Nickel catalyzed intramolecular oxidative coupling: synthesis of 3-aryl benzofurans

Abstract

Recent research has been focused on the transition metal-catalyzed reactions. Herein we have developed nickel-catalyzed synthesis of 3-aryl benzofurans from ortho-alkenyl phenols via intramolecular dehydrogenative coupling. Notably, simple O₂ gas served as an oxidant, without using any sacrificial hydrogen acceptor. The strategy enabled the synthesis of 3-aryl benzofurans in good to excellent yields.

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Introduction

Benzofuran is a heterocyclic compound made up of benzene ring fused with a furan ring and a prominent structural motif that constitutes naturally occurring compounds, pharmaceuticals, photosensitizers and molecules of biological relevance.^1–3 Some of the biologically active compounds containing benzofuran skeleton are fused tricyclic compound (R7000) I, furomollugin II, amiodarone III, Iantheran A IV, viniferifuran V and pterolinus A VI (Fig. 1).³

Fig. 1 Representative examples of benzofurans of biological relevance.

Due to their wide occurrence and interesting biological properties, numerous reports have disclosed the synthesis of benzofurans.^4–22 In this context, most of the reports mainly centered on the synthesis of 2,3-diaryl benzofurans, either via intermolecular annulation of ortho-halophenols with olefins or via intramolecular annulation of ortho-vinyl phenols promoted by Lewis acids/oxidants/some strong acids/bases.^5–9 All of them require stoichiometric amounts of acid/oxidant/base. Arcadi et al. described a first palladium-catalyzed synthesis of 2,3-diaryl benzofuran via intramolecular cyclization of ortho-alkynes substituted phenols.^6a Subsequently, a reasonable number of reports have appeared on the synthesis of 2,3-diarlybenzofurans using transition metal catalysts like Au, Ir, Rh, Cu, Pd and Fe etc.¹⁰ The best synthetic route to accomplish benzofuran could be the intramolecular cyclization from ortho-alkenyl phenol, unfortunately, this protocol requires a stoichiometric amount of sacrificial hydrogen acceptor-like DDQ.^8b Notably, recently, the oxidative C–H functionalization of ortho-alkenyl phenols to generate benzofurans has been accomplished using some transition metals without the need of any sacrificing hydrogen acceptor.^9,22b,22d Most of the earlier reports are devoted to the formation of 2,3-diaryl benzofurans/2-aryl benzofurans, whereas the synthesis of 3-aryl benzofurans from ortho-alkenyl phenols was scarcely explored.^20,22 Some of the representative examples of the previous study versus the present protocol is described in Scheme 1.

Scheme 1 Representative approaches for the synthesis of 3-aryl benzofurans.^{12,14,20a,20b,22a,22b,22d}

We have been interested in the ambitious catalytic nature of late transition metals.²³ Recently, we have developed a synthesis of 2,3-diaryl benzofuran by using phenols and internal alkynes^11a and also reported a synthesis of 2H/4H-chromenes from phenols with terminal alkynes (aryl/alkyl) using Lewis acidic conditions.^11b With this background of phenols and the alkyne chemistry. We intended to develop nickel catalyzed oxidative cross coupling reactions. Herein, we describe an efficient method to cyclize ortho-alkenyl phenols to give benzofurans facilitated by Ni(acac)₂ and O₂ as an oxidant.

Results and discussion

To begin with, it was contemplated that 3-aryl benzofuran can be achieved from ortho-vinyl phenols using intramolecular oxidative coupling feasible by means of a suitable metal catalyst and an oxidant. The required ortho-vinyl phenols have prepared from the reaction of phenols and terminal arylacetylenes using Friedel–Crafts alkenylation induced by a suitable Lewis acid. With the available ortho-alkenyl phenols, it is set for the optimization study to achieve 3-aryl benzofurans. Thus, initially, ortho-alkenyl phenol 1c was chosen as the model compound for the preparation of 3-aryl benzofuran 2c. Various screening conditions (i.e., by varying ligand, additive, oxidant, reaction time and solvent etc.) have explored to find the best-optimized conditions and the outcomes are summarised in Table 1. To begin with, the reaction was performed with Ni(acac)₂ (5 mol%), 1,10-phenanthroline (10 mol%) and DMF as solvent under inert conditions (nitrogen atmosphere) at 140 °C for 48 h. The expected 3-aryl benzofuran 2c was obtained albeit in moderate yield along with a minor side product (2-hydroxy-5-methylphenyl)(phenyl)methanone 3c (Table 1, entry 1). Even switching to PPh₃ as the ligand, furnished the product 2c in more or less same yield (Table 1, entry 2). Interestingly, under the same reaction conditions (i.e. Table 1, entry 2), but with molecular O₂ as the oxidant, there was a drastic change in the yield of 2c along with the minimal amount of ketone 3c (Table 1, entry 3). However, with additive TEMPO and with PPh₃ under open air at 140 °C for 48 h, improved the yield of 2c to 80% (Table 1, entry 4). Performing the reaction with TEMPO/PPh₃ and under an oxygen atmosphere, gave the product 2c in the same yield but with a reduced amount of time 36 h (Table 1, entry 5). On the other hand, the other additives (DDQ, Oxone, K₂S₂O₈ and TBHP/H₂O, under oxygen atmosphere) in the same solvent DMF were not active improve the yields of 2c (Table 1, entries 6 to 9). The reaction was inferior in solvents, such as H₂O and ortho-xylene, under oxygen atmosphere (Table 1, entries 10 & 11), while in DMSO under an oxygen atmosphere, gave 2c in 70% yield (Table 1, entry 12). To our delight, the reaction in solvent DMA under oxygen atmosphere afforded the product 2c in 81% yield (Table 1, entry 13). When the reaction conducted using 2 mol% of the catalyst Ni(acac)₂, under an oxygen atmosphere, afforded the product 2c but with slightly decreased yield (Table 1, entry 14). Replacing the ligand PPh₃ with 1,10-phenanthroline in the open air and an oxygen atmosphere, gave the product 2c in 64% and 60% yields, respectively (Table 1, entries 15 & 16). The reaction without ligand and additive, under oxygen atmosphere, afforded 2c in 45% moderate yield (Table 1, entry 17). On the other hand, treatment of 1c either with TEMPO or DDQ as additive without ligand and in the open air in CH₃CN as a solvent found to be slightly inferior (Table 1, entries 18 & 19). While using K₂CO₃ as the base instead of additive TEMPO, in the open air and in the presence of oxygen atmosphere showed no progress indicating the importance of TEMPO to initiate the reaction (Table 1, entries 20 & 21). On the other hand, by employing NiCl₂ as a catalyst, only a 50% yield of the product 2c was obtained (Table 1, entry 22). Further, the reaction at reduced temperatures 120 °C and 80 °C, showed little conversion and no conversion, respectively (Table 1, entries 23 & 24).

Table 1 Screening conditions for the formation of 3-aryl benzofurans 2c from 1c^a,e

Entry	Catalyst (mol%)	Ligand (10 mol%)	Additives (mol%)	Oxidant	Solvent (mL)	Time (h)	Temp. (°C)	Yield 2c (%)
a All reactions were carried out using ortho-alkenyl phenol 1c (83 mg, 0.4 mmol), Ni(acac)2 [0.008 mmol (2 mol%) to 0.02 mmol (5 mol%)], ligand (0.04 mmol, 10 mol%).b Reaction was conducted under nitrogen atmosphere.c Very less conversion was observed.d The by-product 3c was formed (up-to 5–20% yields).e Some other volatile by-products also formed along with 2c, which were not isolable.
1	Ni(acac)2 (5)	1,10-Phen	—	—^b	DMF (1.5)	48	140	40^c^,^d
2	Ni(acac)2 (5)	PPh3	—	—^b	DMF (1.5)	36	140	42
3	Ni(acac)2 (5)	PPh3	—	O2	DMF (1.5)	36	140	70^d
4	Ni(acac)2 (5)	PPh3	TEMPO (10)	Open air	DMF (2)	48	140	80^d
5	Ni(acac)2 (5)	PPh3	TEMPO (10)	O2	DMF (2)	36	140	80^d
6	Ni(acac)2 (5)	PPh3	DDQ (10)	O2	DMF (1.5)	36	140	—^c
7	Ni(acac)2 (5)	PPh3	OXONE (10)	O2	DMF (1.5)	36	140	30^c^,^d
8	Ni(acac)2 (5)	PPh3	K2S2O8 (10)	O2	DMF (1.5)	48	140	34^c^,^d
9	Ni(acac)2 (5)	PPh3	TBHP in H2O (10)	O2	DMF (1.5)	48	140	48^c^,^d
10	Ni(acac)2 (5)	PPh3	TEMPO (10)	O2	H2O (1)	48	140	—^c
11	Ni(acac)2 (5)	PPh3	TEMPO (10)	O2	o-Xylene (1)	36	140	—^c
12	Ni(acac)2 (5)	PPh3	TEMPO (10)	O2	DMSO (1.5)	36	140	70^c
13	Ni(acac)2 (5)	PPh3	TEMPO (10)	O2	DMA (1)	36	140	81^d
14	Ni(acac)2 (2)	PPh3	TEMPO (10)	O2	DMA (1)	36	140	70^d
15	Ni(acac)2 (5)	1,10-Phen	TEMPO (10)	Open air	DMA (1)	36	140	64^d
16	Ni(acac)2 (5)	1,10-Phen	TEMPO (10)	O2	DMA (1)	40	140	60^d
17	Ni(acac)2 (5)	—	—	O2	DMA (1)	40	140	45
18	Ni(acac)2 (5)	—	TEMPO (5)	Open air	CH3CN (2)	72	140	60^d
19	Ni(acac)2 (5)	—	DDQ (5)	Open air	CH3CN (2)	72	140	50^d
20	Ni(acac)2 (5)	PPh3	K2CO3 (2 equiv.)	Open air	DMA (1)	72	140	—^c
21	Ni(acac)2 (5)	PPh3	K2CO3 (2 equiv.)	O2	DMA (1)	72	140	—^c
22	NiCl2 (5)	PPh3	TEMPO (10)	O2	DMA (1)	48	140	50^d^,^e
23	Ni(acac)2 (5)	PPh3	TEMPO (10)	O2	DMA (1)	36	120	30^c
24	Ni(acac)2 (5)	PPh3	TEMPO (10)	O2	DMA (1)	36	80	—^c
18	Ni(acac)2 (5)	—	TEMPO (5)	Open air	CH3CN (2)	72	140	60^d
19	Ni(acac)2 (5)	—	DDQ (5)	Open air	CH3CN (2)	72	140	50^d

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Now to test the scope and applicability of the strategy, best-optimized conditions (Table 1, entry 15) applied to different ortho-alkenyl phenols 1a–w. This protocol was found to be quite successful and afforded the corresponding 3-aryl benzofurans 2a–w, good to very good yields (Table 2). For example, the reaction was amenable with electron-donating groups like Me, Et, OMe substituents on phenol moiety of ortho-alkenyl phenols (Table 2). The reaction also found smooth with the α-naphthol, β-naphthol, and 6-bromo-2-naphthol derived alkenols (Table 2). Moreover, the reaction was obedient with the electron donating (Me and OMe) and the partial electron withdrawing substituents (F and Br) on the ring of terminal alkynes of ortho-alkenyl phenols (Table 2). All synthesized 3-aryl benzofurans 2a–w, are characterized by spectrometric data (¹H-NMR and ¹³C-NMR and Mass Spectrometry) and also with the earlier literature. However, it is essential to note that even alkenylation reaction did not proceed when electron withdrawing groups such as CHO and NO₂ flanked to the phenol moiety. And it can be justified based on the fact that electron withdrawing functional groups retard the Friedel–Crafts alkylation/alkenylation reactions. Similarly, the attempt made to synthesis ortho-alkenyl phenols were not successful with meta-amino functionality on the aromatic ring of the alkyne. This could be due to the more reactive nature of the amino group under Lewis acid conditions. Moreover, aliphatic alkynes could not make compatible to give ortho-alkenylation products as well.

Table 2 Scope for the formation of 3-aryl benzofurans 2a–w^a,b

a Reactions were carried out using ortho-alkenyl phenols 1a–w (79.0–110.0 mg, 0.4 mmol), Ni(acac)₂ (5.2 mg, 0.02 mmol, 5 mol%), PPh₃ (10.5 mg, 0.04 mmol, 10 mol%), TEMPO (6.5 mg, 0.04 mmol) at 140 °C under oxygen atmosphere.b Yields in the parenthesis are isolated yields of products.

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Plausible mechanism

Though the exact mechanism is not very certain at this stage, based on the present observations and literature reports,^12,20,23 we have attempted to propose a plausible reaction mechanism as depicted in Scheme 2. Initially, Ni(II) could combine with phosphine ligand PPh₃ converted into its reduced Ni(0)-catalyst, which may act as an active catalyst. On the other hand, in an independent path, ortho-alkenyl phenol 1 would be transformed into its oxy-radical A under probable catalytic oxidative conditions of TEMPO/O₂ system. Now coupling of oxy-radical A with Ni(0)-catalyst would lead to the formation of intermediate B. Subsequently, intramolecular π-complexation with olefinic double bond followed by olefinic C–H activation could generate a six-membered oxa-nickelacycle C via the removal of H-radical. Finally, reductive elimination of catalyst from C gives 3-aryl benzofuran 2 and regenerates the Ni(0)-catalyst. Thus, completes the catalytic cycle.

Scheme 2 Plausible mechanism for the formation of 3-aryl benzofurans 2 from 1.

Conclusion

In summary, we have established a nickel-catalyzed synthesis of 3-aryl benzofurans via intramolecular oxidative cyclization of ortho-alkenyl phenols. Notably, simple oxygen served as the sole oxidant and precludes the use of sacrificial hydrogen acceptor. This methodology found viable for accomplishing several different 3-arylbenzofuran derivatives in good to very good yields.

Experimental section

IR spectra recorded on a Bruker Tensor 37 (FT-IR) spectrophotometer. ¹H-NMR spectra recorded on Bruker Avance 400 (400 MHz) spectrometer at 295 K in CDCl₃; chemical shifts (δ in ppm) and coupling constants (J in Hz) reported in standard fashion with reference to either internal standard tetramethylsilane (TMS) (δ_H = 0.00 ppm) or CHCl₃ (δ_H = 7.25 ppm). ¹³C-NMR spectra recorded on Bruker Avance 400 (100 MHz) spectrometer at RT in CDCl₃; chemical shifts (δ in ppm) are reported relative to CDCl₃ [δ_C = 77.00 ppm (central line of the triplet)]. In the ¹³C-NMR, the nature of carbons (C, CH, CH₂ and CH₃) was determined by recording the DEPT-135 spectra, and is given in parentheses and noted as s = singlet (for C), d = doublet (for CH), t = triplet (for CH₂) and q = quartet (for CH₃). In the ¹H-NMR, the following abbreviations were used throughout: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. The assignment of signals confirmed by ¹H, ¹³C CPD and DEPT spectra. High-resolution mass spectra (HR-MS) were recorded on an Agilent 6538 UHD Q-TOF using multimode source. Reactions were monitored by TLC on silica gel coated on alumina plate or glass plate using a mixture of petroleum ether and ethyl acetate as eluents. Reactions carried out under oxygen atmosphere.

Materials

All solvents distilled before using; petroleum ether with a boiling range of 60 to 80 °C, dichloromethane (DCM), ethyl acetate, dry DMA (boiling range 160 to 170 °C; with purity 99%) were purchased from Sigma Aldrich & locally available commercial sources used. Acme's silica gel (100–200 mesh) used for column chromatography.

GP (general procedure for the synthesis of 3-aryl benzofurans)

To an oven dry Schlenk tube was equipped with a magnetic stir bar, were added Ni(acac)₂ (5.2 mg, 0.02 mmol), PPh₃ (10.5 mg, 0.04 mmol), TEMPO (6.3 mg, 0.04 mmol), ortho-alkenyl phenols 1a–w (79–110.0 mg, 0.4 mmol), and DMA (1 mL). Then a balloon filled with O₂ was attached to the Schlenk tube. The reaction mixture stirred at 140 °C for 24 to 36 h. TLC monitored the progress of the reaction. The reaction mixture was then cooled to room temperature and extracted by using ethyl acetate (3 × 20 mL). The organic layers were washed with saturated NH₄Cl solution, dried by Na₂SO₄ and then filtered. Evaporation of the solvent(s) under reduced pressure and refinement of the crude mixture by silica gel column chromatography (petroleum ether/ethyl acetate), gave the 3-aryl benzofurans (68–88%) as semi-solid or liquid.

5-Ethyl-3-phenylbenzofuran (2d).
GP was carried out with 1d (89 mg, 0.4 mmol) using Ni(acac)₂ (5.2 mg, 0.02 mmol), PPh₃ (10.5 mg, 0.04 mmol), TEMPO (6.3 mg, 0.04 mmol) and allowed the reaction mixture to stirred at 140 °C for 36 h for the product 2d formation. Purification of the crude material by silica gel column chromatography (petroleum ether/ethyl acetate, 100 to 99 : 01), furnished the product 2d (71 mg, 80%) as pale yellow viscous liquid. [TLC control (petroleum ether/ethyl acetate 99 : 01), R_f(1d) = 0.10, R_f(2d) = 0.60, UV detection]. ¹H NMR (CDCl₃, 400 MHz): δ = 7.77 (s, 1H, Ar–O–CH), 7.70–7.57 (m, 3H, Ar–H), 7.56–7.44 (m, 3H, Ar–H), 7.43–7.28 (m, 1H, Ar–H), 7.27–7.13 (m, 1H, Ar–H), 2.79 (q, 2H, J = 7.6 Hz, Ar–CH₂CH₃), 1.31 (t, 3H, J = 7.6 Hz, Ar–CH₂CH₃) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 154.3 (s, Ar–C), 141.5 (d, Ar–O–CH), 139.2 (s, Ar–C), 132.3 (s, Ar–C), 128.9 (d, 2C, 2 × Ar–CH), 127.5 (d, 2C, 2 × Ar–CH), 127.3 (d, Ar–CH), 126.5 (s, Ar–C), 124.8 (d, Ar–CH), 122.1 (s, Ar–C), 119.0 (d, Ar–CH), 111.4 (d, Ar–CH), 29.01 (t, Ar–CH₂), 16.44 (q, Ar–CH₂–CH₃) ppm. HR-MS (ESI⁺) m/z calculated for [C₁₆H₁₄OK]⁺ = [M + K]⁺: 261.0676; found 261.0859.

4,6-Dimethyl-3-phenylbenzofuran (2f).
GP was carried out with 1f (89 mg, 0.4 mmol) using Ni(acac)₂ (5.2 mg, 0.02 mmol), PPh₃ (10.5 mg, 0.04 mmol), TEMPO (6.3 mg, 0.04 mmol) and allowed the reaction mixture to stirred at 140 °C for 36 h for the product 2f formation. Purification of the crude material by silica gel column chromatography (petroleum ether/ethyl acetate, 100 to 99 : 01), furnished the product 2f (60 mg, 68%) as pale yellow viscous liquid. [TLC control (petroleum ether/ethyl acetate 99 : 01), R_f(1f) = 0.10, R_f(2f) = 0.60, UV detection]. ¹H NMR (CDCl₃, 400 MHz): δ = 7.47 (s, 1H, Ar–O–CH), 7.46–7.30 (m, 5H, Ar–H), 7.19 (s, 1H, Ar–H), 6.84 (s, 1H, Ar–H), 2.44 (s, 3H, CH₃), 2.21 (s, 3H, CH₃) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 155.9 (s, Ar–C), 141.4 (d, Ar–O–CH), 134.6 (s, Ar–C), 133.1 (s, Ar–C), 131.4 (s, Ar–C), 130.1 (d, 2C, 2 × Ar–CH), 128.0 (s, 2C, Ar–CH), 127.4 (d, Ar–CH), 125.9 (d, Ar–CH), 123.5 (s, Ar–C), 123.2 (s, 1Ar–C), 109.4 (d, Ar–CH), 21.4 (q, CH₃) 19.7 (q, CH₃) ppm. HR-MS (ESI⁺) m/z calculated for [C₁₆H₁₈OFN]⁺ = [M + NH₄]⁺: 240.1383; found 240.2062.

5-Fluoro-3-(p-tolyl)benzofuran (2n).
GP was carried out with 1n (90 mg, 0.4 mmol) using Ni(acac)₂ (5.2 mg, 0.02 mmol), PPh₃ (10.5 mg, 0.04 mmol), TEMPO (6.3 mg, 0.04 mmol) and allowed the reaction mixture to stirred at 140 °C for 36 h for the product 2n formation. Purification of the crude material by silica gel column chromatography (petroleum ether/ethyl acetate, 100 to 99 : 01), furnished the product 2n (68 mg, 75%) as pale yellow viscous liquid. [TLC control (petroleum ether/ethyl acetate 99 : 01), R_f(1n) = 0.10, R_f(2n) = 0.60, UV detection]. ¹H NMR (CDCl₃, 400 MHz): δ = 7.78 (s, 1H, Ar–O–CH), 7.54–7.41 (m, 4H, Ar–H), 7.28 (d, 2H, J = 7.8 Hz, Ar–H), 7.05 (td, 1H, J = 9.1, 2.45 Hz, Ar–H), 2.41 (s, 3H, Ar–CH₃) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 160.6 (s, Ar–C), 158.3 (s, Ar–C), 152.0 (s, Ar–C), 142.7 (d, Ar–O–CH), 137.5 (s, Ar–C), 129.8 (d, 2C, 2 × Ar–CH), 128.5 (s, Ar–C), 127.5 (s, Ar–C), 127.4 (s, Ar–C) 127.2 (d, 2C, 2 × Ar–CH), 122.5 (s, Ar–C), 122.4 (s, Ar–C), 112.4 (d, Ar–CH), 112.3 (d, Ar–CH), 112.1 (d, Ar–CH), 106.2 (d, Ar–CH), 105.9 (d, Ar–CH), 21.23 (q, Ar–CH₃) ppm. HR-MS (ESI⁺) m/z calculated for [C₁₅H₁₀F]⁺ = [(M + H) + (–H₂O)]⁺: 209.0761; found 209.0765.

5-Methyl-3-(m-tolyl)benzofuran (2q).
GP was carried out with 1q (89 mg, 0.4 mmol) using Ni(acac)₂ (5.2 mg, 0.02 mmol), PPh₃ (10.5 mg, 0.04 mmol), TEMPO (6.3 mg, 0.04 mmol) and allowed the reaction mixture to stirred at 140 °C for 36 h for the product 2q formation. Purification of the crude material by silica gel column chromatography (petroleum ether/ethyl acetate, 100 to 99 : 01), furnished the product 2q (70 mg, 79%) as pale yellow viscous liquid. [TLC control (petroleum ether/ethyl acetate 99 : 01), R_f(1q) = 0.10, R_f(2q) = 0.60, UV detection]. ¹H NMR (400 MHz, CDCl₃): δ = 7.73 (s, 1H Ar–O–CH), 7.61 (s, 1H, Ar–H), 7.47–7.33 (m, 4H, Ar–H), 7.23–7.08 (m, 2H, Ar–H), 2.47 (s, 3H, Ar–CH₃), 2.44 (s, 3H, Ar–CH₃) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 154.2 (s, Ar–C), 141.4 (d, Ar–O–CH), 138.6 (s, Ar–C), 132.4 (s, Ar–C), 132.1 (s, Ar–C), 128.8 (d, Ar–CH), 128.2 (d, Ar–CH), 128.1 (d, Ar–CH), 126.6 (s, Ar–C), 125.7 (d, Ar–CH), 124.6 (d, Ar–CH), 122.0 (s, Ar–C), 120.2 (d, Ar–CH), 111.2 (d, Ar–CH), 21.5 (q, Ar–CH₃), 21.5 (q, Ar–CH₃) ppm. HR-MS (ESI⁺) m/z calculated for [C₁₆H₁₈NO]⁺ = [M + NH₄]⁺: 240.1383; found 240.1373.

5-Ethyl-3-(m-tolyl)benzofuran (2r).
GP was carried out with 1r (94 mg, 0.4 mmol) using Ni(acac)₂ (5.2 mg, 0.02 mmol), PPh₃ (10.5 mg, 0.04 mmol), TEMPO (6.3 mg, 0.04 mmol) and allowed the reaction mixture to stirred at 140 °C for 36 h for the product 2r formation. Purification of the crude material by silica gel column chromatography (petroleum ether/ethyl acetate, 100 to 99 : 01), furnished the product 2r (71 mg, 76%) as pale yellow viscous liquid. [TLC control (petroleum ether/ethyl acetate 99 : 01), R_f(1r) = 0.10, R_f(2r) = 0.60, UV detection]. ¹H NMR (400 MHz, CDCl₃): δ = 7.74 (s, 1H, Ar–O–CH), 7.62 (d, 1H, J = 0.1 Hz, Ar–H), 7.51–7.41 (m, 3H, Ar–H), 7.39–7.33 (m, 1H, Ar–H), 7.21–7.15 (m, 2H, Ar–H), 2.77 (q, 2H, J = 7.3 Hz, Ar–CH₂CH₃), 2.44 (s, 3H, CH₃), 1.28 (t, 3H, J = 7.6 Hz, Ar–CH₂CH₃) ppm. ¹³C NMR (CDCl₃, 100 MHz): δ = 154.3 (s, Ar–C), 141.5 (d, Ar–O–CH), 139.1 (s, Ar–C), 138.6 (s, Ar–C), 132.2 (s, Ar–C), 128.8 (d, Ar–CH), 128.2 (d, Ar–CH), 128.2 (d, Ar–CH), 126.6 (s, Ar–C), 124.7 (d, Ar–CH), 124.6 (d, Ar–CH), 122.2 (s, Ar–C), 119.0 (d, Ar–C), 111.3 (d, Ar–C), 29.0 (t, CH₂), 21.5 (q, CH₃), 16.5 (q, CH₃) ppm. HR-MS (ESI⁺) m/z calculated for [C₁₇H₁₉NO]⁺ = [M + NH₄]⁺: 253.1461; found: 254.2219.

3-(3-Fluorophenyl)-5-methoxybenzofuran (2t).
GP was carried out with 1t (98 mg, 0.4 mmol) using Ni(acac)₂ (5.2 mg, 0.02 mmol), PPh₃ (10.5 mg, 0.04 mmol), TEMPO (6.3 mg, 0.04 mmol) and allowed the reaction mixture to stirred at 140 °C for 24 h for the product 2t formation. Purification of the crude material by silica gel column chromatography (petroleum ether/ethyl acetate, 100 to 99 : 01), furnished the product 2t (74 mg, 75%) as pale yellow viscous liquid. [TLC control (petroleum ether/ethyl acetate 99 : 01), R_f(1t) = 0.10, R_f(2t) = 0.60, UV detection]. ¹H NMR (400 MHz, CDCl₃) δ = 7.77 (s, 1H, Ar–O–CH), 7.49–7.43 (m, 2H, Ar–H), 7.41 (dd, J = 3.4, 1.9 Hz, 1H, Ar–H), 7.32 (ddd, J = 9.8, 2.4, 1.6 Hz, 1H, Ar–H), 7.24 (d, J = 2.6 Hz, 1H, Ar–H), 7.11–7.03 (m, 1H, Ar–H), 6.98 (dd, J = 8.9, 2.6 Hz, 1H, Ar–H), 3.88 (s, 3H, OCH₃) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 163.2 (d, J_c–f = 294 Hz, Ar–CF), 156.38 (s, Ar–C), 150.76 (s, Ar–C), 142.57 (d, Ar–CH), 134.3 (d, J_c–f = 8 Hz, Ar–C), 130.5 (d, J_c–f = 9 Hz, Ar–CH), 126.57 (s, Ar–C), 123.02 (d, J_c–f = 2 Hz, Ar–CH), 121.4 (s, Ar–C), 114.2 (d, J_c–f = 21 Hz, Ar–CH), 114.2 (d, J_c–f = 21 Hz, Ar–CH), 113.50 (d, Ar–CH), 112.31 (d, Ar–CH), 102.65 (d, Ar–CH), 56.03 (q, OCH₃) ppm. HR-MS (ESI⁺) m/z calculated for [C₁₅H₁₃FKO₃]⁺ = [(M + K) + (–H₂O)]⁺: 263.0269; found 263.0273.

1-(3-Fluorophenyl)naphtho[2,1-b]furan (2u).
GP was carried out with 1u (105 mg, 0.4 mmol) using Ni(acac)₂ (5.2 mg, 0.02 mmol), PPh₃ (10.5 mg, 0.04 mmol), TEMPO (6.3 mg, 0.04 mmol) and allowed the reaction mixture to stirred at 140 °C for 24 h for the product 2u formation. Purification of the crude material by silica gel column chromatography (petroleum ether/ethyl acetate, 100 to 99 : 01), furnished the product 2u (82 mg, 88%) as pale yellow viscous liquid. [TLC control (petroleum ether/ethyl acetate 99 : 01), R_f(1u) = 0.10, R_f(2u) = 0.60, UV detection]. ¹H NMR (400 MHz, CDCl₃) δ = 7.86 (d, J = 8.2 Hz, 1H, Ar–H), 7.80 (d, J = 8.0 Hz, 1H, Ar–H), 7.63 (d, J = 9.0 Hz, 1H, Ar–H), 7.55 (d, J = 9.8 Hz, 2H, Ar–H), 7.37–7.29 (m, 2H, Ar–H), 7.25 (t, J = 7.5 Hz, 2H, Ar–H), 7.18 (d, J = 9.6 Hz, 1H, Ar–H), 7.09–6.98 (m, 1H, Ar–H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ = 162.8 (d, J_c–f = 245 Hz, Ar–C), 153.2 (s, Ar–C), 141.8 (d, Ar–CH), 135.3 (d, J_c–f = 8 Hz, Ar–C), 130.8 (s, Ar–C), 130.0 (d, J_c–f = 9 Hz, Ar–CH), 129.0 (d, Ar–CH), 128.1 (s, Ar–C), 126.1 (d, J_c–f = 5 Hz, Ar–CH), 125.6 (d, J_c–f = 3 Hz, Ar–CH), 124.5 (d, Ar–CH), 123.3 (d, J_c–f = 2 Hz, Ar–C), 123.2 (d, Ar–CH), 120.3 (s, Ar–C), 116.8 (d, J_c–f = 22 Hz, Ar–CH), 114.8 (d, J_c–f = 21 Hz, Ar–CH), 112.6 (d, Ar–CH) ppm. HR-MS (ESI⁺) m/z calculated for [C₁₈H₁₂FO]⁺ = [M + H]⁺: 263.0867; found 263.0862.

Conflicts of interest

There are no conflicts of interest to declare.

Acknowledgements

We are grateful to the Department of Science and Technology-Science and Engineering Research Board (DST-SERB) [No. EMR/2017/005312], New Delhi, for financial support. C. B. S thanks to UGC and D. S thanks to DST-SERB for the research fellowship.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/d0ra03071f

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