B(C6F5)3-Catalyzed C-C Coupling of 1,4-Naphthoquinones with the C-3 Position of Indole Derivatives in Water.

An atom-economical and environmentally benign approach for the synthesis of indole-substituted 1,4-naphthoquinones from indoles and 1,4-naphthoquinones using readily available Lewis acidic B(C6F5)3 in water and with the recycling of water and part of the catalyst is reported. The reaction proceeded through the B(C6F5)3-catalyzed C(sp2)-H and C(sp2)-H bond coupling of 1,4-naphthoquinones with the C-3 position of indole derivatives in water. This methodology provides a facile protocol for the synthesis of some new indole-substituted 1,4-naphthoquinones in satisfactory yields and with a broad substrate scope. When compared to known methods for the synthesis of indole-substituted 1,4-naphthoquinones, this protocol is practical and efficient and does not require a transition-metal catalyst or toxic organic solvents. In addition, we utilized a simple filtration process for complete recycling of the solvent and the part of the catalyst in each reaction cycle.

Introduction

Indole and its derivatives, as a common subunit in various pharmaceutically attractive and naturally occurring products, have been widely applied in the fields of synthetic chemistry,[1] materials science,[2] and medicinal chemistry.[3] Particularly, the indole nucleus is a structural component of a large number of biologically active natural and unnatural compounds.[4] Incorporation of the indole nucleus into quinone frameworks serves as a platform for the synthesis of a potentially valuable class of indole derivatives where indolylquinones are versatile building blocks for the construction of biologically active natural products.[5] In this regard, indoles represent a system of particular interest and importance. Thus, the C-2 and C-3 selective methods would be valuable. Previous methods reported the incorporation of quinones into the C-3 position of indoles (Scheme ). The Pirrung group[6] and others have reported that the Lewis acids [such as Bi(OTf)3, Pd(OAc)2, CuBr2, InBr3, etc.] can catalyze the conjugate addition reaction of indole compounds with quinones to give 3-indolylquinone compounds.[7] Such a reaction can be catalyzed by some Brønsted acids.[8] Iron hydroxide nanoparticles can catalyze the coupling reaction between p-benzoquinone and 2-methylindole, and 3-indolylquinone was also achieved via oxidative C–C coupling of hydroquinones with indoles over Ag2O and Fe3O4/povidone-phosphotungstic acid catalysts using H2O2 in tetrahydrofuran.[9] All of these methods have certain limitations, such as the need for metals to act as catalysts, the use of a toxic organic solvent, and the limited substrate scope or low yields. It is noteworthy that coupling of indoles with 1,4-benzoquinones provides the desired product “in water”.[10] The method needs long reaction time and involves one indolyl-1,4-naphthoquinone. Therefore, it is highly desirable to develop a simple and environmentally benign protocol to construct indolyl-1,4-naphthoquinones.

Scheme 1

Approaches to 3-Indolylquinone Compounds

In organic chemistry, chemists have an increasing interest in developing “green” processes and sustainability, which are important issues in every area of human activity.[11] The use of solvents is a key aspect among the 12 principles of green chemistry.[12] Water has emerged as a potentially useful and safe solvent[13] and is abundant, nontoxic, noncorrosive, and nonflammable.[14] There are some challenges in organic reactions in aqueous media. First, many reactive substrates, reagents, and catalysts are decomposed or deactivated by water.[15] Second, most organic substances are insoluble in water.[16] On the other hand, water possesses many unique physical and chemical properties: a large temperature window in which it remains in the liquid state; extensive hydrogen bonding; high heat capacity; large dielectric constant; and optimum oxygen solubility to maintain aquatic life forms, which dramatically enhance the rates and affect the selectivity of a wide variety of organic reactions.[17]

Tris(pentafluorophenyl)borane [B(C6F5)3], which has received significant attention as a nonconventional, nontoxic, air-stable, water-tolerant, thermal abiding, and frustrated Lewis acid,[18] has been widely employed in a number of transformations in organic chemistry including hydrogenation reactions,[19] hydrosilylation[20] of unsaturated organic functions, dehydrogenative coupling of alcohols and amines,[21] dehydrogenative oxidation,[22] and other transformations.[23] Owing to its highly electrophilic but sterically protected nature, B(C6F5)3 has been commonly employed as the Lewis acid component in frustrated Lewis pair (FLP) chemistry to activate small molecules and in metal-free catalysis.[24]

Generally, the coordination of water with a Lewis acidic metal complex leads to the weakening of the O–H bond.[25] In this respect, the interaction of B(C6F5)3 with water has been thoroughly investigated by different groups.[26] Recently, the group of Tang reported that B(C6F5)3 catalyzes α-diazoester insertion into the O–H bond in water, affording various α-hydroxyesters.[27] Our concept was to utilize the Brønsted acid B(C6F5)3–H2O for the catalytic activation of C=O and the subsequent nucleophilic addition. Herein, we report a B(C6F5)3-catalyzed C(sp2)–H and C(sp2)–H bond coupling of 1,4-naphthoquinones with the C-3 position of indole derivatives through conjugate addition of indole compounds to 1,4-naphthoquinones, followed by in situ dehydrogenation in water, wherein water and part of the catalyst were recycled under mild conditions.

Results and Discussion

Initially, we commenced our study by monitoring a test reaction of 1,4-naphthoquinone 1a with 1-methyl-1H-indole 2a (1.0 equiv) “in water” for 24 h at room temperature (Table , entry 1). It is noteworthy that our work is different from that of Li’s group about substrates,[10] in which good yields were not obtained in the absence of other catalysts. Thus, the reaction was carried out in the presence of B(C6F5)3 catalyst (3 mol %) in water in open air (entry 2). To our delight, the desired product 3aa was obtained in 70% yield after a reaction time of 2 h at room temperature. It was reported that the C-3 position of 1-methyl-1H-indole is the most reactive among its two reactive positions (C-2 and C-3). Finally, 1H NMR, 13C NMR, mass spectroscopy, and X-ray crystallography of 3ga (Table ) demonstrated that the final product is the expected structure 3aa, and no other products were detected. Furthermore, the reaction was scrutinized with common transition-metal Lewis acids such as Bi(OTf)3, FeCl3, etc. as catalysts, and no products were detected or significantly lower yields were obtained (entries 3–10). In addition, the catalytic amounts of Brønsted acid catalysts were screened, but none provided better yields than B(C6F5)3 (entries 11 and 12). No improvement in the transformation was observed when B(C6F5)3 catalyst (1 mol %) was employed (entry 13). Increasing the catalyst loading resulted in 81% yield of the desired product (entry 14). The ratio of 1,4-naphthoquinone (1a) to 1-methyl-1H-indole (2a) also affected the reaction yield profoundly, and the reaction yield could be decreased when the ratio of 1a/2a was changed to 1:2 or 2:1 (entry 15 and 16). A higher reaction temperature resulted in an increase in yield, affording a yield of 91% for 3aa (entry 17). We have investigated the effect of other boron-containing agents in water, such as B(2,4,6-F3C6H2)3 and B(3,4,5-F3C6H2) (entries 18 and 19), but none provided better yields than B(C6F5)3. The reaction afforded 36% yield for 3aa in the absence of other catalysts under 60 °C for 2 h (entry 20). After the evaluation of various reaction parameters, the best yield of 3aa (91%) was obtained by employing 1a (0.4 mmol), 2a (1 equiv), and B(C6F5)3 (5 mol %) in water as the sole solvent in open air under 60 °C for 2 h (entry 17). A notable B(C6F5)3 acceleration was observed in these reactions for 2 h. Using the ratio of indole/quinone = 1:1 was also atom-economical.

Table 1

Optimization of the Reaction Conditionsa

entry	1a/2ab	catalyst (mol %)	temp (°C)	yieldb (%)
1	1:1		25	33c
2	1:1	B(C6F5)3 (3)	25	70
3	1:1	Bi(OTf)3 (3)	25	19
4	1:1	Cu(OTf)2 (3)	25	10
5	1:1	La(OTf)3 (3)	25	10
6	1:1	Sm(OTf)3 (3)	25	12
7	1:1	Fe(OTf)3 (3)	25	26
8	1:1	FeCl3 (3)	25	24
9	1:1	ZnCl2 (3)	25	trace
10	1:1	BiCl3 (3)	25	57
11	1:1	HCl (3)	25	43
12	1:1	HOAC (3)	25	NRd
13	1:1	B(C6F5)3 (1)	25	55
14	1:1	B(C6F5)3 (5)	25	81
15	1:2	B(C6F5)3 (5)	25	68
16	2:1	B(C6F5)3 (5)	25	64
17	1:1	B(C6F5)3 (5)	60	91
18	1:1	B(2,4,6-F3C6H2) (5)	60	68
19	1:1	B(3,4,5-F3C6H2) (5)	60	71
20	1:1		60	36

Unless otherwise specified, the reactions were carried out in the presence of 1a (0.4 mmol), 2a (0.4 mmol), the Lewis acid catalyst agent (mmol %), and water (2 mL) for 2 h under an air atmosphere.

Isolated yields.

Without catalysts for 24 h.

No reactions.

Table 3

Substrate Scope with Respect to the Quinonesa

Reaction conditions: the reactions were carried out in the presence of 1 (0.4 mmol), 2a (0.4 mmol), and B(C6F5)3 (5 mol %) in water (2 mL) at 60 °C with stirring for the indicated time under an air atmosphere. The isolated yield was based on 1.

With the optimized conditions established, we evaluated the scope and the influence of the substituents on the indole moiety. The results are presented in Table . When free NH-indole (2b) was used as the substrate under identical conditions, 3ab was obtained in 83% yield. It is noteworthy that other N-alkylindoles (2a and 2c) also proved to be suitable coupling partners to provide the corresponding products in good yields (91 and 86%). Unfortunately, due to the highly electron-deficient acetyl present at the N position, no product was detected when N-acetylindole (2d) was used. Notably, N-allylindole (2e) also worked well under this protocol and afforded the desired product 3ae in 75% yield. Unfortunately, the reaction did not work when 2f was used as a substrate (3af). The electron-rich indoles with a substituent at the 2-position are good reactants. 2-Methylindole and 2-phenylindole reacted well to give the corresponding products 3ag and 3ah in 90 and 81% yields, respectively. The electron-withdrawing indoles (2i) with a substituent at the 2-position were used as the substrate, but the desired product (3ai) was obtained in traces, which is possibly due to the electron deficiency. To our delight, 2j worked well and afforded 3aj in 72% yield. The reaction yields decreased dramatically when the most electron-withdrawing groups (2n) were located at the C-5 position in indoles (3an). Better yields were obtained when the functional groups such as methoxy (2m and 2q), fluoro (2k and 2t), chloro (2l, 2o, and 2u), and bromo (2p) were located at C-4, C-5, and C-6 positions. We further tested this method with 5-allyloxyindole (2r) and 5-propargyloxyindole (2s); the reaction proceeded smoothly to provide the desired products in good yields (3ar–as). In addition, 7-azaindole (2v) also worked well with 71% yield.

Table 2

Substrate Scope with Respect to the Indolesa

Reaction conditions: 1a (0.4 mmol), 2 (0.4 mmol), B(C6F5)3 (5 mol %), H2O (2 mL), 60 °C, 2 h, under an air atmosphere. The isolated yield was based on 1a.

We then proceeded to study the scope of quinone derivatives. As shown in Table , a number of quinones underwent under optimal conditions. Menadione was used as the substrate and 3ba was obtained in 75% yield. The above methodology worked for naphthoquinones bearing phenyl and electron-deficient arene substituents (3ca–ea). The sensitive chlorine and bromine at the β- position of naphthoquinone were compatible with the reaction conditions, which can easily be transformed further by cross-coupling reactions. The molecular structure of 3ga was further confirmed by single-crystal X-ray diffraction analysis. Dimethylbenzoquinone and trimethylbenzoquinone were employed, affording corresponding products 3ia and 3ja in moderate yields, respectively. Dichlorobenzoquinone also worked well with N-methylindole and free NH-indole under standard conditions. The work by Li’s group reported that 3ag, 3ja, and 3ka were obtained “in water” in the absence of the catalyst for long reaction time. We obtained products of 3ag, 3ja, and 3ka in good yields when B(C6F5)3 acceleration was observed in these reactions for 2 h.

The scalability of this reaction was tested using 1a (20 mmol, 3.16 g) with 2a (20 mmol, 2.62 g) under the developed optimal reaction conditions. As expected, the desired product 3aa was obtained in 92% yield; these results suggested that the methodology is an economic and practical process for the preparation of indole-substituted quinones (Scheme ).

Scheme 2

Gram-Scale Synthesis of 3aa

Owing to the excellent yield of the reaction of 1,4-naphthoquinone 1a with 1-methyl-1H-indole (2a) (91%), the reaction was chosen to check the recyclability of the catalyst and the solvent. As in the literature, B(C6F5)3 has a similar affinity to the organic phase and the aqueous phase. Considering this property, after the first reaction, the product was easily hot filtered, while the part of B(C6F5)3 catalyst remained in the filtrate. However, a part of the catalyst mass was lost in all trials, because the catalyst was wrapped in the organic product. Thus, we added extra 2 mol % B(C6F5)3 into the filtrate for the next run. The recovered filtrate containing B(C6F5)3 and added extra 2 mol % B(C6F5)3 showed remarkably constant catalytic activity in all of the 10 cycles.

Based on previous reports and summary, the reaction mechanism is hypothesized in Scheme . At first, the Lewis acid B(C6F5)3 with H2O gives a coordinated adduct, which may exist in equilibrium.[28] The reaction is probably the Brønsted acid activation of 1,4-naphthoquinone (1a) by B(C6F5)3–H2O.[29] The in situ generated electrophilic species A reacts with N-methylindole (2b) in the 3-position to form 1,4-hydroquinone intermediate B and generate an anionic hydroxyboron [B(C6F5)3–OH]−. Then 1,4-naphthoquinone oxidized the 1,4-hydroquinone intermediate B into the N-methylindole-substituted 1,4-naphthoquinone (3aa). At the same time, 1a was regenerated by the oxidation of the 1,4-hydroquinone C under an air atmosphere in water.[30]

Scheme 3

Proposed Mechanism of 3aa

Conclusions

In summary, we have developed the B(C6F5)3-catalyzed C(sp2)–H and C(sp2)–H bond coupling of 1,4-naphthoquinones with the C-3 position of indole derivatives. B(C6F5)3 was able to catalyze a wide range of reactions involving indoles and 1,4-naphthoquinones to yield products in moderate to good yields under open-air conditions. Based on previous reports and summary, the proposed reaction mechanism is hypothesized. This new protocol has proved to be economical, practical, and eco-friendly without employing any base and organic solvent. Besides, the recycling and recovery of B(C6F5)3 and H2O as the solvent were reported in the reaction at first. Thus, the easy and rapid recycling protocol met the goal of green and sustainable chemistry. The procedure should be a facile and convenient method with the prospect of industrial applications.

Experimental Section

General Information

Chemicals and analytical-grade solvents were purchased from commercial suppliers and used without further purification unless otherwise stated. All reagents were weighed and handled in air at room temperature. Analytical thin-layer chromatography (TLC) was performed on glass plates of silica gel GF-254 with detection by UV light (254 and 365 nm). Column chromatography was carried out on silica gel (200–300 mesh). 1H NMR spectra were recorded at 400 MHz and 13C NMR spectra were recorded at 101 MHz using an Agilent 400 MHz NMR spectrometer. Chemical shifts were calibrated using a residual undeuterated solvent as an internal reference [1H NMR: CDCl3 7.26 ppm, dimethyl sulfoxide (DMSO)-d6 2.50 ppm; 13C NMR: CDCl3 77.16 ppm, DMSO-d6 39.52 ppm]. Data are reported as follows: chemical shift, multiplicity (s = singlet, br s = broad singlet, d = doublet, t = triplet, q = quartet, m = multiplet); coupling constants (J) are reported in hertz (Hz). High-resolution mass spectrometry (HRMS) was performed on a Thermo Scientific LTQ Orbitrap XL instrument. Melting points were measured with a micro melting point apparatus.

Procedure for the Gam-Scale Reaction

To a solution of H2O (100 mL) were added 1,4-naphthoquinone 1a (3.16 g, 20 mmol), N-methylindole 2a (2.62 g, 20 mmol), and B(C6F5)3 (0.51 g, 1 mmol). The mixture was stirred at 60 °C (the temperature of the oil bath) for 2 h under an air atmosphere. After the completion of the reaction (monitored by TLC), the reaction mixture was quenched with water (100 mL) and the aqueous phase was extracted with EtOAc (3 × 100 mL, then 3 × 30 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel to give 5.29 g of 2-(3-N-methylindolyl)-1,4-naphthoquinone in 92% yield.

General Procedures for the Synthesis of 3-Indolylquinones

To a solution of H2O (2 mL) were added 1 (0.4 mmol), 2 (0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol). The mixture was stirred at 60 °C (the temperature of the oil bath) for about 2–5 h under an air atmosphere. After the completion of the reaction (monitored by TLC), the reaction mixture was quenched with water (2 mL) and then extracted with EtOAc (3 × 5 mL). The combined organic layers were washed with brine, dried over Na2SO4, and filtered, and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc) to afford the desired pure product 3.

2-(1-Methyl-1H-indol-3-yl)naphthalene-1,4-dione (3aa)[31]

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), N-methylindole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3aa as a black solid (91% yield), mp 178–180 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, CDCl3) δ 7.99–7.88 (m, 3H), 7.81–7.76 (m, 1H), 7.57–7.50 (m, 2H), 7.21 (s, 1H), 7.16 (d, J = 10.1 Hz, 1H), 7.11 (dd, J = 14.0, 7.4 Hz, 2H), 3.67 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 185.70, 185.10, 141.81, 137.37, 135.69, 133.61, 133.09, 132.86, 132.24, 128.57, 126.76, 126.26, 125.64, 122.97, 121.73, 120.61, 110.14, 107.35, 33.41.

2-(1H-Indol-3-yl)naphthalene-1,4-dione (3ab)[32]

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), indole (2b, 46.8 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ab as a red solid (83% yield), mp 199–201 °C. R = 0.40 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 12.00 (s, 1H), 8.20 (d, J = 2.1 Hz, 1H), 8.07–8.00 (m, 1H), 7.95 (d, J = 4.8 Hz, 1H), 7.82 (dd, J = 10.7, 6.6 Hz, 3H), 7.49 (d, J = 7.4 Hz, 1H), 7.25–7.13 (m, 3H). 13C NMR (101 MHz, DMSO-d6) δ 185.42, 184.56, 142.54, 137.14, 134.49, 134.03, 132.97, 132.91, 132.10, 128.11, 126.95, 125.59, 123.01, 121.71, 120.44, 113.04, 107.78.

2-(1-Benzyl-1H-indol-3-yl)naphthalene-1,4-dione (3ac)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), N-benzoylindole (2c, 82.9 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ac as a black solid (86% yield), mp 163–165 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.15 (dd, J = 5.8, 3.0 Hz, 1H), 8.10–8.06 (m, 1H), 8.00–7.92 (m, 3H), 7.70–7.66 (m, 1H), 7.44–7.31 (m, 8H), 5.64 (s, 2H). 13C NMR (101 MHz, DMSO-d6) δ 185.25, 184.51, 141.96, 137.61, 136.86, 136.02, 134.48, 134.04, 132.82, 132.04, 129.11, 128.41, 128.10, 127.74, 126.91, 126.30, 125.59, 123.20, 122.09, 120.76, 111.85, 109.99, 107.34, 49.97. HRMS calcd for C25H18NO2+ (M + H)+ 364.1338, found 364.1332.

2-(1-Allyl-1H-indol-3-yl)naphthalene-1,4-dione (3ae)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), N-allylindole (2e, 62.9 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ae as a dark-red solid (75% yield), mp 171–173 °C. R = 0.40 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 8.40 (s, 1H), 8.20–8.16 (m, 1H), 8.12–8.09 (m, 1H), 8.03–7.96 (m, 3H), 7.70 (d, J = 7.8 Hz, 1H), 7.40 (dd, J = 16.9, 9.0 Hz, 3H), 6.22–6.13 (m, 1H), 5.32 (dd, J = 27.8, 13.7 Hz, 2H), 5.08 (d, J = 5.3 Hz, 2H). 13C NMR (101 MHz, DMSO-d6) δ 185.28, 184.49, 141.93, 136.87, 135.72, 134.49, 134.01, 132.80, 132.02, 128.21, 126.89, 126.15, 125.57, 123.12, 122.06, 120.71, 118.13, 111.73, 107.14, 48.97. HRMS calcd for C21H16NO2+ (M + H)+ 314.1176, found 314.1179.

2-(2-Methyl-1H-indol-3-yl)naphthalene-1,4-dione (3ag)[7a]

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 2-methyl-1H-indole (2g, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ag as a dark solid (90% yield), mp 181–183 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 8.06 (d, J = 5.4 Hz, 1H), 7.99 (d, J = 3.7 Hz, 1H), 7.85 (d, J = 4.2 Hz, 2H), 7.40 (d, J = 7.8 Hz, 1H), 7.33 (d, J = 7.9 Hz, 1H), 7.03 (dt, J = 27.9, 7.2 Hz, 2H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 184.84, 184.59, 144.68, 138.72, 135.93, 134.41, 134.19, 133.84, 132.91, 132.20, 127.81, 126.96, 125.74, 121.68, 120.32, 119.54, 111.39, 106.64, 13.86.

2-(2-Phenyl-1H-indol-3-yl)naphthalene-1,4-dione (3ah)[32]

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 2-phenyl-1H-indole (2h, 77.3 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ah as a red solid (81% yield), mp 216–218 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 12.04 (s, 1H), 8.01 (d, J = 6.9 Hz, 1H), 7.87–7.77 (m, 3H), 7.51 (dd, J = 23.5, 7.8 Hz, 4H), 7.39–7.28 (m, 3H), 7.19 (t, J = 7.5 Hz, 1H), 7.13–7.04 (m, 2H). 13C NMR (101 MHz, DMSO-d6) δ 184.62, 184.10, 145.17, 139.55, 136.81, 135.83, 134.48, 134.31, 132.92, 132.84, 132.28, 129.26, 129.15, 128.90, 128.64, 128.50, 128.23, 126.84, 125.88, 122.87, 120.90, 119.56, 112.22, 106.13. HRMS calcd for C25H18NO2+ (M + H)+ 364.1332, found 364.1338.

Methyl 3-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-1-methyl-1H-indole-2-carboxylate (3aj)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), methyl 1-methyl-1H-indole-2-carboxylate (2j, 75.7 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3aj as a red solid (72% yield), mp 206–208 °C. R = 0.30 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, CDCl3) δ 8.23–8.13 (m, 2H), 7.83–7.73 (m, 2H), 7.69 (d, J = 8.1 Hz, 1H), 7.50–7.37 (m, 2H), 7.29–7.23 (m, 1H), 7.17 (s, 1H), 4.11 (s, 3H), 3.70 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 185.03, 184.12, 162.09, 144.30, 138.56, 134.63, 133.71, 132.58, 132.32, 128.28, 126.88, 126.09, 125.50, 125.27, 121.91, 120.27, 113.52, 110.69, 51.84, 32.01. HRMS calcd for C21H16NO4+ (M + H)+ 346.1074, found 346.1072.

2-(4-Fluoro-1H-indol-3-yl)naphthalene-1,4-dione (3ak)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 4-fluoro-1H-indole (2k, 54.0 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3ak as a blackish-purple solid (76% yield), mp 246–248 °C. R = 0.40 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 12.34 (s, 1H), 8.25–8.20 (m, 1H), 8.19–8.08 (m, 2H), 8.04–7.98 (m, 2H), 7.50 (d, J = 8.1 Hz, 1H), 7.35 (td, J = 8.0, 5.2 Hz, 1H), 7.28 (d, J = 2.7 Hz, 1H), 7.06 (dd, J = 12.2, 7.9 Hz, 1H). 13C NMR (101 MHz, DMSO-d6) δ 184.85, 184.61, 157.10, 154.66, 134.53, 134.25, 132.10, 132.05, 131.99, 126.95, 125.74, 114.21, 114.03, 109.99, 109.37, 107.04, 106.79, 106.57. 19F NMR (376 MHz, DMSO-d6) δ −113.74. HRMS calcd for C18H11FNO2+ (M + H)+ 292.0768, found 292.0774.

2-(4-Chloro-1H-indol-3-yl)naphthalene-1,4-dione (3al)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 4- chloro-1H-indole (2l, 60.6 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3al as a red solid (80% yield), mp 261–263 °C. R = 0.40 (petroleum ether/EtOAc = 7/1). 1H NMR (300 MHz, DMSO-d6) δ 12.02 (s, 1H), 8.11–8.02 (m, 2H), 7.90 (dd, J = 5.6, 3.4 Hz, 2H), 7.77 (d, J = 2.6 Hz, 1H), 7.53–7.46 (m, 1H), 7.18 (t, J = 7.8 Hz, 1H), 7.11 (d, J = 6.8 Hz, 1H), 7.03 (s, 1H). 13C NMR (101 MHz, DMSO-d6) δ 185.48, 184.77, 144.86, 138.36, 134.74, 134.58, 134.43, 132.54, 132.18, 129.80, 126.93, 125.97, 124.91, 123.93, 123.32, 121.35, 111.85, 109.07. HRMS calcd for C18H11ClNO2+ (M + H)+ 308.0473, found 308.0476.

2-(4-Methoxy-1H-indol-3-yl)naphthalene-1,4-dione (3am)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 4-methoxy-1H-indole (2m, 58.8 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3am as a black solid (82% yield), mp 192–194 °C. R = 0.40 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 11.96 (s, 1H), 8.19 (dd, J = 5.6, 3.3 Hz, 1H), 8.12 (dd, J = 5.7, 3.3 Hz, 1H), 8.01–7.95 (m, 2H), 7.85 (d, J = 2.7 Hz, 1H), 7.29–7.17 (m, 3H), 6.75 (d, J = 7.4 Hz, 1H), 3.88 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 185.34, 184.63, 153.61, 143.93, 138.58, 134.33, 134.16, 132.91, 132.73, 132.20, 129.76, 126.80, 125.68, 123.88, 115.78, 108.89, 105.92, 102.03, 55.55. HRMS calcd for C19H14NO3+ (M + H)+ 304.0968, found 304.0975.

3-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-1H-indole-5-carbonitrile (3an)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 5-carbonitrile-1H-indole (2n, 56.9 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 5/1) to yield the desired product 3an as an orange solid (67% yield), mp 276–278 °C. R = 0.30 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 12.37 (s, 1H), 8.31 (s, 1H), 8.25 (s, 1H), 8.06 (s, 1H), 7.97 (d, J = 3.3 Hz, 1H), 7.84 (s, 2H), 7.63 (d, J = 8.2 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.27 (s, 1H). 13C NMR (101 MHz, DMSO-d6) δ 184.85, 184.72, 141.70, 138.87, 134.59, 134.23, 134.00, 132.74, 132.05, 130.54, 127.01, 126.28, 125.71, 125.59, 125.51, 120.80, 114.06, 108.85, 103.46. HRMS calcd for C19H11N2O2+ (M + H)+ 299.0815, found 299.0817.

2-(5-Chloro-1H-indol-3-yl)naphthalene-1,4-dione (3ao)[8d]

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 5-chloro-1H-indole (2o, 60.6 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3ao as a blackish-purple solid (75% yield), mp 225–227 °C. R = 0.40 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 12.08 (s, 1H), 8.15 (s, 1H), 7.99 (s, 1H), 7.92 (d, J = 4.3 Hz, 1H), 7.82–7.72 (m, 3H), 7.45 (d, J = 8.5 Hz, 1H), 7.18–7.07 (m, 2H). 13C NMR (101 MHz, DMSO-d6) δ 185.05, 184.58, 142.10, 135.63, 134.50, 134.09, 133.73, 132.79, 132.06, 129.12, 126.96, 126.20, 125.63, 122.90, 119.78, 114.44, 109.99, 107.76.

2-(5-Bromo-1H-indol-3-yl)naphthalene-1,4-dione (3ap)[8d]

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 5-bromo-1H-indole (2p, 78 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3ap as a reddish-purple solid (71% yield), mp 239–241 °C. R = 0.40 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 12.01 (s, 1H), 8.05 (s, 1H), 7.92 (s, 1H), 7.82 (d, J = 15.5 Hz, 2H), 7.71 (d, J = 3.8 Hz, 2H), 7.32 (d, J = 8.5 Hz, 1H), 7.19 (d, J = 7.7 Hz, 1H), 7.03 (d, J = 5.2 Hz, 1H). 13C NMR (101 MHz, DMSO-d6) δ 185.03, 184.61, 142.11, 135.86, 134.52, 134.11, 133.48, 132.78, 132.06, 129.25, 127.44, 126.96, 125.64, 125.45, 122.70, 114.86, 114.18, 107.67.

2-(5-Methoxy-1H-indol-3-yl)naphthalene-1,4-dione (3aq)[7c]

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 5-methoxy-1H-indole (2q, 58.8 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3aq as a black solid (83% yield), mp 152–154 °C. R = 0.40 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 11.85 (s, 1H), 8.09 (d, J = 2.9 Hz, 1H), 8.00–7.95 (m, 1H), 7.92–7.88 (m, 1H), 7.77–7.73 (m, 2H), 7.35 (d, J = 8.8 Hz, 1H), 7.21 (d, J = 1.7 Hz, 1H), 7.11 (s, 1H), 6.81 (dd, J = 8.8, 2.1 Hz, 1H), 3.75 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 185.47, 184.49, 155.41, 142.61, 134.41, 133.90, 133.41, 132.87, 132.12, 127.56, 126.90, 126.20, 125.53, 113.71, 112.48, 107.63, 102.97, 55.91.

2-(5-(Allyloxy)-1H-indol-3-yl)naphthalene-1,4-dione (3ar)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 5-allyloxy-1H-indole (2r, 69.3 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ar as a black solid (78% yield), mp 173–175 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 11.93 (s, 1H), 8.17 (d, J = 2.9 Hz, 1H), 8.07 (dd, J = 6.6, 2.2 Hz, 1H), 7.99 (dd, J = 5.5, 3.3 Hz, 1H), 7.85 (p, J = 7.0 Hz, 2H), 7.42 (d, J = 8.8 Hz, 1H), 7.33 (d, J = 1.8 Hz, 1H), 7.19 (s, 1H), 6.90 (dd, J = 8.8, 2.1 Hz, 1H), 6.16–6.02 (m, 1H), 5.45 (dd, J = 17.3, 1.4 Hz, 1H), 5.28 (dd, J = 10.5, 1.0 Hz, 1H), 4.62 (d, J = 5.2 Hz, 2H). 13C NMR (101 MHz, DMSO-d6) δ 185.48, 184.52, 154.27, 142.60, 134.71, 134.48, 133.97, 133.44, 132.88, 132.16, 132.14, 127.64, 126.93, 126.15, 125.56, 117.63, 113.69, 113.08, 107.60, 104.31, 69.37. HRMS calcd for C21H16NO3+ (M + H)+ 330.1125, found 330.1127.

2-(5-(Prop-2-ynyloxy)-1H-indol-3-yl)naphthalene-1,4-dione (3as)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 5-(prop-2-yn-1-yloxy)-1H-indole (2s, 68.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3as as a black solid (76% yield), mp 179–181 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 11.96 (s, 1H), 8.19 (d, J = 1.7 Hz, 1H), 8.10–8.04 (m, 1H), 8.02–7.97 (m, 1H), 7.88–7.82 (m, 2H), 7.43 (dd, J = 7.0, 5.7 Hz, 2H), 7.23 (s, 1H), 6.93 (dd, J = 8.8, 2.2 Hz, 1H), 4.86 (d, J = 2.2 Hz, 2H), 3.57 (s, 1H). 13C NMR (101 MHz, DMSO-d6) δ 185.47, 184.53, 153.25, 142.55, 134.49, 133.99, 133.62, 132.87, 132.50, 132.12, 127.71, 126.94, 126.01, 125.57, 113.68, 113.25, 107.63, 104.91, 80.13, 78.51, 56.69. HRMS calcd for C21H14NO3+ (M + H)+ 328.0968, found 328.0972.

2-(6-Fluoro-1H-indol-3-yl)naphthalene-1,4-dione (3at)[8d]

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 6-fluoro-1H-indole (2t, 54.0 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3at as a blackish-purple solid (65% yield), mp 258–260 °C. R = 0.40 (petroleum ether/EtOAc). 1H NMR (400 MHz, DMSO-d6) δ 12.18 (s, 1H), 8.34 (d, J = 2.8 Hz, 1H), 8.21 (dd, J = 5.9, 3.0 Hz, 1H), 8.15–8.10 (m, 1H), 7.99 (dd, J = 7.1, 4.5 Hz, 3H), 7.44 (dd, J = 9.6, 2.3 Hz, 1H), 7.36 (s, 1H), 7.18 (td, J = 9.3, 2.3 Hz, 1H). 13C NMR (101 MHz, DMSO-d6) δ 185.18, 184.59, 160.64, 158.28, 142.20, 137.18, 134.51, 134.09, 133.32, 132.84, 132.03, 128.56, 126.95, 125.61, 122.32, 109.93, 109.69, 107.95. 19F NMR (376 MHz, DMSO) δ −120.15.

2-(6-Chloro-1H-indol-3-yl)naphthalene-1,4-dione (3au)[8d]

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 6-chloro-1H-indole (2u, 60.6 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3au as a blackish-purple solid (73% yield), mp 276–278 °C. R = 0.40 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 12.19 (s, 1H), 8.34 (d, J = 2.5 Hz, 1H), 8.22–8.14 (m, 1H), 8.13–8.04 (m, 1H), 7.96 (d, J = 8.2 Hz, 3H), 7.64 (d, J = 14.0 Hz, 1H), 7.40–7.22 (m, 2H). 13C NMR (101 MHz, DMSO-d6) δ 185.11, 184.60, 142.09, 137.58, 134.53, 134.13, 133.52, 132.81, 132.03, 128.91, 127.46, 126.96, 125.63, 124.39, 121.91, 121.73, 112.55, 107.98.

2-(1H-Pyrrolo[2,3-b]pyridin-3-yl)naphthalene-1,4-dione (3av)

The reaction was conducted with 1,4-naphthoquinone (1a, 63.3 mg, 0.4 mmol), 1H-pyrrolo[2,3-b]pyridine (2v, 47.2 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3av as a red-orange solid (71% yield), mp 160–162 °C. R = 0.30 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 3.9 Hz, 1H), 8.20–8.08 (m, 2H), 8.06 (s, 1H), 7.97–7.88 (m, 1H), 7.84 (d, J = 3.9 Hz, 1H), 7.81–7.68 (m, 2H), 7.16 (dd, J = 7.7, 4.8 Hz, 1H), 6.65 (d, J = 3.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 184.96, 181.61, 148.56, 143.51, 140.63, 134.37, 133.68, 131.70, 131.61, 129.42, 129.24, 127.62, 127.07, 126.03, 122.59, 118.21, 103.95. HRMS calcd for C17H11N2O2+ (M + H)+ 275.0815, found 275.0817.

2-Methyl-3-(1-methyl-1H-indol-3-yl)naphthalene-1,4-dione (3ba)

The reaction was conducted with 2-methylnaphthalene-1,4-dione (1b, 68.9 mg, 0.4 mmol), 1-methyl-1H-indole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 5 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ba as a red solid (75% yield), mp 182–184 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, CDCl3) δ 8.03–7.92 (m, 2H), 7.59–7.51 (m, 2H), 7.22 (d, J = 8.2 Hz, 1H), 7.16–7.07 (m, 3H), 7.01 (t, J = 7.1 Hz, 1H), 3.72 (s, 3H), 2.05 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 185.79, 184.65, 142.57, 140.06, 136.67, 133.41, 133.29, 132.45, 131.76, 127.07, 126.61, 126.08, 121.99, 120.63, 120.25, 109.79, 106.91, 33.21, 15.90. HRMS calcd for C20H16NO2+ (M + H)+ 302.1176, found 302.1183.

2-(1-Methyl-1H-indol-3-yl)-3-phenylnaphthalene-1,4-dione (3ca)

The reaction was conducted with 2-phenylnaphthalene-1,4-dione (1c, 93.7 mg, 0.4 mmol), 1-methyl-1H-indole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 5 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ca as a dark-red solid (65% yield), mp 180–182 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, CDCl3) δ 8.20 (dd, J = 4.9, 2.9 Hz, 2H), 7.79–7.72 (m, 2H), 7.31–7.16 (m, 7H), 7.15–7.06 (m, 3H), 6.92 (t, J = 7.5 Hz, 1H), 3.72 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 185.54, 184.43, 142.58, 140.17, 136.60, 134.77, 133.69, 133.38, 133.35, 132.54, 132.44, 130.57, 128.43, 128.03, 127.90, 127.58, 126.63, 126.50, 126.48, 121.80, 120.95, 120.00, 109.26, 107.52, 33.13. HRMS calcd for C25H18NO2+ (M + H)+ 364.1332, found 364.1334.

2-(4-Fluorophenyl)-3-(1-methyl-1H-indol-3-yl)naphthalene-1,4-dione (3da)

The reaction was conducted with 2-(4-fluorophenyl)naphthalene-1,4-dione (1d, 100.9 mg, 0.4 mmol), 1-methyl-1H-indole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 4 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3da as a red solid (68% yield), mp 226–228 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 8.08 (dd, J = 8.5, 4.2 Hz, 2H), 7.91–7.86 (m, 2H), 7.39 (s, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.25 (dd, J = 8.3, 5.8 Hz, 2H), 6.99 (dt, J = 16.8, 8.0 Hz, 4H), 6.78 (t, J = 7.5 Hz, 1H), 3.77 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 185.16, 184.01, 160.54, 141.79, 140.09, 136.60, 134.52, 134.27, 133.16, 133.07, 132.44, 132.40, 131.63, 126.52, 126.44, 126.27, 121.69, 120.67, 119.77, 114.72, 114.50, 110.28, 106.83, 33.21. 19F NMR (376 MHz, DMSO-d6) δ −85.01. HRMS calcd for C25H17FNO2+ (M + H)+ 382.1238, found 382.1246.

2-(4-Bromophenyl)-3-(1-methyl-1H-indol-3-yl)naphthalene-1,4-dione (3ea)

The reaction was conducted with 2-(4-bromophenyl)naphthalene-1,4-dione (1e, 125.6 mg, 0.4 mmol), 1-methyl-1H-indole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 4 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ea as a red solid (62% yield), mp 233–235 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 8.06 (dd, J = 8.5, 4.4 Hz, 2H), 7.91–7.85 (m, 2H), 7.39 (s, 1H), 7.33 (d, J = 8.3 Hz, 3H), 7.15 (d, J = 8.3 Hz, 2H), 7.01 (dd, J = 15.1, 7.6 Hz, 2H), 6.79 (t, J = 7.5 Hz, 1H), 3.76 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 185.08, 183.79, 141.70, 140.08, 136.62, 134.70, 134.55, 134.26, 133.06, 132.38, 130.63, 126.55, 126.45, 126.30, 121.77, 121.39, 120.66, 119.82, 112.49, 110.35, 106.74, 33.23. HRMS calcd for C25H17BrNO2+ (M + H)+ 444.0437, found 444.0438.

2-Chloro-3-(1-methyl-1H-indol-3-yl)naphthalene-1,4-dione (3fa)

The reaction was conducted with 2-chloronaphthalene-1,4-dione (1f, 77.1 mg, 0.4 mmol), 1-methyl-1H-indole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3fa as a black solid (75% yield), mp 205–207 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, CDCl3) δ 8.15–8.08 (m, 1H), 8.08–8.01 (m, 1H), 7.65 (dd, J = 5.4, 2.3 Hz, 2H), 7.45 (s, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H), 7.19 (t, J = 7.6 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 3.80 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 182.83, 178.31, 140.48, 139.05, 136.78, 133.98, 133.94, 133.91, 132.06, 131.70, 127.26, 127.00, 126.19, 122.37, 122.19, 120.58, 109.94, 105.97, 33.44. HRMS calcd for C19H13NO2Cl+ (M + H)+ 322.0629, found 322.0633.

2-Bromo-3-(1-methyl-1H-indol-3-yl)naphthalene-1,4-dione (3ga)

The reaction was conducted with 2-bromonaphthalene-1,4-dione (1g, 94.8 mg, 0.4 mmol), 1-methyl-1H-indole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ga as a black solid (72% yield), mp 219–221 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, CDCl3) δ 8.29–8.21 (m, 1H), 8.20–8.12 (m, 1H), 7.82–7.73 (m, 2H), 7.56 (s, 1H), 7.48 (d, J = 7.9 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 3.92 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 182.27, 178.35, 144.22, 136.73, 135.10, 133.94, 133.90, 133.54, 131.89, 131.38, 127.36, 125.85, 122.33, 122.21, 120.46, 110.00, 107.83, 33.46. HRMS calcd for C19H13BrNO2+ (M + H)+ 366.0124, found 366.0130.

Methyl 3-(3-Bromo-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-1-methyl-1H-indole-2-carboxylate (3ha)

The reaction was conducted with 2-bromonaphthalene-1,4-dione (1h, 94.8 mg, 0.4 mmol), methyl 1-methyl-1H-indole-2-carboxylate (2i, 75.7 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3ha as a black solid (62% yield), mp 223–225 °C. R = 0.30 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, CDCl3) δ 8.39 (dd, J = 5.9, 3.1 Hz, 1H), 8.26 (dd, J = 5.9, 3.0 Hz, 1H), 7.92–7.89 (m, 2H), 7.60–7.51 (m, 3H), 7.30 (t, J = 6.9 Hz, 1H), 4.26 (s, 3H), 3.80 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 181.18, 178.22, 161.70, 146.41, 138.78, 138.08, 134.21, 133.95, 131.95, 131.36, 127.59, 127.38, 126.53, 125.56, 123.98, 121.73, 121.36, 116.03, 110.88, 51.97, 32.29. HRMS calcd for C21H15BrNO4+ (M + H)+ 424.0179, found 424.0180.

3,5-Dimethyl-2-(1-methyl-1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione (3ia)

The reaction was conducted with 2,6-dimethylcyclohexa-2,5-diene-1,4-dione (1i, 54.4 mg, 0.4 mmol), 1-methyl-1H-indole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ia as a dark-red solid (66% yield), mp 118–120 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 7.47 (d, J = 8.2 Hz, 1H), 7.42 (s, 1H), 7.18 (dd, J = 16.3, 8.0 Hz, 2H), 7.05 (t, J = 7.4 Hz, 1H), 6.75 (s, 1H), 3.83 (s, 3H), 2.01 (s, 3H), 1.93 (s, 3H). 13C NMR (101 MHz, DMSO-d6) 13C NMR (101 MHz, DMSO-d6) δ 188.34, 186.98, 145.76, 139.67, 137.51, 136.70, 133.29, 132.73, 127.15, 121.86, 120.67, 120.16, 110.64, 106.64, 33.17, 15.92, 15.29. HRMS calcd for C17H16NO2+ (M + H)+ 266.1176, found 266.1179.

2,3,5-Trimethyl-6-(1-methyl-1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione (3ja)

The reaction was conducted with 2,3,5-trimethylcyclohexa-2,5-diene-1,4-dione (1j, 60.1 mg, 0.4 mmol), 1-methyl-1H-indole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 10/1) to yield the desired product 3ja as a dark-red solid (69% yield), mp 131–133 °C. R = 0.50 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 7.52–7.42 (m, 2H), 7.20 (dd, J = 13.7, 7.7 Hz, 2H), 7.06 (t, J = 7.4 Hz, 1H), 3.86 (s, 3H), 2.01 (d, J = 7.2 Hz, 6H), 1.94 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 187.75, 186.62, 140.51, 140.36, 139.25, 137.46, 136.66, 132.50, 127.22, 121.78, 120.65, 120.07, 110.57, 106.61, 33.13, 15.19, 12.87, 12.69. HRMS calcd for C18H18NO2+ (M + H)+ 280.1332, found 280.1335

2,5-Dichloro-3-(1-methyl-1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione (3ka)[8a]

The reaction was conducted with 2,5-dichlorocyclohexa-2,5-diene-1,4-dione (1k, 70.8 mg, 0.4 mmol), 1-methyl-1H-indole (2a, 52.5 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3ka as a black solid (75% yield), mp 156–158 °C. R = 0.30 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 7.67 (s, 1H), 7.51 (d, J = 6.5 Hz, 2H), 7.33 (d, J = 8.0 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 3.87 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 178.29, 177.61, 143.36, 138.75, 136.83, 135.83, 134.78, 133.57, 126.15, 122.28, 121.98, 120.51, 110.93, 105.34, 33.43.

2,5-Dichloro-3-(1H-indol-3-yl)cyclohexa-2,5-diene-1,4-dione (3kb)[8a]

The reaction was conducted with 2,5-dichlorocyclohexa-2,5-diene-1,4-dione (1l, 70.8 mg, 0.4 mmol), indole (2b, 46.8 mg, 0.4 mmol), and B(C6F5)3 (10.2 mg, 0.02 mmol) in H2O (2 mL) at 60 °C for 2 h under an air atmosphere. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc = 7/1) to yield the desired product 3la as a black solid (72% yield), mp 161–163 °C. R = 0.30 (petroleum ether/EtOAc = 7/1). 1H NMR (400 MHz, DMSO-d6) δ 11.90 (s, 1H), 7.67 (d, J = 2.7 Hz, 1H), 7.53 (s, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.35 (d, J = 7.9 Hz, 1H), 7.17 (t, J = 7.3 Hz, 1H), 7.09 (d, J = 7.5 Hz, 1H). 13C NMR (101 MHz, DMSO-d6) δ 178.33, 177.65, 143.41, 139.15, 136.28, 135.91, 133.54, 131.20, 125.76, 122.20, 121.77, 120.25, 112.55, 106.28.