Nickel-Catalyzed Intramolecular Nucleophilic Addition of Aryl Halides to Aryl Ketones for the Synthesis of Benzofuran Derivatives

Abstract

A nickel-catalyzed intramolecular nucleophilic addition reaction of aryl halides to aryl ketones for the formation of benzofuran derivatives has been developed. A number of substrates bearing electron-donating or electron-withdrawing groups were subjected to the standard reaction conditions, giving the corresponding products in moderate to good yields.

Key words

nickel - zinc powder - intramolecular addition - cyclization - benzofuran

Benzofuran moieties are ubiquitous structural skeletons[1] that are present in both natural products and synthetic pharmaceuticals and have remarkable biological and therapeutic activities[2] (Figure 1 [3]). Several synthetic strategies for the construction of benzofuran skeletons from different starting materials have been developed.[4] Phenols have attracted much attention as starting materials (Scheme [1], eq. 1, 2). Among the strategies, transition-metal­-catalyzed cross-coupling reactions have emerged as an alternative and have attracted much attention for their atom and step economy.[5]

Figure 1 Example natural products or drugs containing benzofuran moieties

Scheme 1 Synthetic methods for the construction of benzofurans

The oxidative addition of aromatic or vinyl halides to palladium or nickel salts for the formation of C–C bonds is one of the most efficient strategies in organic synthesis.[6] Well-established methods for the construction of C–C bonds through Pd(0)/Ni(0)-catalyzed cross-coupling include the Kumada–Corriu reaction[7] and the Negishi[8] and Suzuki[8a] [9] couplings. The scope and application of these reactions has been fully explored. These methods have reliable yields and good functional-group tolerance. However, these strategies usually suffer from some drawbacks, including the need for strong bases, multistep processes, and harsh reaction conditions. The synthesis of benzofurans via nickel-catalyzed intramolecular nucleophilic addition has been less explored than other methods. Recently, Huang, Lv, and co-workers have described a highly enantioselective and straightforward nickel-catalyzed protocol to construct chiral 3-hydroxy-2,3-dihydrobenzofurans with high yield, good functional-group tolerance, and excellent enantio­selectivity (Scheme [1], eq. 3).[10] However, the development of a simple and highly efficient nickel-catalyzed intramolecular nucleophilic addition reaction to synthesize benzo­furans remains highly desirable. Herein, we report a simple and convenient protocol for the formation of benzofuran derivatives that is conducted through a nickel-catalyzed intramolecular nucleophilic addition process (Scheme [1]).

Table 1 Screening for Optimal Conditions ^a

Entry	[Ni]	Ligand	Solvent	Yield b
1	Ni(dppp)2Cl2	2,2′-bpy	MeCN	17
2	Ni(dppp)2Cl2	–	MeCN	ND
3	–	–	MeCN	ND
4	Ni(dppp)2Cl2	PCy3	MeCN	ND
5	Ni(dppp)2Cl2	S-Phos	MeCN	ND
6	Ni(dppp)2Cl2	DABCO	MeCN	trace
7	Ni(dppp)2Cl2	1,10-Phen	MeCN	89
8	Ni(dppp)2Cl2	1,10-Phen	MeOH	67
9	Ni(dppp)2Cl2	1,10-Phen	toluene	20
10	Ni(dppp)2Cl2	1,10-Phen	DCE	19
11	Ni(dppp)2Cl2	1,10-Phen	THF	trace
12	Ni(dppp)2Cl2	1,10-Phen	PrCN	50
13	Ni(OTf)2	1,10-Phen	MeCN	90
14	Ni(PPh3)2Br2	1,10-Phen	MeCN	39
15	Ni(cod)2Cl2	1,10-Phen	MeCN	trace
16	NiCl2·6H2O	1,10-Phen	MeCN	72
17 c	Ni(dppp)2Cl2	1,10-Phen	MeCN	69
18 d	Ni(dppp)2Cl2	1,10-Phen	MeCN	trace
19 e	Ni(dppp)2Cl2	1,10-Phen	MeCN	46
20 f	Ni(dppp)2Cl2	1,10-Phen	MeCN	61

^a Reaction conditions: 1a (0.2 mmol), [Ni] (10 mol%), ligand (10 mol%), Zn powder (2 equiv) in solvent (2 mL) under N₂ at 110 °C for 24 h.

^b Isolated yield.

^c At 130 °C.

^d At 80 °C.

^e Zn powder (3 equiv).

^f [Ni] (3 mol%), ligand (6 mol%).

The substrate 2-(2-iodophenoxy)-1-phenylethanone[11] (1a) was chosen to optimize the reaction conditions, and the results are shown in Table [1]. Firstly, in the presence of Ni(dppp)₂Cl₂ (5 mol%), 2,2′-bipyridine (10 mol%), and Zn powder (2 equiv), the product 3-phenylbenzofuran (2a) was isolated in 17% yield under an N₂ atmosphere (Table [1], entry 1). Absence of the ligand or Ni catalyst resulted in no target product being detected by GC-MS analysis (Table [1], entries 2, 3). These results prompted us to pursue more efficient reaction conditions. A series of ligands, including PCy₃, S-Phos (2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl), DABCO (1,4-diazabicyclo[2.2.2]octane), and 1,10-Phen (1,10-phenanthroline), were tested. The results indicated that 1,10-Phen was the most efficient ligand (Table [1], entries 4–7). Subsequently, various solvents, including MeOH, toluene, DCE, THF, and PrCN, were investigated, and MeCN was found to give the best yield (Table [1], entries 7–12). Then, four other nickel catalysts, Ni(OTf)₂, Ni(PPh₃)₂Br₂, Ni(cod)₂Cl₂, and NiCl₂·6H₂O, were examined. The results demonstrated that all of the nickel catalysts had reactivity for the cyclization, with Ni(OTf)₂ and Ni(dppp)₂Cl₂ providing the best yields (Table [1], entries 6, 13–16). The effect of temperature was also evaluated; an increased or decreased reaction temperature reduced the yield of the target product (Table [1], entries 17, 18). Finally, an increase in the loading of Zn powder or decrease in the amount of [Ni] and ligand also decreased the yield of 2a (Table [1], entries 19, 20).

With this optimized procedure in hand, we aimed to expand the scope of the coupling reaction by screening a range of substrates 1; the results are summarized in Table [2]. Initially, the electronic effects of substrates 1 were examined. The results indicated that substrates bearing electron-withdrawing or electron-donating groups were well tolerated in the reaction and produced the corresponding products in moderate to good yields. For example, substrates 1b–1d, possessing electron-donating groups on the ring, were suitable for the cyclization, giving the target products in moderate yields (Table [2], entries 1–3). Similar results were achieved when substrates 1e–1g were employed for this transformation (Table [2], entries 4–6). Use of the sterically hindered substrates 1h and 1i resulted in the corresponding products 2h and 2i being isolated in 54% and 23% yields, respectively (Table [2], entries 7, 8). Interestingly, two bromo-substituted substrates 1j and 1k also performed well in this transformation, producing the de-brominated product 2a in moderate yields (Table [2], entries 9, 10). The bromine atoms were reduced by the Zn powder. Compounds with substitutions on the Ar group were also investigated and shown to be good substrates for the cyclization. For example, compounds 1l and 1m, bearing Me and OMe groups on the Ar ring, reacted smoothly to afford products 2j and 2k in 89% and 59% yields, respectively (Table [2], entries 11, 12). The halo-containing substrates 1n–1q facilitated the reaction, and the cyclization products 2l–2o were obtained in 27%–65% yields (Table [2], entries 13–16). Substrate 1r also served as an efficient substrate and furnished product 2p in 75% yield (Table [2], entry 17). Use of substrate 1s resulted in a 65% yield of target product 2q, isolated under standard conditions (Table [2], entry 18). Gratifyingly, when 2-(2-iodophenoxy)-1-phenylpropan-1-one (1t) was subjected to the reaction, the 2,3-disubstituted benzofuran 2r was afforded in 55% yield (Table [2], entry 19). Cyclization of the bromo-containing substrate 1u also proceeded rapidly to give a 30% yield of product 2a (Table [2], entry 20).

Table 2 Exploration of the Scope of Substrates 1 ^a

Entry	1		2	Products	Yield (%) b
1 c	1b		2b		55
2 c	1c		2c		70
3 c	1d		2d		46
4 c	1e		2e		75
5 c	1f		2f		79
6 c	1g		2g		48
7	1h		2h		54
8	1i		2i		23
9 c	1j		2a		61
10 c	1k		2a		63
11 c	1l		2j		89
12 c	1m		2k		59
13	1n		2l		32
14 c	1o		2m		65
15	1p		2n		41
16 c	1q		2o		27
17 c	1r		2p		75
18	1s		2q		65
19	1t		2r		55
20	1u		2a		30

^a Reaction conditions: 1a (0.2 mmol), Ni(OTf)₂ (10 mol%), 1,10-Phen (10 mol%), Zn powder (2 equiv) in MeCN (2 mL) under N₂ at 110 °C for 24 h.

^b Isolated yield.

^c Ni(dppp)₂Cl₂ (10 mol%) was used.

The synthesis of benzofuran 2a through a one-pot method was also achieved (Scheme [2]). The reaction of 2-iodophenol with 2-bromo-1-phenylethanone proceeded well in the presence of Ni(dppp)₂Cl₂, ligand, Zn powder, K₂CO₃, and MeCN and led to the formation of target 2a in 30% yield.

Scheme 2 One-pot method for the synthesis of 2a

Based on previous reports, as well as our experimental results,[12] a possible mechanism is outlined in Scheme [3]. Initially, the nickel salts combine with the bidentate ligand 1,10-Phen and are then reduced to Ni(0) by the Zn powder. This is followed by oxidative addition of 1a to generate the Ni(II) species A. The Ni(II) species A, through an intramolecular nucleophilic addition process, produces intermediate B. Subsequently, transmetalation of B by ZnX₂ leads to the Zn intermediate C and regeneration of the Ni catalyst. Finally, intermediate C, via demetallization and dehydration processes, affords the target product 2a.

Scheme 3 Proposed mechanism

In summary, we have developed a nickel-catalyzed intramolecular nucleophilic addition reaction for the formation of benzofuran derivatives. Various functional groups were tolerated well under the standard reaction conditions, regardless of electronic effects, and the target products were formed in moderate to good yields.

Chemicals were either purchased or purified by standard techniques. ¹H NMR and ¹³C NMR spectra were measured on a 500 MHz spectrometer (¹H: 500 MHz, ¹³C: 125 MHz), using CDCl₃ as the solvent with TMS as an internal standard at r.t. Chemical shifts are given in δ relative to TMS, and the coupling constants J are given in Hz. High-resolution mass spectra were recorded on an ESI-Q-TOF mass spectrometer. All reactions were conducted under a nitrogen atmosphere by using standard Schlenk techniques. Column chromatography was performed by using EM silica gel 60 (300–400 mesh).

Benzofurans 2a–2r; General Procedure

A flame-dried Schlenk tube with a magnetic stirring bar was charged with 1 (0.2 mmol), Ni(OTf)₂ (5 mol%), Zn powder (2 equiv), 1.10-Phen (10 mol%), and MeCN (2 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 110 °C for 16 h. After the reaction completed, the reaction mixture was filtered and evaporated under vacuum. The residue was purified by flash column chromatography (hexane) to afford the desired products.

3-Phenylbenzofuran (2a)[2]

Yellow oil (32.2 mg, 83% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.74 (d, J = 8.0 Hz, 1 H), 7.67 (s, 1 H), 7.54 (d, J = 8.0 Hz, 2 H), 7.44 (d, J = 8.0 Hz, 1 H), 7.36 (t, J = 7.5 Hz, 2 H), 7.27–7.23 (m, 2 H), 7.20 (t, J = 7.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.8, 141.3, 132.1, 128.9, 127.5, 127.4, 126.5, 124.5, 123.0, 122.3, 120.4, 111.7.

LRMS (EI, 70 eV): m/z (%) = 193 (M⁺, 100), 165 (98), 164 (66), 194 (34), 166 (31).

5-Methyl-3-phenylbenzofuran (2b)[2]

Yellow oil (22.9 mg, 55% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.66 (s, 1 H), 7.58–7.57 (m, 3 H), 7.42–7.37 (m, 3 H), 7.30 (t, J = 7.0 Hz, 1 H), 7.09 (d, J = 8.0 Hz, 1 H), 2.41 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 154.2, 141.4, 132.4, 132.2, 128.8, 127.4, 127.3, 126.5, 125.7, 122.0, 120.1, 111.2, 21.4.

LRMS (EI, 70 eV): m/z (%) = 206 (M⁺, 100), 207 (33), 206 (31), 164 (23), 178 (22), 177 (19), 89 (16).

5-Ethyl-3-phenylbenzofuran (2c)

Yellow oil (31.1 mg, 70% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.75 (s, 1 H), 7.65–7.63 (m, 3 H), 7.49–7.44 (m, 3 H), 7.37 (t, J = 7.5 Hz, 1 H), 7.19 (d, J = 8.5 Hz, 1 H), 2.77 (q, J = 7.5 Hz, 2 H), 1.29 (t, J = 7.5 Hz, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 154.4, 141.5, 139.2, 132.3, 128.9, 127.5, 127.4, 126.5, 124.8, 122.1, 119.0, 111.4, 29.0, 16.4.

LRMS (EI, 70 eV): m/z (%) = 205 (M⁺, 100), 220 (64), 206 (32), 221 (25), 177 (17).

HRMS (ESI): calcd for C₁₆H₁₄ONa⁺ ([M + Na]⁺): 245.0937; found: 245.0939.

5-(tert-Butyl)-3-phenylbenzofuran (2d)[3]

Yellow oil (23.0 mg, 46% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.72 (s, 1 H), 7.65 (s, 1 H), 7.55 (d, J = 7.5 Hz, 2 H), 7.41–7.38 (m, 3 H), 7.34–7.29 (m, 2 H), 1.31 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃): δ = 154.0, 146.1, 141.5, 132.3, 129.0, 127.6, 127.3, 126.1, 122.5, 122.4, 116.3, 111.0, 34.8, 31.9.

LRMS (EI, 70 eV): m/z (%) = 233 (M⁺, 100), 234 (46), 248 (31), 249 (28), 104 (16).

5-Fluoro-3-phenylbenzofuran (2e)[3]

Yellow oil (31.8 mg, 75% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.67 (s, 1 H), 7.46 (d, J = 7.0 Hz, 2 H), 7.37–7.32 (m, 4 H), 7.26 (t, J = 7.5 Hz, 1 H), 6.97–6.92 (m, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 159.5 (J _C–F = 236.3 Hz), 152.0, 142.9, 131.5, 129.0, 127.7, 127.3, 122.6, 112.42, 112.40, 112.3 (J _C–F = 13.8 Hz), 106.0 (J _C–F = 25.0 Hz).

LRMS (EI, 70 eV): m/z (%) = 211 (M⁺, 100), 182 (64), 212 (26), 183 (21), 91(14).

6-Chloro-3-phenylbenzofuran (2f)[8]

Yellow oil (36.0 mg, 79% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.63–7.59 (m, 2 H), 7.48–7.43 (m, 3 H), 7.37–7.34 (m, 2 H), 7.26 (t, J = 7.5 Hz, 1 H), 7.16 (d, J = 8.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.8, 141.8, 131.4, 130.5, 129.0, 127.7, 127.4, 125.2, 123.7, 122.2, 120.9, 112.3.

LRMS (EI, 70 eV): m/z (%) = 227 (M⁺, 100), 164 (82), 226 (40), 228 (33), 163 (26), 82 (25), 229 (24), 162 (21), 165 (14).

5-Chloro-3-phenylbenzofuran (2g)[3]

Yellow oil (22.0 mg, 48% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.65 (s, 1 H), 7.62 (s, 1 H), 7.44 (d, J = 8.0 Hz, 2 H), 7.33 (t, J = 7.5 Hz, 2 H), 7.30 (d, J = 8.5 Hz, 1 H), 7.24 (d, J = 7.5 Hz, 1 H), 7.16 (d, J = 8.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 154.1, 142.5, 131.2, 129.0, 128.7, 127.8, 127.7, 127.4, 124.8, 122.0, 120.1, 112.7.

LRMS (EI, 70 eV): m/z (%) = 226 (M⁺, 100), 164 (63), 227 (40), 228 (37), 165 (26), 82 (23), 163 (18).

4,5-Dimethyl-3-phenylbenzofuran (2h)

White solid (24.1 mg, 54% yield), mp 50–52 °C.

¹H NMR (500 MHz, CDCl₃): δ = 7.62 (s, 1 H), 7.57 (d, J = 7.5 Hz, 2 H), 7.51 (s, 1 H), 7.40 (t, J = 7.5 Hz, 2 H), 7.28 (t, J = 7.5 Hz, 1 H), 7.26 (s, 1 H), 2.32 (s, 3 H), 2.30 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 154.8, 140.6, 133.7, 132.5, 131.6, 128.9, 127.4, 127.2, 124.3, 121.8, 120.4, 112.1, 20.4, 20.1.

LRMS (EI, 70 eV): m/z (%) = 220 (M⁺, 100), 205 (40), 221 (35), 219 (27), 177 (20).

HRMS (ESI): calcd for C₁₆H₁₄ONa⁺ ([M + Na]⁺): 245.0937; found: 245.0929.

1-Phenylnaphtho[2,1-b]furan (2i)[5]

Yellow oil (11.3 mg, 23% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.99 (d, J = 8.0 Hz, 1 H), 7.94 (d, J = 8.0 Hz, 1 H), 7.77 (d, J = 9.0 Hz, 1 H), 7.70 (d, J = 10.0 Hz, 2 H), 7.61 (d, J = 6.5 Hz, 2 H), 7.52 (t, J = 7.5 Hz, 2 H), 7.47 (t, J = 7.5 Hz, 1 H), 7.43 (t, J = 7.5 Hz, 1 H), 7.35 (t, J = 7.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 153.2, 141.7, 133.1, 130.8, 129.9, 128.9, 128.6, 127.9, 126.0, 125.9, 124.5, 124.3, 123.4, 120.7, 112.6.

LRMS (EI, 70 eV): m/z (%) = 244 (M⁺, 100), 215 (63), 213 (25), 245 (19).

3-(p-Tolyl)benzofuran (2j)[7]

Yellow oil (37.2 mg, 89% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.73 (d, J = 8.0 Hz, 1 H), 7.65 (s, 1 H), 7.44 (d, J = 7.5 Hz, 3 H), 7.24 (t, J = 7.5 Hz, 1 H), 7.21–7.17 (m, 3 H), 2.31 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.8, 141.0, 137.2, 129.6, 129.1, 127.4, 126.6, 124.4, 122.9, 122.1, 120.4, 111.7, 21.2.

LRMS (EI, 70 eV): m/z (%) = 206 (M⁺, 100), 207 (32), 164 (23), 205 (17).

3-(4-Methoxyphenyl)benzofuran (2k)[2]

Yellow oil (26.4 mg, 59% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.73–7.64 (m, 2 H), 7.50–7.45 (m, 3 H), 7.28–7.21 (m, 2 H), 6.93 (d, J = 8.0 Hz, 2 H), 3.78 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 159.1, 155.7, 140.7, 128.6, 126.7, 124.5, 124.4, 122.8, 121.8, 120.3, 114.4, 111.7, 55.3.

LRMS (EI, 70 eV): m/z (%) = 222 (M⁺, 100), 207 (67), 152 (45), 223 (41), 151 (26).

3-(4-Chlorophenyl)benzofuran (2l)[8]

Yellow oil (14.6 mg, 32% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.66 (d, J = 7.5 Hz, 1 H), 7.63 (s, 1 H), 7.44–7.42 (m, 3 H), 7.31 (d, J = 8.5 Hz, 2 H), 7.24 (t, J = 7.0 Hz, 1 H), 7.19 (t, J = 7.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.8, 141.4, 133.3, 130.5, 129.1, 128.6, 126.1, 124.7, 123.1, 121.2, 120.1, 111.8.

LRMS (EI, 70 eV): m/z (%) = 227 (M⁺, 100), 164 (89), 226 (48), 228 (38), 82 (29), 163 (26), 229 (25), 162 (24), 165 (24).

3-(4-Fluorophenyl)benzofuran (2m)[4]

Yellow oil (27.2 mg, 65% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.67 (d, J = 7.5 Hz, 1 H), 7.63 (s, 1 H), 7.49–7.44 (m, 3 H), 7.26 (t, J = 7.5 Hz, 1 H), 7.21 (t, J = 7.5 Hz, 1 H), 7.06 (t, J = 8.5 Hz, 2 H).

¹³C NMR (125 MHz, CDCl₃): δ = 162.3 (J _C–F = 245.0 Hz), 155.7, 141.1, 129.1, 128.0, 126.4, 124.6, 123.0, 121.3, 120.1, 115.9 (J _C–F = 22.5 Hz), 111.8.

LRMS (EI, 70 eV): m/z (%) = 211 (M⁺, 100), 182 (73), 212 (46), 183 (23), 91 (15).

3-(3,4-Dichlorophenyl)benzofuran (2n)

Yellow oil (21.5 mg, 41% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.70–7.67 (m, 2 H), 7.63 (s, 1 H), 7.47 (d, J = 8.5 Hz, 1 H), 7.44 (d, J = 8.0 Hz, 1 H), 7.37 (d, J = 8.0 Hz, 1 H), 7.29 (t, J = 7.5 Hz, 1 H), 7.24 (t, J = 7.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.8, 141.8, 133.1, 132.2, 131.4, 130.9, 129.1, 126.6, 125.8, 125.0, 123.4, 120.3, 120.0, 112.0.

LRMS (EI, 70 eV): m/z (%) = 261 (M⁺, 100), 263 (67), 260 (43), 262 (42), 198 (29), 99 (16), 264 (15), 163 (13).

3-(2-Chlorophenyl)benzofuran (2o)

Yellow oil (12.3 mg, 27% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.76 (s, 1 H), 7.51–7.45 (m, 4 H), 7.29–7.23 (m, 3 H), 7.20 (t, J = 7.5 Hz, 1 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.0, 143.5, 133.5, 131.5, 130.6, 130.2, 128.9, 127.0, 126.8, 124.5, 122.9, 120.8, 119.2, 111.7.

LRMS (EI, 70 eV): m/z (%) = 226 (M⁺, 100), 164 (73), 228 (38), 227 (37), 165 (27), 82 (25).

3-(o-Tolyl)benzofuran (2p)[4]

Yellow oil (31.2 mg, 75% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.62 (s, 1 H), 7.56 (d, J = 8.0 Hz, 1 H), 7.46 (d, J = 7.5 Hz, 1 H), 7.39 (d, J = 7.0 Hz, 1 H), 7.35–7.30 (m, 3 H), 7.29–7.24 (m, 2 H), 2.32 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.1, 142.2, 136.9, 130.9, 130.5, 130.4, 127.84, 127.83, 125.8, 124.4, 122.7, 121.4, 120.7, 111.6, 20.5.

LRMS (EI, 70 eV): m/z (%) = 206 (M⁺, 100), 205 (74), 178 (34), 177 (29), 207 (29).

3-(Naphthalen-2-yl)benzofuran (2q)

White solid (31.5 mg, 65% yield), mp 59–61 °C.

¹H NMR (500 MHz, CDCl₃): δ = 8.03 (s, 1 H), 7.87–7.83 (m, 2 H), 7.81–7.77 (m, 3 H), 7.65 (d, J = 8.5 Hz, 1 H), 7.49 (d, J = 8.5 Hz, 1 H), 7.44–7.39 (m, 2 H), 7.31–7.24 (m, 2 H).

¹³C NMR (125 MHz, CDCl₃): δ = 155.9, 141.7, 133.7, 132.7, 129.5, 128.6, 127.9, 127.8, 126.4, 126.0, 125.9, 125.8, 124.6, 123.1, 122.2, 120.5, 111.8.

LRMS (EI, 70 eV): m/z (%) = 242 (M⁺, 100), 243 (68), 213 (45), 107 (22), 214 (18).

HRMS (ESI): calcd for C₁₈H₁₂ONa⁺ ([M + Na]⁺): 267.0780; found: 267.0784.

2-Methyl-3-phenylbenzofuran (2r)[6]

Yellow oil (22.9 mg, 55% yield).

¹H NMR (500 MHz, CDCl₃): δ = 7.50 (d, J = 7.5 Hz, 1 H), 7.44–7.37 (m, 5 H),7.28 (t, J = 7.0 Hz, 1 H), 7.20–7.14 (m, 2 H), 2.46 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃): δ = 154.0, 151.3, 132.9, 128.9, 128.8, 128.7, 126.9, 123.5, 122.6, 119.3, 116.9, 110.7, 12.8.

LRMS (EI, 70 eV): m/z (%) = 206 (M⁺, 100), 205 (51), 130 (30), 207 (30), 177 (21), 178 (17).

• References

• 1a Suresh JR, Patra PK, Ila H, Junjappa H. Tetrahedron 1997; 53: 14737
• 1b Hara T, Mori K, Mizugaki T, Ebitani K, Kaneda K. Tetrahedron Lett. 2003; 44: 6207
• 1c Li J, Liu L, Ding D, Sun J, Ji Y, Dong J. Org. Lett. 2013; 15: 2884
• 2 Yasuda D, Yuasa A, Obata R, Nakajima M, Takahashi K, Ohe T, Ichimura Y, Komatsu M, Yamamoto M, Imamura R, Kojima H, Okabe T, Nagano T, Mashino T. Bioorg. Med. Chem. Lett. 2017; 27: 5006
• 3a Ha JH, Kang DW, Kim HM, Kang JM, Lee J. J. Med. Chem. 2018; 61: 396
• 3b Dai J.-R, Hallock YF, Cardellina JH, Boyd MR. J. Nat. Prod. 1998; 61: 351
• 4a Hegedu LS. Angew. Chem., Int. Ed. Engl. 1988; 27: 1113
• 4b Pindur U, Adam R. J. Heterocycl. Chem. 1988; 25: 1
• 4c Gilchrist TL. J. Chem. Soc., Perkin Trans. 1 1999; 2849
• 4d Van Order RB, Lindwa HG. Chem. Rev. 1942; 30: 69
• 4e Gribble GW. J. Chem. Soc., Perkin Trans. 1 2000; 1045
• 4f Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
• 4g Cacchi S, Fabrizi G. Chem. Rev. 2005; 105: 2873
• 4h Barluenga J, Rodríguez F, Fañanás FJ. Chem. Asian J. 2009; 4: 1036
• 4i Wang ZX, Gu JZ, Jing HW, Liang YM. Synth. Commun. 2009; 39: 4079
• 4j Kraus GA, Schroeder JD. Synlett 2005; 2504
• 5a Qiao B, Zhang L, Li R. RSC Adv. 2015; 5: 93463
• 5b Elangovan S, Neumann J, Sortais J.-B, Junge K, Darcel C, Beller M. Nat. Commun. 2016; 7: 12641
• 5c Cheng XF, Peng Y, Wu J, Deng GJ. Org. Biomol. Chem. 2016; 14: 2819
• 5d Blanc A, Bénéteau V, Weibel J.-M, Pale P. Org. Biomol. Chem. 2016; 14: 9184
• 5e Jung Y, Kim I. Org. Biomol. Chem. 2016; 14: 10454
• 5f Liu GX, Lu XY. Tetrahedron 2008; 64: 7324
• 6a Metal-catalyzed cross-coupling reactions . de Meijere A, Diederich F. Wiley-VCH; Weinheim: 2004
• 6b Handbook of organopalladium chemistry for organic synthesis. Negishi E.-I. Wiley-Interscience; New York: 2002
• 7a Corriu RJ. P, Masse JP. J. J. Chem. Soc., Chem. Commun. 1972; 144a
• 7b Tamao K, Sumitani K, Kumada M. J. Am. Chem. Soc. 1972; 94: 4374
• 7c Yamamura M, Moritani I, Murahashi S.-I. J. Organomet. Chem. 1975; 91: C39
• 8a Jana R, Pathak TP, Sigman MS. Chem. Rev. 2011; 111: 1417
• 8b Yamamoto K, Otsuka S, Nogi K, Yorimitsu H. ACS Catal. 2017; 7: 7623
• 8c Farmer JL, Pompeo M, Organ MG. Ligand Design in Metal Chemistry: Reactivity and Catalysis . Stradiotto M, Lundgren RJ. John Wiley & Sons; Chichester: 2016
• 8d King AO, Okukado N, Negishi E.-I. J. Chem. Soc., Chem. Commun. 1977; 683
• 9a Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
• 9b Kotha S, Lahiri K, Kashinath D. Tetrahedron 2002; 58: 9633
• 10 Li Y, Li WD, Tian JY, Huang GZ, Lv H. Org. Lett. 2020; 22: 5353
• 11 Friedfeld MR, Shevlin M, Margulieux GW, Campeau L.-C, Chirik PJ. J. Am. Chem. Soc. 2016; 138: 3314
• 12a Majumdar KK, Cheng C.-H. Org. Lett 2000; 2: 2295
• 12b Hu JX, Wu H, Li CY, Sheng WJ, Jia YX, Gao JR. Chem. Eur. J. 2011; 17: 5234
• 12c He J.-Q, Chen C, Yu W.-B, Liu R.-R, Xu M, Li Y.-J, Gao J.-R, Jia Y.-X. Tetrahedron Lett. 2014; 55: 2805
• 12d Rosen BM, Quasdorf KW, Wilson DA, Zhang N, Resmerita A.-M, Garg NK, Percec V. Chem. Rev. 2011; 111: 1346
• 12e Li Z, Zhang SL, Fu Y, Guo QX, Liu L. J. Am. Chem. Soc. 2009; 131: 8815
• 12f Li Z, Liu L. Chin. J. Catal. 2015; 36: 3

Publikationsverlauf

Eingereicht: 10. November 2020

Angenommen nach Revision: 11. Dezember 2020

Artikel online veröffentlicht:
25. Januar 2021