A method for synthesizing iron-catalyzed alkyl internal alkyne compounds

Abstract

The invention discloses a synthesis method of an iron-catalyzed alkyl internal alkyne compound, and belongs to the field of organic alkyne chemical synthesis. The invention uses an iron salt as a catalyst, an alkyne-forming agent and an olefin as raw materials, and phenylsilane as a hydrogen source, and reacts in a mixed solvent with an ethanol and ethylene glycol solvent ratio of 4:1 at a reaction temperature of 35°C to obtain an alkyl internal alkyne compound. The synthesis method of the invention has simple and easy-to-obtain catalysts and reaction raw materials, mild reaction conditions, good functional group compatibility, convenient operation, and good industrial application prospects.

Description

Technical Field

[0001] The invention belongs to the field of organic alkyne chemical synthesis, and particularly relates to a method for synthesizing an iron-catalyzed alkyl internal alkyne compound. Background Art

[0002] Alkynes are unsaturated hydrocarbon compounds containing carbon-carbon triple bonds, which are widely present in molecules such as natural products, drugs, and materials. In addition, alkynes can be used as a practical reaction precursor for the synthesis of a variety of functional molecules. Constructing the molecular skeleton of alkynes has become one of the most important research directions in the field of organic synthesis. The Sonogashira reaction, as a classic coupling reaction, can be used for the synthesis of alkyne compounds. However, since alkyl transition metal complexes are prone to side reactions such as β-H elimination, there are great challenges in the synthesis of alkyl-substituted internal alkyne compounds. Therefore, it is of great practical value to develop a method for synthesizing alkyl internal alkyne compounds under mild conditions using simple and readily available olefins as reaction raw materials.

[0003] A document (Angew. Chem. Int. Ed. 2006, 45, 5847-5849) reports that the product of anti-Markovnikov addition of olefins can be synthesized by using boron hydride and olefin in situ generated alkyl boride and alkynyl reagent under the condition of free radical initiator. The technical content involved in this invention is to realize the Markovnikov hydrogenation alkynylation reaction of olefins through the hydrogenation reaction path of iron hydride and olefins to obtain the corresponding alkyl internal acetylenic compound. Summary of the invention

[0004] The purpose of the present invention is to provide a method for synthesizing an iron-catalyzed alkynylation compound of olefins to prepare an alkyl internal acetylenic compound of olefin anti-Markovnikov addition. The catalyst and raw materials of the method are cheap and easy to obtain, the reaction efficiency is high, the adaptability of the functional group is good, the reaction conditions are mild, the operation is simple, and it has good industrial application prospects.

[0005] A method for synthesizing an alkyl internal alkyne compound by iron catalysis, the method comprising the following steps:

[0006] Using iron salt as catalyst, acetylenic reagent and olefin as raw materials, in a mixed solvent of ethanol and ethylene glycol with a solvent ratio of 4:1, the reaction temperature is 35°C, and phenylsilane is used as a hydrogen source to prepare alkyl internal alkyne compounds;

[0007] The structural formula of the alkene acetylation compound is: Alkynylation reagents: The structural formula of the olefin is:

[0008] Wherein R1 and R2 are substituted or unsubstituted aromatic rings, substituted or unsubstituted alkyl groups, and the substituents are selected from: C1-8 alkyl groups, C1-8 alkoxy groups, halogen (F, Cl, Br), halogen-substituted C1-8 alkyl groups and C1-11 alkanoic acid groups.

[0009] In one embodiment of the present invention, the reaction hydrogen source is PhSiH3 and the reaction time is 12 hours.

[0010] In one embodiment of the present invention, the aromatic ring is a benzene ring.

[0011] In one embodiment of the present invention, the alkynylating agent is selected from any one or more of the following: Specific preference

[0012] In one embodiment of the present invention, the metal salt is selected from any one or more of the following: Fe(acac)3, FeCl3, In(acac)3, and Fe(acac)3 is particularly preferred.

[0013] In one embodiment of the present invention, the solvent is selected from any one or more of the following: ethanol, ethanol:ethylene glycol (4:1), and ethanol:ethylene glycol (4:1) is more preferred.

[0014] In one embodiment of the present invention, the temperature is selected from any one or more of the following: 35°C, 70°C, and 35°C is preferred.

[0015] In one embodiment of the present invention, the molar ratio of the acetylation reagent to the olefin compound reagent is 1:1.5.

[0016] In one embodiment of the present invention, the amount of the iron salt relative to the acetylation agent is 30 mol%.

[0017] In one embodiment of the present invention, the amount of the hydrogen source relative to the acetylation agent is 2 equivalents.

[0018] In one embodiment of the present invention, the amount of the organic solvent used is 1 mL / 0.2 mmol of the alkynylating agent, that is, 5 mL / mmol of the alkynylating agent.

[0019] In one embodiment of the present invention, the reaction is carried out under an inert atmosphere.

[0020] In one embodiment of the present invention, the synthetic route of the reaction is as follows:

[0021]

[0022] In one embodiment of the present invention, the alkynyl compound of olefin specifically comprises the following structure:

[0023]

[0024]

[0025] In one embodiment of the present invention, the method comprises the following specific steps:

[0026] In a reaction tube with a stirrer, under N2 atmosphere, catalyst, acetylation agent, ethanol, ethylene glycol and olefin compound were added in sequence and stirred at 35°C for 12 hours. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the target compound.

[0027] Beneficial Effects

[0028] An alkyl internal alkyne compound is prepared by using iron salt as a catalyst, an acetylenic reagent and olefin as raw materials, phenylsilane as a hydrogen source, in a mixed solvent with an ethanol to ethylene glycol solvent ratio of 4:1, and a reaction temperature of 35°C. The catalyst and reaction raw materials involved in the synthesis method of the present invention are simple and easy to obtain, the reaction conditions are mild, the functional group compatibility is good, the operation is convenient, and the method has good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The schematic diagram of the synthesis method of the present invention is shown in FIG. DETAILED DESCRIPTION

[0030] In order to make the contents of the present invention easier to understand, the technical solution of the present invention is further described below in conjunction with specific implementation methods, but the present invention is not limited to the scope of the embodiments.

[0031] Example 1

[0032] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 81%).

[0033]

[0034] 1 H NMR (500MHz, CDCl3) δ7.39-7.36 (m, 2H), 7.29-7.25 (m, 3H), 3.90 (t, J=7.4Hz, 2H), 1.77 (t, J=7.4Hz, 2H), 1.31 (s, 6H), 0.91 (s, 9H), 0.09 (s, 6H); 13 C NMR (126MHz, CDCl3) δ131.5, 128.1, 127.4, 123.9, 96.6, 80.6, 61.0, 45.6, 30.3, 29.8, 26.0, 18.3, -5.2.

[0035] Example 2

[0036] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 65%).

[0037]

[0038] 1H NMR (400MHz, CDCl3) δ7.39-7.36 (m, 2H), 7.27-7.24 (m, 3H), 1.55-1.42 (m, 2H), 1.47-1.42 (m, 2H), 1.27 (s, 6H), 0.95 (t, J=7.1Hz, 3H); 13 C NMR (101MHz, CDCl3) 6131.5, 128.1, 127.3, 124.2, 97.6, 80.2, 45.9, 31.7, 29.3, 18.7, 14.6.

[0039] Example 3

[0040] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation agent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 56%).

[0041]

[0042] 1 H NMR (400MHz, CDCl3) δ7.41-7.38 (m, 2H), 7.29-7.26 (m, 3H), 1.53 (q, J=7.5Hz, 6H), 0.97 (t, J=7.5Hz, 9H); 13 C NMR (101MHz, CDCl3) δ131.6, 128.1, 127.2, 124.4, 96.0, 82.23, 39.9, 29.8, 8.8.

[0043] Example 4

[0044] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 36%).

[0045]

[0046] 1 H NMR (400MHz, CDCl3) 67.39-7.36 (m, 2H), 7.26-7.23 (m, 3H), 5.41 (d, J=4.5Hz, 1H), 2.17 (d, J=18. 8Hz, 1H), 2.03-1.96 (m, 4H), 1.66 (d, J=1.9Hz, 3H), 1.48-1.42 (m, 2H), 1.30 (s, 3H), 1.26 (s, 3H); 13 C NMR (101MHz, CDCl3) δ131.6, 128.1, 127.3, 120.8, 96.6, 81.0, 43.9, 34.7, 31.0, 29.7, 27.5, 27.3, 27.0, 24.8, 23.3.

[0047] Example 5

[0048] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 50%).

[0049]

[0050] 1H NMR (400MHz, CDCl3) δ7.41-7.38 (m, 2H), 7.28-7.26 (s, 3H), 2.45 (q, J=7.1Hz, 1H), 1.20 (d, J=7.1Hz, 3H), 1.02 (s, 9H); 13 C NMR (101MHz, CDCl3) δ131.5, 128.1, 127.3, 124.3, 93.9, 91.8, 37.8, 33.6, 27.3, 15.9.

[0051] Example 6

[0052] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 65%).

[0053]

[0054] 1 H NMR (400MHz, CDCl3) δ7.41-7.39 (m, 2H), 7.29-7.26 (m, 3H), 2.53-2.50 (m, 1H) , 1.95-1.90(m, 1H), 1.81-1.74(m, 3H), 1.69-1.65(m, 1H), 1.36-1.13(m, 9H); 13 C NMR (101MHz, CDCl3) δ131.5, 128.1, 127.3, 124.2, 93.9, 81.5, 42.9, 32.5, 31.1, 29.5, 26.48, 26.45, 26.4, 18.3.

[0055] Example 7

[0056] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 75%).

[0057]

[0058] 1 H NMR (400MHz, CDCl3) δ7.46-7.43 (m, 2H), 7.32-7.29 (m, 5H), 7.26-7.18 (m, 3H), 2.94-2.8 7 (m, 1H), 2.84-2.76 (m, 1H), 2.71-2.63 (m, 1H), 1.90-1.79 (m, 2H), 1.30 (d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) δ142.1, 131.6, 128.5, 128.3, 128.2, 127.5, 125.8, 124.0, 94.2, 81.3, 38.7, 33.7, 26.0, 21.1.

[0059] Example 8

[0060] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by a rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 83%).

[0061]

[0062] 1H NMR (400MHz, CDCl3) δ7.41-7.36(m, 2H), 7.30-7.27(m, 3H), 2.74-2.60(m, 3H ), 2.18(s, 3H), 1.87-1.83(m, 1H), 1.75-1.68(m, 1H), 1.27(d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) δ208.7, 131.5, 128.2, 127.7, 123.7, 93.4, 81.5, 41.5, 30.6, 30.1, 26.0, 21.1.

[0063] Example 9

[0064] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 55%).

[0065]

[0066] 1 H NMR (400MHz, CDCl3) δ8.11-8.09 (m, 2H), 7.59-7.56 (m, 1H), 7.46 (t, J=7.6Hz, 2H), 7.42-7.39 (m, 2H), 7.28 (q, J=3.2, 2.7Hz, 3H), 4.46-4.43 (m, 1H), 4.35-4.32 (m, 1H), 3.17 (q, J=6.8Hz, 1H), 1.39 (d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) δ166.4, 133.0, 131.6, 130.1, 129.6, 128.3, 128.2, 127.9, 123.3, 90.3, 81.9, 67.9, 26.7, 17.7.

[0067] Example 10

[0068] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 71%).

[0069]

[0070] 1 H NMR (400MHz, CDCl3) δ7.42-7.39 (m, 2H), 7.31-7.29 (m, 3H), 5.30 (q, J=7.1Hz, 1H), 3.66-3. 60 (m, 1H), 3.49-3.43 (m, 1H), 2.44-2.40 (m, 2H), 2.08-2.04 (m, 2H), 1.44 (d, J = 7.0Hz, 3H); 13 C NMR (101MHz, CDCl3) δ173.9, 131.7, 128.3, 128.2, 122.6, 87.3, 83.5, 42.8, 39.3, 31.2, 19.8, 17.7.

[0071] Embodiment 11

[0072] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 84%).

[0073]

[0074] 1H NMR (400MHz, CDCl3) δ7.41-7.38 (m, 5H), 7.36-7.32 (m, 2H), 6.84-6.81 (m, 2H), 4.65 (d, J=13.4Hz, 1H), 3.80 (s, 1H), 3.67-3.65 (m, 1H), 3.45 (t, J=13.1Hz, 1H), 3.24 (d, J=13.3Hz, 1H), 1.89 (d, J=13.2Hz, 1H), 1.70-1.69 (m, 1H), 1.55 (s, 1H), 1.43-1.39 (m, 1H), 1.35 (s, 3H); 13 C NMR (101MHz, CDCl3) δ170.3, 159.3, 136.3, 132.9, 129.5, 128.4, 126.9, 115.4, 113.9, 92.0, 83.2, 55.3, 45.5, 39.8, 39.3, 38.4, 32.3, 29.6.

[0075] Example 12

[0076] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 61%).

[0077]

[0078] 1 H NMR (400MHz, CDCl3) δ7.44-7.29(m, 5H), 7.23-7.18(m, 2H), 6.74-6.67(m, 3H), 4.05(br s, 1H), 3.32-3.22 (m, 2H), 3.05-3.00 (m, 1H), 1.34 (d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) δ147.9, 131.6, 129.3, 128.2, 127.8, 123.4, 117.6, 113.1, 92.0, 82.2, 49.5, 26.8, 18.7.

[0079] Embodiment 13

[0080] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 80%).

[0081]

[0082] 1 H NMR (400MHz, CDCl3) δ7.29-7.27(m, 2H), 7.10-7.07(m, 2H), 3.69-3.65(m, 2 H) 2.69-2.60 (m, 1H), 2.33 (s, 3H), 1.66-1.52 (m, 6H), 1.25 (d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) 6137.4, 131.4, 128.9, 120.9, 93.6, 80.9, 62.9, 36.78, 32.6, 26.5, 23.6, 21.4, 21.1.

[0083] Embodiment 14

[0084] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 82%).

[0085]

[0086] 1H NMR (400MHz, CDCl3) δ7.33-7.31 (m, 2H), 6.82-6.79 (m, 2H), 3.79 (s, 3H), 3.6 9-3.65 (m, 2H), 2.68-2.59 (m, 1H), 1.63-1.51 (m, 6H), 1.24 (d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) 6159.0, 132.9, 116.1, 113.8, 92.8, 80.5, 62.9, 55.2, 36.8, 32.6, 26.5, 23.6, 21.2.

[0087] Embodiment 15

[0088] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence and stirred at 35°C for 12h. 。 After the reaction is completed, the reaction mixture is filtered through silica gel, rinsed with ethyl acetate, the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product. The crude product is separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 84%).

[0089]

[0090] 1 H NMR (400MHz, CDCl3) δ7.60-7.57(m, 2H), 7.54-7.51(m, 2H), 7.48-7.42(m, 4H), 7.37-7.3 4(m, 1H), 3.71-3.67(m, 2H), 2.73-2.65(m, 1H), 1.66-1.56(m, 6H), 1.28(d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) δ140.5, 140.2, 131.9, 128.8, 127.4, 126.9, 126.8, 122.9, 95.2, 80.7, 62.9, 36.7, 32.6, 26.6, 23.7, 21.1.

[0091] Example 16

[0092] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 84%).

[0093]

[0094] 1 H NMR (400MHz, CDCl3) δ7.32-7.29(m, 2H), 7.26-7.23(m, 2H), 3.68-3.65(m, 2H), 2.62-2.67(m, 1H), 1.63-1.50(m, 6H), 1.25(d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) δ133.4, 132.8, 128.4, 122.5, 95.5, 79.8, 62.9, 36.6, 32.5, 26.5, 23.6, 21.0.

[0095] Embodiment 17

[0096] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 85%).

[0097]

[0098] 1H NMR (400MHz, CDCl3) δ7.41-7.39(m, 2H), 7.26-7.23(m, 2H), 3.68-3.65(m, 2H), 2.68-2.59(m, 1H), 1.65-1.52(m, 6H), 1.24(d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) δ 133.0, 131.3, 122.9, 121.5, 95.7, 79.9, 62.9, 36.6, 32.5, 26.6, 23.6, 20.9.

[0099] Embodiment 18

[0100] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv) were added in sequence, and stirred at 35°C for 12h. After the reaction was completed, the reaction mixture was filtered through silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed by rotary evaporator to obtain a crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the compound of formula 1 (isolation yield 71%).

[0101]

[0102] 1 H NMR (400MHz, CDCl3) δ7.37-7.34 (m, 2H), 6.98-6.95 (m, 2H), 3.67 (t, J=6.0Hz, 2H), 2.66-2.61 (m, 1H), 1.65-1.48 (m, 6H), 1.25 (d, J=6.9Hz, 3H); 13 C NMR (101MHz, CDCl3) δ162.0 (d, J=248.1Hz), 133.3 (d, J=8.1Hz), 115.3 (d, J=22.4Hz), 94.1, 79.8, 62.9, 36.7, 32.5, 26.5, 23.6, 21.0; 19 F NMR (376MHz, CDCl3) δ-112.6.

[0103] Example 19 Synthesis of target product using different acetylation reagents

[0104] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06mmol, 30mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), and phenylsilane (0.4mmol, 2equiv) were added in sequence and stirred at 35°C for 12h.

[0105] Table 1 Synthesis results of different acetylenic reagents

[0106]

[0107] Example 20 Synthesis of target product from different metal salts

[0108] In a reaction tube with a stirrer, under N2 atmosphere, metal catalyst (0.06 mmol, 30 mol%), acetylation reagent (0.2 mmol, 1 equiv), ethanol solvent (0.8 mL), ethylene glycol solvent (0.2 mL), olefin (0.3 mmol, 1.5 equiv), phenylsilane (0.4 mmol, 2 equiv), stirred at 35°C for 12 h.

[0109] Table 2 Synthesis results of different metal salts

[0110] Metal Salts Gas phase-mass spectrometry yield of the compound of formula 1 <![CDATA[Fe(acac)3]]> 85％ <![CDATA[In(acac)3]]> ND <![CDATA[FeCl3]]> 45％

[0111] Example 21 Synthesis of target product using different organic solvents

[0112] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06 mmol, 30 mol%), acetylation reagent (0.2 mmol, 1 equiv), solvent (1.0 mL), olefin (0.3 mmol, 1.5 equiv), phenylsilane (0.4 mmol, 2 equiv), stirred at 35 °C for 12 h

[0113] Table 3 Synthesis results of different organic solvents

[0114] Organic solvents Mass spectrometry yield of compound 1 1ml ethanol 62％ 0.8mL ethanol + 0.7mL ethylene glycol 85％

[0115] Example 22 Synthesis of target product at different temperatures

[0116] In a reaction tube with a stirrer, under N2 atmosphere, catalyst Fe(acac)3 (0.06 mmol, 30 mol%), acetylation reagent (0.2mmol, 1equiv), ethanol solvent (0.8mL), ethylene glycol solvent (0.2mL), olefin (0.3mmol, 1.5equiv), phenylsilane (0.4mmol, 2equiv), stirred at a certain temperature for 12h.

[0117] Table 4 Synthesis results at different temperatures

[0118] temperature Mass spectrometry yield of compound 1 70℃ 31％ 35℃ 85％

[0119] Although the present invention has been described by the specific embodiments above, it should not be construed as being limited thereto; rather, the present invention encompasses the general aspects disclosed above. Various modifications and various embodiments are possible without departing from the spirit and scope of the present invention.

Claims

1. A method for synthesizing an iron-catalyzed alkyl internal alkyne, characterized in that: The method comprises the following steps: using iron salt as a catalyst, an acetylation agent and olefin as raw materials, and phenylsilane as a hydrogen source to react and obtain an alkyl internal acetylenic compound; The structural formula of the alkyl internal alkyne compound is: Alkynylation reagents: The structural formula of the olefin is: R1 is a substituted or unsubstituted aromatic ring, and the substituent is selected from: C1-8 alkyl, C1-8 alkoxy, halogen; R2 is a substituted or unsubstituted aromatic ring, a substituted alkyl group, the substituent being selected from: C1-8 alkyl, C1-8 alkoxy, halogen, nitro, halogen-substituted C1-8 alkyl; The alkyl internal alkyne compound is selected from: The catalyst is selected from any one or more of the following: Fe(OAc)3, FeCl3; The solvent of the reaction is selected from any one of the following: ethanol, a mixed solvent with a solvent ratio of ethanol to ethylene glycol of 4:1; The reaction temperature is selected from any one of the following: 35°C, 70°C.

2. The method according to claim 1, characterized in that The synthetic route of the reaction is as follows:

3. The method according to claim 1, characterized in that The molar ratio of the acetylation reagent to the olefin compound reagent is 1:1.

5.

4. The method according to claim 1, characterized in that: The amount of the iron salt used relative to the acetylation agent is 30 mol%.

5. The method according to claim 1, characterized in that The amount of hydrogen source used is 2 equivalents relative to the acetylation reagent.

6. The method for synthesizing an iron-catalyzed alkynylation compound of claim 1, characterized in that: The specific steps are as follows: In a reaction tube with a stirrer, under a N2 atmosphere, catalyst, acetylation reagent, ethanol, ethylene glycol, silicon hydrogen and olefin compounds were added in sequence and stirred at 35°C for 12 hours. After the reaction was completed, the reaction mixture was filtered through silica gel and rinsed with ethyl acetate. The organic phases were combined and the solvent was removed by a rotary evaporator to obtain a crude product. The crude product was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to finally obtain the target compound.

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