One-pot two-step synthesis of N-arylcarbazole-based skeleton

Abstract

A highly site-selective, one-pot, sequential C–N and C–C bond forming process was developed, affording a carbazole-based skeleton that contains biphenyl and diarylacetylene cores. The success of this process is attributed to the use of fluorinated iodoarenes as the starting material, the fluorine group of which preferentially reacts with carbazole. The subsequent coupling of the intermediate iodinated N-arylcarbazole with arylboronic acid or arylacetylene produced the desired products. The intermediate underwent a Pd-catalyzed Ullmann coupling with excess fluorinated iodoarenes in the absence of arylboronic acid or arylacetylene, resulting in Ullmann coupling products in a one-pot process.

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Introduction

Carbazole-based skeletons that contain biphenyl and diarylacetylene cores are widely applied in dye-sensitized solar cells¹ and organic light-emitting diodes,² and as a key component in the construction of natural products.³

Carbazole-based skeleton compounds are synthesized via two-pot synthetic approaches.⁴ N-Arylated carbazoles are prepared through a copper-catalyzed C–N forming reaction between carbazoles and dihalobenzene. After purification, the intermediate undergoes cross-coupling with arylboronic acid⁵ or arylacetylene⁶ in the presence of palladium as a catalyst. The one-pot strategy is a useful technique in synthetic organic chemistry because it can minimize solvent use, time, and the number of purification steps compared with individual multi-step syntheses.⁷ We attempted to develop a one-pot method without a purification step to prepare carbazole-based skeleton compounds. We have recently developed a copper-catalysed method for N-arylation of carbazole.⁸ The study showed that halogenated fluorobenzenes undergo a highly site-selective coupling at the fluoride group with carbazole through a nucleophilic substitution reaction in the metal-free condition. We infer that the metal-free condition eliminates the interference of metal for the succeeding transformation, and the tolerated halides provide an opportunity to enhance the N-arylated carbazole compounds further and convert them into useful compounds. In this paper, fluorinated iodobenzenes underwent sequential N-arylation and palladium-catalysed cross-coupling to achieve the desired products with good yields. In the absence of arylboronic acids or arylacetylene, Ullmann coupling between 9-(4-iodophenyl)-9H-carbazole and 4-fluoro-iodobenzene smoothly proceeded and then resulted in products (Fig. 1).

Fig. 1 Methods for the synthesis of carbazole-based skeletons.

Results and discussion

The one-pot two-step N-arylation and Pd-catalysed Suzuki coupling of 4-fluoro-iodobenzene, carbazole, and phenylboronic acid was selected as the model reaction to optimize the reaction conditions. The reaction conditions, including Pd sources, solvents, and molar ratios of the substrates, were evaluated.

The effect of the molar ratio of the substrates on the coupling of 4-fluoro-iodobenzene with carbazole was initially examined. Molar ratio is a crucial factor for product yield. A 1.0 : 0.5 : 1.0 molar ratio of 4-fluoro-iodobenzene, carbazole, and phenylboronic acid was the optimal reaction condition for the one-pot two-step method (Table 1, entry 8).

Table 1 One-pot substitution-Suzuki coupling process: optimization of reaction conditions^a

Entry	Solvent	Molar ratio (1a : 1b : 1c)	Palladium	Yield (%)
a Reaction conditions: (1) 4-fluoro-iodobenzene, carbazole, Cs2CO3 (1.0 mmol) in solvent (1 mL) under air, 150 °C, 24 h. (2) Phenylboronic acid, palladium source (5 mol%), and PPh3 (10 mol%) were added without a purification step, 130 °C, 6 h. Isolated yields.b 130 °C.c 170 °C.d 120 °C.e 110 °C.f 90 °C.
1	DMA	0.5 : 0.5 : 0.5	Pd(OAc)2	22
2	DMA	0.5 : 0.75 : 0.5	Pd(OAc)2	42
3	DMA	0.5 : 1.0 : 0.5	Pd(OAc)2	38
4	DMA	0.5 : 1.0 : 1.0	Pd(OAc)2	31
5	DMA	1.0 : 0.5 : 0.5	Pd(OAc)2	73
6	DMA	2.0 : 0.5 : 0.5	Pd(OAc)2	63
7	DMA	1.0 : 0.5 : 2.0	Pd(OAc)2	79
8	DMA	1.0 : 0.5 : 1.0	Pd(OAc)2	83
9	DMF	1.0 : 0.5 : 1.0	Pd(OAc)2	51
10	DMSO	1.0 : 0.5 : 1.0	Pd(OAc)2	72
11	NMP	1.0 : 0.5 : 1.0	Pd(OAc)2	49
12	DMA	1.0 : 0.5 : 1.0	PdCl2	88
13	DMA	1.0 : 0.5 : 1.0	Pd(OH)2	81
14	DMA	1.0 : 0.5 : 1.0	Pd/C	74
15^b	DMA	1.0 : 0.5 : 1.0	PdCl2	62
16^c	DMA	1.0 : 0.5 : 1.0	PdCl2	83
17^d	DMA	1.0 : 0.5 : 1.0	PdCl2	89
18^e	DMA	1.0 : 0.5 : 1.0	PdCl2	80
19^f	DMA	1.0 : 0.5 : 1.0	PdCl2	52

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The effect of different solvents was also determined. The reaction carried out in DMA (N,N-dimethylacetamide) produced the best yields (Table 1, entry 8). The yield decreased upon switching to DMF (N,N-dimethylformamide), NMP (N-methyl-2-pyrrolidone), or DMSO (dimethyl sulfoxide) (Table 1, entries 9, 10, and 11). Pd-catalysed cross-coupling is often affected by Pd source. Therefore, we evaluated different Pd sources. The experimental results show that PdCl₂ was more catalytically active than the other Pd sources (Table 1, entry 12).

The effect of temperature for the N-arylation was investigated. The reaction rate remarkably accelerated when the increasing temperature from 130 °C to 150 °C (Table 1, entries 15 and 12). Upon further increase of the reaction temperature to 170 °C, the isolated yield slightly decreased to 83% (Table 1, entry 16). Nuclear magnetic resonance analysis showed that a reaction temperature too high was likely to form disubstituted side-products due to the selectivity decrease of 4-fluoro-iodobenzene.

The effect of temperature for the Suzuki coupling was also investigated. The temperature has an evident promoting effect on the reaction rate when increasing from 90 °C to 120 °C (Table 1, entries 17, 18, and 19). Upon further increase of the reaction temperature to 130 °C, there was no evident change in the yield (Table 1, entry 12). Therefore, 120 °C was selected as the optimal reaction temperature used in subsequent studies.

The scope and limitations for the Suzuki coupling of arylboronic acids were initially examined (Table 2).

Table 2 One-pot substitution-Suzuki coupling process^a

a Reaction conditions: (1) fluorinated iodobenzenes (1.0 mmol), carbazoles (0.5 mmol), Cs₂CO₃ (1.0 mmol) in DMA (1 mL) under air, 150 °C, 24 h. (2) Phenylboronic acid (1.0 mmol), PdCl₂ (5 mol%), and PPh₃ (10 mol%) were added without a purification step, 120 °C, 6 h. Isolated yields.b 130 °C.

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The reactivity of arylboronic acids was tested under the optimised reaction conditions. The desired products were obtained in good-to-excellent yields (Table 2, 2a–h). The electronic effect of para-substituents that bear the aromatic ring of boronic acids was observed. Arylboronic acids that contained electron-donating and electron-neutral groups such as 4-H, 4-Me, and 4-nPr, smoothly reacted with the intermediates generated from the N-arylation, resulting in high-yield products (Table 2, 2a–c). However, the arylboronic acids that contained electron-withdrawing groups were less reactive in the developed system and produced moderate product yields (Table 2, 2d–f). The electronic effect of meta-substituted arylboronic acids was not evident in the developed one-pot system. 3-Methylphenylboronic acid successfully reacted with 9-(4-iodophenyl)-9H-carbazole to provide good results (Table 2, 2g). The steric hindrance effect of ortho-substituted arylboronic acids presented a certain influence on the reaction rate. 2-Methylphenylboronic acid showed a considerably slower conversion and obtained a moderate yield (Table 2, 2h).

The Suzuki coupling was not affected by the electronic nature and steric hindrance effects of fluorinated iodobenzenes. Thus, 3-iodo- or 2-iodo-substituted carbazolylbenzene smoothly underwent coupling with arylboronic acids and resulted in moderate to good yield products (Table 2, 2i–l).

The scope of coupling for carbazoles was also investigated under the optimised reaction conditions. The electronic effect of the carbazoles was not evident. Thus, 3,6-ditert-butyl-3,6-dibromo and 2,7-dibromo group substituted carbazoles smoothly underwent coupling and produced good yields (Table 2, 2m–p).

Arylboronic acids containing sensitive groups such as 4-OH, 4-CHO, 4-COOEt, 4-CN, and 4-OMe, were evaluated in the developed catalytic system. The results showed that no desired products were obtained. Arylboronic acids bearing 4-OH, 4-CHO, 4-COOEt, and 4-CN, have not participated in the reaction, but a sequential N-arylation and Ullmann coupling occurred between 4-fluoro-iodobenzene and carbazole (Table 2). 4-Methoxyphenylboronic acid preferentially reacted with 4-fluoro-iodobenzene to generate a 4-fluoro-4′-methoxy-1,1′-biphenyl compound instead of attacking on the intermediate from the N-arylation between 4-fluoro-iodobenzene and carbazole (Table 2, 2q).

The one-pot two-step process of N-arylation and Pd-catalyzed Sonogashira coupling of 4-fluoro-iodobenzene, carbazole, and phenylacetylene was selected as the model reaction to optimize the reaction conditions. In this model, different reaction conditions, including Pd sources, solvents, and molar ratios of the substrates, were evaluated. A 1.0 : 0.5 : 1.0 molar ratio of 4-fluoro-iodobenzene, carbazole, and phenylacetylene was the optimal reaction condition for the one-pot method (Table 3, entry 5).

Table 3 One-pot substitution-Sonogashira coupling process: optimization of reaction conditions^a

Entry	Solvent	Molar ratio (1a : 1b : 1d)	Palladium	Yield (%)
a Reaction conditions: (1) 4-fluoro-iodobenzene, carbazole, Cs2CO3 (1.0 mmol) in solvent (1 mL) under air, 150 °C, 24 h. (2) Phenylacetylene (1.0 mmol), palladium source (5 mol%), CuI (2.5 mol%), PPh3 (10 mol%), and Et3N (1 mmol) were added without a purification step, 130 °C, 6 h. Isolated yields.b Without CuI.c Without Et3N.d 120 °C.e 110 °C.f 90 °C.
1	DMA	0.5 : 0.5 : 1.0	PdCl2	67
2	DMA	0.5 : 0.75 : 1.0	PdCl2	52
3	DMA	0.5 : 1.0 : 1.0	PdCl2	81
4	DMA	0.5 : 2.0 : 1.0	PdCl2	41
5	DMA	1.0 : 0.5 : 1.0	PdCl2	93
6	DMSO	1.0 : 0.5 : 1.0	PdCl2	84
7	DMF	1.0 : 0.5 : 1.0	PdCl2	46
8	NMP	1.0 : 0.5 : 1.0	Pd(OAc)2	78
9	DMA	1.0 : 0.5 : 1.0	Pd(OH)2	68
10	DMA	1.0 : 0.5 : 1.0	Pd/C	63
11^b	DMA	1.0 : 0.5 : 1.0	PdCl2	75
12^c	DMA	1.0 : 0.5 : 1.0	PdCl2	13
13^d	DMA	1.0 : 0.5 : 1.0	PdCl2	89
14^e	DMA	1.0 : 0.5 : 1.0	PdCl2	83
15^f	DMA	1.0 : 0.5 : 1.0	PdCl2	70

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To probe the efficiency of CuI and Et₃N, we designed control experiments by conducting the reaction in the absence of CuI and Et₃N, respectively. The results indicated that the CuI can efficiently promote the coupling reaction from 75% to 93% of the product yield (Table 3, entry 5 vs. 11). Et₃N is crucial for the reaction. The reaction was difficult to proceed in the absence of Et₃N, and only 13% product yield was obtained (Table 3, entry 12).

The effect of temperature on the Sonogashira coupling was investigated (Table 3, entries 5, 13, 14, and 15). 130 °C was selected as the optimal reaction temperature for Sonogashira coupling (Table 3, entry 5).

The scope and limitations for the Sonogashira coupling of arylacetylenes were examined. The reactivity of arylacetylenes was tested under the optimised reaction conditions, and the desired products were obtained in good to excellent yields (Table 4).

Table 4 One-pot substitution-Sonogashira coupling process^a

a Reaction conditions: (1) fluorinated iodobenzenes (1.0 mmol), carbazoles (0.5 mmol), Cs₂CO₃ (1.0 mmol) in DMA (1 mL) under air, 150 °C, 24 h. (2) Arylacetylene (1.0 mmol), PdCl₂ (5 mol%), CuI (2.5 mol%), PPh₃ (10 mol%), and Et₃N (1 mmol) were added without a purification step, 130 °C, 6 h. Isolated yields.

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The electronic effect of para-substituents bearing the aromatic ring of arylacetylenes was evident. Arylacetylenes containing electron-donating and electron-neutral groups were highly reactive and resulted in excellent yields (Table 4, 3a–c). However, the arylacetylenes bearing electron-withdrawing groups were less reactive in the developed one-pot system and resulted in moderate product yields (Table 4, 3d and 3e). The reactivity of arylacetylenes decreased when their groups were in the meta-position (Table 4, 3f and 3g). The steric hindrance effect of ortho-substituted arylacetylenes was not observed in the developed system (Table 4, 3h).

The scope of the one-pot method for carbazoles was also investigated under the optimised reaction conditions. The electronic effect of the carbazoles was significantly evident. Carbazoles bearing a 3,6-ditert-butyl group exhibited higher reactivity than those bearing 3,6-dibromo and 2,7-dibromo groups (Table 4, 3i vs. 3j–l).

The optimised reaction conditions were also applied in the coupling of alicyclic and aliphatic alkynes. The reactivity of alicyclic alkynes was evidently higher than aliphatic alkynes (Table 4, 3m–o vs. 3p). Alicyclic alkynes were successfully converted to the desired products with excellent yields (Table 4, 3m–o). However, aliphatic alkynes showed a considerably slower conversion and resulted in a moderate product yield under the same reaction conditions (Table 4, 3p).

Arylacetylenes containing sensitive groups such as 3-OH, 3-NH₂, 4-COOMe, 4-CH₂CN, and 4-OMe, were evaluated in the developed catalytic system. 3-Ethynylphenol and 3-ethynylaniline have not participated in the reaction, but a coupling product through sequential N-arylation and Ullmann coupling was obtained (Table 4). Arylacetylenes bearing 4-COOMe, 4-CH₂CN, and 4-OMe, preferentially reacted with 4-fluoro-iodobenzene instead of attacking on the intermediate from the N-arylation between 4-fluoro-iodobenzene and carbazole (Table 4, 3q–s).

In view of the unexpected results shown in Tables 2 and 4, arylboronic acid or arylacetylene was eliminated from the reaction system. The results showed that the reaction process was not terminated in the N-arylation of carbazole in the presence of a palladium catalyst. Instead, the process continued to react with fluorinated iodobenzenes through Ullmann coupling and yielded products.

The reaction conditions of the one-pot two-step method for N-arylation and Ullmann coupling were evaluated (Table 5). A 1.5 : 0.5 molar ratio of 4-fluoro-iodobenzene and carbazole was the optimal reaction condition for the one-pot two-step method in DMA in the presence of PdCl₂ as catalyst (Table 5, entry 3). The palladium catalyst was crucial for Ullmann coupling between 9-(4-iodophenyl)-9H-carbazole and 4-fluoro-iodobenzene.

Table 5 One-pot substitution-Ullmann coupling process: optimization of reaction conditions^a

Entry	Solvent	Molar ratio (1a : 1b)	Palladium	Yield (%)
a Reaction conditions: (1) 4-fluoro-iodobenzene, carbazole, Cs2CO3 (1.0 mmol) in solvent (1 mL) under air, 150 °C, 24 h. (2) Phenylacetylene (1.0 mmol), palladium source (5 mol%), PPh3 (10 mol%), and Et3N (1 mmol) were added without a purification step, 130 °C, 6 h. Isolated yields.b Adding CuI (2.5 mol%).c Without Et3N.d Without PdCl2.e 120 °C.f 110 °C.g 90 °C.
1	DMA	0.75 : 0.5	PdCl2	47
2	DMA	1.0 : 0.5	PdCl2	68
3	DMA	1.5 : 0.5	PdCl2	83
4	DMA	2.0 : 0.5	PdCl2	85
5	DMSO	1.5 : 0.5	PdCl2	72
6	DMF	1.5 : 0.5	PdCl2	58
7	NMP	1.5 : 0.5	PdCl2	64
8	DMA	1.5 : 0.5	Pd(OAc)2	77
9	DMA	1.5 : 0.5	Pd(OH)2	69
10	DMA	1.5 : 0.5	Pd/C	65
11^b	DMA	1.5 : 0.5	PdCl2	73
12^c	DMA	1.5 : 0.5	PdCl2	53
13^d	DMA	1.5 : 0.5	No	0
14^e	DMA	1.5 : 0.5	PdCl2	66
15^f	DMA	1.5 : 0.5	PdCl2	57
16^g	DMA	1.5 : 0.5	PdCl2	35

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To investigate the efficiency of CuI, PdCl₂, and Et₃N, we designed three control experiments (Table 5, entries 11–13). The results showed that CuI inhibited the Ullmann coupling reaction and homo-coupling of 4-fluoro-iodobenzene increased (Table 5, entry 11). Et₃N can efficiently promote the coupling reaction (Table 5, entry 12). The coupling reaction was difficult to start in the absence of Pd catalyst (Table 5, entry 13).

The effect of temperature on Ullmann coupling was investigated (Table 5, entries 3, 14, 15, and 16). The results showed that the temperature served a crucial function in Ullmann coupling. A higher reaction temperature is necessary to activate the intermediate from N-arylation between fluorinated iodobenzenes and carbazole, so 130 °C was selected as the optimal reaction temperature (Table 5, entry 3).

The scope and limitations for N-arylation and Pd-catalyzed Ullmann coupling were evaluated (Table 6). The electronic effect of the fluorine group bearing the iodobenzene ring was not observed. The iodobenzene with fluorine substitution at the para or meta position to the aromatic ring showed similar reactivity and produced moderate yields (Table 6, 2d and 4a). The steric hindrance effect of fluorinated iodobenzene was evident and only 19% desired product yield was obtained (Table 6, 4b). The electronic effect of carbazole was also evident for Ullmann coupling. The carbazole with an electronic-withdrawing group at the para position to the aromatic ring showed higher reactivity than that with an electronic-donating group (Table 6, 4c vs. 4d–g).

Table 6 One-pot substitution-Ullmann coupling process^a

a Reaction conditions: (1) fluorinated iodobenzenes (1.0 mmol), carbazoles (0.5 mmol), Cs₂CO₃ (1.0 mmol) in DMA (1 mL) under air, 150 °C, 24 h. (2) PdCl₂ (5 mol%), PPh₃ (10 mol%), and Et₃N (1.0 mmol) were added without a purification step, 130 °C, 6 h. Isolated yields.

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To simplify the operating procedures, we simultaneously conducted N-arylation and Pd-catalysed cross coupling reactions in one-pot (Fig. 2). Interestingly, the one-pot method for N-arylation and Pd-catalysed Sonogashira coupling showed a slight decrease in yield and achieved high conversion (Fig. 2). However, N-arylation and Pd-catalysed Suzuki coupling in one-pot is difficult to perform simultaneously (Fig. 2). In the presence of Pd-catalyst, 4-fluoro-iodobenzene preferred to react with phenylboronic acid or undergo homo-coupling to afford products 5a and 5b. The one-pot method for N-arylation and Pd-catalysed Ullmann coupling showed an evident decrease in yield and achieved high conversion (Fig. 2). The product analysis revealed that the Pd-catalyst activated the C–I bond of fluorinated iodobenzene and leads to decreased reaction selectivity.

Fig. 2 Trial experiments for simultaneous S_NAr substitution and cross-coupling.

A one-pot four-compound competing reaction was conducted as shown in Fig. 3. The reaction processes composed of competing reactions, namely, the Suzuki coupling reaction, Sonogashira coupling reaction and Ullmann coupling reaction. The one-pot procedure for N-arylation and Pd-catalysed Sonogashira performed coupling smoothly and produced a good yield (Fig. 3).

Fig. 3 One-pot competing reaction.

Experimental

General experimental methods

All reactions were performed in a glass vial under an air atmosphere. DMF, DMSO, DMA, and NMP were distilled from 4 Å-molecular sieves. Other reagents were purchased from commercial sources and used without additional purification. NMR spectra were recorded on a Bruker Avance III HD 400 spectrometer using TMS as an internal standard (400 MHz for ¹H NMR, 100 MHz for ¹³C NMR and 376 MHz for ¹⁹F NMR). The mass data of the compounds were collected on a Bruker ultrafleXtreme mass spectrometer. All products were isolated by short chromatography on a silica gel (200–300 mesh) column.

General procedure for the substitution-Suzuki coupling process

A mixture of 4-fluoro-iodobenzene (1.0 mmol), carbazoles (0.5 mmol), and Cs₂CO₃ (0.05 mmol) was added to a glass vial in solvent (1 mL) under an air atmosphere. The reaction mixture was heated to 150 °C for 24 h. The reaction mixture was cooled to room temperature. To this mixture arylboronic acid (1.0 mmol), palladium sources (0.025 mmol), and PPh₃ (0.05 mmol) were added, and the mixture was heated to 130 °C for 6 h. The reaction mixture was added to brine (15 mL) and extracted three times with dichloromethane (3 × 15 mL). The solvent was concentrated under vacuum and the product was isolated by short chromatography on a silica gel (200–300 mesh) column.

General procedure for the substitution-Sonogashira coupling process

A mixture of 4-fluoro-iodobenzene (1.0 mmol), carbazoles (0.5 mmol), and Cs₂CO₃ (0.05 mmol) was added to a glass vial in solvent (1 mL) under an air atmosphere. The reaction mixture was heated to 150 °C for 24 h. The reaction mixture was cooled to room temperature. To this mixture arylacetylene (1.0 mmol), palladium sources (0.025 mmol), PPh₃ (0.05 mmol), CuI (0.0125 mmol), and Et₃N (1 mmol) were added, and the mixture was heated to 130 °C for 6 h. The reaction mixture was added to brine (15 mL) and extracted three times with dichloromethane (3 × 15 mL). The solvent was concentrated under vacuum and the product was isolated by short chromatography on a silica gel (200–300 mesh) column.

General procedure for the substitution-Ullmann coupling process

A mixture of 4-fluoro-iodobenzene (1.0 mmol), carbazoles (0.5 mmol), and Cs₂CO₃ (0.05 mmol) was added to a glass vial in solvent (1 mL) under an air atmosphere. The reaction mixture was heated to 150 °C for 24 h. The reaction mixture was cooled to room temperature. To this mixture palladium sources (0.025 mmol), PPh₃ (0.05 mmol), CuI (0.0125 mmol), and Et₃N (1 mmol) were added, and the mixture was heated to 130 °C for 6 h. The reaction mixture was added to brine (15 mL) and extracted three times with dichloromethane (3 × 15 mL). The solvent was concentrated under vacuum and the product was isolated by short chromatography on a silica gel (200–300 mesh) column.

9-([1,1′-Biphenyl]-4-yl)-9H-carbazole (2a)^4c

Purification by flash chromatography (petroleum ether): a white solid (145 mg, 91%), mp = 227–228 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.19 (dd, J = 1.2 Hz, J = 0.8 Hz, 1H), 8.17 (dd, J = 1.2 Hz, J = 0.8 Hz, 1H), 7.86–7.83 (m, 2H), 7.73–7.70 (m, 2H), 7.68–7.65 (m, 2H), 7.55–7.41 (m, 7H), 7.35–7.31 (m, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.81, 140.26, 140.23, 136.82, 128.91, 128.46, 127.60, 127.28, 127.10, 125.91, 123.38, 120.28, 119.92, 109.79, ppm.

9-(4′-Methyl-[1,1′-biphenyl]-4-yl)-9H-carbazole (2b)

Purification by flash chromatography (petroleum ether): a white solid (135 mg, 81%), mp = 235–236 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.20 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 7.67–7.62 (m, 4H), 7.53–7.45 (m, 4H), 7.36–7.32 (m, 4H), 2.48 (s, 3H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.93, 140.28, 137.52, 137.42, 136.60, 129.72, 128.31, 127.34, 127.00, 125.99, 123.44, 120.35, 119.97, 109.90, 21.21, ppm; HRMS (EI): m/z calcd for C₂₅H₁₉N [M]⁺ 333.1517, found 333.1520.

9-(4′-Propyl-[1,1′-biphenyl]-4-yl)-9H-carbazole (2c)

Purification by flash chromatography (petroleum ether): a white solid (161 mg, 89%), mp = 161–162 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.19 (d, J = 7.6 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.64 (q, J = 4.0 Hz, 4H), 7.51–7.43 (m, 4H), 7.36–7.31 (m, 4H), 2.70 (t, J = 7.6 Hz, 2H), 1.75 (sext, J = 7.6 Hz, 2H), 1.03 (t, J = 7.2 Hz, 3H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 142.31, 140.90, 140.30, 137.62, 136.55, 129.09, 128.30, 127.30, 126.96, 125.94, 123.40, 120.30, 119.92, 109.86, 37.74, 24.57, 13.91, ppm; HRMS (EI): m/z calcd for C₂₇H₂₃N [M]⁺ 361.1830, found 361.1834.

9-(4′-Fluoro-[1,1′-biphenyl]-4-yl)-9H-carbazole (2d)⁸

Purification by flash chromatography (petroleum ether): a white solid (98 mg, 58%), mp = 186–187 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.20 (d, J = 7.6 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.70–7.66 (m, 4H), 7.51–7.44 (m, 4H), 7.34 (t, J = 8.0 Hz, 2H), 7.23 (t, J = 8.4 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.69 (d, J_C–F = 245.4 Hz), 140.85, 139.32, 136.91, 136.42 (d, J_C–F = 3.2 Hz), 128.74 (d, J_C–F = 8.0 Hz), 128.40, 127.41, 126.01, 123.47, 120.37, 120.04, 115.89 (d, J_C–F = 21.3 Hz), 109.81, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −115.04, ppm; HRMS (MALDI): m/z calcd for C₂₄H₁₆FN [M]⁺ 337.1261, found 337.1263.

9-(4′-(Trifluoromethyl)-[1,1′-biphenyl]-4-yl)-9H-carbazole (2e)

Purification by flash chromatography (petroleum ether): a white solid (132 mg, 68%), mp = 251–252 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.20 (d, J = 7.6 Hz, 2H), 7.87–7.78 (m, 6H), 7.72 (d, J = 8.4 Hz, 2H), 7.53–7.45 (m, 4H), 7.35 (t, J = 8.0 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 143.76, 140.72, 138.71, 137.82, 128.72, 127.49, 127.43, 126.05, 125.95, 125.91, 123.54, 120.40, 120.16, 109.77, 29.72, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −62.41, ppm.

9-(3′,4′,5′-Trifluoro-[1,1′-biphenyl]-4-yl)-9H-carbazole (2f)

Purification by flash chromatography (petroleum ether): a white solid (125 mg, 67%), mp = 184–185 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.22–8.19 (m, 2H), 7.76–7.68 (m, 4H), 7.51–7.45 (m, 4H), 7.38–7.30 (m, 4H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 151.66 (ddd, J_C–F = 248.4 Hz, J_C–F = 10.0 Hz, J_C–F = 4.3 Hz), 140.67, 138.01, 137.07 (dd, J_C–F = 3.7 Hz, J_C–F = 2.1 Hz), 136.39 (ddd, J_C–F = 12.4 Hz, J_C–F = 7.7 Hz, J_C–F = 4.6 Hz), 128.33, 128.32, 127.52, 126.13, 123.61, 120.46, 120.29, 111.13 (dd, J_C–F = 16.0 Hz, J_C–F = 6.1 Hz), 109.74, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −133.58 (d, J_F–F = 20.3 Hz), 161.89 (t, J_F–F = 20.3 Hz), ppm.

9-(3′-Methyl-[1,1′-biphenyl]-4-yl)-9H-carbazole (2g)

Purification by flash chromatography (petroleum ether): a white solid (160 mg, 96%), mp = 153–154 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.20 (d, J = 7.6 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.8 Hz, 2H), 7.55–7.41 (m, 7H), 7.36–7.32 (m, 2H), 7.26 (d, J = 7.6 Hz, 2H), 2.51 (s, 3H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.89, 140.47, 140.29, 138.58, 136.77, 128.87, 128.53, 128.40, 127.98, 127.29, 125.96, 124.26, 123.42, 120.33, 119.95, 109.86, 21.61, ppm; HRMS (EI): m/z calcd for C₂₅H₁₉N [M]⁺ 333.1517, found 333.1520.

9-(2′-Methyl-[1,1′-biphenyl]-4-yl)-9H-carbazole (2h)

Purification by flash chromatography (petroleum ether): a white solid (104 mg, 65%), mp = 140–141 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.21 (d, J = 8.0 Hz, 2H), 7.67–7.46 (m, 8H), 7.41–7.33 (m, 6H), 2.44 (s, 3H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 141.12, 141.08, 140.93, 136.40, 135.45, 130.69, 130.58, 129.88, 127.66, 126.66, 126.02, 125.99, 123.46, 120.38, 120.01, 109.92, 20.66, ppm; HRMS (EI): m/z calcd for C₂₅H₁₉N [M]⁺ 333.1517, found 333.1520.

9-([1,1′-Biphenyl]-3-yl)-9H-carbazole (2i)⁹

Purification by flash chromatography (petroleum ether): a white solid (140 mg, 88%), mp = 113–115 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.21 (d, J = 7.6 Hz, 2H), 7.85 (t, J = 2.0 Hz, 1H), 7.75–7.68 (m, 4H), 7.61–7.58 (m, 1H), 7.53–7.40 (m, 7H), 7.36–7.32 (m, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 143.14, 140.90, 140.14, 138.24, 130.28, 128.98, 127.87, 127.19, 126.14, 126.00, 125.83, 125.75, 123.43, 120.36, 119.99, 109.84, ppm.

9-(4′-Methyl-[1,1′-biphenyl]-3-yl)-9H-carbazole (2j)

Purification by flash chromatography (petroleum ether): a white solid (128 mg, 77%), mp = 72–73 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.21 (d, J = 7.6 Hz, 2H), 7.84 (t, J = 2.0 Hz, 1H), 7.74–7.68 (m, 2H), 7.61–7.45 (m, 7H), 7.37–7.31 (m, 4H), 2.45 (s, 3H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 143.07, 140.92, 138.19, 137.76, 137.27, 130.23, 129.71, 127.02, 126.00, 125.94, 125.53, 123.43, 120.36, 119.97, 109.89, 21.17, ppm; HRMS (EI): m/z calcd for C₂₅H₁₉N [M]⁺ 333.1517, found 333.1520.

9-(4′-Fluoro-[1,1′-biphenyl]-3-yl)-9H-carbazole (2k)

Purification by flash chromatography (petroleum ether): a white solid (108 mg, 64%), mp = 67 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.25–8.22 (m, 2H), 7.85–7.81 (m, 1H), 7.73–7.59 (m, 5H), 7.55–7.46 (m, 4H), 7.40–7.35 (m, 2H), 7.23–7.18 (m, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.81 (d, J_C–F = 245.8 Hz), 142.16, 140.91, 138.35, 136.27 (d, J_C–F = 3.3 Hz), 130.40, 129.74, 128.82 (d, J_C–F = 8.0 Hz), 127.04, 126.08, 126.00, 125.87, 125.62, 123.50, 120.44, 120.10, 115.93 (d, J_C–F = 21.4 Hz), 109.82, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −114.60 to −114.62 (m), ppm; HRMS (MALDI): m/z calcd for C₂₄H₁₆FN [M]⁺ 337.1261, found 337.1263.

9-([1,1′-Biphenyl]-2-yl)-9H-carbazole (2l)

Purification by flash chromatography (petroleum ether): a white solid (147 mg, 92%), mp = 152–153 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.07 (d, J = 7.6 Hz, 2H), 7.71 (dd, J = 7.2 Hz, J = 1.6 Hz, 1H), 7.65–7.51 (m, 3H), 7.32–7.29 (m, 2H), 7.23–7.19 (m, 2H), 7.12–7.00 (m, 7H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 141.15, 141.08, 138.61, 134.80, 131.55, 129.80, 128.80, 128.74, 128.07, 127.76, 127.25, 125.62, 123.06, 120.04, 119.44, 109.98, ppm; HRMS (EI): m/z calcd for C₂₄H₁₇N [M]⁺ 319.1361, found 319.1369.

9-([1,1′-Biphenyl]-4-yl)-3,6-di-tert-butyl-9H-carbazole (2m)

Purification by flash chromatography (petroleum ether): a white solid (175 mg, 81%), mp = 185–186 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.20 (s, 2H), 7.84 (d, J = 8.0 Hz, 2H), 7.73 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H), 7.56–7.51 (m, 4H), 7.45 (d, J = 8.8 Hz, 3H), 1.52 (d, J = 1.6 Hz, 18H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 142.95, 140.40, 139.80, 139.28, 137.44, 128.98, 128.43, 127.60, 127.16, 126.97, 123.69, 123.49, 116.31, 109.35, 34.82, 32.11, ppm.

9-([1,1′-Biphenyl]-4-yl)-3-bromo-9H-carbazole (2n)¹⁰

Purification by flash chromatography (petroleum ether): a white solid (135 mg, 68%), mp = 153–154 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.31 (d, J = 1.6 Hz, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.4 Hz, 2H), 7.74–7.71 (m, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.57–7.53 (m, 3H), 7.50–7.44 (m, 3H), 7.37 (d, J = 8.4 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 141.22, 140.67, 140.14, 139.55, 136.38, 129.03, 128.67, 128.64, 127.79, 127.26, 127.17, 126.75, 125.20, 123.10, 122.38, 120.55, 120.43, 112.79, 111.37, 110.12, ppm.

9-([1,1′-Biphenyl]-4-yl)-3,6-dibromo-9H-carbazole (2o)

Purification by flash chromatography (petroleum ether): a white solid (174 mg, 73%), mp = 218–219 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.23 (d, J = 1.6 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H), 7.72–7.69 (m, 2H), 7.59–7.52 (m, 6H), 7.47–7.43 (m, 1H), 7.34 (d, J = 8.8 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 141.03, 139.98, 139.85, 135.88, 129.43, 129.03, 128.74, 127.87, 127.18, 127.16, 124.01, 123.25, 113.14, 111.59, ppm; HRMS (EI): m/z calcd for C₂₄H₁₅Br₂N [M]⁺ 474.9571, found 474.9580.

9-([1,1′-Biphenyl]-4-yl)-2,7-dibromo-9H-carbazole (2p)

Purification by flash chromatography (petroleum ether): a white solid (155 mg, 65%), mp = 199–201 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.98 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 7.6 Hz, 2H), 7.60–7.53 (m, 6H), 7.47–7.43 (m, 3H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 141.89, 141.37, 139.99, 135.49, 129.02, 128.92, 127.88, 127.34, 127.22, 123.69, 121.75, 121.50, 120.04, 113.12, ppm; HRMS (EI): m/z calcd for C₂₄H₁₅Br₂N [M]⁺ 474.9571, found 474.9580.

4-Fluoro-4′-methoxy-1,1′-biphenyl (2q)¹¹

Purification by flash chromatography (petroleum ether): a white solid (138 mg, 68%), mp = 79 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.53–7.48 (m, 4H), 7.12 (t, J = 8.8 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.09 (d, J_C–F = 244.0 Hz), 159.11, 136.96 (d, J_C–F = 3.3 Hz), 132.84, 128.21 (d, J_C–F = 7.8 Hz), 128.03, 115.52 (d, J_C–F = 21.1 Hz), 114.25, 55.37, ppm.

9-(4-(Phenylethynyl)phenyl)-9H-carbazole (3a)^6a

Purification by flash chromatography (petroleum ether): a white solid (160 mg, 93%), mp = 137–138 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.17 (t, J = 1.2 Hz, 1H), 8.15 (dd, J = 1.2 Hz, J = 0.8 Hz, 1H), 7.79 (t, J = 2.0 Hz, 1H), 7.77 (t, J = 2.0 Hz, 1H), 7.62–7.58 (m, 4H), 7.46–7.38 (m, 7H), 7.34–7.30 (m, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.51, 137.50, 133.06, 131.63, 128.45, 128.38, 126.80, 126.00, 123.49, 122.98, 122.23, 120.31, 120.15, 109.69, 90.26, 88.60, ppm.

9-(4-(p-Tolylethynyl)phenyl)-9H-carbazole (3b)

Purification by flash chromatography (petroleum ether): a white solid (170 mg, 95%), mp = 200–201 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.17 (d, J = 7.6 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 7.52–745 (m, 6H), 7.35–7.31 (m, 2H), 7.22 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.59, 138.70, 137.37, 133.04, 131.58, 129.21, 126.85, 126.05, 123.53, 122.52, 120.36, 120.18, 119.95, 109.76, 90.54, 88.03, 21.57, ppm; HRMS (EI): m/z calcd for C₂₇H₁₉N [M]⁺ 357.1512, found 357.1513.

9-(4-((4-Ethylphenyl)ethynyl)phenyl)-9H-carbazole (3c)

Purification by flash chromatography (petroleum ether): a white solid (152 mg, 82%), mp = 191–192 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.18 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H), 7.49–7.43 (m, 4H), 7.35–7.31 (m, 2H), 7.25 (d, J = 8.0 Hz, 2H), 2.72 (q, J = 7.6 Hz, 2H), 1.30 (t, J = 7.6 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 145.01, 140.60, 137.38, 133.06, 131.68, 128.03, 126.85, 126.06, 123.55, 122.54, 120.37, 120.19, 109.77, 90.59, 88.04, 28.90, 15.39, ppm; HRMS (EI): m/z calcd for C₂₈H₂₁N [M]⁺ 371.1674, found 371.1680.

9-(4-((4-Chlorophenyl)ethynyl)phenyl)-9H-carbazole (3d)

Purification by flash chromatography (petroleum ether): a white solid (117 mg, 62%), mp = 234–235 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.18 (d, J = 7.6 Hz, 2H), 7.78 (d, J = 8.8 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.48–7.43 (m, 4H), 7.39 (d, J = 8.4 Hz, 2H), 7.35–7.31 (m, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.52, 137.80, 134.55, 133.12, 132.89, 128.80, 126.88, 126.08, 123.59, 121.89, 121.55, 120.40, 120.27, 109.73, 89.61, 89.18, ppm; HRMS (EI): m/z calcd for C₂₆H₁₆ClN [M]⁺ 377.0971, found 377.0975.

9-(4-((4-Fluorophenyl)ethynyl)phenyl)-9H-carbazole (3e)

Purification by flash chromatography (petroleum ether): a white solid (92 mg, 51%), mp = 254 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.18 (d, J = 7.6 Hz, 2H), 7.78 (d, J = 8.8 Hz, 2H), 7.62–7.58 (m, 4H), 7.48–7.43 (m, 4H), 7.35–7.31 (m, 2H), 7.11 (t, J = 8.4 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.67 (d, J_C–F = 248.5 Hz), 140.56, 137.67, 133.60 (d, J_C–F = 8.3 Hz), 133.08, 126.89, 126.09, 123.60, 122.09, 120.41, 120.27, 119.16 (d, J_C–F = 3.6 Hz), 115.78 (d, J_C–F = 21.9 Hz), 109.75, 89.26, 88.39 (d, J_C–F = 1.5 Hz), ppm.

9-(4-(m-Tolylethynyl)phenyl)-9H-carbazole (3f)⁸

Purification by flash chromatography (petroleum ether): a white solid (109 mg, 61%), mp = 109–110 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.18 (d, J = 8.0 Hz, 2H), 7.81–7.77 (m, 2H), 7.62–7.59 (m, 2H), 7.50–7.42 (m, 6H), 7.36–7.29 (m, 3H), 7.22 (d, J = 7.6 Hz, 1H), 2.42 (s, 3H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.61, 138.18, 137.53, 133.14, 132.31, 129.48, 128.84, 128.40, 126.88, 126.12, 123.61, 122.90, 122.43, 120.43, 120.27, 109.81, 90.61, 88.42, 21.34, ppm; HRMS (MALDI): m/z calcd for C₂₇H₁₉N [M]⁺ 357.1512, found 357.1513.

9-(4-((3-Fluorophenyl)ethynyl)phenyl)-9H-carbazole (3g)

Purification by flash chromatography (petroleum ether): a white solid (139 mg, 77%), mp = 134–135 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.18 (d, J = 7.6 Hz, 2H), 7.79 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.49–7.43 (m, 4H), 7.40–7.29 (m, 5H), 7.14–7.08 (m, 1H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.45 (d, J_C–F = 245.1 Hz), 140.52, 137.91, 133.21, 130.03 (d, J_C–F = 8.6 Hz), 127.57 (d, J_C–F = 3.1 Hz), 126.88, 126.09, 124.90 (d, J_C–F = 9.4 Hz), 123.60, 121.74, 120.30 (d, J_C–F = 11.7 Hz), 118.46 (d, J_C–F = 22.7 Hz), 115.81 (d, J_C–F = 21.1 Hz), 109.74, 89.54, 89.01 (d, J_C–F = 3.3 Hz), ppm.

9-(2-(Phenylethynyl)phenyl)-9H-carbazole (3h)

Purification by flash chromatography (petroleum ether): a white solid (149 mg, 87%), mp = 108–109 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.27 (d, J = 8.4 Hz, 2H), 7.87 (dd, J = 8.0 Hz, J = 1.6 Hz, 2H), 7.68–7.54 (m, 3H), 7.51–7.47 (m, 2H), 7.41–7.37 (m, 4H), 7.23–7.12 (m, 3H), 6.71 (dd, J = 8.4 Hz, J = 1.6 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 141.04, 139.13, 133.47, 131.38, 129.50, 129.08, 128.38, 128.16, 128.08, 125.89, 123.48, 123.09, 122.61, 120.32, 119.94, 110.70, 95.57, 86.24, ppm; HRMS (EI): m/z calcd for C₂₆H₁₇N [M]⁺ 343.1361, found 343.1362.

3,6-Di-tert-butyl-9-(4-(phenylethynyl)phenyl)-9H-carbazole (3i)^6a

Purification by flash chromatography (petroleum ether): a white solid (188 mg, 87%), mp = 185–186 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.16 (d, J = 2.0 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.62–7.58 (m, 4H), 7.50 (dd, J = 8.4 Hz, J = 2.0 Hz, 2H), 7.43–7.40 (m, 5H), 1.49 (s, 18H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 143.21, 138.93, 138.13, 133.06, 131.70, 128.46, 126.42, 123.76, 123.61, 123.16, 121.69, 116.33, 109.25, 90.16, 88.86, 34.80, 32.05, ppm.

3-Bromo-9-(4-(phenylethynyl)phenyl)-9H-carbazole (3j)

Purification by flash chromatography (petroleum ether): a white solid (36 mg, 17%), mp = 206–207 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.27 (d, J = 2.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 7.6 Hz, 2H), 7.62–7.53 (m, 5H), 7.48–7.40 (m, 5H), 7.36–7.32 (m, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.92, 139.26, 137.03, 133.21, 131.70, 128.74, 128.58, 128.45, 126.81, 126.80, 125.30, 123.13, 122.95, 122.71, 122.47, 120.62, 120.56, 112.98, 111.24, 109.98, 90.57, 88.48, ppm; HRMS (EI): m/z calcd for C₂₆H₁₆BrN [M]⁺ 421.0466, found 421.0473.

3,6-Dibromo-9-(4-(phenylethynyl)phenyl)-9H-carbazole (3k)

Purification by flash chromatography (petroleum ether): a white solid (13 mg, 5%), mp = 148–149 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.22 (d, J = 2.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.62–7.60 (m, 2H), 7.56–7.51 (m, 4H), 7.43–7.40 (m, 3H), 7.31 (d, J = 8.4 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 139.59, 136.51, 133.31, 131.70, 129.53, 128.65, 128.46, 126.74, 124.13, 123.31, 123.14, 122.85, 113.35, 111.48, 90.80, 88.30, ppm.

2,7-Dibromo-9-(4-(phenylethynyl)phenyl)-9H-carbazole (3l)

Purification by flash chromatography (petroleum ether): a white solid (50 mg, 20%), mp = 228–229 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.97 (d, J = 8.0 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.63–7.61 (m, 2H), 7.53 (d, J = 8.0 Hz, 4H), 7.45 (d, J = 1.6 Hz, 1H), 7.43–7.41 (m, 4H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 141.61, 136.12, 133.45, 131.73, 128.64, 128.46, 126.92, 123.90, 123.47, 122.87, 121.85, 121.54, 120.10, 113.05, 90.92, 88.26, ppm HRMS (EI): m/z calcd for C₂₆H₁₅Br₂N [M]⁺ 498.9571, found 498.9567.

9-(4-(Cyclohex-1-en-1-ylethynyl)phenyl)-9H-carbazole (3m)

Purification by flash chromatography (petroleum ether): a white solid (149 mg, 86%), mp = 150–151 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.17 (d, J = 7.6 Hz, 2H), 7.68 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.45–7.44 (m, 4H), 7.35–7.30 (m, 2H), 6.33–630 (m, 1H), 2.33–2.28 (m, 2H), 2.24–2.19 (m, 2H), 1.78–1.65 (m, 4H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.61, 137.02, 135.73, 132.91, 126.78, 126.01, 123.49, 122.86, 120.63, 120.33, 120.12, 109.75, 92.26, 86.09, 29.23, 25.84, 22.36, 21.53, ppm; HRMS (EI): m/z calcd for C₂₆H₂₁N [M]⁺ 347.1674, found 347.1680.

9-(4-(Cyclohexylethynyl)phenyl)-9H-carbazole (3n)

Purification by flash chromatography (petroleum ether): a white solid (166 mg, 95%), mp = 151–152 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.17 (d, J = 7.6 Hz, 2H), 7.66 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 7.46–7.41 (m, 4H), 7.34–7.30 (m, 2H), 2.71–2.65 (m, 1H), 1.98–1.80 (m, 4H), 1.67–1.57 (m, 4H), 1.47–1.38 (m, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.67, 136.75, 133.07, 126.78, 125.99, 123.45, 123.29, 120.33, 120.06, 109.73, 95.61, 79.90, 32.71, 29.74, 25.95, 24.94, ppm; HRMS (EI): m/z calcd for C₂₆H₂₃N [M]⁺ 349.1830, found 349.1839.

9-(4-(Thiophen-3-ylethynyl)phenyl)-9H-carbazole (3o)

Purification by flash chromatography (petroleum ether): a white solid (168 mg, 96%), mp = 158 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.17 (d, J = 7.6 Hz, 2H), 7.77 (d, J = 7.6 Hz, 2H), 7.62–7.58 (m, 3H), 7.48–7.43 (m, 4H), 7.38–7.27 (m, 4H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.56, 137.52, 133.02, 129.89, 128.95, 126.86, 126.06, 125.53, 123.55, 122.23, 122.09, 120.37, 120.21, 109.75, 88.19, 85.46, ppm; HRMS (EI): m/z calcd for C₂₄H₁₅NS [M]⁺ 349.0925, found 349.0923.

9-(4-(Hept-1-yn-1-yl)phenyl)-9H-carbazole (3p)

Purification by flash chromatography (petroleum ether): a white solid (91 mg, 54%), mp = 60–61 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.20 (d, J = 7.6 Hz, 2H), 7.69 (dd, J = 8.4 Hz, J = 2.0 Hz, 2H), 7.55 (dd, J = 8.4 Hz, J = 1.6 Hz, 2H), 7.47 (d, J = 8.0 Hz, 4H), 7.38–7.33 (m, 2H), 2.53 (t, J = 7.2 Hz, 2H), 1.73 (q, J = 6.8 Hz, 2H), 1.59–1.44 (m, 4H), 1.03 (d, J = 7.2 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.72, 136.87, 133.10, 126.84, 126.07, 123.54, 123.31, 120.40, 120.15, 109.80, 91.71, 80.05, 31.27, 28.55, 22.38, 19.56, 14.15, ppm.

Fluoro-4-((4-methoxyphenyl)ethynyl)benzene (3q)¹²

Purification by flash chromatography (petroleum ether): a white solid (167 mg, 74%), mp = 91–92 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.53–7.47 (m, 4H), 7.06 (t, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), ppm.

2-(4-((4-Fluorophenyl)ethynyl)phenyl)acetonitrile (3r)

Purification by flash chromatography (petroleum ether): a white solid (66 mg, 28%), mp = 94–95 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.56–7.52 (m, 4H), 7.35 (d, J = 8.0 Hz, 2H), 7.08 (t, J = 8.8 Hz, 2H), 3.80 (s, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.63 (d, J_C–F = 248.5 Hz), 133.54 (d, J_C–F = 8.3 Hz), 132.23, 129.90, 127.99, 123.4, 119.03 (d, J_C–F = 34.6 Hz), 117.40, 115.72 (d, J_C–F = 22.1 Hz), 89.17, 88.14, 23.60, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −110.52, ppm.

Methyl 4-((4-fluorophenyl)ethynyl)benzoate (3s)¹³

Purification by flash chromatography (petroleum ether): a white solid (134 mg, 53%), mp = 104–105 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.04 (d, J = 8.0 Hz, 2H), 7.61–7.53 (m, 4H), 7.09 (t, J = 8.8 Hz, 2H), 3.95 (s, 3H), ppm.

9-(3′-Fluoro-[1,1′-biphenyl]-3-yl)-9H-carbazole (4a)

Purification by flash chromatography (petroleum ether): a white solid (94 mg, 56%), mp = 128–129 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.21 (dd, J = 8.0 Hz, J = 1.2 Hz, 2H), 7.83 (s, 1H), 7.74–7.70 (m, 2H), 7.65–7.61 (m, 1H), 7.52–7.45 (m, 6H), 7.40–7.33 (m, 3H), 7.16–7.09 (m, 1H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 163.27 (d, J_C–F = 244.6 Hz), 142.38 (d, J_C–F = 7.6 Hz), 141.86 (d, J_C–F = 2.2 Hz), 140.85, 138.40, 130.54, 130.46, 126.43, 126.09, 126.07, 125.72, 123.49, 122.83 (d, J_C–F = 2.8 Hz), 120.42, 120.10, 114.70 (d, J_C–F = 21.0 Hz), 114.12 (d, J_C–F = 22.0 Hz), 109.76, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −112.58, ppm; HRMS (MALDI): m/z calcd for C₂₄H₁₆FN [M]⁺ 337.1261, found 337.1263.

9-(2′-Fluoro-[1,1′-biphenyl]-2-yl)-9H-carbazole (4b)

Purification by flash chromatography (petroleum ether): a colorless oil (32 mg, 19%); ¹H NMR (400 MHz, CDCl₃): δ 8.05 (d, J = 8.0 Hz, 2H), 7.72–7.68 (m, 1H), 7.65–7.56 (m, 3H), 7.35–7.30 (m, 2H), 7.23–7.16 (m, 4H), 7.02–6.96 (m, 1H), 6.89–6.83 (m, 2H), 6.69–6.65 (m, 1H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 159.11 (d, J_C–F = 245.3 Hz), 141.19, 135.83, 135.14, 132.46 (d, J_C–F = 2.1 Hz), 130.22 (d, J_C–F = 3.1 Hz), 129.59, 129.46, 129.33 (d, J_C–F = 8.2 Hz), 128.28, 125.64, 123.58 (d, J_C–F = 3.6 Hz), 123.05, 120.00, 119.53, 115.51 (d, J_C–F = 22.1 Hz), 109.85, 109.84; ¹⁹F NMR (376 MHz, CDCl₃): δ −116.28, ppm; HRMS (MALDI): m/z calcd for C₂₄H₁₆FN [M]⁺ 337.1261, found 337.1263.

3,6-Di-tert-butyl-9-(4′-fluoro-[1,1′-biphenyl]-4-yl)-9H-carbazole (4c)

Purification by flash chromatography (petroleum ether): a white solid (63 mg, 28%), mp = 192 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.18 (d, J = 1.6 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.69–7.64 (m, 4H), 7.50 (dd, J = 8.8 Hz, J = 2.0 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.21 (t, J = 8.4 Hz, 2H), 1.50 (s, 18H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 142.94, 139.18, 138.76, 137.41, 136.50 (d, J_C–F = 3.1 Hz), 128.68 (d, J_C–F = 8.0 Hz), 128.26 (d, J_C–F = 0.6 Hz), 126.98, 123.63, 123.43, 116.27, 115.82 (d, J_C–F = 21.3 Hz), 109.22, 34.76, 32.03, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −115.29, ppm; HRMS (EI): m/z calcd for C₃₂H₃₂FN [M]⁺ 449.2519, found 449.2528.

3-Bromo-9-(4′-fluoro-[1,1′-biphenyl]-4-yl)-9H-carbazole (4d)

Purification by flash chromatography (petroleum ether): a white solid (89 mg, 43%), mp = 189–190 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.29 (d, J = 2.0 Hz, 1H), 8.13 (d, J = 7.6 Hz, 1H), 7.79 (d, J = 8.8 Hz, 2H), 7.68–7.61 (m, 4H), 7.53 (dd, J = 8.8 Hz, J = 2.0 Hz, 1H), 7.48–7.47 (m, 2H), 7.36–7.32 (m, 2H), 7.22 (t, J = 8.8 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.74 (d, J_C–F = 145.7 Hz), 141.18, 139.69, 139.52, 136.40, 136.26 (d, J_C–F = 3.3 Hz), 128.79, 128.68 (d, J_C–F = 4.4 Hz), 128.50, 127.33, 126.73, 125.19, 123.10, 122.37, 120.49 (d, J_C–F = 9.9 Hz), 116.02, 115.81, 112.79, 111.29, 110.04, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −114.87, ppm; HRMS (EI): m/z calcd for C₂₄H₁₅BrFN [M]⁺ 415.0372, found 415.0374.

3,6-Dibromo-9-(4′-fluoro-[1,1′-biphenyl]-4-yl)-9H-carbazole (4e)

Purification by flash chromatography (petroleum ether): a white solid (111 mg, 45%), mp = 217 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.22 (d, J = 2.0 Hz, 2H), 7.78 (d, J = 8.8 Hz, 2H), 7.67–7.64 (m, 2H), 7.58–7.53 (m, 4H), 7.32 (d, J = 8.8 Hz, 2H), 7.22 (d, J = 8.8 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.78 (d, J_C–F = 245.9 Hz), 140.04, 139.83, 136.10 (d, J_C–F = 3.3 Hz), 135.91, 129.45, 128.76 (d, J_C–F = 8.1 Hz), 128.61, 127.25, 124.02, 123.27, 115.96 (d, J_C–F = 21.5 Hz), 113.17, 111.53, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −114.65, ppm; HRMS (EI): m/z calcd for C₂₄H₁₄Br₂FN [M]⁺ 492.9477, found 492.9474.

2,7-Dibromo-9-(4′-fluoro-[1,1′-biphenyl]-4-yl)-9H-carbazole (4f)

Purification by flash chromatography (petroleum ether): a white solid (97 mg, 39%), mp = 172–173 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.98 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.69–7.66 (m, 2H), 7.60–7.56 (m, 4H), 7.44 (dd, J = 8.4 Hz, J = 2.0 Hz, 2H), 7.23 (t, J = 8.4 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.81 (d, J_C–F = 245.8 Hz), 141.86, 140.36, 136.12 (d, J_C–F = 3.3 Hz), 135.53, 128.86, 128.78 (d, J_C–F = 1.0 Hz), 127.42, 123.72, 121.76, 121.52, 120.05, 115.96 (d, J_C–F = 21.4 Hz), 113.07, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −114.68, ppm; HRMS (EI): m/z calcd for C₂₄H₁₄Br₂FN [M]⁺ 492.9477, found 492.9474.

9-(4′-Fluoro-[1,1′-biphenyl]-4-yl)-3-nitro-9H-carbazole (4g)

Purification by flash chromatography (petroleum ether): a yellow solid (92 mg, 48%), mp = 189 °C; ¹H NMR (400 MHz, CDCl₃): δ 9.12 (d, J = 2.4 Hz, 1H), 8.37 (dd, J = 9.2 Hz, J = 2.4 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.9 Hz, 2H), 7.70–7.63 (m, 4H), 7.50–7.43 (m, 4H), 7.24 (t, J = 8.8 Hz, 2H), ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.86 (d, J_C–F = 246.1 Hz), 143.93, 142.33, 141.50, 140.64, 136.00 (d, J_C–F = 4.0 Hz), 135.44, 128.82 (d, J_C–F = 8.1 Hz), 128.76, 127.70, 127.47, 123.21, 123.09, 121.88, 121.68, 120.98, 117.34, 116.12, 115.96 (d, J_C–F = 21.4 Hz), 110.71, 109.57, ppm; ¹⁹F NMR (376 MHz, CDCl₃): δ −114.47, ppm.

Conclusions

We developed a series of efficient one-pot N-arylation and Pd-catalysed cross-coupling procedures to produce a carbazole-based skeleton with good yields and high selectivity. The carbazole-based skeleton contained biphenyl and diarylacetylene cores. A wide range of functional groups, including aryl acetylene, boronic acid, and fluorinated iodobenzene, are compatible under the developed one-pot reaction conditions. The use of metal-free N-arylation is the key starting reaction to form iodinated N-arylcarbazole which is not isolated, but subjected to further structure elongation. N-Arylation and Pd-catalysed Sonogashira coupling via a one-pot process was successfully obtained in contrast to N-arylation and Pd-catalysed Suzuki or Ullmann coupling. The Pd-catalyst activated the C–I bond of fluorinated iodobenzene to decrease reaction selectivity, which is responsible for the poor results. The competing reaction showed that N-arylation and Pd-catalysed Sonogashira coupling was superior among the one-pot four-compound processes.

Acknowledgements

The authors thank the financial support from the National Natural Science Foundation of China (grant number 21466033).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra26698j

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