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Synthesis 2015; 47(24): 3990-3996
DOI: 10.1055/s-0035-1560268
paper
© Georg Thieme Verlag Stuttgart · New York

Iodine-Mediated, Microwave-Assisted Synthesis of 1-Arylnaphthofurans via Cyclization of 1-(1′-Arylvinyl)-2-naphthols

V. Kameshwara Rao
a   Department of Chemistry, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India   Email: anilkumar@pilani.bits-pilani.ac.in
,
Pinku Kaswan
a   Department of Chemistry, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India   Email: anilkumar@pilani.bits-pilani.ac.in
,
Ganesh M. Shelke
a   Department of Chemistry, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India   Email: anilkumar@pilani.bits-pilani.ac.in
b   Department of Biology and Chemistry, Nipissing University, North Bay, ON, P1B 8L7, Canada
,
Ashley Ryan
b   Department of Biology and Chemistry, Nipissing University, North Bay, ON, P1B 8L7, Canada
,
Mukund Jha
b   Department of Biology and Chemistry, Nipissing University, North Bay, ON, P1B 8L7, Canada
,
Anil Kumar*
a   Department of Chemistry, Birla Institute of Technology and Science, Pilani, 333031 Rajasthan, India   Email: anilkumar@pilani.bits-pilani.ac.in
› Author Affiliations
Further Information

Publication History

Received: 30 June 2015

Accepted after revision: 24 August 2015

Publication Date:
18 September 2015 (online)

 
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Abstract

A metal-free, one-pot, iodine-mediated, microwave-assisted cyclization of 1-(1′-arylvinyl)-2-naphthols (ortho-vinylnaphthols) into 1-arylnaphthofurans is developed. The 1-arylnaphthofurans are isolated in good to excellent yields (65–90%) using two equivalents of iodine in acetonitrile. The reactions proceed via the formation of 1-(2-iodo-1-phenylvinyl)naphthalen-2-ols as intermediates. Overall, the protocol is convenient as the reactions occur smoothly without the requirement of a transition-metal catalyst.


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Key words

iodine-mediated - microwave-assisted - hydroarylation - 1-arylnaphthofurans - one-pot reaction

Benzo[b]furan is an important structural motif frequently found in natural and biologically active synthetic molecules.[2] Derivatives of this fused furan skeleton have been shown to exhibit a wide-spectrum of biological activities such as anti-inflammatory,[3] antitumor,[2] mutagenic,[4] adenosine antagonist XH-14 inhibition[5], and 5-lipoxygenase inhibition.[6] Representative examples of natural and synthetic compounds comprising benzo[b]furan and naphthofuran skeletons include viniferifuran, 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000) and pterolinus A (Figure [1]).[7] As a result of their wide range of bioactivity and their exceptional ability to function as synthetic precursors, continued attention has been devoted toward the development of facile synthetic methods to access these fused furans.

Zoom Image
Figure 1 Representative examples of bioactive benzo[b]furans and naphthofurans

The most widely used approach for their synthesis is via the heterocyclization of 2-alkynylphenols using transition-metal catalysts (Scheme [1]).[8] Another tactic involves base-promoted or transition-metal-catalyzed intramolecular cyclization of vinyl phenols or gem-dihaloolefins, which leads to the formation of 2-halobenzo[b]furans.[9] In addition to these two approaches, a number of different synthetic methods such as cyclodehydration of aryloxyketones using bismuth(III) trifluoromethanesulfonate [Bi(OTf)3], [10] electrophilic iodocyclization of 2-(1-alkynyl)phenols,[11] reactions of 2,3-dibromoprop-1-enes with β-ketoesters and 1,3-diketones in the presence of copper(I) catalysts,[12] cyclization of 2-propargyl phenols,[13] and reactions of arenols with Morita–Baylis–Hillman acetates of nitroalkene[14] have been reported to access this class of molecules. In 2013, we reported a convenient and simple synthesis of 2,3-diarylnaphthofurans from naphthols via sequential hydroarylation/Heck-oxyarylation.[15] However, most of these methods are based mainly on transition-metal-catalyzed reactions.[16] Only a handful of reports are available on metal-free syntheses of these types of heterocycles.[17] For example, in 2006, Zhou’s group[18] reported the iodine-mediated intramolecular cyclization of o-hydroxystilbenes, and later, in 2012, Singh and Wirth[19] developed a procedure for the (di­acetoxyiodo)benzene [PhI(OAc)2] mediated cyclization of o-hydroxystilbenes to give 2-arylbenzofurans (Scheme [1]).

Zoom Image
Scheme 1 Examples of synthetic approaches for the synthesis of fused furans

In continuation of our efforts toward developing methodologies to access naphthofurans,[15] we envisioned that a strategy involving the hydroarylation of naphthols followed by a cyclization step would lead to the formation of the desired­ compounds. Herein, we report our results on the metal-free, iodine-mediated, microwave-assisted synthesis of 1-arylnaphthofurans.

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Scheme 2 Synthesis of 1-vinylnaphthols 3 via the hydroarylation of naphthols

Initially, the hydroarylations of naphthols 1 with terminal alkynes 2 were performed under microwave irradiation using indium(III) trifluoromethanesulfonate [In(OTf)3] (10 mol%) in toluene to generate a series of 1-vinylnaphthols 3 (Scheme [2]).[15] These 1-vinylnaphthols were obtained in good to excellent yields (63–95%). Functional groups such as methoxy, bromine and fluorine were well tolerated under these reaction conditions. The structures of 1-vinylnaphthols 3a–n were ascertained from NMR and mass spectrometric data.

Having synthesized 1-vinylnaphthols 3, attempts were made to carry out the desired heterocyclization using 1-(1-phenylvinyl)naphthalen-2-ol (3a) as a model reactant. To optimize the reaction conditions for the oxidative cyclization, the effects of base, solvent, reaction time and heating method were investigated. As shown in Table [1], microwave irradiation of 3a in acetonitrile for one hour in the presence of iodine and potassium carbonate gave an excellent yield (90%) of the desired cyclized product, 1-phenylnaphtho[2,1-b]furan (4a), whereas conventional heating of the reaction mixture for five hours resulted in only a 57% yield of isolated 4a (Table [1], entries 4 and 3). Screening of bases revealed that potassium carbonate was the most suitable for this heterocyclization (Table [1], entry 4). While cesium carbonate, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) were moderately good bases, triethylamine (Et3N) and piperidine were found to be inferior (Table [1], entries 6–10) for the synthesis of the desired fused furan. Decreasing the time that the reaction mixture was subjected to microwave irradiation resulted in a reduced yield of 4a (Table [1], entry 5). The best yield of 4a was obtained in acetonitrile; the use of other solvents such as toluene, tetrahydrofuran, polyethylene glycol 400 (PEG 400) and N,N-dimethylacetamide (DMAc) resulted in lower yields of 4a (Table [1], entries 11–14).

Table 1 Optimization of the Reaction Conditions for the Cyclization of 3a into 4a a

Entry

Iodine source

Base

Solvent

Time (h)

Yield (%)b

 1

PhI(OAc)2

K2CO3

MeCN

1

NRc

 2

I2

K2CO3

MeCN

4

20d

 3

I2

K2CO3

MeCN

5

57e

 4

I2

K2CO3

MeCN

1

90

 5

I2

K2CO3

MeCN

0.5

61

 6

I2

DBU

MeCN

1

77

 7

I2

Et3N

MeCN

1

NRc

 8

I2

piperidine

MeCN

1

NRc

 9

I2

Cs2CO3

MeCN

1

70

10

I2

TBD

MeCN

1

50

11

I2

K2CO3

toluene

1

30

12

I2

K2CO3

THF

1

70

13

I2

K2CO3

PEG 400

1

59

14

I2

K2CO3

DMAc

1

60

a Reaction conditions: 3a (1.0 mmol), iodine source (2 mmol), base (2.0 mmol), solvent (3 mL), MW (250 W), 120 °C.

b Yield of isolated product.

c NR = no reaction.

d Reaction performed at r.t.

e Conventional heating at reflux temperature.

An attempt to replace iodine with (diacetoxyiodo)benzene was unsuccessful (Table [1], entry 1). It is worth mentioning that in the absence of iodine and potassium carbonate, the cyclization of 3a did not proceed. The structure of 4a was elucidated using 1H and 13C NMR spectroscopic and mass spectrometric data. In the 1H NMR spectrum of 4a, a singlet at δ 7.65 was observed for the proton at C2 along with those of other protons. The proton-decoupled 13C NMR spectrum of 4a showed a signal for the C-2 carbon at δ 141.8. The presence of a peak at m/z 245.0968 corresponding to the C18H13O+ mass ion in the HRMS spectrum of 4a further confirmed the structure.

Having identified optimum reaction conditions, we next studied the scope of this cyclization by using other 1-vinylnaphthols (3b–n) for the synthesis of different 1-arylnaphthofurans. As shown in Table [2], the oxidative cyclization of substituted 1-vinylnaphthols 3b–n proceeded smoothly to give the corresponding 1-substituted naphthofurans 4b–n in good to excellent yields (65–90%). A wide range of functional groups such as methoxy, methyl, fluorine and bromine were tolerated under these conditions. All the cyclized products were characterized by NMR and mass spectrometric data (see the Supporting information). The presence of both electron-donating and electron-withdrawing groups (either R3 or R4) on the 1-vinylnaphthol resulted in good to excellent yields of the corresponding cyclized products.

Table 2 Synthesis of 1-Arylnaphthofuransa

Entry

R3

R4

Product

Yield (%)b

 1

H

H

4a

90

 2

H

4-Me

4b

77

 3

H

4-MeO

4c

81

 4

H

4-F

4d

65

 5

7-MeO

H

4e

71

 6

7-MeO

4-Me

4f

72

 7

7-MeO

4-F

4g

76

 8

6-Br

H

4h

69

 9

6-Br

4-Me

4i

78

10

6-Br

4-MeO

4j

82

11

6-C6H5

H

4k

90

12

6-C6H5

4-Me

4l

86

13

6-(4′-MeO)C6H4

H

4m

87

14

6-(3′,4′-MeO)2C6H3

H

4n

83

a Reaction conditions: 3 (1.0 mmol), I2 (2.0 mmol), K2CO3 (2.0 mmol), MeCN (3 mL), MW (250 W), 120 °C, 1 h.

b Yield of isolated product.

The application of the developed method is not limited to the preparation of 1-arylnaphthofurans as 3-arylbenzo[b]furans can also be synthesized from electron-rich phenols. We thus synthesized 4-methoxy-2-(1-phenylvinyl)phenol (6a) and 4-methoxy-2-[1-(p-tolyl)vinyl]phenol (6b) via the reaction of 4-methoxyphenol (5) with phenyl­acetylene (2a) and 4-methylphenylacetylene (2b), respectively. The reactions of 6a and 6b with iodine in the presence of potassium carbonate under microwave irradiation for 45 minutes gave the corresponding benzo[b]furans, 5-methoxy-3-phenylbenzofuran (7a) and 5-methoxy-3-(p-tolyl)benzofuran (7b) in 75% and 77% yields, respectively (Scheme [3]).

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Scheme 3 Synthesis of 3-arylbenzo[b]furans 7a and 7b

In an attempt to gain insight into the reaction mechanism, several control experiments were performed (Scheme [4]). Unfortunately, we were unable to isolate any intermediates from the microwave-assisted reaction under the optimized conditions. However, 1-(2-iodo-1-phenylvinyl)naphthalen-2-ol (8a) was isolated in 87% yield from the reaction of 3a with iodine (2.5 equiv) in the absence of potassium carbonate under conventional heating for four hours. The structure of 8a was determined by NMR and mass spectrometric data. A characteristic signal due to the vinylic proton appeared at δ 5.20 in the 1H NMR spectrum along with other protons. In the 13C NMR spectrum, the vinylic carbon appeared at δ 86.04. To our delight, 2-arylnaphthofuran 4a was obtained in 89% yield when compound 8a was subjected to microwave irradiation at 120 °C for 45 minutes in the presence of potassium carbonate. Furthermore, compound 4a was obtained in 52% yield when the reaction of 3a was performed in the presence of the radical scavenger, (2,2,6,6-tetramethylpiperdin-1-yl)oxy (TEMPO), suggesting that the reaction proceeds via a non-radical mechanism.

Zoom Image
Scheme 4 Control experiments
Zoom Image
Scheme 5 A proposed reaction pathway

Based on previous reports[18] [19] and the results of the control experiments, the reaction is believed to proceed via vinylic iodination as shown in Scheme [5]. It is expected that insertion of iodine at the vinylic bond produces the three-membered iodonium intermediate A,[20] which on elimination of hydrogen iodide produces 1-(2-iodo-1-phenylvinyl)naphthalen-2-ol (8a). Further cyclization of 8a, followed by elimination of hydrogen iodide gives rise to 1-phenylnaphtho[2,1-b]furan (4a). However, at this stage, the exact mechanism involved in the cyclization of 8a into 4a is not clear.

In conclusion, we have developed a metal-free, one-pot, iodine-mediated, microwave-assisted approach for the synthesis of 1-arylnaphthofurans and 3-arylbenzo[b]furans. The reported method delivers good to high yields (65–90%) of the corresponding cyclized products starting from readily available substrates.

All chemicals were purchased from Spectrochem India Pvt. Ltd, Sigma­-Aldrich, and Alfa Aesar, and were used without further purification. Solvents were purchased from SD Fine (India) and were distilled and dried before use. Reactions were monitored by TLC on silica gel 60 F254 plates (Merck). The products were purified by column chromatography on Merck silica gel (100–200 mesh) using EtOAc–hexane as the eluent. Melting points were determined using an EZ-Melt apparatus. NMR spectra were recorded on Bruker 300 and Bruker 400 spectrometers. HRMS were recorded on an AB SCIEX TOF/TOF 5800 spectrometer. The reactions were carried out in a CEM Discover BenchMate reactor in 10 mL pressure vials at 250 W. Characterization data for compounds 3a–n, 6a,b, and copies of the 1H and 13C NMR data for products 3a–n, 6a,b, 4a–n, 7a,b and 8a are available in the Supporting Information.


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1-Phenylnaphtho[2,1-b]furan (4a); Typical Procedure

To an oven-dried microwave vial (10 mL) were added 1-(1-phenylvinyl)naphthalen-2-ol (3a) (247 mg, 1.0 mmol), I2 (509 mg, 2.0 mmol), K2CO3 (277 mg, 2.0 mmol) and MeCN (2 mL). The mixture was subjected to microwave irradiation (250 W, 30 psi) at 120 °C for 60 min. The reaction mixture was quenched by the addition of Na2S2O3 solution and then extracted with EtOAc (2 × 5 mL). The combined organic layer was dried over anhydrous Na2SO4 and then concentrated under vacuum on a rotatory evaporator. The crude residue was purified by column chromatography over silica gel (4% hexane–EtOAc) to give 2-arylnaphthofuran 4a.

Yield: 221 mg (90%); pale yellow viscous liquid; Rf = 0.68 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 7.99 (d, J = 8.2 Hz, 1 H), 7.91 (d, J = 7.8 Hz, 1 H), 7.77–7.67 (m, 2 H), 7.65 (s, 1 H), 7.59 (dd, J = 7.8, 1.6 Hz, 2 H), 7.52–7.42 (m, 3 H), 7.43–7.30 (m, 2 H).

13C NMR (75 MHz, CDCl3): δ = 153.2, 141.8, 133.2, 130.9, 129.9, 129.0, 128.7, 128.4, 127.9, 126.03, 126.01, 124.5, 124.4, 123.4, 120.8, 112.7.

HRMS (ESI): m/z [M + H]+ calcd for C18H13O: 245.0961; found: 245.0968.


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1-(p-Tolyl)naphtho[2,1-b]furan (4b)

Yield: 199 mg (77%); pale yellow liquid; Rf = 0.67 (10% EtOAc–hexane­).

1H NMR (300 MHz, CDCl3): δ = 7.94 (d, J = 8.2 Hz, 1 H), 7.86–7.80 (m, 1 H), 7.67–7.59 (m, 2 H), 7.55 (s, 1 H), 7.39 (d, J = 8.0 Hz, 2 H), 7.36–7.29 (m, 1 H), 7.29–7.25 (m, 1 H), 7.22 (d, J = 7.8 Hz, 2 H), 2.37 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 153.2, 141.7, 137.7, 130.8, 130.3, 130.1, 129.8, 129.6, 129.4, 128.9, 128.4, 126.0, 125.9, 124.4, 124.3, 123.5, 120.9, 112.7, 21.4.

HRMS (ESI): m/z [M + H]+ calcd for C19H15O: 259.1117; found: 259.1121.


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1-(4-Methoxyphenyl)naphtho[2,1-b]furan (4c)

Yield: 222 mg (81%); brown liquid; Rf = 0.62 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 8.03–7.98 (m, 1 H), 7.92 (dd, J = 8.3, 0.9 Hz, 1 H), 7.77–7.65 (m, 2 H), 7.64 (s, 1 H), 7.54–7.47 (m, 2 H), 7.45–7.39 (m, 1 H), 7.38–7.32 (m, 1 H), 7.07–7.00 (m, 2 H), 3.90 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 159.4, 153.1, 141.6, 131.0, 130.8, 128.9, 128.4, 126.0, 125.8, 125.2, 124.3, 124.0, 123.4, 121.0, 114.1, 112.7, 55.4.

HRMS (ESI): m/z [M + H]+ calcd for C19H15O2: 275.1067; found: 275.1064.


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1-(4-Fluorophenyl)naphtho[2,1-b]furan (4d)

Yield: 171 mg (65%); pale yellow viscous liquid; Rf = 0.66 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 7.93 (t, J = 7.7 Hz, 2 H), 7.77 (d, J = 9.0 Hz, 1 H), 7.70–7.65 (m, 2 H), 7.55 (dd, J = 8.5, 5.5 Hz, 2 H), 7.46–7.27 (m, 2 H), 7.25–7.15 (m, 2 H).

13C NMR (75 MHz, CDCl3): δ = 162.7 (d, J C–F = 246.9 Hz), 153.1, 141.7, 131.5 (d, J C–F = 8.0 Hz), 130.8, 129.0, 128.2, 126.1, 124.4, 123.4, 123.1, 120.7, 115.6 (d, J C–F = 21.5 Hz), 112.7.

HRMS (ESI): m/z [M + H]+ calcd for C18H12FO: 263.0867; found: 263.0868.


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8-Methoxy-1-phenylnaphtho[2,1-b]furan (4e)

Yield: 193 mg (71%); pale yellow solid; mp 78–80 °C; Rf = 0.63 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 7.72 (d, J = 8.9 Hz, 1 H), 7.63–7.50 (m, 4 H), 7.47–7.35 (m, 4 H), 7.19 (d, J = 2.4 Hz, 1 H), 6.98 (dd, J = 8.9, 2.5 Hz, 1 H), 3.47 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 157.8, 153.6, 141.2, 133.2, 130.3, 130.1, 129.5, 128.4, 127.9, 125.71, 125.67, 124.2, 120.1, 116.4, 110.1, 102.9, 54.9.

HRMS (ESI): m/z [M + H]+ calcd for C19H15O2: 275.1067; found: 275.1068.


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8-Methoxy-1-(p-tolyl)naphtho[2,1-b]furan (4f)

Yield: 208 mg (72%); pale yellow solid; mp 118–120 °C; Rf = 0.60 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 7.80 (d, J = 8.9 Hz, 1 H), 7.67 (d, J = 8.9 Hz, 1 H), 7.63 (s, 1 H), 7.57–7.47 (m, 3 H), 7.34 (d, J = 2.6 Hz, 1 H), 7.30 (d, J = 7.8 Hz, 2 H), 7.06 (dd, J = 8.9, 2.6 Hz, 1 H), 3.58 (s, 3 H), 2.44 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 157.7, 153.6, 141.1, 137.6, 130.3, 130.1, 129.9, 129.6, 129.1, 125.7, 125.6, 124.2, 120.2, 116.2, 110.2, 103.1, 55.0, 21.3.

HRMS (ESI): m/z [M + H]+ calcd for C20H17O2: 289.1223; found: 289.1125.


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1-(4-Fluorophenyl)-8-methoxynaphtho[2,1-b]furan (4g)

Yield: 223 mg (76%); viscous liquid; Rf = 0.61 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 7.74 (d, J = 8.9 Hz, 1 H), 7.61 (d, J = 8.9 Hz, 1 H), 7.56 (s, 1 H), 7.53–7.44 (m, 3 H), 7.18–7.08 (m, 3 H), 7.00 (dd, J = 8.9, 2.4 Hz, 1 H), 3.51 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 161.6 (d, J C–F = 247.0 Hz), 156.8, 152.6, 140.2, 130.7 (d, J C–F = 8.0 Hz), 129.3, 128.3, 128.1 (d, J C–F = 3.4 Hz), 124.8, 124.7, 122.1, 118.9, 115.3, 114.4 (d, J C–F = 21.4 Hz), 109.1, 101.7, 53.9.

HRMS (ESI): m/z [M + H]+ calcd for C19H14FO2: 293.0972; found: 293.0965.


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7-Bromo-1-phenylnaphtho[2,1-b]furan (4h)

Yield: 224 mg (69%); pale yellow solid; mp 84–86 °C; Rf = 0.63 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 8.05 (d, J = 1.6 Hz, 1 H), 7.83 (d, J = 8.9 Hz, 1 H), 7.71–7.59 (m, 3 H), 7.57–7.45 (m, 5 H), 7.40 (dd, J = 8.9, 1.8 Hz, 1 H).

13C NMR (75 MHz, CDCl3): δ = 153.2, 142.1, 132.7, 132.2, 130.9, 129.8, 129.2, 128.8, 128.1, 126.8, 125.1, 124.9, 124.3, 120.9, 118.1, 113.8.

HRMS (ESI): m/z [M + H]+ calcd for C18H12 79BrO: 323.0066; found: 323.0068.

HRMS (ESI): m/z [M + H]+ calcd for C18H12 81BrO: 325.0051; found: 325.0049.


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7-Bromo-1-(p-tolyl)naphtho[2,1-b]furan (4i)

Yield: 264 mg (78%); pale green solid; mp 86–88 °C; Rf = 0.66 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 8.08–8.04 (m, 1 H), 7.88 (d, J = 8.9 Hz, 1 H), 7.73–7.61 (m, 3 H), 7.47–7.38 (m, 3 H), 7.31 (d, J = 7.6 Hz, 2 H), 2.47 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 153.1, 142.0, 137.9, 132.1, 130.8, 129.64, 129.59, 129.4, 129.1, 126.9, 125.1, 124.8, 124.2, 121.0, 118.0, 113.7, 21.4.

HRMS (ESI): m/z [M + H]+ calcd for C19H14 79BrO: 337.0223; found: 337.0225.

HRMS (ESI): m/z [M + H]+ calcd for C19H14 81BrO: 339.0208; found: 339.0214.


#

7-Bromo-1-(4-methoxyphenyl)naphtho[2,1-b]furan (4j)

Yield: 290 mg (82%); viscous liquid; Rf = 0.57 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 8.07–8.02 (m, 1 H), 8.00–7.94 (m, 1 H), 7.79–7.73 (m, 1 H), 7.70 (d, J = 5.4 Hz, 1 H), 7.58–7.50 (m, 2 H), 7.50–7.37 (m, 2 H), 7.12–7.04 (m, 2 H), 3.94 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 159.6, 153.2, 141.7, 131.1, 130.9, 129.0, 128.5, 126.1, 125.9, 125.3, 124.4, 124.1, 123.5, 121.1, 114.2, 112.8, 55.5.

HRMS (ESI): m/z [M + H]+ calcd for C19H14 79BrO2: 353.0172; found: 353.0168.

HRMS (ESI): m/z [M + H]+ calcd for C19H14 81BrO2: 355.0157; found: 355.0156.


#

1,7-Diphenylnaphtho[2,1-b]furan (4k)

Yield: 289 mg (90%); pale yellow liquid; Rf = 0.65 (10% EtOAc–hexane).

1H NMR (400 MHz, CDCl3): δ = 8.20 (d, J = 1.8 Hz, 1 H), 8.13 (d, J = 8.7 Hz, 1 H), 7.87 (d, J = 9.0 Hz, 1 H), 7.79 (s, 1 H), 7.77–7.74 (m, 3 H), 7.70 (d, J = 1.7 Hz, 1 H), 7.69–7.67 (m, 1 H), 7.62–7.50 (m, 6 H), 7.45–7.39 (m, 1 H).

13C NMR (101 MHz, CDCl3): δ = 153.3, 141.9, 141.1, 137.1, 133.1, 131.2, 129.9, 128.9, 128.7, 128.0, 127.4, 127.3, 127.3, 126.9, 126.3, 125.6, 124.5, 123.9, 120.7, 113.1.

HRMS (ESI): m/z [M + H]+ calcd for C24H17O: 321.1274; found: 321.1270.


#

7-Phenyl-1-(p-tolyl)naphtho[2,1-b]furan (4l)

Yield 288 mg (86%); viscous liquid; Rf = 0.59 (10% EtOAc–hexane).

1H NMR (400 MHz, CDCl3): δ = 8.21 (d, J = 10.2 Hz, 2 H), 7.88 (d, J = 9.0 Hz, 1 H), 7.80–7.75 (m, 4 H), 7.72 (dd, J = 8.7, 1.6 Hz, 1 H), 7.60 (d, J = 7.9 Hz, 2 H), 7.59–7.48 (m, 2 H), 7.46–7.38 (m, 2 H), 2.57 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 153.3, 141.8, 141.1, 137.7, 137.1, 131.2, 130.0, 129.8, 129.4, 128.9, 127.6, 127.4, 127.3, 126.9, 126.2, 125.5, 124.4, 124.0, 120.9, 113.1, 21.5.

HRMS (ESI): m/z [M + H]+ calcd for C25H19O: 335.1430; found: 335.1426.


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7-(4-Methoxyphenyl)-1-phenylnaphtho[2,1-b]furan (4m)

Yield: 304 mg (87%); pale yellow solid; mp 136–138 °C; Rf = 0.60 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 8.01 (s, 1 H), 7.95 (d, J = 8.7 Hz, 1 H), 7.72 (d, J = 9.0 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 2 H), 7.57–7.49 (m, 5 H), 7.46–7.37 (m, 3 H), 6.92 (d, J = 8.6 Hz, 2 H), 3.78 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 158.1, 152.1, 140.7, 135.7, 132.6, 132.1, 130.2, 128.8, 127.6, 127.2, 126.9, 126.0, 125.12, 125.10, 124.3, 123.4, 122.8, 119.7, 113.3, 112.0, 54.3.

HRMS (ESI): m/z [M + H]+ calcd for C25H19O2: 351.1380; found: 351.1378.


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7-(3,4-Dimethoxyphenyl)-1-phenylnaphtho[2,1-b]furan (4n)

Yield: 316 mg (83%); pale yellow viscous liquid; Rf = 0.56 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 8.09 (s, 1 H), 8.04 (d, J = 8.7 Hz, 1 H), 7.82 (d, J = 9.0 Hz, 1 H), 7.72 (d, J = 9.1 Hz, 2 H), 7.65–7.50 (m, 3 H), 7.51–7.46 (m, 3 H), 7.22 (d, J = 4.0 Hz, 1 H), 6.97 (d, J = 8.2 Hz, 1 H), 5.29 (s, 1 H), 3.97 (s, 3 H), 3.93 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 153.2, 149.3, 148.6, 141.8, 136.9, 134.1, 133.1, 131.2, 129.9, 128.6, 127.9, 127.1, 126.3, 126.1, 125.4, 124.4, 123.8, 120.7, 119.5, 113.1, 111.6, 110.6, 56.01, 55.99.

HRMS (ESI): m/z [M + H]+ calcd for C26H21O3: 381.1485; found: 381.1481.


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5-Methoxy-3-phenylbenzofuran (7a)

Yield: 168 mg (75%); viscous liquid; Rf = 0.43 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 7.67 (s, 1 H), 7.54 (d, J = 7.1 Hz, 2 H), 7.43–7.30 (m, 4 H), 7.19 (d, J = 2.5 Hz, 1 H), 6.88 (dd, J = 8.9, 2.5 Hz, 1 H), 3.78 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 156.3, 150.8, 142.2, 132.2, 129.0, 127.5, 127.4, 127.0, 122.4, 113.3, 112.2, 102.9, 56.0.

HRMS (ESI): m/z [M + H]+ calcd for C15H13O2: 225.0910; found: 225.0907.


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5-Methoxy-3-(p-tolyl)benzofuran (7b)

Yield: 184 mg (77%); viscous liquid; Rf = 0.44 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 7.72 (s, 1 H), 7.51 (d, J = 8.1 Hz, 2 H), 7.42 (d, J = 8.9 Hz, 1 H), 7.31–7.24 (m, 3 H), 6.94 (dd, J = 8.9, 2.6 Hz, 1 H), 3.85 (s, 3 H), 2.41 (s, 3 H).

13C NMR (75 MHz, CDCl3): δ = 156.2, 150.6, 141.9, 137.2, 129.7, 129.2, 127.4, 127.2, 122.3, 113.2, 112.2, 102.9, 56.0, 21.3.

HRMS (ESI): m/z [M + H]+ calcd for C16H15O2: 239.1067; found: 239.1064.


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1-(2-Iodo-1-phenylvinyl)naphthalen-2-ol (8a)

Yield: 332 mg (89%); off-white viscous liquid; Rf = 0.49 (10% EtOAc–hexane).

1H NMR (300 MHz, CDCl3): δ = 7.83 (dd, J = 14.9, 5.6 Hz, 2 H), 7.63 (s, 1 H), 7.50–7.44 (m, 1 H), 7.39–7.22 (m, 8 H), 5.20 (s, 1 H).

13C NMR (75 MHz, CDCl3): δ = 149.4, 146.9, 138.7, 131.5, 130.4, 129.2, 129.0, 128.9, 128.3, 127.1, 126.5, 124.1, 123.7, 121.1, 117.7, 86.0.

HRMS (ESI): m/z [M + H]+ calcd for C18H14IO: 373.0084; found: 373.0082.


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Acknowledgment

The authors gratefully acknowledge the financial support provided by DST-FIST (CSI-174/2008) and the Canada Foundation for Innovation (CFI) to conduct this research. P.K., G.M.S. and V.K.R. thank the Council of Scientific and Industrial Research (CSIR), New Delhi, for senior research fellowships.

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org.accesdistant.sorbonne-universite.fr/10.1055/s-0035-1560268.
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Figure 1 Representative examples of bioactive benzo[b]furans and naphthofurans
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Scheme 1 Examples of synthetic approaches for the synthesis of fused furans
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Scheme 2 Synthesis of 1-vinylnaphthols 3 via the hydroarylation of naphthols
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Scheme 3 Synthesis of 3-arylbenzo[b]furans 7a and 7b
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Scheme 4 Control experiments
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Scheme 5 A proposed reaction pathway