Synthesis method of a 2-(2-arylbutyl)pyridine compound

Abstract

The present invention belongs to the technical field of organic synthesis, and discloses a method for synthesizing 2-(2-arylbutyl)pyridine compounds, which comprises the following steps: under a nitrogen atmosphere, sequentially adding boric acid, a base, a cobalt catalyst, a nitrogen-containing ligand, an organic solvent, a silicon hydride reagent and a 2-(3-butenyl)pyridine substrate into a reaction tube, reacting at a temperature of 70-80 °C for 8 h, and obtaining the 2-(2-arylbutyl)pyridine compound through extraction, drying and concentration; the boric acid is arylboronic acid, heterocyclic boronic acid or alkylboronic acid. The present invention uses 2-(3-butenyl)pyridine, arylboronic acid or heterocyclic boronic acid or alkylboronic acid as substrates, and synthesizes a series of 2-(2-arylbutyl)pyridine compounds under the catalysis of cobalt, and the yield is relatively high.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis and relates to a method for synthesizing 2-(2-arylbutyl)pyridine compounds. Background Art

[0002] Nitrogen-containing compounds widely exist in nature. Alkylpyridines are an important class of organic nitrogen-containing compounds and are widely used in the fields of natural products, pharmaceuticals, organic ligands, fine chemical materials, etc. They are important organic core structures. Due to the influence of the N atom in pyridine, the pyridine ring becomes an electron-deficient aromatic heterocycle. In the past research on the pyridine ring, most of them focused on the development of pyridinium salts and some ortho- and para-nucleophilic substitution reactions. There are few reports on the synthesis of 2-(2-arylbutyl)pyridine compounds directly starting from alkylpyridines. Summary of the Invention

[0003] In view of the above technical problems, the present invention provides a method for synthesizing 2-(2-arylbutyl)pyridine compounds. The reaction conditions are mild, a series of 2-(2-arylbutyl)pyridine compounds can be synthesized, the substrate scope is wide, and the yield is relatively high.

[0004] To achieve the above object, the present invention adopts the following technical solutions:

[0005] The present invention provides a method for synthesizing 2-(2-arylbutyl)pyridine compounds, comprising the following steps: under a nitrogen atmosphere, arylboric acid, a base, a cobalt catalyst, a nitrogen-containing ligand, an organic solvent, a hydrosilicon reagent, and a 2-(3-butenyl)pyridine substrate are sequentially added to a reaction tube, and the reaction is carried out at a temperature of 70-80 °C for 8 h. After extraction, drying, and concentration, a 2-(2-arylbutyl)pyridine compound is obtained; the arylboric acid is arylboronic acid, heterocyclic boronic acid, or alkylboronic acid.

[0006] Preferably, the meta-position or para-position of the boronic acid group on the benzene ring of the arylboronic acid is substituted by a halogen, an ester group, a trifluoromethyl group, a trifluoromethoxy group, a phenyl group, a cyano group, an alkyl group, a thiomethyl group, or an alkoxy group; the hydrogen on the heterocycle of the heterocyclic boronic acid is substituted by a methyl group or a phenyl group.

[0007] Preferably, the molar ratio of the boronic acid to 2-(3-butenyl)pyridine is 2-2.5:1.

[0008] Preferably, the base is selected from one of KHCO3, CsF2, Cs2CO3, Li3PO4, CsHCO3, KH2PO4, or KF, and the molar ratio of the amount of the base used to the amount of 2-(3-butenyl)pyridine used is 2-4:1.

[0009] Preferably, the cobalt catalyst is selected from one of cobalt chloride, cobalt iodide, cobalt sulfate, cobalt acetylacetonate, cobalt fluoride, or cobalt bromide.

[0010] Preferably, the dosage of the cobalt catalyst is 10% - 20% of the molar amount of 2-(3-butenyl)pyridine.

[0011] Preferably, the nitrogen-containing ligand is selected from one of 2,2'-bipyridine (Bpy), 2,2'-biquinoline, 4,4'-dimethyl-2,2'-bipyridine, 6,6'-dimethyl-2,2'-bipyridine, or 2,6-bis(1-pyrazolyl)pyridine.

[0012] Preferably, the dosage of the nitrogen-containing ligand is 15% - 30% of the molar amount of 2-(3-butenyl)pyridine.

[0013] Preferably, the organic solvent is selected from 1,4-dioxane (1,4-Dioxane), tetrahydrofuran (THF), dimethyl sulfoxide (DSMO), N-methylpyrrolidone (NMP), N,N-dimethylacetamide (DMA).

[0014] Preferably, the hydrosilane reagent is selected from one of triethylsilane (Et3SiH), diphenylsilane (Ph2SiH2), or triphenylsilane (Ph3SiH), and the molar ratio of the hydrosilane reagent to 2-(3-butenyl)pyridine is 2 - 4:1.

[0015] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0016] The present invention uses 2-(3-butenyl)pyridine, arylboronic acid, heterocyclic boronic acid, or alkylboronic acid as substrates, and a series of 2-(2-arylbutyl)pyridine compounds are synthesized under the catalysis of cobalt with relatively high yields.

[0017] The raw materials of the present invention are cheap and easily available, the reaction conditions are mild, and the functional group tolerance is good. Description of the Drawings

[0018] Figure 1 It is a schematic diagram of the reaction mechanism of the present invention. Detailed Embodiments

[0019] The following examples are used to illustrate the present invention, but are not used to limit the protection scope of the present invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art. The test methods in the following examples are all conventional methods unless otherwise specified.

[0020] The 2-(3-butenyl)pyridine used in the embodiments of the present invention can be prepared with reference to the literature method (J. J. Gladfelder, S. Ghosh, M. Podunavac, A. W. Cook, Y. Ma, R. A. Woltornist, I. Keresztes, T. W. Hayton, D. B. Collum, A. Zakarian, J. Am. Chem. Soc. 2019, 141, 15024–15028.).

[0021] Example 1 Synthesis of 2-(2-(4-fluorophenyl)butyl)pyridine

[0022]

[0023] Under a nitrogen atmosphere, 4-fluorobenzeneboronic acid 2a (0.4 mmol, 56.0 mg), CsF (0.8 mmol, 121.5 mg), cobalt(II) acetylacetonate (0.02 mmol, 5.2 mg), 6,6'-dimethyl-2,2'-bipyridine (0.04 mmol, 7.4 mg), DMA (1 mL), Et3SiH (0.6 mmol, 96 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0024] The above mixture was reacted at 80 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 35.5 mg of a colorless oily liquid with a yield of 78%.

[0025] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(4-fluorophenyl)butyl)pyridine) are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.51 (d, J = 4.2 Hz, 1H), 7.44 (td, J = 7.6, 1.8 Hz, 1H), 7.06–7.02 (m, 3H), 6.92–6.89 (t, J = 8.7 Hz, 2H), 6.82 (d, J = 7.8 Hz, 1H), 3.12–3.08 (m, 1H), 3.04–2.98 (m, 1H), 2.96–2.91 (m, 1H), 1.78–1.70 (m, 1H), 1.67–1.58 (m, 1H), 0.77 (t, J = 7.4 Hz, 3H); 1313C NMR (100 MHz, CDCl3) δ 162.38, 160.32, 159.96, 149.12, 140.11, 140.08, 135.89, 129.01, 128.93, 123.60, 120.94, 114.95, 114.75, 47.44, 45.75, 28.87, 11.97.

[0026] Taking this example as an illustration, the reaction mechanism of the present invention is described (see Figure 1 ): First, the nitrogen-containing ligand (6,6'-dimethyl-2,2'-bipyridine), cobalt acetylacetonate, and the silane reagent Et3SiH react in situ to generate the LCo(I)H intermediate I, which then undergoes hydrometalation with 2-(3-butenyl)pyridine 1 to produce intermediate II; intermediate II subsequently undergoes an irreversible β-hydride elimination and reinsertion operation to obtain intermediate III; intermediate III, under the promotion of a base, undergoes a transmetalation process with 4-fluorophenylboronic acid 2a to obtain intermediate IV; intermediate IV subsequently undergoes reductive elimination to produce the target product 3a and regenerate the catalyst.

[0027] Example 2 Synthesis of 2-(2-(4-(tert-butyl)phenyl)butyl)pyridine

[0028]

[0029] Under a nitrogen atmosphere, 4-tert-butylphenylboronic acid 2b (0.5 mmol, 89.1 mg), KHCO3 (0.8 mmol, 80.1 mg), cobalt fluoride (0.04 mmol, 3.9 mg), 2,2'-biquinoline (0.06 mmol, 15.4 mg), DMSO (1 mL), Ph2SiH2 (0.8 mmol, 148 μL), and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0030] The above mixture was reacted at 75 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 48.1 mg of a colorless oily liquid with a yield of 90%.

[0031] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(4-(tert-butyl)phenyl)butyl)pyridine) are as follows: 11H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 5.5 Hz, 1H), 7.38 (td, J = 7.7, 1.8 Hz, 1H), 7.19–7.17 (m, 2H), 7.00–6.95 (m, 3H), 6.83 (d, J = 7.8 Hz, 1H), 3.02–2.86 (m, 3H), 1.66–1.51 (m, 2H), 1.22 (s, 9H), 0.69 (t, J = 7.4 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 160.82, 149.03, 148.57, 141.51, 135.79, 127.22, 124.92, 123.60, 120.81, 47.44, 45.61, 34.24, 31.34, 28.43, 12.05.

[0032] Example 3 Synthesis of 2-(2-(4-(methylthio)phenyl)butyl)pyridine

[0033]

[0034] Under a nitrogen atmosphere, 4-(methylthio)phenylboronic acid 2c (0.5 mmol, 84.0 mg), Cs2CO3 (0.6 mmol, 195.5 mg), cobalt sulfate (0.04 mmol, 6.2 mg), 4,4'-dimethyl-2,2'-bipyridine (0.06 mmol, 11.1 mg), THF (1 mL), Ph3SiH (0.6 mmol, 156 mg) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0035] The above mixture was reacted at 80 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 44.2 mg of a colorless oily liquid with a yield of 86%.

[0036] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(4-(methylthio)phenyl)butyl)pyridine) are as follows: 11H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 4.8 Hz, 1H), 7.43 (td, J = 7.7, 1.8 Hz, 1H), 7.13 (d, J = 8.3 Hz, 2H), 7.04–7.01 (m, 3H), 6.84 (d, J = 7.8 Hz, 1H), 3.12–2.93 (m, 3H), 2.44 (s, 3H), 1.77–1.56 (m, 2H), 0.77 (t, J = 7.4 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 160.44, 149.11, 141.64, 135.87, 135.27, 128.24, 126.66, 123.60, 120.89, 47.59, 45.57, 28.72, 16.00, 11.99.

[0037] Example 4 Synthesis of 2-(2-(4-(methyl)phenyl)butyl)pyridine

[0038]

[0039] Under a nitrogen atmosphere, 4-methylphenylboronic acid 2d (0.4 mmol, 54.8 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), 1,4-Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0040] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 37.4 mg of a colorless oily liquid with a yield of 83%.

[0041] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(4-(methyl)phenyl)butyl)pyridine) are as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 4.8 Hz, 1H), 7.44 (td, J = 7.6, 1.8 Hz, 1H), 7.06–7.00 (m, 5H), 6.87 (d, J = 7.8 Hz, 1H), 3.12–2.93 (m, 3H), 2.29 (s, 3H), 1.76–1.57 (m, 2H), 0.77 (t, J = 7.4 Hz, 3H);13 13C NMR (100 MHz, CDCl3) δ 160.75, 149.07, 141.50, 135.83, 135.30, 128.83, 127.57, 123.62, 120.83, 47.67, 45.72, 28.71, 20.98, 12.04。

[0042] Example 5 Synthesis of 2-(2-(4-(methoxycarbonyl)phenyl)butyl)pyridine

[0043]

[0044] Under a nitrogen atmosphere, 4-methoxycarbonylphenylboronic acid 2e (0.4 mmol, 72.1 mg), CsHCO3 (0.6 mmol, 116.4 mg), cobalt(II) fluoride tetrahydrate (0.02 mmol, 4.3 mg), 2,6-bis(1-pyrazolyl)pyridine (0.04 mmol, 8.4 mg), DMA (1 mL), Et3SiH (0.8 mmol, 128 μL), and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0045] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 6 / 1 gave 47.4 mg of a colorless oily liquid with a yield of 88%.

[0046] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(4-(methoxycarbonyl)phenyl)butyl)pyridine) are as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.48 (d, J = 4.8 Hz, 1H), 7.88 (d, J = 8.3 Hz, 2H), 7.40 (td, J = 7.7, 1.8 Hz, 1H), 7.16 (d, J = 8.3 Hz, 2H), 7.02–6.99 (m, 1H), 6.79 (d, J = 7.8 Hz, 1H), 3.86 (s, 3H), 3.15–3.05 (m, 2H), 2.98–2.94 (m, 1H), 1.81–1.63 (m, 2H), 0.76 (t, J = 7.4 Hz, 3H); 1313C NMR (100 MHz, CDCl3) δ 167.07, 159.95, 150.18, 149.14, 135.92, 129.48, 127.77, 127.77, 123.54, 121.00, 51.87, 48.16, 45.27, 28.62, 11.93。

[0047] Example 6 Synthesis of 2-(2-(4-(trifluoromethyl)phenyl)butyl)pyridine

[0048]

[0049] Under a nitrogen atmosphere, 4-trifluoromethylphenylboronic acid 2f (0.4 mmol, 76.0 mg), CsHCO3 (0.6 mmol, 116.4 mg), cobalt iodide (0.03 mmol, 9.4 mg), 2,6-bis(1-pyrazolyl)pyridine (0.04 mmol, 8.4 mg), NMP (1 mL), Et3SiH (0.8 mmol, 128 μL), and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0050] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 44.7 mg of a colorless oily liquid with a yield of 80%.

[0051] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(4-(trifluoromethyl)phenyl)butyl)pyridine) are as follows: 1 1H NMR (300 MHz, CDCl3) δ 8.51–8.50 (m, 1H), 7.49–7.42 (m, 3H), 7.22 (d, J = 8.0 Hz, 2H), 7.07–7.03 (m, 1H), 6.85 (d, J = 7.7 Hz, 1H), 3.17–3.07 (m, 2H), 3.02–2.93 (m, 1H), 1.82–1.59 (m, 2H), 0.78 (d, J = 7.4 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 159.91, 149.22, 148.80, 136.03, 128.43, 128.04, 125.14, 125.10, 125.06, 125.03, 123.58, 121.11, 47.96, 45.30, 28.62, 11.92; 19FNMR (375 MHz, CDCl3) δ -62.31.

[0052] Example 7 Synthesis of 2-(2-(3-(methyl)phenyl)butyl)pyridine

[0053]

[0054] Under a nitrogen atmosphere, 2 g (0.4 mmol, 54.8 mg) of 3-methylphenylboronic acid, KF (0.8 mmol, 46.5 mg), cobalt bromide (0.04 mmol, 8.7 mg), 2,2'-bipyridine (0.06 mmol, 9.3 mg), NMP (1 mL), Et3SiH (0.8 mmol, 128 μL), and 2-(3-butenyl)pyridine 1 (2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0055] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 41.0 mg of a colorless oily liquid with a yield of 91%.

[0056] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(3-(methyl)phenyl)butyl)pyridine) are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 5.7 Hz, 1H), 7.44 (td, J = 7.6, 1.8 Hz, 1H), 7.13 (t, J = 7.4 Hz, 1H), 7.05–7.02 (m, 1H), 6.97–6.92 (m, 3H), 6.87 (d, J = 7.8 Hz, 1H), 3.11–2.93 (m, 3H), 2.29 (s, 3H), 1.76–1.60 (m, 2H), 0.77 (t, J = 7.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 160.74, 149.08, 144.59, 137.56, 135.56, 128.53, 127.97, 126.69, 124.72, 123.62, 120.86, 48.03, 45.70, 28.57, 21.43.

[0057] Example 8 Synthesis of 2-(2-([1,1':3',1'-triphenyl])butyl)pyridine

[0058]

[0059] Under a nitrogen atmosphere, 3,5-diphenylphenylboronic acid 2h (0.4 mmol, 109.6 mg), KH2PO4 (0.8 mmol, 108.9 mg), cobalt bromide (0.04 mmol, 8.7 mg), 2,2'-bipyridine (0.06 mmol, 9.3 mg), THF (1 mL), Ph3SiH (0.4 mmol, 104.1 mg) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0060] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. Column chromatography separation was carried out with an eluent of petroleum ether / ethyl acetate = 10 / 1 to obtain 54.5 mg of a colorless oily liquid with a yield of 75%.

[0061] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-([1,1':3',1'-triphenyl]-5'-yl)butyl)pyridine) are as follows: 1 HNMR(500MHz,CDCl3)δ8.58(d,J=4.8Hz,1H),7.62–7.60(m,5H),7.48–7.44(m,5H),7.38–7.35(m,4H),7.08–7.06(m,1H),6.92(d,J=7.8Hz,1H),3.23–2.05(m,3H),1.81–1.76(m,2H),0.88(td,J=6.9,3.5Hz,3H); 13 C NMR(100MHz,CDCl3)δ160.50,149.19,145.63,141.48,141.30,135.91,128.66,127.22,127.17,125.66,123.95,123.74,120.97,48.24,45.73,28.54,12.18.

[0062] Example 9 Synthesis of 2-(2-(3-chlorophenyl)butyl)pyridine

[0063]

[0064] Under a nitrogen atmosphere, 3-chlorophenylboronic acid 2i (0.4 mmol, 62.4 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt bromide (0.02 mmol, 4.4 mg), 2,2'-bipyridine (0.06 mmol, 4.7 mg), THF (1 mL), Ph3SiH (0.4 mmol, 104.1 mg) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0065] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. Column chromatography separation was carried out with an eluent of petroleum ether / ethyl acetate = 10 / 1 to obtain 37.7 mg of a colorless oily liquid, with a yield of 77%.

[0066] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(3-chlorophenyl)butyl)pyridine) are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.52 (d, J = 4.7 Hz, 1H), 7.46 (td, J = 7.6, 1.7 Hz, 1H), 7.17–7.11 (m, 3H), 7.06–7.04 (m, 1H), 6.99 (d, J = 7.2 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 3.12–3.08 (m, 1H), 3.05–2.94 (m, 2H), 1.78–1.59 (m, 2H), 0.78 (t, J = 7.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 160.08, 149.21, 146.80, 135.97, 133.93, 129.39, 127.75, 126.18, 126.06, 123.62, 121.06, 47.90, 45.44, 28.60, 11.98.

[0067] Example 10 Synthesis of 2-(2-(4-methoxyphenyl)butyl)pyridine

[0068]

[0069] Under a nitrogen atmosphere, 4-methoxyphenylboronic acid 2j (0.4 mmol, 60.8 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt bromide (0.02 mmol, 4.4 mg), 2,2'-bipyridine (0.06 mmol, 4.7 mg), THF (1 mL), Ph2SiH2 (0.4 mmol, 74 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0070] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 33.8 mg of a colorless oily liquid with a yield of 70%.

[0071] The NMR spectrum data of the obtained product (2-(2-(4-methoxyphenyl)butyl)pyridine) are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 4.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 8.4 Hz, 3H), 6.85 (d, J = 7.6 Hz, 1H), 6.78 (d, J = 8.4 Hz, 2H), 3.76 (s, 3H), 3.09–3.05 (m, 1H), 2.99–2.95 (m, 2H), 1.71–1.59 (m, 2H), 0.79 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 160.72, 157.71, 149.02, 136.59, 135.86, 128.56, 123.66, 120.85, 113.49, 55.10, 47.33, 45.84, 28.89, 12.04.

[0072] Example 11 Synthesis of 2-(2-(cyclohex-1-en-1-yl)butyl)pyridine

[0073]

[0074] Under a nitrogen atmosphere, cyclohexene-1-boronic acid 2k (0.4 mmol, 50.8 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt bromide (0.02 mmol, 4.4 mg), 2,2'-bipyridine (0.06 mmol, 4.7 mg), THF (1 mL), Ph2SiH2 (0.4 mmol, 74 μL), and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0075] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 37.0 mg of a colorless oily liquid with a yield of 86%.

[0076] The NMR spectral data of the obtained product (2-(2-(cyclohex-1-en-1-yl)butyl)pyridine) are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.48 (dd, J = 5.6, 1.6 Hz, 1H), 7.53–7.49 (m, 1H), 7.04–7.02 (m, 2H), 5.25 (s, 1H), 2.77 (d, J = 8.0 Hz, 2H), 2.33–2.26 (m, 1H), 1.93–1.77 (m, 4H), 1.56–1.44 (m, 4H), 1.41–1.34 (m, 2H), 0.78 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 161.48, 148.98, 138.20, 135.64, 123.43, 122.97, 120.62, 49.90, 42.83, 25.50, 25.17, 24.66, 22.94, 22.76, 11.91.

[0077] Example 12 Synthesis of 2-methyl-5-(1-(pyridin-2-yl)butan-2-yl)pyridine

[0078]

[0079] Under a nitrogen atmosphere, 2-methylpyridine-5-boronic acid 2l (0.4 mmol, 54.8 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt bromide (0.02 mmol, 4.4 mg), 2,2'-bipyridine (0.06 mmol, 4.7 mg), THF (1 mL), Ph2SiH2 (0.4 mmol, 74 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0080] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. Column chromatography separation was carried out with an eluent of petroleum ether / ethyl acetate = 10 / 1 to obtain 34.9 mg of a colorless oily liquid with a yield of 77%.

[0081] The NMR spectrum data of the obtained product (2-methyl-5-(1-(pyridin-2-yl)butan-2-yl)pyridine) are as follows: 1 HNMR(400MHz,CDCl3)δ8.45–8.41(m,2H),7.66(t,J=7.3Hz,1H),7.56(d,J=8.0Hz,1H),7.22–7.16(m,3H),3.27–3.06(m,3H),2.42(s,3H),1.52–1.37(m,2H),0.76(t,J=7.2Hz,3H); 13 C NMR(100MHz,CDCl3)δ158.71,157.03,148.29,148.14,136.62,136.63,135.16,124.04,122.78,43.02,42.34,29.40,23.94,11.54.

[0082] Example 13 Synthesis of 4-(1-(pyridin-2-yl)butan-2-yl)benzonitrile

[0083]

[0084] Under a nitrogen atmosphere, 4-cyanobenzeneboronic acid 2m (0.4 mmol, 58.8 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0085] The above mixture was placed at 70 °C and reacted for 8 h. After the reaction temperature dropped to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution. The mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. Column chromatography separation was carried out with an eluent of petroleum ether / ethyl acetate = 10 / 1 to obtain 37.8 mg of a colorless oily liquid with a yield of 80%.

[0086] The nuclear magnetic resonance spectrum data of the obtained product (4-(1-(pyridin-2-yl)butan-2-yl)benzonitrile) are as follows: 1 H NMR(400MHz,CDCl3)δ8.45(d,J=4.3Hz,1H),7.73–7.66(m,3H),7.61–7.50(m,2H),7.23–7.16(m,2H),3.27–3.06(m,3H),1.59–1.48(m,2H),0.77(t,J=7.4Hz,3H); 13 C NMR(100MHz,CDCl3)δ158.77,149.99,148.23,136.63,132.30,128.83,123.57,122.62,118.83,109.98,43.04,42.35,29.41,11.04。

[0087] Example 14 Synthesis of 2-(2-(4-(trifluoromethoxy)phenyl)butyl)pyridine

[0088]

[0089] Under a nitrogen atmosphere, 4-trifluoromethoxyphenylboronic acid 2n (0.4 mmol, 82.4 mg), Li3PO4 (0.4 mmol, 46.33 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), 1,4-Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL), and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0090] The above mixture was placed at 70 °C and reacted for 8 h. After the reaction temperature dropped to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution. The mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. Column chromatography separation was carried out with an eluent of petroleum ether / ethyl acetate = 10 / 1 to obtain 49.6 mg of a colorless oily liquid with a yield of 84%.

[0091] The NMR spectrum data of the obtained product (2-(2-(4-(trifluoromethoxy)phenyl)butyl)pyridine) are as follows: 1 HNMR(400MHz,CDCl3)δ8.54(d,J=4.3Hz,1H),7.69–7.63(m,1H),7.39–7.33(m,2H),7.22–7.12(m,2H),6.86(d,J=4.0Hz,2H),3.30–3.06(m,3H),1.50–1.48(m,2H),0.75(t,J=7.8Hz,3H); 13 C NMR(100MHz,CDCl3)δ158.79,148.59,144.93,136.63,129.76,129.33,123.83,122.57,114.62,43.14,42.25,29.31,11.00; 19 F NMR(375MHz,CDCl3)δ-57.93。

[0092] Example 15 Synthesis of phenyl(4-(1-(pyridin-2-yl)butan-2-yl)phenyl)methanone

[0093]

[0094] Under a nitrogen atmosphere, benzophenone-4-boronic acid 2o (0.4 mmol, 90.4 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), 1,4-Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0095] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 49.2 mg of a colorless oily liquid with a yield of 78%.

[0096] The NMR spectrum data of the obtained product (phenyl(4-(1-(pyridin-2-yl)butan-2-yl)phenyl)methanone) are as follows: 11H NMR (400 MHz, CDCl3) δ 8.44 (d, J = 4.3 Hz, 1H), 7.81–7.42 (m, 10H), 7.22–7.12 (m, 2H), 3.34–3.15 (m, 3H), 1.50–1.44 (m, 2H), 0.78 (t, J = 7.5 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 194.33, 158.69, 149.39, 148.93, 138.33, 136.76, 135.33, 132.83, 130.47, 130.37, 127.62, 122.77, 43.04, 42.15, 29.21, 11.10.

[0097] Example 16 Synthesis of 2-(2-(5-methylthiophen-2-yl)butyl)pyridine

[0098]

[0099] Under a nitrogen atmosphere, 5-methylthiophene-2-boronic acid 2p (0.4 mmol, 56.8 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), 1,4-Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0100] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 35.1 mg of a colorless oily liquid with a yield of 76%.

[0101] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(5-methylthiophen-2-yl)butyl)pyridine) are as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 4.3 Hz, 1H), 7.70–7.55 (m, 1H), 7.25–7.11 (m, 2H), 6.80 (d, J = 4.4 Hz, 1H), 6.55 (d, J = 5.3 Hz, 1H), 3.24–3.05 (m, 3H), 2.37 (s, 3H), 1.47–1.34 (m, 2H), 0.77 (t, J = 7.3 Hz, 3H); 1313C NMR (100 MHz, CDCl3) δ 158.59, 148.39, 142.33, 136.63, 136.16, 124.33, 123.33, 44.04, 43.15, 30.01, 15.21, 11.50.

[0102] Example 17 Synthesis of 2-(2-(5-methylfuran-2-yl)butyl)pyridine

[0103]

[0104] Under a nitrogen atmosphere, 5-methylfuran-2-boronic acid 2q (0.4 mmol, 50.4 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), 1,4-Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0105] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 33.6 mg of a colorless oily liquid with a yield of 78%.

[0106] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(5-methylfuran-2-yl)butyl)pyridine) are as follows: 1 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 4.3 Hz, 1H), 7.73–7.53 (m, 1H), 7.26–7.09 (m, 2H), 5.96–5.83 (m, 2H), 3.34–3.25 (m, 3H), 2.20 (s, 3H), 1.52–1.36 (m, 2H), 0.75 (t, J = 7.5 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 158.66, 154.39, 150.02, 148.33, 136.53, 123.86, 122.23, 105.63, 104.33, 44.54, 40.15, 27.61, 13.71, 9.50.

[0107] Example 18 Synthesis of 2-(2-(benzothiophen-2-yl)butyl)pyridine

[0108]

[0109] Under a nitrogen atmosphere, 2-benzothiophene-2-boronic acid 2r (0.4 mmol, 71.2 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), 1,4-Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0110] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 43.8 mg of a colorless oily liquid with a yield of 82%.

[0111] The nuclear magnetic resonance spectrum data of the obtained product (2-(2-(benzothiophen-2-yl)butyl)pyridine) are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 4.3 Hz, 1H), 7.93–7.85 (m, 1H), 7.79–7.70 (m, 1H), 7.66–7.55 (m, 1H), 7.49–7.41 (m, 1H), 7.40–7.32 (m, 2H), 7.28–7.15 (m, 2H), 3.19–3.06 (m, 3H), 1.42–1.36 (m, 2H), 0.76 (t, J = 7.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 158.76, 146.19, 139.21, 139.12, 123.83, 122.23, 118.01, 44.44, 43.35, 30.11, 9.50.

[0112] Example 19 Synthesis of 2-(2-(benzofuran-2-yl)butyl)pyridine

[0113]

[0114] Under a nitrogen atmosphere, 2s (0.4 mmol, 64.8 mg) of benzofuran-2-boronic acid, Li3PO4 (0.4 mmol, 46.3 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), 1,4-Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0115] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation was carried out with an eluent of petroleum ether / ethyl acetate = 10 / 1 to obtain 42.7 mg of a colorless oily liquid with a yield of 85%.

[0116] The NMR spectral data of the obtained product (2-(2-(benzofuran-2-yl)butyl)pyridine) are as follows: 1 H NMR(400MHz,CDCl3)δ8.52(d,J=4.3Hz,1H),7.66–7.59(m,3H),7.39–7.25(m,1H),7.22–7.16(m,3H),6.72(d,J=7.4Hz,1H),3.33–3.25(m,3H),1.52–1.46(m,2H),0.76(t,J=7.5Hz,3H); 13 C NMR(100MHz,CDCl3)δ166.33,158.77,154.16,148.24,136.65,126.98,124.74,123.83,122.72,120.23,111.51,99.15,45.35,40.51,27.67,9.13.

[0117] Example 20 Synthesis of (E)-2-(2-ethyl-4-phenylbut-3-en-1-yl)pyridine

[0118]

[0119] Under a nitrogen atmosphere, 2-styrylboronic acid 2t (0.4 mmol, 59.2 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), 1,4-Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL), and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0120] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation was performed with an eluent of petroleum ether / ethyl acetate = 10 / 1 to obtain 36.5 mg of a colorless oily liquid with a yield of 77%.

[0121] The NMR spectral data of the obtained product ((E)-2-(2-ethyl-4-phenylbut-3-en-1-yl)pyridine) are as follows: 1 HNMR(400MHz,CDCl3)δ8.49(d,J=4.4Hz,1H),7.68–7.60(m,1H),7.36–7.11(m,7H),6.51–6.43(m,1H),6.11–6.02(m,1H),3.08–2.73(m,2H),2.56–2.46(m,1H),1.51–1.37(m,2H),0.77(t,J=7.4Hz,3H); 13 C NMR(100MHz,CDCl3)δ158.76,148.27,136.66,136.35,128.65,128.58,123.72,122.74,43.82,42.83,28.67,12.13.

[0122] Example 21 Synthesis of (E)-2-(2-ethyloct-3-en-1-yl)pyridine

[0123]

[0124] Under a nitrogen atmosphere, 2-butyl-vinylboronic acid 2u (0.4 mmol, 51.2 mg), Li3PO4 (0.4 mmol, 46.3 mg), cobalt chloride (0.02 mmol, 2.6 mg), 2,2'-bipyridine (0.03 mmol, 4.7 mg), 1,4-Dioxane (1 mL), Et3SiH (0.4 mmol, 64 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0125] The above mixture was reacted at 70 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation was carried out with an eluent of petroleum ether / ethyl acetate = 10 / 1 to obtain 31.7 mg of a colorless oily liquid with a yield of 73%.

[0126] The NMR spectrum data of the obtained product (E)-2-(2-ethyloct-3-en-1-yl)pyridine) are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 4.4 Hz, 1H), 7.68–7.60 (m, 1H), 7.36–7.11 (m, 2H), 5.48–5.33 (m, 2H), 2.98–2.86 (m, 2H), 2.55–2.34 (m, 1H), 1.96–1.91 (m, 2H), 1.50–1.29 (m, 6H), 0.92–0.87 (m, 6H); 13 C NMR (100 MHz, CDCl3) δ 158.68, 148.31, 136.56, 134.98, 129.35, 123.95, 122.72, 122.74, 43.77, 42.66, 33.76, 32.41, 28.93, 22.85, 14.24, 12.13.

[0127] Example 22 Control experiment without cobalt acetylacetonate

[0128]

[0129] Under a nitrogen atmosphere, 4-fluorophenylboronic acid 2a (0.4 mmol, 56.0 mg), CsF (0.8 mmol, 121.5 mg), 6,6'-dimethyl-2,2'-bipyridine (0.04 mmol, 7.4 mg), DMA (1 mL), Et3SiH (0.6 mmol, 96 μL) and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0130] The above mixture was placed at 80 °C for reaction for 8 h. After the reaction temperature dropped to room temperature, 2 mL of a saturated NaHCO₃ solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. It was identified by ¹H NMR that the reaction did not occur.

[0131] Example 23 Control experiment without 6,6'-dimethyl-2,2'-bipyridine

[0132]

[0133] Under a nitrogen atmosphere, 4-fluorophenylboronic acid 2a (0.4 mmol, 56.0 mg), CsF (0.8 mmol, 121.5 mg), cobalt(II) acetylacetonate (0.02 mmol, 5.2 mg), DMA (1 mL), Et₃SiH (0.6 mmol, 96 μL), and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0134] The above mixture was placed at 80 °C for reaction for 8 h. After the reaction temperature dropped to room temperature, 2 mL of a saturated NaHCO₃ solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. It was identified by ¹H NMR that the reaction did not occur.

[0135] Example 24 Control experiment without triethylsilane

[0136]

[0137] Under a nitrogen atmosphere, 4-fluorophenylboronic acid 2a (0.4 mmol, 56.0 mg), CsF (0.8 mmol, 121.5 mg), cobalt(II) acetylacetonate (0.02 mmol, 5.2 mg), 6,6'-dimethyl-2,2'-bipyridine (0.04 mmol, 7.4 mg), DMA (1 mL), and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0138] The above mixture was placed at 80 °C for reaction for 8 h. After the reaction temperature dropped to room temperature, 2 mL of a saturated NaHCO₃ solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and the organic phase was concentrated. It was identified by ¹H NMR that the reaction did not occur.

[0139] Example 25 Control experiment without cesium fluoride

[0140]

[0141] Under a nitrogen atmosphere, 4-fluorophenylboronic acid 2a (0.4 mmol, 56.0 mg), cobalt(II) acetylacetonate (0.02 mmol, 5.2 mg), 6,6'-dimethyl-2,2'-bipyridine (0.04 mmol, 7.4 mg), DMA (1 mL), Et3SiH (0.6 mmol, 96 μL), and 2-(3-butenyl)pyridine 1 (0.2 mmol, 29 μL) were successively added to a 25 mL reaction tube.

[0142] The above mixture was reacted at 80 °C for 8 h. After the reaction temperature was cooled to room temperature, 2 mL of a saturated NaHCO3 solution was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. Column chromatography separation with an eluent of petroleum ether / ethyl acetate = 10 / 1 gave 15.4 mg of product 1a′ (E)-2-(but-1-en-1-yl)pyridine with a yield of 58%; product 1a″: (E)-2-(but-2-en-1-yl)pyridine as a colorless oily liquid, 5.9 mg, with a yield of 22%.

[0143] The NMR spectral data of the obtained product (E)-2-(but-1-en-1-yl)pyridine 1a′ are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 4.2 Hz, 1H), 7.67–7.41 (m, 3H), 6.69–6.53 (m, 2H), 2.07–1.99 (m, 2H), 0.77 (t, J = 7.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 154.78, 148.88, 137.04, 134.33, 128.12, 124.35, 127.76, 26.17, 14.37.

[0144] The NMR spectral data of the obtained product (E)-2-(but-2-en-1-yl)pyridine 1a″ are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 4.2 Hz, 1H), 7.73–7.61 (m, 1H), 7.23–7.15 (m, 2H), 6.49–6.37 (m, 2H), 3.55 (d, J = 7.2 Hz, 2H), 1.63 (d, J = 7.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 156.48, 148.68, 136.24, 127.63, 122.92, 120.99, 109.11, 36.14, 17.67.

[0145] The above-described embodiments are only preferred embodiments of the present invention, and are merely used to explain the present invention, not to limit the scope of implementation of the present invention. For those skilled in the art of this technology, of course, other implementation manners can be easily made by means of replacement or change according to the technical content disclosed in this specification. Therefore, all changes and improvements made on the principle of the present invention should be included within the scope of the patent application of the present invention.

Claims

1. A method for synthesizing a 2-(2-arylbutyl)pyridine compound, characterized in that, It includes the following steps: Under a nitrogen atmosphere, boric acid, a base, a cobalt catalyst, a nitrogen-containing ligand, an organic solvent, a hydrosilicon reagent, and a 2-(3-butenyl)pyridine substrate are successively added to a reaction tube, and the reaction is carried out at a temperature of 70-80 °C for 8 h. After extraction, drying, and concentration, a 2-(2-arylbutyl)pyridine compound is obtained; The boric acid is selected from one of 4-fluorobenzeneboronic acid, 4-tert-butyl-benzeneboronic acid, 4-methylthiophenylboronic acid, 4-methylbenzeneboronic acid, 4-methoxycarbonylbenzeneboronic acid, 4-trifluoromethylbenzeneboronic acid, 3-methylbenzeneboronic acid, 3,5-diphenylbenzeneboronic acid, 3-chlorobenzeneboronic acid, 4-methoxybenzeneboronic acid, cyclohexene-1-boronic acid, 2-methylpyridine-5-boronic acid, 4-cyanobenzeneboronic acid, 4-trifluoromethoxybenzeneboronic acid, benzophenone-4-boronic acid, 5-methylthiophene-2-boronic acid, 5-methylfuran-2-boronic acid, benzothiophene-2-boronic acid, benzofuran-2-boronic acid, 2-styrylboronic acid or 2-n-butyl-vinylboronic acid, and the corresponding 2-(2-arylbutyl)pyridine compound is 2-(2-(4-fluorophenyl)butyl)pyridine, 2-(2-(4-(tert-butyl)phenyl)butyl)pyridine, 2-(2-(4-(methylthio)phenyl)butyl)pyridine, 2-(2-(4-(methyl)phenyl)butyl)pyridine, 2-(2-(4-(methyl ester)phenyl)butyl)pyridine, 2-(2-(4-(trifluoromethyl)phenyl)butyl)pyridine, 2-(2-(3-(methyl)phenyl)butyl)pyridine, 2-(2-([1,1':3',1'-terphenyl])butyl)pyridine, 2-(2-(3-chlorophenyl)butyl)pyridine, 2-(2-(4-methoxyphenyl)butyl)pyridine, 2-(2-(cyclohex-1-en-1-yl)butyl)pyridine, 2-methyl-5-(1-(pyridin-2-yl)butan-2-yl)pyridine, 4-(1-(pyridin-2-yl)butan-2-yl)benzonitrile, 2-(2-(4-(trifluoromethoxy)phenyl)butyl)pyridine, phenyl(4-(1-(pyridin-2-yl)butan-2-yl)phenyl)methanone, 2-(2-(5-methylthiophen-2-yl)butyl)pyridine, 2-(2-(5-methylfuran-2-yl)butyl)pyridine, 2-(2-(benzothiophen-2-yl)butyl)pyridine, 2-(2-(benzofuran-2-yl)butyl)pyridine, ( E )-2-(2-ethyl-4-phenylbut-3-en-1-yl)pyridine, ( E )-2-(2-ethyloct-3-en-1-yl)pyridine; The base is selected from one of KHCO3, CsF, Cs2CO3, Li3PO4, CsHCO3, KH2PO4, or KF; The cobalt catalyst is selected from one of cobalt chloride, cobalt iodide, cobalt sulfate, cobalt acetylacetonate, cobalt fluoride, or cobalt bromide; The nitrogen-containing ligand is selected from one of 2,2'-bipyridine, 2,2'-biquinoline, 4,4'-dimethyl-2,2'-bipyridine, 6,6'-dimethyl-2,2'-bipyridine, or 2,6-bis(1-pyrazolyl)pyridine; The hydrosilicon reagent is selected from one of triethylsilane, diphenylsilane, or triphenylsilane.

2. The synthesis method according to claim 1, characterized in that, The molar ratio of boric acid to 2-(3-butenyl)pyridine is 2-2.5:

1.

3. The synthesis method according to claim 1, characterized in that, The molar ratio of the amount of the base used to the amount of 2-(3-butenyl)pyridine used is 2-4:

1.

4. The synthesis method according to claim 1, characterized in that, The amount of the cobalt catalyst used is 10%-20% of the molar amount of 2-(3-butenyl)pyridine.

5. The synthesis method according to claim 1, characterized in that, The amount of the nitrogen-containing ligand used is 15%-30% of the molar amount of 2-(3-butenyl)pyridine.

6. The synthesis method according to claim 1, characterized in that, The organic solvent is selected from 1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, N-methylpyrrolidone, N,N-dimethylacetamide.

7. The synthesis method according to claim 1, characterized in that, The molar ratio of the hydrosilicon reagent to 2-(3-butenyl)pyridine is 2-4:1.

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