Method for carrying out cyclization reaction on 2-biphenyl fluorosulfonate compound and alkyne under catalysis of palladium

Abstract

The invention discloses a method for catalyzing cyclization reaction of a 2-biphenyl fluorosulfonate compound and alkyne by palladium, which comprises the following steps: by taking 2-biphenyl fluorosulfonate as a raw material, adding alkyne as shown in a formula (II), a palladium catalyst, a ligand, alkali and a solvent into a reactor to prepare a phenanthrene compound as shown in a formula (III), substituent groups R1 and R2 are respectively and independently selected from hydrogen, chlorine group, fluorine group, methyl group, methoxyl group, trifluoromethyl group, isopropyl group, phenyl group, cyano group, tert-butyl group or naphthyl group; substituent groups R3 and R4 are respectively and independently selected from methyl, ethyl, n-butyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl or 4-ketophenyl. According to the invention, the simple and easily available 2-biphenyl fluorosulfonate compound is used as a raw material, and the corresponding phenanthrene compound can be obtained at a relatively high yield.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, specifically relating to a palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes. Background Technology

[0002] Phenanthrene compounds are polycyclic aromatic hydrocarbons containing three benzene rings and can be used in the synthesis of resins, plant growth hormones, vat dyes, tanning agents, etc. To date, nearly a hundred natural phenanthrenes have been isolated, but only eight species have been isolated, including monophenanthrene, diphenanthrene, and phenanthrene glycosides. Many isolated compounds are substituted with vinyl groups. Therefore, it is particularly important to develop new synthetic methods for phenanthrene compounds. The synthetic methods for aryl ether compounds reported in the literature mainly include: (1) Aromatic hydrocarbons can be converted into triphenyls through an efficient palladium (0)-catalyzed cyclotrimerization reaction, thus confirming this possibility. Phenanthrene compounds are prepared by cocyclization of alkynes and alkynes, but the functional group tolerance is poor and the group substitution is limited. (2) Various alkynes are coupled with diaryl Grignard reagents. Oxidative coupling conditions allow the reaction to proceed with significant chemoselectivity, but the potential problems of Grignard reagents limit its application. (3) Phenanthrenes can be synthesized by free radical initiators, photocatalysts, and electrocatalysis, but there are problems such as harsh conditions and poor functional group tolerance.

[0003] The fluorosulfonate group (-OSO2F) possesses similar reactivity to -OTf, bromides, or chlorides, and is an easily leaving group. Currently, -OSO2F has been widely used in various types of chemical transformations, including reduction, metal-catalyzed cross-coupling, deoxyfluorination, amination, and methoxycarbonylation. Summary of the Invention

[0004] To address the deficiencies in existing technologies, this invention provides a palladium-catalyzed method for the cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes. To achieve the above objective, this invention employs a palladium catalyst to efficiently promote the cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes to prepare phenanthrene compounds.

[0005] This invention relates to a method for preparing phenanthrene compounds using inexpensive, readily available, and highly stable fluorosulfonates as raw materials and with palladium catalysis.

[0006] The technical solution adopted in this invention is: A palladium-catalyzed cyclization reaction between 2-biphenyl fluorosulfonate compounds and alkynes, the method comprising the following steps: Using 2-biphenyl fluorosulfonate compounds as shown in formula (I) as raw materials, alkynes, palladium catalysts, ligands, bases, and solvents as shown in formula (II) are added to a reactor to prepare phenanthrene compounds as shown in formula (III). The reaction formula is as follows: , The substituents R1 and R2 in formula (I) and formula (III) are each independently selected from hydrogen, chloro, fluoro, methyl, methoxy, trifluoromethyl, isopropyl, phenyl, tert-butyl, cyano or naphthyl; the substituents R3 and R4 in formula (II) and formula (III) are each independently selected from methyl, ethyl, n-butyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl or 4-ketophenyl.

[0007] Furthermore, the molar ratio of the 2-biphenyl fluorosulfonate compound shown in formula (Ⅰ) to the alkyne shown in formula (Ⅱ) is 1:1~20.

[0008] Furthermore, the molar ratio of the 2-biphenyl fluorosulfonate compound shown in formula (I) to the palladium catalyst is 1:0.05~0.2.

[0009] Furthermore, the molar ratio of the 2-biphenyl fluorosulfonate compound to the ligand shown in formula (I) is 1:0.05~0.2.

[0010] Furthermore, the molar ratio of the 2-biphenyl fluorosulfonate compound shown in formula (I) to the base is 1:1 to 5.

[0011] Furthermore, the molar ratio of the 2-biphenyl fluorosulfonate compound shown in formula (I) to the solvent is 1:1 to 30.

[0012] Furthermore, the reaction temperature is 70°C. o C~150 o C, the reaction time is 8h~22h.

[0013] Furthermore, the palladium catalyst is Pd(OAc)2, Pd(dba)2, PdCl2 or Pd(PPh3)2Cl2, and the ligand is triphenylphosphine, 1,2-bis(diphenylphosphine)ethane, 1,2-bis(diphenylphosphine)ethane, 1,3-bis(diphenylphosphine)propane, 1,1'-bis(diphenylphosphine)ferrocene, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl or 2,2'-bipyridine.

[0014] Furthermore, the base is CsF, DBU, n -Pr2NH、 n -Et2NH or n -Me2NH in THF.

[0015] Furthermore, the solvent is 1,4-Dioxane, DCE, DMF, or DMSO.

[0016] The beneficial effects of this invention are mainly reflected in: 1) The raw materials used in this invention are readily available, and the selectivity is high due to the synergistic effect of the palladium catalyst and ligands.

[0017] 2) The method of the present invention has broad functional group tolerance and can obtain the corresponding phenanthrene compounds in good yield.

[0018] 3) The operation process of this invention is simple and efficient. Detailed Implementation

[0019] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0020] The reaction equation for the method of this invention is as follows: .

[0021] Example 1: Preparation of 9,10-diphenylphenanthrene

[0022] In a 25 mL Schleck tube, 0.2 mmol of 2-biphenyl fluorosulfonate (Formula I, R1=H, R2=H) and 0.24 mmol of diphenylacetylene (Formula II, R1=Ph, R2=Ph) were added sequentially. l The reaction mixture was prepared by stirring at 130 °C for 14 h, with the following steps: Pd(OAc)2 (0.02 mmol), 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl (0.02 mmol), 2 mol / L dimethylamine in tetrahydrofuran solution (0.3 mL), and N,N-dimethylformamide (2 mL). After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, 20 mL of ethyl acetate was added for dilution, and then 20 mL of water was added for washing three times. The mixture was concentrated under reduced pressure and separated by column chromatography to obtain 9,10-diphenylphenanthrene with a purity of 99% and a yield of 90%.

[0023] 1H NMR spectrum: 1 H NMR (400 MHz, Chloroform- d ) δ 8.85 (dd, J = 8.4, 1.1Hz, 2H), 7.71 (ddd, J = 8.3, 6.8, 1.5 Hz, 2H), 7.61 (dd, J = 8.4, 1.4 Hz, 2H), 7.53 (ddd, J = 8.2, 6.8, 1.2 Hz, 2H), 7.31 – 7.18 (m, 10H).

[0024] Example 2: Preparation of 1-chloro-9,10-diphenylphenanthrene

[0025] In a 25 mL Schleck tube, 0.2 mmol of 4'-chlorobiphenyl-2-fluorosulfonate (Formula I, R1=H, R2=Cl), 0.24 mmol of diphenylacetylene (Formula II, R1=Ph, R2=Ph), 0.02 mmol of Pd(OAc)2, 0.02 mmol of 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl (0.02 mmol), 0.3 mL of 2 mol / L tetrahydrofuran solution of dimethylamine, and 2 mL of N,N-dimethylformamide were added sequentially. The mixture was stirred at 130 °C for 14 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the mixture was diluted with 20 mL of ethyl acetate. Then, it was washed three times with 20 mL of water, concentrated under reduced pressure, and separated by column chromatography to obtain 1-chloro-9,10-diphenylphenanthrene with a purity of 99% and a yield of 86%.

[0026] 1H NMR spectrum: 1 H NMR (400 MHz, Chloroform- d ) δ 8.76 (dd, J = 8.6, 5.4Hz, 2H), 7.70 (ddd, J = 8.3, 6.8, 1.5 Hz, 1H), 7.64 (dd, J = 8.9, 2.2 Hz, 1H), 7.61 – 7.50 (m, 3H), 7.32 – 7.12 (m, 10H).

[0027] Example 3: Preparation of 1-fluoro-9,10-diphenylphenanthrene

[0028] In a 25 mL Schleck tube, 0.2 mmol of 4'-fluorobiphenyl-2-fluorosulfonate (Formula I, R1=H, R2=F), 0.24 mmol of diphenylacetylene (Formula II, R1=Ph, R2=Ph), 0.02 mmol of Pd(OAc)2, 0.02 mmol of 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl (0.02 mmol), 0.3 mL of 2 mol / L dimethylamine in tetrahydrofuran, and 2 mL of N,N-dimethylformamide were added sequentially. The mixture was stirred at 130 °C for 14 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the mixture was diluted with 20 mL of ethyl acetate. Then, it was washed three times with 20 mL of water, concentrated under reduced pressure, and separated by column chromatography to obtain 1-fluoro-9,10-diphenylphenanthrene with a purity of 99% and a yield of 80%.

[0029] 1H NMR spectrum: 1H NMR (400 MHz, Chloroform- d ) δ 8.86 – 8.72 (m, 2H),7.71 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.60 (dd, J = 8.3, 1.4 Hz, 1H), 7.52 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.43 (ddd, J = 9.1, 7.9, 2.7 Hz, 1H), 7.36 – 7.12 (m,11H).

[0030] Example 4: Preparation of 1-methyl-9,10-diphenylphenanthrene

[0031] In a 25 mL Schleck tube, 0.2 mmol of 4'-methylbiphenyl-2-fluorosulfonate (Formula I, R1=H, R2=Me), 0.24 mmol of diphenylacetylene (Formula II, R1=Ph, R2=Ph), 0.02 mmol of Pd(OAc)2, 0.02 mmol of 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl (0.02 mmol), 0.3 mL of 2 mol / L tetrahydrofuran solution of dimethylamine, and 2 mL of N,N-dimethylformamide were added sequentially. The mixture was stirred at 130 °C for 14 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the mixture was diluted with 20 mL of ethyl acetate. Then, it was washed three times with 20 mL of water, concentrated under reduced pressure, and separated by column chromatography to obtain 1-methyl-9,10-diphenylphenanthrene with a purity of 99% and a yield of 90%.

[0032] 1H NMR spectrum: 1 H NMR (400 MHz, Chloroform- d ) δ 8.80 (dd, J = 8.4, 1.1Hz, 1H), 8.73 (d, J = 8.5 Hz, 1H), 7.67 (ddd, J = 8.3, 6.8, 1.5 Hz, 1H), 7.59 –7.45 (m, 3H), 7.36 (s, 1H), 7.31 – 7.15 (m, 10H), 2.45 (s, 3H).

[0033] Example 5: Preparation of 1-trifluoromethyl-9,10-diphenylphenanthrene

[0034] In a 25 mL Schleck tube, 0.2 mmol of 4'-trifluoromethylbiphenyl-2-fluorosulfonate (Formula I, R1=H, R2=CF3), 0.3 mL of diphenylacetylene (Formula II, R1=Ph, R2=Ph), 0.02 mmol of Pd(OAc)2, 0.02 mmol of 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl (0.02 mmol), 0.3 mL of 2 mol / L tetrahydrofuran solution of dimethylamine, and 2 mL of N,N-dimethylformamide were added sequentially. The mixture was stirred at 130 °C for 14 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the mixture was diluted with 20 mL of ethyl acetate. Then, it was washed three times with 20 mL of water, concentrated under reduced pressure, and separated by column chromatography to obtain 1-trifluoromethyl-9,10-diphenylphenanthrene with a purity of 99% and a yield of 76%.

[0035] 1H NMR spectrum: 1 H NMR (400 MHz, Chloroform- d ) δ 8.94 (d, J = 9.1 Hz, 1H), 8.85 (dd, J = 8.3, 1.1 Hz, 1H), 7.93 – 7.85 (m, 2H), 7.75 (ddd, J = 8.3, 6.6, 1.7Hz, 1H), 7.66 – 7.56 (m, 2H), 7.28 (qdd, J = 8.5, 4.8, 2.7 Hz, 6H), 7.18 (ddd, J = 7.8, 2.8, 1.7 Hz, 4H).

[0036] Example 6: Preparation of 1,9,10-Triphenylphenanthrene

[0037] In a 25 mL Schleck tube, 0.2 mmol of 4'-phenylbiphenyl-2-fluorosulfonate (Formula I, R1=H, R2=Ph), 0.24 mmol of diphenylacetylene (Formula II, R1=Ph, R2=Ph), 0.02 mmol of Pd(OAc)2, 0.02 mmol of 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl (0.02 mmol), 0.3 mL of 2 mol / L tetrahydrofuran solution of dimethylamine, and 2 mL of N,N-dimethylformamide were added sequentially. The mixture was stirred at 130 °C for 14 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the mixture was diluted with 20 mL of ethyl acetate. Then, it was washed three times with 20 mL of water, concentrated under reduced pressure, and separated by column chromatography to obtain 1,9,10-triphenylphenanthrene with a purity of 99% and a yield of 89%.

[0038] 1H NMR spectrum: 1 H NMR (400 MHz, Chloroform- d ) δ 7.96 (dd, J = 8.6, 2.0Hz, 1H), 7.82 (d, J = 1.9 Hz, 1H), 7.71 (ddd, J = 8.3, 6.8, 1.5 Hz, 1H), 7.60(ddd, J = 8.1, 3.4, 1.2 Hz, 3H), 7.52 (ddd, J = 8.2, 6.7, 1.2 Hz, 1H), 7.44 (dd, J = 8.4, 6.8 Hz, 2H), 7.38 – 7.33 (m, 1H), 7.30 – 7.18 (m, 12H).

[0039] Example 7: Preparation of 1-tert-butyl-9,10-diphenylphenanthrene

[0040] In a 25 mL Schleck tube, 4'-tert-butylbiphenyl-2-fluorosulfonate (Formula I, R1=H, R2=) is added sequentially. tBu (0.2 mmol), diphenylacetylene (Formula II, R1=Ph, R2=Ph) (0.3 mL), Pd(OAc)2 (0.02 mmol), 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl (0.02 mmol), a 2 mol / L tetrahydrofuran solution of dimethylamine (0.3 mL), and N,N-dimethylformamide (2 mL) were stirred at 130 °C for 14 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, 20 mL of ethyl acetate was added for dilution, and then 20 mL of water was added for washing three times. The mixture was concentrated under reduced pressure and separated by column chromatography to obtain 1-tert-butyl-9,10-diphenylphenanthrene with a purity of 99% and a yield of 88%.

[0041] 1H NMR spectrum: 1 H NMR (400 MHz, Chloroform- d ) δ 8.79 (dd, J = 14.3, 8.5Hz, 2H), 7.77 (dd, J = 8.7, 2.1 Hz, 1H), 7.67 (ddd, J = 8.2, 6.6, 1.4 Hz, 1H),7.60 – 7.54 (m, 2H), 7.48 (ddd, J = 8.1, 6.8, 1.1 Hz, 1H), 7.31 – 7.16 (m, 10H), 1.31 (s, 9H).

[0042] Example 8: Preparation of 9-(4-methoxyphenyl)-10-phenylphenanthrene

[0043] In a 25 mL Schleeck container, 2-biphenyl fluorosulfonate (Formula I, R1=H, R2=) is added sequentially. t Bu (0.2 mmol), (4-methylphenyl)phenylacetylene (Formula II, R1=4-OMe-Ph, R2=Ph) (0.24 mL), Pd(OAc)2 (0.02 mmol), 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl (0.02 mmol), 2 mol / L dimethylamine in tetrahydrofuran solution (0.3 mL), N,N-dimethylformamide (2 mL), stirred at 130 °C for 14 h. After the reaction was completed, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, diluted with 20 mL of ethyl acetate, and then washed three times with 20 mL of water. The mixture was concentrated under reduced pressure and separated by column chromatography to obtain 9-(4-methoxyphenyl)-10-phenylphenanthrene with a purity of 99% and a yield of 89%.

[0044] 1H NMR spectrum: 1 H NMR (400 MHz, Chloroform- d ) δ 8.84 (d, J = 8.3 Hz, 2H),7.74 – 7.66 (m, 2H), 7.63 (d, J = 7.3 Hz, 1H), 7.58 (d, J = 7.1 Hz, 1H), 7.52 (q, J = 7.0, 6.4 Hz, 2H), 7.33 – 7.17 (m, 5H), 7.10 (d, J = 8.7 Hz, 2H), 6.82 (d, J =8.7 Hz, 2H), 3.81 (s, 3H).

Claims

1. A method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes, characterized in that, The method includes the following procedures: Using 2-biphenyl fluorosulfonate compounds as shown in formula (I) as raw materials, alkynes, palladium catalysts, ligands, bases, and solvents as shown in formula (II) are added to a reactor to prepare phenanthrene compounds as shown in formula (III). The reaction formula is as follows: ， The substituents R1 and R2 in formula (I) and formula (III) are each independently selected from hydrogen, chloro, fluoro, methyl, methoxy, trifluoromethyl, isopropyl, phenyl, tert-butyl, cyano or naphthyl; the substituents R3 and R4 in formula (II) and formula (III) are each independently selected from methyl, ethyl, n-butyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl or 4-ketophenyl.

2. The method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes as described in claim 1, characterized in that, The molar ratio of the 2-biphenyl fluorosulfonate compound shown in formula (Ⅰ) to the alkyne shown in formula (Ⅱ) is 1:1~20.

3. The method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes as described in claim 1, characterized in that, The molar ratio of the 2-biphenyl fluorosulfonate compound shown in formula (I) to the palladium catalyst is 1:0.05~0.

2.

4. The method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes as described in claim 1, characterized in that, The molar ratio of the 2-biphenyl fluorosulfonate compound to the ligand shown in formula (I) is 1:0.05~0.

2.

5. The method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes as described in claim 1, characterized in that, The molar ratio of the 2-biphenyl fluorosulfonate compound shown in formula (I) to the base is 1:1~5.

6. The method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes as described in claim 1, characterized in that, The molar ratio of the 2-biphenyl fluorosulfonate compound shown in formula (I) to the solvent is 1:1 to 30.

7. The method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes as described in claim 1, characterized in that, The reaction temperature is 70℃~150℃, and the reaction time is 8h~22h.

8. The method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes as described in claim 1, characterized in that, The palladium catalyst is Pd(OAc)2, Pd(dba)2, PdCl2 or Pd(PPh3)2Cl2, and the ligand is triphenylphosphine, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, 1,1'-bis(diphenylphosphino)ferrocene, 2-dicyclohexylphosphine-2',6'-dimethoxybiphenyl or 2,2'-bipyridine.

9. The method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes as described in claim 1, characterized in that, The base is CsF, DBU, n -Pr2NH、 n -Et2NH or n -Me2NH in THF.

10. The method for palladium-catalyzed cyclization reaction of 2-biphenyl fluorosulfonate compounds and alkynes as described in claim 1, characterized in that, The solvent is 1,4-Dioxane, DCE, DMF, or DMSO.

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