A method for synthesizing monofluoroalkenyl silicon

Abstract

This invention belongs to the field of organic synthesis and relates to a method for synthesizing monofluoroalkenyl silicon. Using terpyridine ruthenium chloride hexahydrate as a catalyst, triethylenediamine as a base, tert-butyl peroxybenzoate as an initiator, and dimethyl sulfoxide as a solvent, the following reaction formula is carried out to produce a class of E-configuration monofluoroalkenyl silicon compounds. The starting materials are readily available and inexpensive, with high selectivity. The reaction requires only a single step, resulting in a short route and no pre-prepared special reagents, resulting in high economic value. This provides an efficient, practical, and convenient method for synthesizing E-configuration monofluoroalkenyl silicon compounds. #imgabs0#

Description

Technical Field

[0001] The present invention relates to compound preparation, belongs to the field of organic synthesis, and specifically relates to a method for synthesizing monofluoroalkenyl silicon. Background Art

[0002] Organosilicon compounds, due to their unique physical and chemical properties, play an important role in medical imaging procedures, agricultural / pharmaceutical chemistry, organic synthetic chemistry, and materials science. Among them, alkenyl silicons are a class of organosilicon compounds with significant application potential and serve as important building blocks in organic synthesis. Consequently, the synthesis of alkenyl silicon compounds has garnered widespread interest among chemists.

[0003] On the other hand, the introduction of fluorine atoms can improve the physical and chemical properties of the parent organic molecule, including metabolic stability, lipophilicity and bioavailability. More importantly, alkenyl fluoride compounds are an important organic synthon. They can not only participate in various types of conversion to obtain fluorinated compounds, but also can be used as the electronic isostere of amide bonds in drug discovery research, increasing the stability of conformation and peptidase. Combining the above two points, the synthesis of single fluorinated alkenyl silicon compounds has great potential application value. The first synthesis of single fluorinated alkenyl silicon compounds needs to be carried out by olefination under harsh conditions (Formula 1, Bull.Chem.Soc.Jpn.2000,73,1685-1690), and the method first synthesizes specific fluorinated and silicon reagents when needed. It is necessary to use butyl lithium strong base, carry out under the conditions of minus 78 degrees Celsius to minus 98 degrees Celsius, and the reaction conditions are harsh. And the method obtains a mixture of E / Z two configurations, with low selectivity and difficulty in product classification.

[0004]

[0005] Recently, the Wang group achieved the synthesis of monofluoroolefin silanes through the defluorination silanization reaction of geminal difluoroolefins. However, this strategy requires the use of expensive iridium catalysts to prepare silaboranes, and the reaction requires multi-step operation. At the same time, the reaction requires the use of 3 equivalents of the strong base lithium tert-butoxide, which limits its practicality in synthetic chemistry (Formula 2, Adv.Synth.Catal.2018, 360, 1032-1037).

[0006]

[0007] Given the current challenges in synthesizing monofluoroolefin silicon, including harsh reaction conditions, poor reaction selectivity, a limited substrate range, the need for expensive iridium metal catalysts to prepare the silicon-boron raw materials, and the multi-step process, the development of a highly selective synthesis of monofluoroolefin silicon compounds using inexpensive, readily available raw materials and metals has important synthetic application value. Summary of the Invention

[0008] The present invention addresses the shortcomings of current methods for synthesizing monofluoroalkenyl silicon compounds, such as harsh reaction conditions, poor stereoselectivity, the need for multi-step synthesis, and the need to use expensive iridium to prepare the reaction raw materials. This invention realizes a method for synthesizing monofluoroalkenyl silicon compounds efficiently and selectively using fluoroacrylic acid and inexpensive, commercial silane compounds as raw materials.

[0009] To solve the above technical problems, the present invention adopts the following technical solution: a method for synthesizing monofluoroalkenyl silicon, characterized in that: fluoroacrylic acid and a silane compound are used as raw materials, terpyridine ruthenium chloride hexahydrate is used as a catalyst, triethylenediamine is used as a base, tert-butyl perbenzoate is used as an initiator, and dimethyl sulfoxide is used as a solvent, and a reaction is carried out according to the following reaction formula to obtain a type of E-configuration monofluoroalkenyl silicon compound having the general formula (I):

[0010]

[0011] where R 1 It is hydrogen, fluorine, ester, cyano, trifluoromethyl, trifluoromethoxy and sulfone; R is ethyl, methyl or isopropyl.

[0012] Preferably, the amount of the terpyridyl ruthenium chloride hexahydrate is 3% of the amount of fluoroacrylic acid.

[0013] Preferably, the amount of triethylenediamine is twice the amount of fluoroacrylic acid.

[0014] Preferably, the amount of the silane compound is 5 times the amount of the fluoroacrylic acid.

[0015] Preferably, the amount of t-butyl peroxybenzoate is 3 times the amount of fluoroacrylic acid.

[0016] Preferably, the illumination wavelength is 465 nanometers, the reaction time is 20 hours, and the reaction temperature is room temperature.

[0017] This method enables the efficient and convenient preparation of monofluoroalkenyl silicon compounds using fluoroacrylic acid and silane compounds as raw materials. The reaction raw materials are inexpensive and readily available, with high selectivity. The reaction requires only a single step, requiring no pre-prepared special reagents, resulting in a highly economical synthesis. This provides an efficient, practical, and convenient method for the synthesis of E-configured monofluoroalkenyl silicon compounds. DETAILED DESCRIPTION

[0018] The technical solution of the present invention is further described below through specific implementation methods:

[0019] Example 1, the reaction formula of this embodiment is as follows:

[0020]

[0021] (1) Under air, terpyridylruthenium chloride hexahydrate (1 mol%), triethylenediamine (2 equiv), and 2-fluoro-3-phenylacrylic acid (0.2 mmol, 1 equiv) were added to a sealed reaction tube with a branch tube and a magnet. The reaction tube was evacuated with argon three times. Under argon protection, 1.5 mL of dimethyl sulfoxide and triethylsilane (5 equiv) were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 20 hours.

[0022] (2) The solvent in the organic phase obtained in step (2) was dried to obtain a crude product, which was then purified using a silica gel column. The separation yield was 65%, E / Z>30:1, and the product purity was 100%.

[0023] Example 2

[0024] The reaction formula of this embodiment is shown below:

[0025]

[0026] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and 2-fluoro-3-(p-fluorophenyl)acrylic acid (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic rod. The reaction tube was evacuated with argon three times. Under argon protection, 1.5 mL of dimethyl sulfoxide and triethylsilane (5 equiv) were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 20 hours.

[0027] (2) The solvent in the organic phase obtained in step (2) was dried to obtain a crude product, which was then purified using a silica gel column. The separation yield was 66%, E / Z>30:1, and the product purity was 100%.

[0028] Example 3

[0029] The reaction formula of this embodiment is shown below:

[0030]

[0031] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and tert-butyl 2-fluoro-3-benzoate (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic rod. The reaction tube was evacuated with argon three times. Under argon protection, 1.5 mL of dimethyl sulfoxide and triethylsilane (5 equiv) were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 20 hours.

[0032] (2) The solvent in the organic phase obtained in step (2) was dried by spin drying to obtain a crude product, which was then purified using a silica gel column. The separation yield was 62%, E / Z>30:1, and the product purity was 100%.

[0033] Example 4

[0034] The reaction formula of this embodiment is shown below:

[0035]

[0036] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and 2-fluoro-3-benzothiophene acrylic acid (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic rod. The reaction tube was evacuated with argon three times. Under argon protection, 1.5 mL of dimethyl sulfoxide and triethylsilane (5 equiv) were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 20 hours.

[0037] (2) The solvent in the organic phase obtained in step (2) was dried by spin drying to obtain a crude product, which was then purified using a silica gel column. The separation yield was 62%, E / Z>30:1, and the product purity was 100%.

[0038] Example 5

[0039] The reaction formula of this embodiment is shown below:

[0040]

[0041] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and 2-fluoro-3-(p-sulfone)phenylacrylic acid (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic rod. The reaction tube was evacuated with argon three times. Under argon protection, 1.5 mL of dimethyl sulfoxide and triethylsilane (5 equiv) were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 20 hours.

[0042] (2) The solvent in the organic phase obtained in step (2) was dried by spin drying to obtain a crude product, which was then purified using a silica gel column. The separation yield was 62%, E / Z>30:1, and the product purity was 100%.

[0043] The amounts of the substances used and the reaction conditions were the same as those in the examples to carry out an experimental expansion to illustrate that the technical solution of the present invention has good functional group compatibility.

[0044]

[0045] The present invention has been described in detail above. The above descriptions are merely embodiments of the present invention and should not limit the scope of implementation of the present application. In other words, all equivalent changes and modifications made within the scope of the present application should still fall within the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the product 1s prepared in the present invention;

[0047] Figure 2 This is the NMR fluorine spectrum of the product 1s prepared in the present invention;

[0048] Figure 3 This is the carbon NMR spectrum of the product 1s prepared in the present invention;

[0049] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of the product 2s prepared in the present invention;

[0050] Figure 5 This is the NMR fluorine spectrum of the product 2s prepared in the present invention;

[0051] Figure 6 This is the carbon NMR spectrum of the product 2s prepared in the present invention;

[0052] Figure 7 This is the H NMR spectrum of the product 5s prepared in the present invention;

[0053] Figure 8 This is the NMR fluorine spectrum of the product 5s prepared in the present invention;

[0054] Figure 9 This is the carbon NMR spectrum of the product 5s prepared in the present invention;

[0055] Figure 10 This is the hydrogen nuclear magnetic resonance spectrum of the product 6s prepared in the present invention;

[0056] Figure 11 This is the NMR fluorine spectrum of the product 6s prepared in the present invention;

[0057] Figure 12 This is the carbon NMR spectrum of the product 6s prepared in the present invention.

Claims

1. A method for synthesizing monofluoroalkenyl silicon, characterized in that: Using fluoroacrylic acid and a silane compound as raw materials, 3 mol% terpyridine ruthenium chloride hexahydrate as a catalyst, triethylenediamine as a base, tert-butyl perbenzoate as an initiator, and dimethyl sulfoxide as a solvent, the reaction was carried out under 465 nm light at room temperature for 20 hours to obtain a type of E-configuration monofluoroalkenyl silicon compound.

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