Organic Reactions Promoted by Metal-Free Organic Dyes Under Visible Light Irradiation Organic Reactions Promoted by Metal-Free Organic Dyes Under Visible Light Irradiation

Although dyes have received much attention as the visible light-activated photocatalysts, the use of metal-free organic dyes in synthetic organic chemistry is still limited. This chapter summarizes the recent progress in the visible light photocatalysis promoted by metal- free organic dyes. Eosin Y is the typical organic dyes to induce the photoredox catalysis. Recently, other organic dyes such as Rose Bengal, fluorescein, and methylene blue have been studied as photocatalysts to promote the single-electron transfer processes.


Introduction
The use of abundant sunlight as a clean source of energy is an important aim of green chemistry. In recent years, dyes have attracted a great deal of attention as the visible light-activated photocatalysts in synthetic organic chemistry. However, these studies have mainly concentrated on the redox transformations using transition metal dyes such as ruthenium or iridium photocatalysts [1][2][3][4][5][6][7][8][9]. In contrast, the use of metal-free dyes still remains rather underdeveloped, although organic dyes are more environmentally friendly and cheaper. Eosin Y is the typical organic dyes to induce the photoredox catalysis [10]. Recently, Rose Bengal, fluorescein, methylene blue, and other organic dyes have been studied as photocatalysts to promote the single-electron transfer processes [11][12][13]. Additionally, 3-cyano-1-methylquinolinium, 9-mesityl-10-methylacridinium ion, and acridinium salts were developed as organic photocatalysts [12,13].
The photoredox cycle is initiated by the visible light irradiation of dye in the ground state to produce the high-energy excited state of dye (Dye*) (Figure 1). Two distinctive pathways from dye in the excited state (Dye*) are described for the mechanism of visible light photoredox catalysis. The reductive property of Dye* can be used in the presence of a sacrificial electron acceptor. In other words, Dye* serves as an electron donor leading the radical cation species of Dye. In contrast, Dye* also acts as an electron acceptor in the presence of a sacrificial electron donor.
The EY-catalyzed generation of aryl radicals from aryl diazonium salts was studied by König's group [14]. The direct C−H bond arylation of heteroarenes with aryl diazonium salts was achieved by employing only 1 mol% of EY (Figure 2). The arylation of furan with diazonium salt 1 in dimethyl sulfoxide (DMSO) proceeded smoothly under the visible light irradiation to give the desired coupling product 2 in 85% yield. This transformation proceeds through the radical mechanism. Initially, aryl radical is produced by the single-electron transfer from the excited EY (EY*) to aryl diazonium salt 1. The addition of aryl radical to furan leads to the formation of the radical intermediate A, which is further oxidized to cation intermediate B. Final deprotonation gives the coupling product 2. Next, the EY-catalyzed arylation of simple arenes with fluorinated aryl bromides was developed [15]. In the presence of EY (5 mol%) and triethylamine as an electron donor, the direct arylation using 1-bromo-2,3,4,5,6-pentafluorobenzene 3 and benzene gave the coupling product 4 in 85% yield. The mechanistic investigations reveal that the photooxidation of Visible-Light Photocatalysis of Carbon-Based Materials triethylamine by the excited EY (EY*), and the subsequent single-electron transfer from the radical anion species of EY to 3 leads to the formation of the polyfluorinated aryl radical. The mild visible light-mediated generation of aryl radicals from diazonium salts was also investigated by Wangelin's group [16][17][18]. The coupling reaction catalyzed by EY was investigated with no use of any sacrificial oxidants [19,20].
The vinyl sulfones were synthesized by the EY-catalyzed reaction of alkenes with sodium aryl sulfinates [21]. The reaction of 1,2-dihydronaphthalene 6 with sodium benzenesulfinate 5 was performed in the presence of EY (10 mol%) and nitrobenzene as a terminal oxidant (Figure 3). The desired vinyl sulfone 7 was obtained in 99% yield. In this reaction, sodium sulfinate 5 is oxidized by the excited EY (EY*) to give the sulfonyl radical, which attacks the double bond of 6 to form the radical intermediate C.
Nitrobenzene oxidizes the radical cation species of EY to give EY in the ground state and the radical anion species D of nitrobenzene, which reacts with radical intermediate C to give the vinyl sulfone 7.
The oxidative cyclization reaction between 3-phenylpropiolate 8 and 4-methylbenzenesulfinic acid 9 was studied (Figure 4) [22]. In the presence of EY (1 mol%) and tert-butyl hydroperoxide (TBHP), the reaction between 8 and 9 was performed in MeCN-  Visible-Light Photocatalysis of Carbon-Based Materials visible light irradiation. The desired coumarin 10 was obtained in 78% isolated yield. Initially, tert-butoxyl radical is produced by the single-electron transfer from the excited EY (EY*) to TBHP. The cyclization reaction is promoted by the addition of sulfonyl radical, generated from sulfinic acid 9 and tert-butoxyl radical, to alkyne moiety of 8. The coumarin 10 is formed via the oxidation of the cyclized radical intermediate E by the radical cation species of EY.
The EY-catalyzed cyclization of 2-isocyanobiphenyls with arylsulfonyl chlorides took place under the oxidant-free visible light irradiation conditions [23]. In the presence of K 2 HPO 4 as a base, the EY-catalyzed reaction of benzenesulfonyl chloride 11 and 2-isocyanobiphenyl 12 proceeded smoothly to give the 6-phenyl-substituted phenanthridine 13 in 79% yield ( Figure 5).
Initially, the single-electron transfer from the excited EY (EY*) to sulfonyl chloride 11 gives the phenyl radical, which adds to isocyanide 12 to form the imidoyl radical intermediate F.
The subsequent cyclization gives the cyclized radical intermediate G, which is oxidized by the radical cation species of EY. Finally, the deprotonation leads to 13.
EY could be used as the photocatalyst for the 5-exo-trig cyclization of iminyl radicals generated from O-aryl oximes [24]. Among several aryl oximes evaluated, 2,4-dinitro-substituted aryl oxime 14 has the excellent reactivity due to its low reduction potential (Figure 6). In the presence of cyclohexadiene (CHD) as a H-donor, EY-catalyzed photoreaction of 14 gave the cyclized product 15 in 78% yield. In this transformation, the iminyl radical I is generated via the reduction of 14 by the excited EY (EY*) followed by the fragmentation of radical anion H. The cyclization of I gives the cyclized C-centered radical J, which abstracts H-atom from CHD to give the desired product 15. Furthermore, the formation of product 15 was observed even in the absence of EY, when the MeCN solution of 14 was treated with Et 3 N under the visible The EY-induced photocatalysis was applied to the radical cascade cyclization of polyenes [25]. The photocatalytic cascade cyclization of polyene 16 proceeded by employing EY (Figure 7). Hexafluoro-2-propanol (HFIP) was identified as the optimal solvent. The cyclized product 17 was obtained in 93% yield with the excellent diastereoselectivity via the radical cation intermediate K generated by the single-electron transfer from 16 to the excited EY (EY*). In this process, the OH moiety of 16 would act as a terminator.
Eosin B is also the active catalyst under the visible light irradiation [31]. The C−H functionalization of thiazole derivatives with diarylphosphine oxides was achieved by the eosin B-catalyzed photoredox process. When eosin B was employed as a photocatalyst, the phosphorylation of benzothiazole 18 with diphenylphosphine oxide proceeded effectively to give the phosphorylation product 19 in 87% yield (Figure 8). In this transformation, hydrogen (H 2 ) is the only by-product.

Rose Bengal
Rose Bengal (RB) was widely used as a visible light-activated photocatalyst [32][33][34][35][36][37][38][39][40][41][42][43][44]. Tan's group studied the photoredox catalysis using RB [32][33][34][35][36]. RB was a good catalyst for the dehydrogenative coupling reaction between tetrahydroisoquinolines and nitroalkanes (Figure 9) [33]. In the presence of RB (5 mol%), the reaction of N-phenyl-tetrahydroisoquinoline 20 with nitromethane gave the adduct 21 in 92% yield. In the absence of O 2 , a much lower yield was obtained relative to the reaction performed in open air; thus, air is important for this reaction as an oxidant. Additionally, this reaction was expanded to the dehydrogenative Mannich reaction using enamine nucleophiles generated from ketones and pyrrolidine.   Next, the combination of graphene oxide and RB was studied in the reaction between tetrahydroisoquinolines with TMSCN or TMSCF 3 [34]. In the presence of RB (5 mol%) and graphene oxide (50 wt%), the reaction of 20 with TMSCN proceeded effectively to give the adduct 22 in 99% yield, while the yield of 22 decreased to 45% in the absence of graphene oxide. The use of graphene oxide as a cocatalyst improves the reaction rates and yields.
New method for the synthesis of Meyers's bicyclic lactams was developed by using RB photocatalysis [37][38][39]. This cascade transformation is the one-pot reaction which begins from furan substrates (Figure 10) [37]. The aerobic visible light-promoted indole C3 formylation reaction was achieved by using RB as a photocatalyst and N,N,N′,N′-tetramethylenediamine (TMEDA) as a one-carbon source (Figure 11) [40]. Upon the irradiation of visible light, the reaction of N-methylindole 26 with TMEDA in the presence of RB (5 mol%) and KI as an additive under air afforded 3-formyl-N-methylindole 27 in 70% yield. This transformation proceeds via the addition of N-methylindole 26 to iminium ion O generated by the oxidation of TMEDA. Next, the C3 thiocyanation reaction of indoles was developed by using ammonium thiocyanate (NH 4 SCN) as a thiocyanate radical source [41]. In the presence of RB (1 mol%), the reaction of indole 28 with NH 4 SCN gave the adduct 29 in 98% yield. In this reaction, thiocyanate radical is generated by the single-electron transfer between thiocyanate anion and the excited RB (RB*). The thiocyanate radical adds to indole 28. The subsequent oxidation leads to 29.   The new method for the synthesis of quinazolines was developed by using RB as a photocatalyst (Figure 12) [42]. In the presence of RB (1 mol%), CBr 4 as an oxidant, and K 2 CO 3 as a base, the oxidative carbon-carbon bond-forming cyclization of N-benzyl-N′-phenyl benzimidamide 30 proceeded smoothly under the visible light irradiation. The desired quinazoline 31 was obtained in 88% yield. In this transformation, CBr 3 radical is generated by the reaction between CBr 4 and the radical anion species of RB. Next, the iminium ion intermediate Q is formed from the radical cation intermediate P by the association of CBr 3 radical. Finally, the intramolecular Friedel-Craft reaction of iminium ion Q leads to quinazoline 31.

Fluorescein and rhodamine B
The utility of fluorescein was demonstrated in the alkoxycarboxylation of aryldiazonium salts using CO gas [45]. In the presence of 0.5 mol% of fluorescein as a photocatalyst, treatment of diazonium tetrafluoroborate 32 with CO (80 atm pressure) in methanol under the irradiation of visible light gave methyl ester 33 in 80% yield (Figure 13). Initially, the phenyl radical is generated from diazonium 32 by the single-electron transfer from the excited state of fluorescein (Dye*). Next, benzoyl radical R is formed via trapping of CO molecule by phenyl radical. The methyl ester 33 is obtained via the oxidation of benzoyl radical R by the reactive radical cation species of dye followed by trapping of the resulting benzylidyneoxonium S with methanol. Furthermore, the dual catalytic system using photocatalyst and gold catalyst was studied by Glorius's group [46]. The utility of rhodamine B as a water-soluble photocatalyst was demonstrated in the aqueousmedium carbon-carbon bond-forming radical reactions [47]. In the presence of (i-Pr) 2 NEt as a reductive quencher, the rhodamine B-catalyzed reaction of alkene 34 with i-C 3 F 7 I in H 2 O proceeded smoothly to give the product 35 in 90% yield (Figure 14). In this transformation, the photo-induced electron transfer from the excited singlet state (S 1 ) of rhodamine B to i-C 3 F 7 I was proposed. This electron transfer process was supported by the fluorescence quenching of rhodamine B with addition of i-C 3 F 7 I. Additionally, the aqueous-medium radical additioncyclization-trapping reaction of 36 proceeded effectively even in the absence of (i-Pr) 2 NEt. In this transformation, the single-electron transfer from iodine ion (I − ) to the radical cation species of rhodamine B in an ion pair would proceed to give I 2 , because the oxidation potential of rhodamine B is positive enough to oxidize I − into I 2 .

Methylene blue and acridine red
Methylene blue (MB) is a member of the thiazine dye family. Scaiano's group used MB as a photocatalyst under the visible light irradiation [48]. The radical trifluoromethylation of electron-rich heterocycles was studied by the use of Togni's reagent 39 as a CF 3 radical source (Figure 15). The trifluoromethylation of 3-methylindole 38 proceeded with good yield at low catalyst concentration, when N,N,N′,N′-tetramethylenediamine (TMEDA) was used as an electron donor. In the presence of 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) as an electron donor, the reaction of terminal alkene 41 with Togni's reagent 39 also gave the hydrotrifluoromethylation product 42 in 67% yield as a major product, because the fully reduced form of MB, leuco-MB, acts as a hydrogen source [49]. The possible mechanism for the catalytic formation of CF 3 radical is shown. The visible light-excited MB (MB*) is readily quenched by aliphatic amines such as TMEDA or DBU to form the semi-reduced MB as a radical anion and an α-amino radical. CF 3 radical is generated via the reduction of Togni's reagent 39 with semireduced MB and/or an α-amino radical.
The one-pot transformation of furans into 5-hydroxy-1H-pyrrol-2(5H)-ones was investigated by using MB as a photocatalyst [50]. In the presence of MB (2 mol%) and oxygen, the reaction of furan 43 with benzylamine gave lactam 44 in 72% yield via the reduction of the intermediate by Me 2 S (Figure 16). The use of 2-(3,4-dimethoxyphenyl)ethanamine 45 instead of benzylamine led to the formation of tricycle 46 via Pictet-Spengler cyclization process. For Pictet-Spengler cyclization, HCOOH was added as an acid leading to N-acyliminium ion, which spontaneously cyclized to form 46.
New phenothiazine-based organic dye was also developed as a visible light-activated photocatalyst [51].
Acridine red was used as a photocatalyst for the visible light-induced direct thiolation of ethers (Figure 17) [52]. The thiolation of tetrahydrofuran (THF) using diphenyl disulfide 47 was carried out in the presence of acridine red (2 mol%) and tert-butyl hydroperoxide (TBHP) as an oxidant. The reaction occurred at ambient conditions to give α-arylthioether 48 in 82% yield. This transformation proceeds via the generation of radical intermediate from THF, which reacts with diphenyl disulfide 47 to afford 2-(phenylthio)-tetrahydrofuran 48.

Concluding remarks
Organic dyes that absorbed visible light induce the synthetically valuable photochemical transformations. The metal-free photocatalysis using organic dyes rapidly progresses in the last few years. In addition to the organic dyes shown in this chapter, Fukuzumi' group has developed 3-cyano-1-methylquinolinium and 9-mesityl-10-methylacridinium ions as photocatalysts [13]. More recently, Nicewicz' group has studied the photocatalysis using acridinium salts [12]. These visible light-induced catalysis disclosed a broader aspect of the utility of organic photocatalysts for synthetic organic chemistry. This chapter will inspire creative new contributions to organic chemists. Visible-Light Photocatalysis of Carbon-Based Materials