenes and electron-deficient 6-membered heteroarenes were trifluoromethylated in the presence of Ir(Fppy) 3 or Ru(phe) 3 Cl 2 as the photocatalyst, CF 3 SO 2 Cl as the fluorinating reactant, and gelator under aerated conditions. The yields were comparable to those obtained in solution under an inert atmosphere. The further study revealed that, when the same reaction proceeded in solution in the presence of gelator at a concentration marginally below the critical gelation concentration (CGC), the final obtained product yields were ∼10−15% lower compared to the reaction carried out in gel phase at a concentration above the CGC. This effect was explained on the basis of the oxygenblocking efficiency achieved with the gel network. The authors stress that gel media seem to be a promising candidate to facilitate photochemical reactions under aerobic conditions, outcompeting the MacMillan procedure requiring a strict inert oxygen-free atmosphere.  [41][42][43][44][45][46][47]. However, the gaseous state of CF3I makes it hard to handle, causing difficulties in knowing the exact concentration present in the reaction mixture. Ye and coworkers have reported the trifluoromethylation of arylboronic acids by applying their strategy of merging photoredox catalysis with transition metal catalysis (Scheme 5) [48]. The combination of the Cu/Ru dual catalytic system has enabled the trifluoromethylation of a wide variety of aromatic and heteroaromatic substrates bearing many common functional groups. According to the presented mechanism, CF3I is reduced by the reduced photocatalyst [Ru(bpy)3]Cl2 12 with formation of •CF3 13. Addition of •CF3 to the copper(II) species 15 formed in the photocatalytic cycle from the Cu(I) salt 14 oxidizes the metal to give the high-valent trifluoromethyl−copper(III) species 16. Transmetalation of arylboronic acid 17 to give aryl−copper(III) intermediate 18 is followed by aryl-CF3 bond-forming reductive elimination to give the final product and regenerate the copper(I) species 14.
The interesting extention of this work reported by the Ritter group involves a siteselective late-stage introduction of trifluoromethyl groups into arenes using Cu-CF3 as the radical source (Scheme 6) [49]. The Cu-CF3 reagent was obtained by mixing CuSCN, CsF, and TMSCF3 at 23 °C in DMF prior to addition of the Ru(II) catalyst and thiantrenium salt. The two-step procedure entails exquisitely selective thianthrenation followed by chemoselective photoredox-mediated trifluoromethylation of the aryl thianthrenium salts. The reaction proceeds with broad functional group tolerance, even for complex small molecules on the gram scale. The proposed mechanism involves oxidation of Cu(I)-CF3 19 by the excited Ru(II) 20, affording Cu(II)-CF3 21, which is followed by oxidative addition of the aryl radical 22 forming the aryl−copper(III) intermediate 23. The aryl radicals 22 are formed upon C-S bond fragmentation of the reduced thianthrenium salt 25 which is obtained in the photocatalytic cycle via single-electron transfer from Ru(I) 26 to 24. The aryl-CF3 bond-forming reductive elimination of 23 gives the final product. However, the additional experiments performed by the authors involving a Stern-Volmer analysis and trapping of radicals by TEMPO suggest that the reaction occurs not only via a CF3 radical pathway. Recently, Cho and coworkers reported the trifluoromethylation of electron-rich heterocycles with Ru(bpy)3Cl2 as the photosensitizer and CF3I as the CF3 radical source (Scheme 7) [50]. Scheme 4. Photocatalytic trifluoromethylation of (hetero)arenes in gel media.

CF 3 I as the Fluorinating Reactant
CF 3 radicals can be generated under mild, neutral conditions from commercially available and relatively inexpensive CF 3 [41][42][43][44][45][46][47]. However, the gaseous state of CF 3 I makes it hard to handle, causing difficulties in knowing the exact concentration present in the reaction mixture. Ye and coworkers have reported the trifluoromethylation of arylboronic acids by applying their strategy of merging photoredox catalysis with transition metal catalysis (Scheme 5) [48]. The combination of the Cu/Ru dual catalytic system has enabled the trifluoromethylation of a wide variety of aromatic and heteroaromatic substrates bearing many common functional groups. According to the presented mechanism, CF 3 I is reduced by the reduced photocatalyst [Ru(bpy) 3 ]Cl 2 12 with formation of •CF 3 13. Addition of •CF 3 to the copper(II) species 15 formed in the photocatalytic cycle from the Cu(I) salt 14 oxidizes the metal to give the high-valent trifluoromethyl−copper(III) species 16. Transmetalation of arylboronic acid 17 to give aryl−copper(III) intermediate 18 is followed by aryl-CF 3 bond-forming reductive elimination to give the final product and regenerate the copper(I) species 14. The interesting extention of this work reported by the Ritter group involves a siteselective late-stage introduction of trifluoromethyl groups into arenes using Cu-CF 3 as the radical source (Scheme 6) [49]. The Cu-CF 3 reagent was obtained by mixing CuSCN, CsF, and TMSCF 3 at 23 • C in DMF prior to addition of the Ru(II) catalyst and thiantrenium salt. The two-step procedure entails exquisitely selective thianthrenation followed by chemoselective photoredox-mediated trifluoromethylation of the aryl thianthrenium salts. The reaction proceeds with broad functional group tolerance, even for complex small molecules on the gram scale. The proposed mechanism involves oxidation of Cu(I)-CF 3 19 by the excited Ru(II) 20, affording Cu(II)-CF 3 21, which is followed by oxidative addition of the aryl radical 22 forming the aryl−copper(III) intermediate 23. The aryl radicals 22 are formed upon C-S bond fragmentation of the reduced thianthrenium salt 25 which is obtained in the photocatalytic cycle via single-electron transfer from Ru(I) 26 to 24. The aryl-CF 3 bond-forming reductive elimination of 23 gives the final product. However, the additional experiments performed by the authors involving a Stern-Volmer analysis and trapping of radicals by TEMPO suggest that the reaction occurs not only via a CF 3 radical pathway. Recently, Cho and coworkers reported the trifluoromethylation of electronrich heterocycles with Ru(bpy) 3 Cl 2 as the photosensitizer and CF 3 I as the CF 3 radical source (Scheme 7) [50]. A variety of aromatic compounds were transformed into trifluoromethylated products under mild reaction conditions. In the proposed mechanism, Ru(bpy) 3 2+ 27 is excited by visible light, providing *Ru(bpy) 3 2+ 28 that is then reductively quenched by an amine to produce Ru(bpy) 3 + 29 and the ammonium radical cation 30. The Ru(bpy) 3 + species 29 in turn performs a single-electron reduction of the F 3 C-I bond, regenerating 27 and forming a carbon-centered •CF 3 . Finally, coupling of this electron-deficient radical with an electron-rich heterocycle 31 and the oxidation of the resulting radical 32 to 33 followed by rearomatization gives the trifluoromethylated product. The Fukuzumi group reported the use of cyclometalated platinum(II) complexes as photocatalyst for trifluoromethylation reactions (Scheme 8) [51]. A variety of aromatic compounds were transformed into trifluoromethylated products under mild reaction conditions. In the proposed mechanism, Ru(bpy)3 2+ 27 is excited by visible light, providing *Ru(bpy)3 2+ 28 that is then reductively quenched by an amine to produce Ru(bpy)3 + 29 and the ammonium radical cation 30. The Ru(bpy)3 + species 29 in turn performs a single-electron reduction of the F3C-I bond, regenerating 27 and forming a carbon-centered •CF3. Finally, coupling of this electron-deficient radical with an electron-rich heterocycle 31 and the oxidation of the resulting radical 32 to 33 followed by rearomatization gives the trifluoromethylated product. The Fukuzumi group reported the use of cyclometalated platinum(II) complexes as photocatalyst for trifluoromethylation reactions (Scheme 8) [51].
A series of indoles and pyrroles were trifluoromethylated in good to excellent yields upon reaction with N,N,N',N'-tetramethylethylenediamine as an electron donor and CF3I. According to the proposed mechanism, photoexcitation of the platinum(II) catalyst 34 would promote an electronic transition to a singlet MLCT state which would undergo fast intersystem crossing to a triplet MLCT state 35. Reaction between this triplet state and trifluoromethyl iodide affords the CF3 radical that can be added to heteroaromatic substrates to give the desired aryl radical 36. The final product can be formed by oxidation of 36 to 37 followed by addition of I¯ and dehydrohalogenation with amine. The alternative pathway involves iodination of 36 with CF3I via a chain propagation mechanism followed by dehydrohalogenation with amine. Reductive regeneration of the platinum(II) in the presence of a sacrificial electron donor 36 or amine would then close the catalytic cycle. Scheme 7. Visible-light-driven Ru-catalyzed trifluoromethylation of electron rich heteroaromatic compounds using CF 3 I.

Hypervalent Iodine and Sulfur Compounds as the Fluorinating Reactants
Hypervalent iodine(III) reagents are widely used in organic synthesis, because of their low toxicity, strong electrophilicity, and valuable oxidizing properties [52][53][54][55][56]. The Scaiano group decided to employ electrophilic CF3 reagents, such as Togni hypervalentiodine compounds, for the trifluoromethylation of electron-rich heterocycles. Using  A series of indoles and pyrroles were trifluoromethylated in good to excellent yields upon reaction with N,N,N ,N -tetramethylethylenediamine as an electron donor and CF 3 I. According to the proposed mechanism, photoexcitation of the platinum(II) catalyst 34 would promote an electronic transition to a singlet MLCT state which would undergo fast intersystem crossing to a triplet MLCT state 35. Reaction between this triplet state and trifluoromethyl iodide affords the CF 3 radical that can be added to heteroaromatic substrates to give the desired aryl radical 36. The final product can be formed by oxidation of 36 to 37 followed by addition of I and dehydrohalogenation with amine. The alternative pathway involves iodination of 36 with CF 3 I via a chain propagation mechanism followed by dehydrohalogenation with amine. Reductive regeneration of the platinum(II) in the presence of a sacrificial electron donor 36 or amine would then close the catalytic cycle.

Hypervalent Iodine and Sulfur Compounds as the Fluorinating Reactants
Hypervalent iodine(III) reagents are widely used in organic synthesis, because of their low toxicity, strong electrophilicity, and valuable oxidizing properties [52][53][54][55][56]. The Scaiano group decided to employ electrophilic CF 3 reagents, such as Togni hypervalent-iodine compounds, for the trifluoromethylation of electron-rich heterocycles. Using methyl blue (MB) as a photocatalyst and TMEDA as the sacrificial reductant, trifluoromethylation of electron-rich heterocycles was demonstrated, which proceeded in moderate to good yield (Scheme 9) [57]. Final product hν Scheme 9. Visible-light-driven trifluoromethylation of heteroaromatic compounds using methyl blue as a photocatalyst and Togni reagent.
A possible mechanism for the catalytic formation of •CF3 involves formation of the triplet state of MB 38 upon visible light irradiation. The excited photocatalyst can be quenched by amine (TMEDA) to form the semireduced MB radical 39 and an α-amino radical 40. Both of these species can in turn reduce Togni reagent 41, resulting in the release of a •CF3 which is added next to the aromatic molecule, affording the final product. At the same time, Ma and coworkers developed the first visible-light-induced Ir-catalyzed radical trifluoromethylation of free anilines with Togni reagent at room temperature (Scheme 10) [58]. A variety of aniline derivatives have been tested and high functional group tolerance was observed, indicating that the method can be used for the late incorporation of a CF3 group into an aniline moiety. According to the mechanism, single- oromethylation of free anilines with Togni reagent at room temperature (Scheme 10) [58]. A variety of aniline derivatives have been tested and high functional group tolerance was observed, indicating that the method can be used for the late incorporation of a CF 3 group into an aniline moiety. According to the mechanism, single-electron transfer from the excited photocatalyst 42 to Togni reagent 43 generates a strong oxidant 44 and 45 which would then collapse to •CF 3 46. The obtained 46 is added to the most electron-rich position of aniline derivative to form the radical 47. Subsequently, the cation species 48 is formed upon oxidation with strong oxidant 44. Finally, deprotonation of 48 could afford the final product.  The commercially available dimesithylsulfoniumtrimethyl trifluoromethanesulfonate (dMesCF3) was applied as the •CF3 source to a trifluoromethylation of aryl bromides through dual copper-photoredox catalysis (Scheme 12) [60]. The mechanism is similar to that presented in Scheme 4, however, Ir(dFFppy)2(4,4'-dCF3bpy)PF6 E[*A/A −1 ] = (+1.55 V vs. SCE) was used as photocatalyst. During the reaction, •CF3 is generated by reduction of dMesCF3 55 in the photocatalytic cycle. Noteworthily, tris-(trimethylsilyl) silanol 56 E[A/A −1 ] = 1.54 V is oxidized in the photocatalytic cycle to afford after the rearrangement the silyl radical 57 which is then engaged in the bromine atom abstraction, affording the respective aryl radical 58. The oxidative addition of •CF3 to the Cu(I) species 59 gives the Cu(II) intermediate 60 and, followed by the oxidative addition of the aryl radical 58, affords the respective Cu(III) adduct 61. Reductive elimination from this high-valent Cu(III) intermediate yields the desired product and simultaneously regenerates Cu(I) catalyst 59. A broad range of electronically differentiated parasubstituted bromoarenes including fused cyclic motifs were found to give good to excellent yields of the desired products. Regarding the scope of heteroarylbromides, pyridine derivatives as well as bromopyrazines, pyrimidines, and pyridazines or five-membered heteroarylbromides, such as imidazoles, pyrazoles, and thiazoles, were competent substrates, providing the desired products in good yields.
In the search for new trifluoromethylation reactions with inexpensive and easily handled •CF 3 sources, the Quing group developed a practical visible-light-induced decarboxylative trifluoromethylation of (hetero)arenes using the easily accessible [bis(trifluoroacetoxy)iodo]perfluorobenzene as the trifluoromethylating reagent (Scheme 11) [59]. This method proved to be tolerant of various (hetero)arenes and functional groups, however, in some cases, the trifluoromethylated products were obtained as a mixture of isomers. Meanwhile, electron-deficient heteroarenes (pyridines, pyrimidines, pyrazines, and thiazoles) were also amenable to the reaction. The plausible reaction mechanism involves oxidation of *Ru(bpy) 3 Proposed mechanism: The commercially available dimesithylsulfoniumtrimethyl trifluoromethanesulfonate (dMesCF 3 ) was applied as the •CF 3 source to a trifluoromethylation of aryl bromides through dual copper-photoredox catalysis (Scheme 12) [60]. The mechanism is similar to that presented in Scheme 4, however, Ir(dFFppy) 2 (4,4 -dCF 3 bpy)PF 6 E[*A/A −1 ] = (+1.55 V vs. SCE) was used as photocatalyst. During the reaction, •CF 3 is generated by reduction of dMesCF 3 55 in the photocatalytic cycle. Noteworthily, tris-(trimethylsilyl) silanol 56 E[A/A −1 ] = 1.54 V is oxidized in the photocatalytic cycle to afford after the rearrangement the silyl radical 57 which is then engaged in the bromine atom abstraction, affording the respective aryl radical 58. The oxidative addition of •CF 3 to the Cu(I) species 59 gives the Cu(II) intermediate 60 and, followed by the oxidative addition of the aryl radical 58, affords the respective Cu(III) adduct 61. Reductive elimination from this high-valent Cu(III) intermediate yields the desired product and simultaneously regenerates Cu(I) catalyst 59. A broad range of electronically differentiated parasubstituted bromoarenes including fused cyclic motifs were found to give good to excellent yields of the desired products. Regarding the scope of heteroarylbromides, pyridine derivatives as well as bromopyrazines, pyrimidines, and pyridazines or five-membered heteroarylbromides, such as imidazoles, pyrazoles, and thiazoles, were competent substrates, providing the desired products in good yields.

Trifluoromethyl Acid and Anhydride as the Fluorinating Reactants
Trifluoroacetic acid and its anhydride (TFAA) are desirable •CF3 sourc perspective of availability and cost, but have traditionally proven challengin Scheme 12. Visible-light-driven trifluoromethylation of arenes using dimesithylsulfoniumtrimethyl trifluoromethanesulfonate in the Ir/Cu dual catalytic system.

Trifluoromethyl Acid and Anhydride as the Fluorinating Reactants
Trifluoroacetic acid and its anhydride (TFAA) are desirable •CF 3 sources from the perspective of availability and cost, but have traditionally proven challenging to utilize because of the high oxidation potential E[A/A −1 ] > 2.4 V of the CF 3 COO − anion formed during reaction. Stephenson reported a strategy for the use of trifluoroacetic anhydride for a scalable and operationally simple trifluoromethylation reaction using pyridine N-oxide and photoredox catalysis to affect a facile decarboxylation to •CF 3 (Scheme 13) [61]. Pyridine Noxide was identified as the reagent of choice for the formation of a reducible TFAA adduct E[A/A −1 ] = (−1.10 V vs. SCE). The reagent combination is effective in equal stoichiometry with respect to the substrate, and is sufficiently inexpensive for large-scale implementation. Furthermore, following cleavage of the weak N-O bond and CO 2 extrusion, the generation of pyridine as a byproduct is a highly beneficial design feature, preventing the need for exogenous base. Using this methodology, trifluoromethylation of vinyl, aryl, and heteroaryl substrates was performed in acetonitrile, with 1-2 equivalents of pyridine Noxide providing generally optimal results. In some cases, however, Friedel-Crafts, N-, and O-acylation with trifluoroacetic anhydride was also observed. Importantly, the reaction was found to be tolerant of air and moisture. The same group later reported the use of 4-phenylpyridine N-oxide as a redox trigger which improved the trifluoromethylation yields and allowed a kilogram scale-up in a flow reactor [62]. The trifluoromethylation protocol developed by the Jin group is worth noting (Scheme 14). The reaction requires the use of trifluoroacetic acid in the presence of ruthenium catalyst and diaryl sulfoxides. Various heteroarenes were successfully trifluoromethylated, however, the exact role of diarylsulfoxides in the reaction mechanism is unclear [63]. trifluoromethylation yields and allowed a kilogram scale-up in a flow trifluoromethylation protocol developed by the Jin group is worth no The reaction requires the use of trifluoroacetic acid in the presence of r and diaryl sulfoxides. Various heteroarenes were successfully tri however, the exact role of diarylsulfoxides in the reaction later reported the use of 4-phenylpyridine N-oxide as a redox trigger which imp trifluoromethylation yields and allowed a kilogram scale-up in a flow reacto trifluoromethylation protocol developed by the Jin group is worth noting (Sc The reaction requires the use of trifluoroacetic acid in the presence of rutheniu and diaryl sulfoxides.

Sodium Triflinate as the Fluorinating Reactant
Sodium triflinate CF3SO2Na (Langlois reagent) can be regarded as an easy-to-handle, inexpensive, and solid trifluoromethylating agent, capable of generating CF3 radicals in the presence of a strong oxidant (e.g., t-BuOOH) [64,65]. The Itoh group reported the visible-light-induced trifluoromethylation of arenes and heteroarenes using CF3SO2Na catalyzed by anthraquinone-2-carboxylic acid AQN (Scheme 15) [66].  The Ackermann group developed the first electrophotochemical trifluoromethylation enabled by the cooperative action of electrochemistry and photochemistry in the presence of [Mes-Acr + ]ClO 4 − as a photocatalyst and CF 3 SO 2 Na as the fluorinating agent (Scheme 17) [68]. This strategy avoids the use of expensive and toxic chemical oxidants. The mechanistic considerations suggest the initial irradiation of the organic dye Mes-Acr + 68 to generate its oxidized excited state Mes-Acr + * 69. A single-electron transfer process between 69 E[*A/A −1 ] = (+2.06 V vs. SCE) and the sulfinate anion results in the generation of the acridinyl radical 70 and formation of •CF 3 . Anodic electrooxidation of the acridinyl radical 70 subsequently regenerates the ground state catalyst Mes-Acr + . The addition of •CF 3 to arene affords the radical adduct 71 which can be oxidized to the cationic Wheland complex 72 by Mes-Acr + or directly at the anode. Finally, proton abstraction delivers the desired product, whereas protons are reduced to generate H 2 at the cathode. The reaction features a broad substrate scope and a high tolerance of synthetically useful functional groups including furan, thiophene, benzofuran, benzo[b]thiophene, indole, quinoline, and pyrimidine derivatives. Remarkably, the reaction allowed for the efficient conversion of naturally occurring motifs, such as caffeine, pentoxifylline, doxofylline, theobromine, methyl estrone, and tryptophan derivatives, thereby highlighting the utility of the electrophotochemical transformation strategy for late-stage trifluoromethylations. The electrophotochemical trifluoromethylations were further achieved in a flow setup affording trifluoromethylated mesitylene in high yield.
In recent years, many other methods for photoredox catalytic oxidation of CF 3 SO 2 Na have been established. Sharada and coworkers reported a methylene blue-promoted regioselective C3-trifluoromethylation of 2H-indazoles (Scheme 18) [69].
The combination of photocatalysis and hypervalent iodine reagent provides a practical approach to a variety of trifluoromethylated indazoles in 35−83% yields. In the proposed mechanism, the indazole 73 undergoes oxidation by the excited photocatalyst MB and then the photocatalytic cycle is closed via reduction of the photocatalyst by the acetate radical. On the other hand, the fluorinating agent is formed in the reaction of CF 3 SO 2 Na with phenyliodine(III) diacetate and the obtained adduct decomposes spontaneously, affording the •CF 3 . The addition of •CF 3 to the oxidized indazole 74 followed by proton abstraction affords the final product. The presented mechanism is in contrast to that previously reported (Scheme 11) where the •CF 3 is formed after reduction of hypervalent compound in the photocatalytic cycle. In the visible-light-mediated ortho-C−H trifluoromethylation of aniline derivatives using an Eosin Y/Cu dual catalytic system, CF 3 SO 2 Na is oxidized by SO 4˙ formed by reduction of (NH 4 ) 2 S 2 O 8 (Scheme 19) [70].
The trifluoromethyl radical would be rapidly captured by Cu(II) species 75, affording a Cu(III)-CF3 intermediate 76. It should be stressed that the reaction is regiospecific, affording exclusively ortho-substituted aniline derivatives. The oxidation of CF 3 SO 2 Na by SO 4 to form the •CF 3 is also a key step in the trifluoromethylation of arylcarbamates using 4,5-dichlorofluorescein (DCFS) as a photocatalyst [71]. In this case, however, the steric effect of DCFS would increase the steric hindrance of the orthoand meta-positions on the phenyl ring, leading to the highly para-selective trifluoromethylation. Wang and coworkers developed a visible-light-induced Pd-catalyzed ortho-trifluoromethylation of acetanilides with CF 3 SO 2 Na (Scheme 20) [72]. Interestingly, both the substrate and products undergo excitation by a blue LED (410-415 nm) to generate the excited species, which acts as a photocatalyst. It was revealed that the 1 O 2 generated via energy transfer between excited photocatalyst and 3 O 2 can react with CF 3 SO 2 Na via single electron transfer to afford the superoxide radical anion O 2˙ 80 and a CF 3 SO 2 radical 81, which decomposes, generating a CF 3 radical. On the other hand, the Pd catalytic cycle is initiated by C-H activation to afford palladacycle intermediate 82, which undergoes a reaction with the formed •CF 3 to afford 83. The oxidation of 83 to 84 is followed by reductive elimination affording the final product and regenerating the Pd catalyst.   [68]. This strategy avoids the use of expensive a chemical oxidants. The mechanistic considerations suggest the initial irradiatio organic dye Mes-Acr + 68 to generate its oxidized excited state Mes-Acr + * 69. A electron transfer process between 69 E[*A/A −1 ] = (+2.06 V vs. SCE) and the sulfina results in the generation of the acridinyl radical 70 and formation of •CF3. electrooxidation of the acridinyl radical 70 subsequently regenerates the groun catalyst Mes-Acr + . The addition of •CF3 to arene affords the radical adduct 71 wh be oxidized to the cationic Wheland complex 72 by Mes-Acr + or directly at the Finally, proton abstraction delivers the desired product, whereas protons are red generate H2 at the cathode. The reaction features a broad substrate scope and tolerance of synthetically useful functional groups including furan, thi benzofuran, benzo[b]thiophene, indole, quinoline, and pyrimidine deri Remarkably, the reaction allowed for the efficient conversion of naturally oc motifs, such as caffeine, pentoxifylline, doxofylline, theobromine, methyl estro tryptophan derivatives, thereby highlighting the utility of the electrophotoc transformation strategy for late-stage trifluoromethylations. The electrophotoc trifluoromethylations were further achieved in a flow setup affording trifluoromet mesitylene in high yield. photocatalyst. It was revealed that the 1 O2 generated via energy transfer between excited photocatalyst and 3 O2 can react with CF3SO2Na via single electron transfer to afford the superoxide radical anion O2˙¯ 80 and a CF3SO2 radical 81, which decomposes, generating a CF3 radical. On the other hand, the Pd catalytic cycle is initiated by C-H activation to afford palladacycle intermediate 82, which undergoes a reaction with the formed •CF3 to afford 83. The oxidation of 83 to 84 is followed by reductive elimination affording the final product and regenerating the Pd catalyst.

Trifluoromethylthiolation and Trifluoromethoxylation of Arenes
The Wangelin group reported a protocol of radical aromatic trifluoromethylthiolation of arenediazonium salts that is based on the facile generation of intermediate aryl radicals ( Bis(trifluoromethyl) disulfide (F3CS-SCF3), which was us species, is a commercial reagent that can also be freshly prepared b Scheme 21. Visible-light-driven Ru-catalyzed trifluoromethylthiolation of arenediazonium salts using F 3 CS-SCF 3 . Bis(trifluoromethyl) disulfide (F 3 CS-SCF 3 ), which was used as the fluorinating species, is a commercial reagent that can also be freshly prepared by a literature procedure [74]. A series of arenediazonium salts were transformed into the desired aryl trifluoromethylsulfides in the presence of [Ru(bpy) 3 ]Cl 2 under irradiation with blue light (450 nm, 3.8 W LED) in moderate to good yields. The authors postulate a radical mechanism that is initiated by the photocatalytic reduction of the diazoacetate adduct formed in the reaction of arenediazonium salt with sodium acetate affording the aryl radical Ar•. The obtained Ar• undergoes rapid reaction with (SCF 3 ) 2 affording Ar-SCF 3 and generating the trifluoromethylthiyl radical F 3 CS•. The formation of Ar• and F 3 CS• was confirmed by trapping with TEMPO. The authors hypothesize recombination of F 3 CS• with suitable nucleophiles (Nu = DMSO or acetate anion) during the reaction. Back-electron transfer (formally from the elusive [NuSCF 3 ] •− ) could be a potential pathway of photocatalyst regeneration.
Trifluoromethoxylation of arenes can be performed employing either radical fluoroalkoxylating reagents or some nucleophilic trifluoromethoxylating sources [75]. However, the photocatalytic approach of the synthesis of trifluoromethoxyarenes is worth mentioning. Ngai and coworkers reported the catalytic intermolecular trifluoromethoxylation of (hetero)arenes under photocatalytic conditions (Scheme 22) [76]. The key to success of this procedure was development of an easy-to-handle, photoactive trifluoromethoxylating reagent 85. This protocol was applicable to simple arenes containing common function groups including halides, carboxylic acids, ketones, esters, ethers, nitriles, carbonates, and phosphine oxides. Later, the same group reported a redox-active cationic reagent 86 capable of forming the OCF 3 radical exclusively upon photocatalytic reduction [77]. This reagent is also applicable to the catalytic (hetero)aryl trifluoromethoxylation including a number of biorelevant compounds.

Perfluoroalkylation of Arenes
Even though several perfluorinated compounds are commercially available, the development of novel methods for efficient and selective introduction of fluorinated motifs is a growing area of interest because of the expansion of applications in medicinal, synthetic, industrial, and agricultural chemistry [79][80][81][82]. Synthetic procedures for direct couplings with perfluoroalkyl groups are relatively limited compared to trifluoromethylations. Perfluoroalkylated arenes were usually obtained utilizing the procedures developed for trifluoromethylation of aromatic compounds. For example, the conditions applied by Ye and coworkers [48] for trifluoromethylation of arylboronic acids using CF3I in a Cu/Ru dual catalytic system can also be utilized for perfluoroalkylation reactions. Using commercially available perfluorobutyl and perfluorodecyl iodides, the respective perfluoroalkylated biphenyls were obtained in good yields (Scheme 23). Similarly, the procedures of trifluoromethylation of arenes can also be extended for installation of -C2F5, -C3F7, -C6F13, and -C8F16 motifs into the aromatic system of alkoxybenzenes and nitrogen-based heterocycles [  At the same time, Togni and coworkers disclosed the work on radical trifluoromethoxylation using a pyridinium-based reagent 87 [78]. A variety of simple aryl trifluoromethyl ethers bearing common functional groups were prepared and the reaction was also applicable to more complex structures including e.a. Femara ® (anticancer treatment) or procymidone (a fruit fungicide). In the case of 85 and 87, the reaction occurs via photoreduction of these compounds with the formation of the •OCH 3 followed by the addition of •OCH 3 to the arene and the concomitant oxidation-deprotonation affording the final product. However, for 86 an alternative mechanism is proposed as it was found by the authors that the formation of the •OCF 3 via the reduction of 86 by excited Ru(bpy) 3 (PF 6 ) 2 is unlikely. The reaction starts with the photoexcitation of the OCF 3 reagent 86. This direct excitation is followed by a homolytic cleavage of the N-OCF 3 bond to afford •OCF 3 and an N-centered benzimidazole radical 88. The •OCF 3 adds to an arene to afford the radical 89, while 88 is reduced by *Ru(bpy) 3 to benzimidazole anion 90 (path A). The subsequent single-electron transfer from 89 to Ru(III) affords cyclohexadienyl cation 91 (path B), deprotonation of which restores the aromaticity and yields the desired aryl trifluoromethyl ether.

Perfluoroalkylation of Arenes
Even though several perfluorinated compounds are commercially available, the development of novel methods for efficient and selective introduction of fluorinated motifs is a growing area of interest because of the expansion of applications in medicinal, synthetic, industrial, and agricultural chemistry [79][80][81][82]. Synthetic procedures for direct couplings with perfluoroalkyl groups are relatively limited compared to trifluoromethylations. Perfluoroalkylated arenes were usually obtained utilizing the procedures developed for trifluoromethylation of aromatic compounds. For example, the conditions applied by Ye and coworkers [48] for trifluoromethylation of arylboronic acids using CF 3 I in a Cu/Ru dual catalytic system can also be utilized for perfluoroalkylation reactions. Using commercially available perfluorobutyl and perfluorodecyl iodides, the respective perfluoroalkylated biphenyls were obtained in good yields (Scheme 23). Similarly, the procedures of trifluoromethylation of arenes can also be extended for installation of -C 2 F 5 , -C 3 F 7 , -C 6 F 13 , and -C 8 F 16 motifs into the aromatic system of alkoxybenzenes and nitrogen-based heterocycles [62,63,66,67].

Perfluoroalkylation of Arenes
Even though several perfluorinated compounds are commercially availa development of novel methods for efficient and selective introduction of flu motifs is a growing area of interest because of the expansion of applications in m synthetic, industrial, and agricultural chemistry [79][80][81][82]. Synthetic procedures fo couplings with perfluoroalkyl groups are relatively limited compa trifluoromethylations. Perfluoroalkylated arenes were usually obtained utiliz procedures developed for trifluoromethylation of aromatic compounds. For exam conditions applied by Ye and coworkers [48] for trifluoromethylation of arylboron using CF3I in a Cu/Ru dual catalytic system can also be utilized for perfluoroal reactions. Using commercially available perfluorobutyl and perfluorodecyl iodi respective perfluoroalkylated biphenyls were obtained in good yields (Sche Similarly, the procedures of trifluoromethylation of arenes can also be exten installation of -C2F5, -C3F7, -C6F13, and -C8F16 motifs into the aromatic sy alkoxybenzenes and nitrogen-based heterocycles [62,63,66,67]. A simple and straightforward photocatalytic perfluoroalkylation method h developed in continuous microflow, using commercially available [Ru(bpy)3] photocatalyst and selected perfluoroalkyl iodides [83]. A selection of five-me heteroaromatics were successfully perfluoroalkylated within several minutes. T synthesis technology exhibits merits such as high reaction yield (55-88 %), mild conditions (room temperature), atmospheric pressure, and excellent scale-up p Scheme 23. Visible-light-driven perfluoroalkylation of arylboronic acids using perfluoroalkyl iodides in Ru/Cu dual catalytic system. A simple and straightforward photocatalytic perfluoroalkylation method has been developed in continuous microflow, using commercially available [Ru(bpy) 3 ]Cl 2 as a photocatalyst and selected perfluoroalkyl iodides [83]. A selection of five-membered heteroaromatics were successfully perfluoroalkylated within several minutes. This flow synthesis technology exhibits merits such as high reaction yield (55-88%), mild reaction conditions (room temperature), atmospheric pressure, and excellent scale-up potential, which should allow easy implementation of this methodology in both academia and industry (Scheme 24). In the same year, the Noël group developed a remarkably efficient visible-light-photoinduced catalytic perfluoroalkylation of pyrroles and indoles in continuous flow using Eosin Y as the photoredox catalyst [84]. The Postigo group extended these studies, presenting a visible-light-driven transition-metal-free radical aromatic substitution reaction of aniline derivatives with perfluoroalkyl iodides in the presence of cesium carbonate as base and inexpensive Rose Bengal (RB) as organophotocatalyst in MeCN as solvent (Scheme 25) [85]. A series of perfluoroalkyl-substituted aniline derivatives were obtained in good to excellent yields, however, in the case of unsubstituted aniline the formation of the mixture of paraand ortho-isomers was observed. The proposed mechanism involves the excitation of RB 92 to RB* 93, which transfers an electron to n-C 4 F 9 I, generating •C 4 F 9 radical 94 and the radical cation RB ·+ . The addition of 94 to aniline affords the radical 95 which is next oxidized by n-C 4 F 9 I to 96. This step can propagate the chain process of the formation of •C 4 F 9 . The hydrogen abstraction from 96 by Cs 2 CO 3 affords the final product. The authors hypothesize that the RB ·+ radical cation also accepts an electron from Cs 2 CO 3 to regenerate RB. The fact that addition of Cs 2 CO 3 to the photocatalytic reactions significantly improved the perfluorobutylation yields could support the role of the base as an electron-donor adjuvant to regenerate the catalyst.
addition of 94 to aniline affords the radical 95 which is next oxidized b step can propagate the chain process of the formation of •C4F9. The hy from 96 by Cs2CO3 affords the final product. The authors hypothesize cation also accepts an electron from Cs2CO3 to regenerate RB. The f Cs2CO3 to the photocatalytic reactions significantly improved the p yields could support the role of the base as an electron-donor adjuva catalyst. addition of 94 to aniline affords the radical 95 which is next oxidized by n step can propagate the chain process of the formation of •C4F9. The hyd from 96 by Cs2CO3 affords the final product. The authors hypothesize th cation also accepts an electron from Cs2CO3 to regenerate RB. The fact Cs2CO3 to the photocatalytic reactions significantly improved the pe yields could support the role of the base as an electron-donor adjuvant catalyst. A series of aniline derivatives were efficiently perfluoroalkylated using fac-Ir(ppy) 3 (0.1%) in the presence of K 2 CO 3 in DCM at room temperature under blue light irradiation (Scheme 26) [86].
A series of aniline derivatives were efficiently perfluoroalkylated using fac-Ir(ppy) (0.1%) in the presence of K2CO3 in DCM at room temperature under blue light irradiation (Scheme 26) [ Final product Scheme 26. Visible-light-driven Ir-catalyzed perfluoroalkylation of aniline derivatives using perfluoroalkyl iodides.
The substrates bearing electro-neutral and electro-donating groups underwent the perfluoroalkylation smoothly and furnished products in good to excellent yields. For para substituted derivatives, only ortho-substituted aniline was formed, however, a mixture of regio-isomers with an almost 1/1 ratio (ortho/para) was obtained when methyl 3-amino-4 iodobenzoate was examined. Meanwhile, only para-substituted perfluoroalkylated aniline was formed when di-ortho-substituted aniline was employed as a substrate. According to the proposed mechanism, the reaction starts with the excitation of the photocatalys [Ir(ppy)3] 97 with blue LEDs. Subsequent single-electron transfer from 98 to RfI generates perfluoroalkyl radical 99 and Ir(IV)(ppy)3 100. The newly formed radical intermediate reacts with free aniline to produce intermediate 101, which is oxidized by 100, followed by the abstraction of a proton with the base to provide the perfluoroalkylated product The Ritter group has revealed that photoredox-catalyzed cross-coupling of ary thianthrenium salts with a copper-based trifluoromethyl reagent for a site-selective trifluoromethylation can also be utilized for the introduction of a pentafluoroethyl group (Scheme 27) [49]. The mesoporous graphitic carbon nitride (mpg-CN) photocatalys utilized by the Blechert group to trifluoromethylate various arenes was further applied to obtain 2-perfluorobutyl pyrrole (Scheme 28) [39]. High reactivity (85%) was observed in the case of perfluorobutyl sulfonyl chloride as the fluorinating agent, however, double fluoroalkylation product at positions 2 and 5 of pyrrole was also obtained (8%). The use of perfluorobutyl sulfonyl fluoride showed only a slow reaction with a low conversion to the desired product (17%). This can be explained by the stronger S-F bond compared to Scheme 26. Visible-light-driven Ir-catalyzed perfluoroalkylation of aniline derivatives using perfluoroalkyl iodides.
The substrates bearing electro-neutral and electro-donating groups underwent the perfluoroalkylation smoothly and furnished products in good to excellent yields. For parasubstituted derivatives, only ortho-substituted aniline was formed, however, a mixture of regio-isomers with an almost 1/1 ratio (ortho/para) was obtained when methyl 3-amino-4iodobenzoate was examined. Meanwhile, only para-substituted perfluoroalkylated aniline was formed when di-ortho-substituted aniline was employed as a substrate. According to the proposed mechanism, the reaction starts with the excitation of the photocatalyst [Ir(ppy) 3 ] 97 with blue LEDs. Subsequent single-electron transfer from 98 to R f I generates perfluoroalkyl radical 99 and Ir(IV)(ppy) 3 100. The newly formed radical intermediate reacts with free aniline to produce intermediate 101, which is oxidized by 100, followed by the abstraction of a proton with the base to provide the perfluoroalkylated product. The Ritter group has revealed that photoredox-catalyzed cross-coupling of aryl thianthrenium salts with a copper-based trifluoromethyl reagent for a site-selective trifluoromethylation can also be utilized for the introduction of a pentafluoroethyl group (Scheme 27) [49]. The mesoporous graphitic carbon nitride (mpg-CN) photocatalyst utilized by the Blechert group to trifluoromethylate various arenes was further applied to obtain 2-perfluorobutyl pyrrole (Scheme 28) [39]. High reactivity (85%) was observed in the case of perfluorobutyl sulfonyl chloride as the fluorinating agent, however, double fluoroalkylation product at positions 2 and 5 of pyrrole was also obtained (8%). The use of perfluorobutyl sulfonyl fluoride showed only a slow reaction with a low conversion to the desired product (17%). This can be explained by the stronger S-F bond compared to the S-Cl bond that inhibits a fast degradation after reduction to generate the perfluoroalkyl radical. On the other site, using perfluorobutyl iodide, the reaction was slower than with perfluorobutyl sulfonyl chloride, but a good yield of 68% of the desired product was achieved. the S-Cl bond that inhibits a fast degradation after reduction to generate the perfluo radical. On the other site, using perfluorobutyl iodide, the reaction was slower th perfluorobutyl sulfonyl chloride, but a good yield of 68% of the desired prod achieved. Wang and coworkers reported a photocatalyzed, copper-mediated system fo perfluoroalkylation of 8-aminoquinoline-derived benzamides using Eosin Y photocatalyst (Scheme 29) [87]. the S-Cl bond that inhibits a fast degradation after reduction to generate the perfluo radical. On the other site, using perfluorobutyl iodide, the reaction was slower th perfluorobutyl sulfonyl chloride, but a good yield of 68% of the desired prod achieved. Wang and coworkers reported a photocatalyzed, copper-mediated system fo perfluoroalkylation of 8-aminoquinoline-derived benzamides using Eosin Y photocatalyst (Scheme 29) [87]. Wang and coworkers reported a photocatalyzed, copper-mediated system for ortho-perfluoroalkylation of 8-aminoquinoline-derived benzamides using Eosin Y as the photocatalyst (Scheme 29) [87]. the S-Cl bond that inhibits a fast degradation after reduction to generate the perfluoroalkyl radical. On the other site, using perfluorobutyl iodide, the reaction was slower than with perfluorobutyl sulfonyl chloride, but a good yield of 68% of the desired product was achieved. Wang and coworkers reported a photocatalyzed, copper-mediated system for orthoperfluoroalkylation of 8-aminoquinoline-derived benzamides using Eosin Y as the photocatalyst (Scheme 29) [87]. A series of benzamides were selectively perfluoroalkylated at the ortho-position. A plausible mechanism involves formation of cyclometalated complex 103 from C-H activation of 102 with copper salt. Perfluoroalkyl radicals formed by the reaction of perfluoroalkyl iodides with excited photocatalyst react with 103 to form a Cu III complex 104. Finally, reductive elimination of 104 affords the desired product. Arenes could also be perfluoroalkylated using perfluoroalkyl iodides in the presence of heterogenic photocatalysts such as TiO 2 , carbon nitride or via formation of EDA complexes [88][89][90].
To extend the application of hypervalent iodine(III) acetates utilized by the Qing group, the analogous fluoroalkylation reactions were examined using perfluoroethyl and perfluoropropyl derivatives C 6 F 5 I(OCOR f ) 2 (Scheme 30) [59]. activation of 102 with copper salt. Perfluoroalkyl ra perfluoroalkyl iodides with excited photocatalyst react 104. Finally, reductive elimination of 104 affords the d be perfluoroalkylated using perfluoroalkyl iodides photocatalysts such as TiO2, carbon nitride or via forma To extend the application of hypervalent iodine( group, the analogous fluoroalkylation reactions were e perfluoropropyl derivatives C6F5I(OCORf)2 (Scheme 30 These reactions proceeded smoothly under the sta pentafluoroethylated and heptafluoropropylated produ

Monofluorination of Arenes
Although various fluorination procedures hav synthetic methods usually involve the use of toxic and d often affording a mixture of mono-and difluorina fluorination reactions have been developed as an fluorination of complex molecules [95][96][97]. However, th mainly involving the improvement of regiospecificity readily available starting materials. The concept of visib Scheme 30. Visible-light-driven Ru-catalyzed perfluoroalkylation using perfluoroalkylated hypervalent iodine(III) acetates.
These reactions proceeded smoothly under the standard conditions, resulting in the pentafluoroethylated and heptafluoropropylated products in moderate yields.

Monofluorination of Arenes
Although various fluorination procedures have been developed, the known synthetic methods usually involve the use of toxic and dangerous atomic fluorine sources, often affording a mixture of mono-and difluorinated compounds [91][92][93][94]. Radical fluorination reactions have been developed as an efficient methodology for the fluorination of complex molecules [95][96][97]. However, these reactions require further study mainly involving the improvement of regiospecificity and the ability to use cheap and readily available starting materials. The concept of visible-light-driven photocatalysis has been proved attractive for the direct C-F bond formation. Fukuzumi and coworkers reported the photocatalytic system using tetraethylammonium fluoride tetrahydrogen fluoride salt (TEAF•4HF) as fluorinating reagent in the presence of 3-cyano-1-methylquinolinium perchlorate (QuCN + ClO 4 − ) as photocatalyst (Scheme 31) [98]. Using acetonitrile as a solvent under irradiation of a 500 W xenon lamp, fluorobenzene was obtained in 20% yield after 50 min of irradiation. Chloroand bromobenzene were also fluorinated, however, the corresponding para-substituted products were formed in low yield (7 and 6%). The proposed mechanism involves reaction of the excited photocatalyst 105 with arene 106 to generate arene radical cation 107 existing in equilibrium with its dimer radical cation 108. TEAF•4HF reacts with 107, affording the aryl radical 109. The O 2 •− radical formed upon reduction of oxygen in the photocatalytic cycle abstracts hydrogen from radical 109 to afford the desired fluorinated product. The Nicewicz group developed an organic photoredox system for direct are radiofluorination, using 18 F − NBu4 + as a fluorinating agent and molecular oxyge oxidant [99]. This procedure is especially valuable because fluorine-18 is the mos used positron emission tomography (PET) isotope. Using laser irradiation to e acridinium photocatalyst, unactivated arenes were effectively fluorinated, affo wide range of 18 F-labeled arenes and heteroaromatics, including pharma compounds and PET tracers. In order to replace the expensive laser light sourc exclude the necessity of bubbling the oxygen through the reaction vessel, the sam developed a photoredox system and apparatus that allow for direc radiofluorination, using a readily available 425 nm LED light source (Scheme 32) order to increase the overall light influx needed, the reactions were performed microtubing reactor that greatly increased the surface area being exposed to t source. After optimization studies, tert-butylperoxy acetate (TBPA) was selecte optimal oxidant in tert-butanol as the optimal solvent. The availability of the wid of organic photocatalysts prompted the authors to perform a catalyst sc Generally, acridinium salts were the most suitable catalysts for radiofluorination compound 110 was selected as the most efficient photocatalyst. Amongst twe examples of examined arenes, eleven of the substrates demonstrated improved yie ten of them showed comparable or decreased yields. A significant improveme yield) was observed for 4-chromanone for which the previous method prove ineffective. The regioselectivity observed in this study generally follows the sam observed in previous photoredox arene C−H fluorination studies a functionalization occurring ortho or para to an electron-donating group. The mec proposal for this reaction involves oxidation of an arene 111 by the excited photo 110* affording the carbocation 112 which undergoes nucleophilic attack by F − . The The Nicewicz group developed an organic photoredox system for direct arene C−H radiofluorination, using 18 F − NBu 4 + as a fluorinating agent and molecular oxygen as an oxidant [99]. This procedure is especially valuable because fluorine-18 is the most widely used positron emission tomography (PET) isotope. Using laser irradiation to excite an acridinium photocatalyst, unactivated arenes were effectively fluorinated, affording a wide range of 18 F-labeled arenes and heteroaromatics, including pharmaceutical compounds and PET tracers. In order to replace the expensive laser light source and to exclude the necessity of bubbling the oxygen through the reaction vessel, the same group developed a photoredox system and apparatus that allow for direct C−H radiofluorination, using a readily available 425 nm LED light source (Scheme 32) [100]. In order to increase the overall light influx needed, the reactions were performed using a microtubing reactor that greatly increased the surface area being exposed to the light source. After optimization studies, tert-butylperoxy acetate (TBPA) was selected as the optimal oxidant in tert-butanol as the optimal solvent. The availability of the wide range of organic photocatalysts prompted the authors to perform a catalyst screening. Generally, acridinium salts were the most suitable catalysts for radiofluorination and the compound 110 was selected as the most efficient photocatalyst. Amongst twenty-two examples of examined arenes, eleven of the substrates demonstrated improved yields, and ten of them showed comparable or decreased yields. A significant improvement (23% yield) was observed for 4-chromanone for which the previous method proved to be ineffective. The regioselectivity observed in this study generally follows the same trends observed in previous photoredox arene C−H fluorination studies affording functionalization occurring ortho or para to an electron-donating group. The mechanistic proposal for this reaction involves oxidation of an arene 111 by the excited photocatalyst 110* affording the carbocation 112 which undergoes nucleophilic attack by F − . The oxidant is presumed to react with the radical 113 to lead to alkylperoxyl radical 114. Intramolecular hydrogen atom transfer and extrusion of an alcohol unit (R'OH) would then furnish the fluorinated arene. The radical scavenger (TEMPO) reacts rapidly with the cyclohexadienyl radical via hydrogen atom abstraction to yield the corresponding aromatic compound. Ritter and coworkers revealed that metallophotoredox catalysis co exquisitely selective aromatic C-H functionalization by thianthrenation employed to produce synthetically valuable fluorinated analogues of c molecules (Scheme 33) [101]. Fluorination is successful on electron-deficient -rich arenes, as well as on substrates that bear ortho-substituents. The react towards aldehydes, esters, heterocycles, benzyl ethers, carbamates, amides, glycosidic linkages, and ketones. Protic groups, which are not compatib nucleophilic and electrophilic transition metal-catalyzed fluorination tolerated in copper-mediated photoredox fluorination. In the proposed arylthianthrenium salt 115 is reduced by the photocatalyst 116, repelling t 117 and affording the aryl radical 118. The obtained radical 118 undergoes a Cu(II) compound 119 followed by complexation with F − , affording the inte The reductive elimination of 120 gives the final product and the Cu(I) 1 which is next oxidized to Cu(II) 119 by the thianthrenium radical 122 o oxidation of thianthrene in the photocatalytic cycle. The mechanism of t accurately supported by kinetical experiments (fragmentation rates of arylt Scheme 32. Visible-light-driven acridinium dye-catalyzed radiofluorination of arenes using 18 FNBu 4 . Ritter and coworkers revealed that metallophotoredox catalysis combined with exquisitely selective aromatic C-H functionalization by thianthrenation can now be employed to produce synthetically valuable fluorinated analogues of complex small molecules (Scheme 33) [101]. Fluorination is successful on electron-deficient, -neutral, and -rich arenes, as well as on substrates that bear ortho-substituents. The reaction is tolerant towards aldehydes, esters, heterocycles, benzyl ethers, carbamates, amides, acid-sensitive glycosidic linkages, and ketones. Protic groups, which are not compatible with other nucleophilic and electrophilic transition metal-catalyzed fluorination reactions, are tolerated in copper-mediated photoredox fluorination. In the proposed mechanism, arylthianthrenium salt 115 is reduced by the photocatalyst 116, repelling thianthrenium 117 and affording the aryl radical 118. The obtained radical 118 undergoes addition to the Cu(II) compound 119 followed by complexation with F − , affording the intermediate 120. The reductive elimination of 120 gives the final product and the Cu(I) 121 compound which is next oxidized to Cu(II) 119 by the thianthrenium radical 122 obtained after oxidation of thianthrene in the photocatalytic cycle. The mechanism of the reaction is accurately supported by kinetical experiments (fragmentation rates of arylthianthrenium salts), Stern-Volmer measurements (effective reductive quenching of the excited iridium photocatalyst by thianthrene), and TEMPO trapping studies (formation of adducts with aryl radicals).

Fluorosulfonation of Arenes
Tlili and coworkers reported the first photocatalytic metal-free procedure fo synthesis of arylsulfonyl fluorides (Scheme 34) [102]. The reaction involves the use o diazonium salts, 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO) fluorine source, and the cyanoarene photocatalyst 123 under blue LED irradiation mild conditions afforded a broad scope and high functional group tolerance incl electron-donating and -accepting substituents in benzene derivatives. Steric hind was not deleterious to the reaction outcome, since up to 80% yields were reached for substituted methoxyphenyl derivative. Interestingly, heterocyclic compounds could be converted to their corresponding sulfonyl fluorides in moderate yields. Accord the proposed mechanism, photoinduced reduction of the diazonium salt by the ex 123* yields arene radical 124 and radical cation photocatalyst 125. Subsequently, th radical collapses with SO2 to form a new radical tosyl species 126. The released DA 127 regenerates the photocatalyst 123 in its ground state and 128. The latter may com with 126 to generate the sulfonium salt intermediate 129. The nucleophilic fluorine on 129 affords the final product and regenerates DABCO. It should be stressed th Scheme 33. Visible-light-driven Ir-catalyzed fluorination of arenes using arylthianthrenium salts.

Fluorosulfonation of Arenes
Tlili and coworkers reported the first photocatalytic metal-free procedure for the synthesis of arylsulfonyl fluorides (Scheme 34) [102]. The reaction involves the use of aryl diazonium salts, 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO) as the fluorine source, and the cyanoarene photocatalyst 123 under blue LED irradiation. The mild conditions afforded a broad scope and high functional group tolerance including electron-donating and -accepting substituents in benzene derivatives. Steric hindrance was not deleterious to the reaction outcome, since up to 80% yields were reached for orthosubstituted methoxyphenyl derivative. Interestingly, heterocyclic compounds could also be converted to their corresponding sulfonyl fluorides in moderate yields. According to the proposed mechanism, photoinduced reduction of the diazonium salt by the excited 123* yields arene radical 124 and radical cation photocatalyst 125. Subsequently, the aryl radical collapses with SO 2 to form a new radical tosyl species 126. The released DABCO 127 regenerates the photocatalyst 123 in its ground state and 128. The latter may combine with 126 to generate the sulfonium salt intermediate 129. The nucleophilic fluorine attack on 129 affords the final product and regenerates DABCO. It should be stressed that the presented mechanism is supported by quantum-mechanical calculations.

Tandem Photocatalytic Fluorination-Aromatization Processes
The previously reported general methods for the synthesis of aromatic deri bearing a fluorine or perfluoroalkyl group in a specific position display in some cas regioselectivity and require the direct use of preformed or commercially av aromatic counterparts. The alternative strategy exploits tandem reactions by com organo-photoredox-catalyzed radical fluoroalkylation of the non-aromatic part molecule followed by a reaction sequence leading to aromatization [103,104]. Ho in this review article, the emphasis will be put exclusively on reactions leading installation of the fluorinated group directly into the aromatic core. Yu and cow developed a convenient approach to obtain 6-alkylated phenanthridines using v biphenyl-based isocyanides and alkyl bromides in the presence of fac-Ir(ppy)3 photocatalyst (Scheme 35) [105]. The reaction proceeded at room temperature in g excellent yields in the absence of external stoichiometric oxidants. Within a substrate scope, two fluorinated bromides were used, affording the res perfluoroalkylated products. Based on the authors' observations, photocataly Ir(ppy)3 is irradiated to the excited state 130 which is oxidatively quenched by 13 the formation of 132 and a radical species 133. The radical 133 is added to 134 to p the imidoyl radical intermediate 135, which undergoes intramolecular cyclization Scheme 34. Visible-light-driven cyanoarene-catalyzed fluorosulfonation of arenes using DABSO.

Tandem Photocatalytic Fluorination-Aromatization Processes
The previously reported general methods for the synthesis of aromatic derivatives bearing a fluorine or perfluoroalkyl group in a specific position display in some cases poor regioselectivity and require the direct use of preformed or commercially available aromatic counterparts. The alternative strategy exploits tandem reactions by combining organophotoredox-catalyzed radical fluoroalkylation of the non-aromatic part of the molecule followed by a reaction sequence leading to aromatization [103,104]. However, in this review article, the emphasis will be put exclusively on reactions leading to the installation of the fluorinated group directly into the aromatic core. Yu and coworkers developed a convenient approach to obtain 6-alkylated phenanthridines using various biphenylbased isocyanides and alkyl bromides in the presence of fac-Ir(ppy) 3 as the photocatalyst (Scheme 35) [105]. The reaction proceeded at room temperature in good to excellent yields in the absence of external stoichiometric oxidants. Within a broad substrate scope, two fluorinated bromides were used, affording the respective perfluoroalkylated products.   Li and coworkers developed a radical-triggered cyclization of o-alkenyl a isocyanides prepared from accessible starting materials (Scheme 37) [107]. The provides a general and efficient method for the synthesis of 4-CN-2-CF2H-con quinolines under visible-light photoredox catalysis in a one-pot synthetic proce wide scope of o-alkenyl aromatic isocyanides bearing different electron-withdraw electron-donating groups at the ortho-, meta-, and para-position of phenyl rin tolerated, affording the products in moderate to high yields. The thiophene or cyc substrate also furnished the products in 23 and 39% yields, respectively. Based proposed mechanism, the reaction involves reduction of 146 by the excited photo affording the •CHF2 radical 147. The subsequent addition of 147 to the C=N bon isonitrile group affords the radical 148 which next cyclizes to 149 via a 6-endo pa alternative three-step cyclization path is also considered. The obtained radical oxidized to 150 and after H + abstraction the final product is formed. Shen and cow have developed a metal-free, visible-light photoredox-catalyzed three-com Li and coworkers developed a radical-triggered cyclization of o-alkenyl aromatic isocyanides prepared from accessible starting materials (Scheme 37) [107]. The reaction provides a general and efficient method for the synthesis of 4-CN-2-CF 2 H-containing quinolines under visible-light photoredox catalysis in a one-pot synthetic procedure. A wide scope of o-alkenyl aromatic isocyanides bearing different electron-withdrawing and electron-donating groups at the ortho-, meta-, and para-position of phenyl ring were tolerated, affording the products in moderate to high yields. The thiophene or cyclohexyl substrate also furnished the products in 23 and 39% yields, respectively. Based on the proposed mechanism, the reaction involves reduction of 146 by the excited photocatalyst affording the •CHF 2 radical 147. The subsequent addition of 147 to the C=N bond of the isonitrile group affords the radical 148 which next cyclizes to 149 via a 6-endo path. The alternative three-step cyclization path is also considered. The obtained radical is next oxidized to 150 and after H + abstraction the final product is formed. Shen and coworkers have developed a metal-free, visible-light photoredox-catalyzed three-component reaction for the facile assembly of fluoroalkylated pyrimidine derivatives in a regiodefined [3 + 2 + 1] manner, starting from readily available building blocks of silyl enol ether, amidine, and fluoroalkyl halide (Scheme 38) [108]. A concise, two-step, one-flask procedure was designed for the synthesis of the test pyrimidine derivative (84% yield) by using benzamidine hydrochloride, triisopropylsilyl enol ether (1.8 equiv.), perfluorobutyliodide (3 equiv.), DABCO (3 equiv.), and Eosin Y (3%) as the photocatalyst. With the optimal reaction conditions in hand, the authors successfully extended the substrate scope of the reaction to benzamidines containing diverse substituents of varying electronic character and steric hindrance on the phenyl moieties, affording the corresponding products in high yields (70-98%). In the same manner, the reactions worked equally well with heteroaryl amidines and C-alkylated reactants. The substrate scope with respect to a series of structurally varied silyl enol ethers also led to satisfactory yields. In addition to perfluorobutyl iodide, the applicability of this transformation to a broad spectrum of fluoroalkyl halides (C2F5I, C5F11I, C7H15I, and C8F17I) was observed. According to the proposed mechanism, the reaction involves a single-electron transfer from the excited photocatalyst EY* to fluoroalkyl halide to produce the •C4F9 radical and a radical cation EY •+ . Next, tertiary carbocation 153 is generated via the addition of a perfluoroalkyl radical to the C=C bond of silyl enol ether 151, followed by further oxidation with the aid of the oxidative radical cation EY •+ . After rapid attack by an I − ion, the α-perfluoroalkylated ketone 154 is formed. In a defluorination step, α,β-desaturation of 154 is enabled by eliminating a molecule of HF under basic conditions, affording 155. Finally, ring closure involving intermolecular [3 + 3] condensation of 155 with amidine 156 proceeds to afford the final product. It is worth noting that the reaction allowed efficient access to heterocyclic adducts with appreciable yields by utilizing in situ formed enolsilanes 151 from related ketones, followed by exposure to photocatalytic conditions in a single reaction vessel. A concise, two-step, one-flask procedure was designed for the synthesis of the test pyrimidine derivative (84% yield) by using benzamidine hydrochloride, triisopropylsilyl enol ether (1.8 equiv.), perfluorobutyliodide (3 equiv.), DABCO (3 equiv.), and Eosin Y (3%) as the photocatalyst. With the optimal reaction conditions in hand, the authors successfully extended the substrate scope of the reaction to benzamidines containing diverse substituents of varying electronic character and steric hindrance on the phenyl moieties, affording the corresponding products in high yields (70-98%). In the same manner, the reactions worked equally well with heteroaryl amidines and C-alkylated reactants. The substrate scope with respect to a series of structurally varied silyl enol ethers also led to satisfactory yields. In addition to perfluorobutyl iodide, the applicability of this transformation to a broad spectrum of fluoroalkyl halides (C 2 F 5 I, C 5 F 11 I, C 7 H 15 I, and C 8 F 17 I) was observed. According to the proposed mechanism, the reaction involves a single-electron transfer from the excited photocatalyst EY* to fluoroalkyl halide to produce the •C 4 F 9 radical and a radical cation EY •+ . Next, tertiary carbocation 153 is generated via the addition of a perfluoroalkyl radical to the C=C bond of silyl enol ether 151, followed by further oxidation with the aid of the oxidative radical cation EY •+ . After rapid attack by an I − ion, the α-perfluoroalkylated ketone 154 is formed. In a defluorination step, α,β-desaturation of 154 is enabled by eliminating a molecule of HF under basic conditions, affording 155. Finally, ring closure involving intermolecular [3 + 3] condensation of 155 with amidine 156 proceeds to afford the final product. It is worth noting that the reaction allowed efficient access to heterocyclic adducts with appreciable yields by utilizing in situ formed enolsilanes 151 from related ketones, followed by exposure to photocatalytic conditions in a single reaction vessel.

Conclusions
This review demonstrates that visible-light-driven photocatalysis contributed essentially to the development of reactions, allowing the easy formation of fluorinated aromatic compounds. Diverse methods to install a fluorine atom or the fluorine-containing moiety have been successfully employed, including generation of reactive perfluoroalkyl radicals by direct reduction of the C-I bond in perfluoroalkyl iodides, single-electron reduction of trifluoromethylsulfonyl chloride, hypervalent iodine, and sulfur compounds, or oxidation of sodium triflinate. The monofluorination of arene procedures are noteworthy, including addition of the fluorine anion to the aryl radicals formed in the photocatalytic cycle. Interestingly, we have seen progress in the development of new fluorine-containing precursors allowing the introduction of SCF 3 , OCF 3 , or SO 2 F moiety to the aromatic system. The photocatalytic fluorination of arenes in a dual catalytic system (Ir/Cu or Ru/Cu) enabled the easy fluorination of a variety of arenes. In particular, the strategy developed by MacMillan's group is noteworthy, allowing a general trifluoromethylation of aryl bromides through dual copper-photoredox catalysis by overcoming the copper oxidative addition problem with an aryl radical capture mechanism. The novel strategy exploiting a tandem relay by combining organo-photoredox-catalyzed radical fluoroalkylation and post-photocatalytic aromatization provides a general and highly efficient method for the one-pot synthesis of quinolines and pyrimidines from acyclic starting materials. In spite of its attractive features such as synthetic simplicity, a broad substrate scope, and excellent functional group compatibility under mild reaction conditions, further research work in this field is still needed. We predict that merging of different photocatalytic approaches to incorporate perfluoroalkyl groups will be developed, such as scale-up flow synthesis and enantioselective catalysis, which would result in novel types of fluorinated aromatic compounds which will serve in agrochemical, pharmaceutical, and material chemical industries.