CN111217847A - Thiosilane ligand, preparation method thereof and application thereof in aryl boronization catalytic reaction - Google Patents
Thiosilane ligand, preparation method thereof and application thereof in aryl boronization catalytic reaction Download PDFInfo
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
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- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
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- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
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- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
- C07F7/0827—Syntheses with formation of a Si-C bond
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- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
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- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/827—Iridium
Abstract
The invention provides a thiosilane ligand, a preparation method thereof and application thereof in aryl boronization catalytic reaction, wherein the structural formula of the thiosilane ligand is shown in the specification
Description
Technical Field
The invention belongs to the technical field of fine chemical engineering, and relates to a thiosilane ligand, a preparation method thereof and application thereof in aryl boronization catalytic reaction.
Background
Boronic acid ester compounds are an important class of compounds that can be used to synthesize many drugs/pesticides. As an important organic drug intermediate, a carbon-hydrogen bond boronation catalysis method is generally adopted to prepare the compound. The best synthesis method at present is a bipyridine ligand and an iridium catalyst, and a catalytic system using a borane pyridine ligand and an iridium catalyst, wherein the yield of the bipyridine ligand is low, particularly for some electron-rich substrates, the separation difficulty and the cost are increased due to the fact that the polarity of the bipyridine ligand is close to that of a product, and the borane pyridine system is relatively complex in synthesis and not suitable for large-scale industrial production, so that the finding of a ligand which is efficient, stable and convenient to store has important industrial value.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a thiosilane ligand, a preparation method thereof and application thereof in aryl boronation catalytic reaction, wherein the ligand can be synthesized efficiently, and the aryl boronic acid compound synthesized by catalysis has high yield, is easy to purify and high in atom economy, and is suitable for industrial mass synthesis.
The invention is realized by the following technical scheme:
a thiosilane ligand which is a compound of formula L1, L2, or L3:
the preparation method of the thiosilane ligand comprises the steps of carrying out bromine-lithium exchange reaction on a 2-bromobenzene thioether compound and n-butyl lithium in tetrahydrofuran at-30 to-80 ℃ under the protective atmosphere to obtain a bromine-lithium exchanged thiophenol compound; adding diisopropylchlorosilane into a lithium bromide-exchanged thiophenol compound, carrying out a silanization reaction, and purifying to obtain a thiosilane ligand after the reaction is finished;
wherein the 2-bromobenzene thioether compound is a compound shown as a formula L1 ', L2 ' or L3 ':
preferably, the compound of formula L1' is prepared by a process comprising: adding 2-bromothioanisole, tert-butyl alcohol and sulfuric acid into water, and reacting to obtain a compound shown as a formula L1';
the compound of formula L2' is prepared by the following process: 2-bromothioanisole, 2-iodoethane and K2CO3And CsCO3Sulfuric acid is added into DMF and reacted at normal temperature to obtain the compound of the formula L2'.
Preferably, the reaction time of the lithium bromide exchange reaction is 1 to 2 hours.
Preferably, the molar ratio of the 2-bromobenzene thioether compound to the n-butyl lithium is 1: (1.1-1.3), the molar ratio of the 2-bromobenzene thioether compound to the diisopropylchlorosilane is 1 (1.3-1.4).
Preferably, the reaction temperature of the silanization reaction is 0-25 ℃ and the time is 8-12 h.
The application of the thiosilane ligand as a catalyst ligand in preparing arylboronic acid ester.
Preferably, the method comprises the following steps: mixing an aryl compound, pinacol ester diboron, (1, 5-cyclooctadiene) (methoxyl) iridium (I) dimer, a thiosilane ligand and a 2-methyltetrahydrofuran solvent under a protective atmosphere, and reacting for 10-48 hours at 30-120 ℃; after the reaction is finished, purifying to obtain arylboronic acid ester;
the structural formulas of the arylboronic acid ester and the aryl compound are respectively shown as a formula (1) and a formula (2):
R1represents an alkyl group, R2Represents a hydrogen atom, an alkyl group, a halogen atom, a nitrogen-dimethyl group, a methoxy group, a carbonyl group, a cyano group, a thioether group or an ester group.
Further, the reaction concentration of the aryl compound is 0.1-2mol/L, the usage amount of the pinacol ester diborate is 0.5-2.5 times of the material amount of the aryl compound, the usage amount of the (1, 5-cyclooctadiene) (methoxy) iridium (I) dimer is 0.2-2.5% of the material amount of the aryl compound, and the usage amount of the thiosilane ligand is 2-3 times of the material amount of the iridium catalyst.
Further, the purification specifically comprises: filtering, decompressing and evaporating 2-methyltetrahydrofuran to dryness, and separating and purifying the obtained crude product by column chromatography, wherein the conditions of the column chromatography are as follows: 200-300 mesh silica gel is used, the mass ratio of the silica gel to the crude product to be purified is (50-100):1, the eluent is mixed liquid of petroleum ether and ethyl acetate or n-pentane, the petroleum ether in the mixed liquid: the volume ratio of the ethyl acetate is (20-50): 1.
Compared with the prior art, the invention has the following beneficial technical effects:
the thiosilane ligand can be simply synthesized and prepared by 1-2 steps of reaction, the cost of raw materials of the ligand is low, and the ligand can stably exist at normal temperature and is convenient to store. The mechanism is that the thiosilane ligand is firstly coordinated with the iridium catalyst to form an intermediate, and then the intermediate is coordinated with a guide group ester group of a substrate to activate an ortho-position carbon-hydrogen bond, and a pinacol ester diboride reagent is added to realize the boronation of the carbon-hydrogen bond, so that the atom economy is high, and the method is suitable for industrial mass synthesis; because the ligand has a special structure, the yield is higher for some substrates with low reactivity and strong electron-withdrawing group substituent groups, and the substrates are easier to separate and purify.
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum of preparation example 1 of L1.
FIG. 2 is a nuclear magnetic resonance spectrum of preparation example 1 of L2.
FIG. 3 is a nuclear magnetic resonance spectrum of preparation example 1 of L3.
Detailed Description
The present invention will now be described in further detail with reference to specific examples, which are intended to be illustrative, but not limiting, of the invention.
The thiosilane ligand is a compound with a structure shown as a formula L1, L2 or L3:
the preparation method of the thiosilane ligand comprises the following steps:
under the protection of nitrogen, 2-bromobenzene thioether compounds and n-butyl lithium are reacted in tetrahydrofuran at-30 to-80 ℃ for 1 to 2 hours in a molar ratio of 1 (1.1 to 1.3) to obtain a thiophenol compound exchanged with lithium bromide, then diisopropylchlorosilane is added into the thiophenol compound exchanged with lithium bromide, the temperature is slowly recovered to the room temperature, after the reaction is finished, sodium bicarbonate is subjected to quenching reaction and ether extraction, an organic phase is concentrated, and the obtained crude product is subjected to separation and purification by a silica gel chromatographic column to obtain a thiosilane ligand which is a light yellow oily liquid. The molar ratio of the lithium bromide-exchanged thiophenol compound to the diisopropylchlorosilane is 1 (1.2-1.5),
the 2-bromobenzene thioether compound is a compound with a structure shown in a formula L1 ', L2 ' or L3 '.
The preparation method of the 2-bromobenzene thioether compound comprises the following steps:
wherein the compound of formula L3' is commercially available at low cost.
Synthesis of a compound of formula L2': reacting 2-bromothioanisole with 2-iodoethane according to the molar ratio of 1:1.5, using DMF as a solvent, and K2CO31.5 equivalents and CsCO30.2 equivalent of alkali is used as the base to react for 8-18h at normal temperature to obtain a target product, the mixture is washed by water for several times, extracted by ether, dried and dried by spinning to obtain a light yellow oily liquid, and the obtained crude product is separated and purified by column chromatography to obtain the yellow oily target product.
Synthesis of a compound of formula L1': reacting 2-bromothioanisole with tert-butyl alcohol according to a molar ratio of 1:1.5, using water as a solvent, using equivalent sulfuric acid as a catalyst, adding a small amount of water firstly under the condition of 10 ℃ below zero, then adding a catalytic amount of concentrated sulfuric acid, reacting for 10-16 hours, treating a mixture after reaction under ice bath, extracting an organic phase for multiple times by using diethyl ether firstly, then adding sodium bicarbonate to adjust the pH to be 8-10, drying the organic phase, concentrating, and separating and purifying an obtained crude product by using column chromatography to finally obtain a yellow oily target product.
The application of the thiosilane ligand in preparing arylborate comprises the following steps:
1) the thiosilane ligand and (1, 5-cyclooctadiene) (methoxy) iridium (I) dimer are pre-stirred at room temperature for 1-2 hours with the addition of a small amount of 2-methyltetrahydrofuran under argon.
Then adding pinacol diboron into the system, stirring uniformly, then adding an aryl compound, and reacting for 10-48 hours at 30-120 ℃;
2) after the reaction is finished, filtering, performing vacuum rotary evaporation to remove the solvent, and then purifying by using column chromatography to obtain the arylboronic acid ester.
In the step 1), the reaction concentration of the aryl compound is 0.1-2mol/L, the usage amount of the pinacol ester diboron is 0.5-2.5 times of the material amount of the aryl compound, the usage amount of the (1, 5-cyclooctadiene) (methoxy) iridium (I) dimer is 0.2-2.5% of the material amount of the aryl compound, the usage amount of the thiosilane ligand is 2-3 times of the material amount of the iridium catalyst, and the thiosilane ligand is a compound having a structure shown as L1, L2 or L3:
the arylboronic acid ester has a structure shown in a formula (1):
wherein R is1Represents an alkyl group, R2Represents a hydrogen atom, an alkyl group, a halogen atom, a nitrogen-dimethyl group, a methoxy group, a carbonyl group, a cyano group, a thioether group or an ester group.
The structural formula of the aryl compound is shown as a formula (2):
R1represents an alkyl group, R2Represents a hydrogen atom, an alkyl group, a halogen atom, a nitrogen-dimethyl group, a methoxy group, a carbonyl group, a cyano group, a thioether group or an ester group.
In the step 2), the column chromatography conditions are as follows: 200-300 mesh silica gel is used, the mass ratio of the silica gel to the substance to be purified is (50-100):1, the eluent is a mixed solution of redistilled petroleum ether and ethyl acetate, and the petroleum ether: the volume ratio of the ethyl acetate is (20-50): 1.
Specific examples are as follows.
Preparation of (mono) thiosilane ligands
The thiosilane ligand is a compound with a structure shown as a formula L1, L2 or L3:
example preparation method:
preparation example 1 of L1
1) Adding 20ml of water into a flask, adding 25ml of concentrated sulfuric acid, placing at zero degree, adding 2-bromothioanisole (1.89g, 10mmol) and tert-butyl alcohol (1.11mg, 15mmol), mixing and stirring, placing at room temperature after the reaction starts, stirring for 8 hours, stopping the reaction, placing at zero degree, adding 30ml of multiplied by 3 ethyl ether to extract an organic phase, adding a proper amount of sodium bicarbonate into the organic phase to adjust the pH value to be 8-10, extracting with ethyl ether, filtering, drying with anhydrous sodium carbonate, and spin-drying the solvent to obtain a crude product. The crude product was purified by column chromatography (using 300 mesh size silica gel, 50:1 mass ratio of silica gel to the substance to be purified, 50:1 volume ratio of eluent petroleum ether and ethyl acetate) to give a yellow oily liquid in 85% yield (2.08g), identified by 1H NMR (400MHz, Chloroform-d) δ 7.65(t, J ═ 6.9Hz,2H),7.25(t, J ═ 7.5Hz,1H),7.16(t, J ═ 7.6Hz,1H),1.33(s,9H).
The product of the step 1) is specifically 2-tert-butylsulfanyl bromobenzene (shown as a formula L1').
2) Reacting 2-tert-butylsulfanyl bromobenzene (1.83g,7.5mmoL formula L1') and n-butyl lithium (1.86mL, 9mmoL) in tetrahydrofuran (10mL) at-80 deg.C for 2 hr under nitrogen protection, adding diisopropyl chlorosilane (2.13mL, 9.75mmoL, formula (3)) after 2 hr, reacting at 10 deg.C for 8 hr, removing tetrahydrofuran under vacuum condition (room temperature) to obtain crude product, purifying by column chromatography (using 300 mesh silica gel with mass ratio of 50:1, eluent of petroleum ether and ethyl acetate, and volume ratio of 30:1) to obtain productTo a pale yellow liquid, in 83% yield (1.74g), which was characterized1H NMR (400MHz, Chloroform-d) δ 7.65-7.55 (m,1H), 7.53-7.44 (m,1H), 7.38-7.18 (m,2H),4.31(t, J ═ 3.7Hz,1H),1.34(s,9H),1.09(d, J ═ 7.3Hz,6H),0.96(d, J ═ 7.4Hz,6H), nuclear magnetic resonance spectrum as shown in fig. 1, demonstrating the structure of the product as shown in formula L1.
Preparation example 2 of L1
1) Same as in preparation example 1
2) Reacting 2-tert-butylsulfanyl bromobenzene (1.83g,7.5mmoL formula L1') and n-butyl lithium (1.70mL, 8.25mmoL) in tetrahydrofuran (10mL) at-30 deg.C for 1 hr under nitrogen protection, adding diisopropyl chlorosilane (2.29mL, 10.5mmoL, formula (3)) after 1 hr, reacting at 5 deg.C for 12 hr, removing tetrahydrofuran under vacuum condition (room temperature) to obtain crude product, purifying by column chromatography (using 300 mesh silica gel, silica gel/to-be-purified substance ratio is 50:1, eluent is petroleum ether and ethyl acetate, volume ratio is 30:1) to obtain light yellow liquid, yield is 80% (1.67g), and identifying1H NMR (400MHz, Chloroform-d) δ 7.65-7.55 (m,1H), 7.53-7.44 (m,1H), 7.38-7.18 (m,2H),4.31(t, J ═ 3.7Hz,1H),1.34(s,9H),1.09(d, J ═ 7.3Hz,6H),0.96(d, J ═ 7.4Hz,6H), nuclear magnetic resonance spectrum as shown in fig. 1, demonstrating the structure of the product as shown in formula L1.
Preparation example 3 of L1
1) Same as in preparation example 1
2) Reacting 2-tert-butylsulfanyl bromobenzene (1.83g,7.5mmoL formula L1') and n-butyllithium (1.86mL, 9mmoL) in tetrahydrofuran (10mL) at-50 deg.C for 1.5 hr under nitrogen protection, adding diisopropyl chlorosilane (2.29mL, 10.5mmoL, formula (3)) after 1.5 hr, reacting at 15 deg.C for 8 hr, removing tetrahydrofuran under vacuum condition (room temperature) to obtain crude product, and performing column chromatography (using 300 mesh silica gel, silica gel and the crude product to be purified)The eluent is petroleum ether and ethyl acetate with the mass ratio of 50:1, the volume ratio is 30:1) is purified to obtain light yellow liquid, the yield is 82 percent (1.72g), and the identification is carried out1H NMR (400MHz, Chloroform-d) δ 7.65-7.55 (m,1H), 7.53-7.44 (m,1H), 7.38-7.18 (m,2H),4.31(t, J ═ 3.7Hz,1H),1.34(s,9H),1.09(d, J ═ 7.3Hz,6H),0.96(d, J ═ 7.4Hz,6H), nuclear magnetic resonance spectrum as shown in fig. 1, demonstrating the structure of the product as shown in formula L1.
Preparation example 1 of L2
(1) First, potassium carbonate (2.22g, 16.05mmol) and cesium carbonate (0.72g, 2.25mmol) were sequentially charged into a flask, 30ml of DMF was added, and then 2-bromothioanisole (1.5g, 10.7mmol) and 2-iodoethane (2.1g, 22.2mmol) were added, and mixed and stirred at room temperature for 8 hours, and after the reaction was stopped, the mixture was washed with 15 ml. times.3 of water, extracted with ether 3 times, dried, and the solvent was spin-dried to obtain a crude product. Purifying the crude product by column chromatography (using 300 mesh silica gel, the mass ratio of the silica gel to the to-be-purified substance is 50:1, the eluent is petroleum ether and ethyl acetate, the volume ratio is 30: 1-50: 1) to obtain yellow oily liquid, the yield is 81% (1.99g), and identifying1HNMR (400MHz, Chloroform-d) δ 7.51(d, J ═ 8.0Hz,1H),7.31(d, J ═ 7.9Hz,1H),7.20(t, J ═ 7.6Hz,1H),6.98(t, J ═ 7.6Hz,1H),3.44(hept, J ═ 6.6Hz,1H),1.30(d, J ═ 6.9Hz,6H), this product is in particular 2-isopropylsulfanylbromide (formula L2').
(2) Reacting 2-isopropylsulfanyl bromobenzene (1.72g,7.5mmoL, formula L2') and n-butyl lithium (1.86mL, 9mmoL) in tetrahydrofuran (10mL) at-80 deg.C for 2 hr under nitrogen protection, adding diisopropyl chlorosilane (2.13mL, 9.75mmoL formula (3)) after 2 hr, reacting at 20 deg.C for 10 hr, and vacuum extracting tetrahydrofuran to obtain crude product by column chromatography (using 300 mesh silica gel with mass ratio of 50:1, eluent of petroleum ether and ethyl acetate, and volume ratio of 50:11) purification to give a pale yellow liquid in 80% yield (1.26g), which was characterized1H NMR (400MHz, Chloroform-d) δ 7.39(d, J ═ 7.3Hz,1H),7.33(d, J ═ 7.8Hz,1H),7.22(t, J ═ 7.6Hz,1H),7.08(t, J ═ 7.3Hz,1H),3.99(t, J ═ 4.0Hz,1H),3.34(hept, J ═ 6.6Hz,1H),1.31(ddq, J ═ 11.3,7.3,3.7Hz,2H),1.23(d, J ═ 6.7Hz,6H),1.04(d, J ═ 7.3Hz,6H),0.89(d, J ═ 7.4Hz,6H), nuclear magnetic resonance map, as shown in fig. 2, the product structure is shown in fig. 2L 2.
Preparation example 2 of L2
(1) Same as in preparation example 1
(2) Reacting 2-isopropylsulfanyl bromobenzene (1.72g,7.5mmoL, formula L2') and n-butyl lithium (1.75mL, 8.25mmoL) in tetrahydrofuran (10mL) at-30 ℃ for 1 hour under the protection of nitrogen, adding diisopropyl chlorosilane (2.29mL, 10.5mmoL formula (3)) after 1 hour, reacting at 25 ℃ for 9 hours, and extracting tetrahydrofuran under vacuum condition (room temperature) after the reaction to obtain crude product, purifying the crude product by column chromatography (using 300-mesh silica gel, the mass ratio of the silica gel to the substance to be purified is 50:1, the eluent is petroleum ether and ethyl acetate, the volume ratio is 50:1) to obtain light yellow liquid, the yield is 76% (1.178g), and identifying1H NMR (400MHz, Chloroform-d) δ 7.39(d, J ═ 7.3Hz,1H),7.33(d, J ═ 7.8Hz,1H),7.22(t, J ═ 7.6Hz,1H),7.08(t, J ═ 7.3Hz,1H),3.99(t, J ═ 4.0Hz,1H),3.34(hept, J ═ 6.6Hz,1H),1.31(ddq, J ═ 11.3,7.3,3.7Hz,2H),1.23(d, J ═ 6.7Hz,6H),1.04(d, J ═ 7.3Hz,6H),0.89(d, J ═ 7.4Hz,6H), nuclear magnetic resonance map, as shown in fig. 2, the product structure is shown in fig. 2L 2.
Preparation example 3 of L2
(1) Same as in preparation example 1
(2) Reacting 2-isopropylsulfanyl bromobenzene (1.72g,7.5mmoL, formula L2') and n-butyl lithium (1.86mL, 9mmoL) in tetrahydrofuran (10mL) at-80 deg.C for 2 hours under nitrogen protection, adding diisopropyl chlorosilane (2.29mL, 10.5mmoL formula (3)) after 2 hours, reacting at 2 deg.C for 12 hours, and after the reaction, removing tetrahydrofuran under vacuum (room temperature) to obtain crude product, purifying the crude product by column chromatography (using 300 mesh silica gel with a mass ratio of silica gel to the substance to be purified of 50:1, and petroleum ether and ethyl acetate as eluent, volume ratio of 50:1) to obtain pale yellow liquid, yield (82% 1.271g), identifying 1H NMR (400MHz, Chloroform-d) delta 7.39(d, J ═ 7.3Hz,1H),7.33(d, J ═ 7.8, 1H),7.22(t ═ 7.6, t ═ 7.08 Hz), 7.08 Hz (t ═ 7.7.7H, 7H, 7.08 Hz), j ═ 7.3Hz,1H),3.99(t, J ═ 4.0Hz,1H),3.34(hept, J ═ 6.6Hz,1H),1.31(ddq, J ═ 11.3,7.3,3.7Hz,2H),1.23(d, J ═ 6.7Hz,6H),1.04(d, J ═ 7.3Hz,6H),0.89(d, J ═ 7.4Hz,6H), nuclear magnetic resonance spectrum as shown in fig. 2, demonstrating the structure of the product shown in formula L2.
Preparation example 1 of L3
Commercially available 2-bromothioanisole (1.52g,7.5mmoL) and n-butyl lithium (1.86mL, 9mmoL) are reacted in tetrahydrofuran (10mL) at-80 ℃ for 2 hours, diisopropyl chlorosilane (2.13mL, 9.75mmoL (3)) is added after 2 hours, the reaction is carried out at 10 ℃ for 8 hours, after the reaction is finished, tetrahydrofuran is extracted under vacuum condition (room temperature) to obtain crude product, the crude product is purified by column chromatography (200-300 mesh silica gel is used, the mass ratio of the silica gel to the substance to be purified is 50-100:1, petroleum ether and ethyl acetate are used as eluent, the volume ratio is 30: 1-50: 1) to obtain light yellow liquid, the yield is 83% (1.13g), and the 1H NMR (400MHz, Chloroform-d) delta 7.44(d, J is 7.3Hz,1H), 7.36-7.30 (m,1H),7.28(s,1H),7.11(t is 7.8Hz,1H) 4.08(t, J ═ 4.0Hz,1H),2.46(s,3H),1.40(ddp, J ═ 11.3,7.3,4.0Hz,2H),1.11(d, J ═ 7.4Hz,6H),0.98(d, J ═ 7.4Hz,6H), a nuclear magnetic resonance spectrum is shown in fig. 3, demonstrating that the product structure is shown in formula L3.
Preparation example 2 of L3
Commercially available 2-bromothioanisole (1.52g,7.5mmoL) and n-butyl lithium (1.7mL, 8.25mmoL) are reacted in tetrahydrofuran (10mL) at-30 ℃ for 2 hours, diisopropyl chlorosilane (2.29mL, 10.5mmoL (3)) is added after 2 hours, reaction is carried out at 8 ℃ for 11 hours, and after the reaction is finished, tetrahydrofuran is extracted under vacuum condition (room temperature) to obtain crude product, which is purified by column chromatography (using 300 mesh silica gel, the mass ratio of silica gel to substance to be purified is 50:1, eluent is petroleum ether and ethyl acetate, the volume ratio is 50:1) to obtain light yellow liquid, the yield is 79% (1.075g), 1H NMR (400MHz, Chloroform-d) delta 7.44(d, J is 7.3Hz,1H), 7.36-7.30 (m,1H),7.28(s,1H),7.11(t, J is 7.8, J is 4H, t is 4.08 Hz, 0.0 Hz,1H) 2.46(s,3H),1.40(ddp, J ═ 11.3,7.3,4.0Hz,2H),1.11(d, J ═ 7.4Hz,6H),0.98(d, J ═ 7.4Hz,6H), nuclear magnetic resonance spectrum as shown in fig. 3, proving that the product structure is shown in formula L3.
Preparation example 3 of L3
Reacting commercially available 2-bromothioanisole (1.52g,7.5mmoL) and n-butyl lithium (1.86mL, 9mmoL) in tetrahydrofuran (10mL) at-50 ℃ for 1 hour, adding diisopropylchlorosilane (2.29mL, 10.5mmoL formula (3)) after 1 hour, reacting at 10 ℃ for 9 hours, extracting tetrahydrofuran under vacuum condition (room temperature) after reaction to obtain crude product, purifying the crude product by column chromatography (using 300-mesh silica gel, the mass ratio of the silica gel to the substance to be purified is 50:1, and the eluent is petroleum ether and ethyl acetate, the volume ratio is 50:1) to obtain light yellow liquid, wherein the yield is 84% (1.143g), and identifying1H NMR (400MHz, Chloroform-d) δ 7.44(d, J ═ 7.3Hz,1H), 7.36-7.30 (m,1H),7.28(s,1H),7.11(t, J ═ 7.8Hz,1H),4.08(t, J ═ 4.0Hz,1H),2.46(s,3H),1.40(ddp, J ═ 11.3,7.3,4.0Hz,2H),1.11(d, J ═ 7.4Hz,6H),0.98(d, J ═ 7.4Hz,6H). nuclear magnetic resonance spectroscopy is as shown in fig. 3, and the product structure is as shown in formula L3.
Preparation of (di) arylboronic acid esters
Application example 1
This example is a milligram scale standard substrate of formula (4) and the preparation of 2-carbomethoxyphenylboronic acid pinacol ester of formula (5) comprises the following steps: under argon atmosphere, adding methyl benzoate (68mg, 0.5mmoL), pinacol diborate (127mg, 0.5mmoL L),1, 5-cyclooctadienemethoxyiridium dimer (5mg, 0.0075mmoL l.5%), a thiosilane ligand (4.50mg, 0.015mmoL, 3%, formula L1) and 2-methyltetrahydrofuran (0.5mL) into a reaction vessel, reacting at 100 ℃ for 16h, removing the solvent (2-methyltetrahydrofuran) by rotary evaporation (40-50 ℃) after the reaction is finished, and purifying the product by column chromatography (using 200-mesh specification silica gel, the mass ratio of the silica gel to the substance to be purified is 50:1, and the eluent is petroleum ether and ethyl acetate, and the volume ratio is 20:1) to obtain colorless pinacol 2-carbomethoxyphenylboronate solid (90mg, 69%), wherein the nuclear magnetic spectrum of the product is completely the same as the reported nuclear magnetic spectrum information.
Application example 2
This example is a milligram scale preparation of 2-methyl formate-3-bromo-phenylboronic acid pinacol ester, comprising the following steps: methyl 2-bromobenzoate (107.5mg, 0.5mmoL), pinacol diborate (154mg, 0.6mmoL),1, 5-cyclooctadienemethoxyiridium dimer (5mg, 0.0075mmoL, l.5%), thiosilane ligand (4.50mg, 0.015mmoL, 3%, formula L1) and 2-methyltetrahydrofuran (0.5mL) were added to the reaction vessel under argon atmosphere, reacted at 100 ℃ for 10h, after completion of the reaction the solvent (2-methyltetrahydrofuran) was removed by rotary evaporation (40-50 ℃), and the product was purified by column chromatography (using 200 mesh size silica gel, 50:1 weight ratio of silica gel to the substance to be purified, eluent petroleum ether and ethyl acetate, volume ratio 20:1) to give colorless pinacol 2-methyl formate-3-bromo-phenylboronate (146.1mg, 86%, formula (6)), which had a nuclear magnetic spectrum identical to reported information.
Application example 3
This example is a milligram scale preparation of 2-methyl formate-3-chloro-phenylboronic acid pinacol ester, comprising the following steps: methyl 2-chlorobenzoate (86mg, 0.5mmoL) pinacol diboron (154mg, 0.6mmoL),1, 5-cyclooctadienemethoxyiridium dimer (10mg, 0.015mmoL, 3%), thiosilane ligand (4.50mg, 0.015mmoL, 3%, formula L2) and 2-methyltetrahydrofuran (0.5mL) were added to the reaction vessel under argon atmosphere, reacted at 80 ℃ for 16h, after completion of the reaction the solvent (2-methyltetrahydrofuran) was removed by rotary evaporation (40-50 ℃), and the product was purified by column chromatography (using 300 mesh size silica gel, silica gel and to-be-purified substance in a 50:1 ratio, and eluent petroleum ether and ethyl acetate in a 50:1 volume ratio) to give colorless methyl 2-formate-3-bromo-phenylboronic acid pinacol ester (124.5mg, 83%, formula (7)), which showed a nuclear magnetic spectrum completely identical to the reported nuclear magnetic information.
Application example 4
This example is a milligram scale preparation of 2-ethyl formate-3-methyl-phenylboronic acid pinacol ester, comprising the following steps: under argon atmosphere, adding ethyl 2-methylbenzoate (84mg, 0.5mmoL) pinacol diborate (254mg, 1mmoL),1, 5-cyclooctadienemethoxyiridium dimer (5mg, 0.0075mmoL, l.5%), a thiosilane ligand (4.50mg, 0.015mmoL, 3%, formula L2) and 2-methyltetrahydrofuran (0.5mL) into a reaction vessel, reacting at 80 ℃ for 24 hours, removing the solvent (2-methyltetrahydrofuran) by rotary evaporation (40-50 ℃) after the reaction is finished, and purifying the product by column chromatography (using 300-mesh silica gel, the silica gel and the substance to be purified are in a mass ratio of 100:1, and the eluent is petroleum ether and ethyl acetate in a volume ratio of 50:1) to obtain colorless ethyl 2-formate-3-methyl-pinacol phenylboronate (87.3mg, 60%, formula (8)), wherein the nuclear magnetic spectrum of the product is completely identical to the reported nuclear magnetic information.
Application example 5
This example is a milligram scale preparation of 2-methyl formate-3-trifluoromethyl-phenylboronic acid pinacol ester, comprising the following steps: methyl p-trifluoromethylbenzoate (107.5mg, 0.5mmoL) pinacol diboron (317.5mg, 1.25mmoL),1, 5-cyclooctadienemethoxyiridium dimer (15mg, 0.015mmoL, 3%), a thiosilane ligand (10mg, 0.015mmoL, 3%, formula L2) and 2-methyltetrahydrofuran (0.5mL) were added to a reaction vessel under an argon atmosphere, reacted at 100 ℃ for 30 hours, and after the reaction was completed, the solvent (2-methyltetrahydrofuran) was removed by rotary evaporation (40-50 ℃), and the product was purified by column chromatography (using 300 mesh size silica gel, an amount ratio of silica gel to the substance to be purified of 80:1, an eluent comprising petroleum ether and ethyl acetate, and a volume ratio of 30:1) to obtain colorless methyl 2-formate-3-bromo-phenylboronic acid pinacol ester (142.3mg, 86%, formula (9)), which had a nuclear magnetic spectrum completely identical to that reported nuclear magnetic information.
Application example 6
This example is a milligram scale preparation of 2-isocyanatopropylphenylboronic acid pinacol ester, comprising the following steps: adding isopropyl benzoate (82mg, 0.5mmoL) pinacol diboron (154mg, 0.6mmoL),1, 5-cyclooctadienemethoxyiridium dimer (5mg, 0.0075mmoL, l.5%), thiosilane ligand (9mg, 0.03mmoL, 6%, formula L3) and 2-methyltetrahydrofuran (0.5mL) into a reaction vessel under argon atmosphere, reacting at 120 ℃ for 48h, removing the solvent (2-methyltetrahydrofuran) by rotary evaporation (40-50 ℃) after the reaction is finished, and purifying the product by column chromatography (using 300-mesh silica gel, wherein the mass ratio of the silica gel to the substance to be purified is 50:1, and the eluent is petroleum ether and ethyl acetate, and the volume ratio is 40:1) to obtain colorless 2-methyl formate-3-bromo-phenylboronic acid pinacol ester (120.8mg, 83%, formula (10)), and the nuclear magnetic spectrum of the product is completely identical to the reported nuclear magnetic information.
Application example 7
This example is a milligram scale preparation of 2-methyl formate-3-methyl-phenylboronic acid pinacol ester, comprising the following steps: methyl p-methylbenzoate (82mg, 0.5mmoL) pinacol diboron (154mg, 0.6mmoL),1, 5-cyclooctadienemethoxyiridium dimer (6.67mg, 0.01mmoL, 2%), thiosilane ligand (4.50mg, 0.015mmoL, 3%, formula L3) and 2-methyltetrahydrofuran (0.5mL) were added to a reaction vessel under an argon atmosphere, reacted at 30 ℃ for 16 hours, after the reaction was completed, solvent (2-methyltetrahydrofuran) was removed by rotary evaporation (40-50 ℃), and the product was purified by column chromatography (using 300 mesh size silica gel, silica gel and to-be-purified substance ratio 50:1, eluent petroleum ether and ethyl acetate, volume ratio 450:1) to give colorless methyl 2-formate-3-bromo-phenylboronic acid pinacol ester (98mg, 71%, formula (11)), and nuclear magnetic spectrum of the product was completely identical to reported nuclear magnetic information.
Application example 8
This example is a milligram scale preparation of methyl 2-carboxylate-4-methoxy-phenylboronic acid pinacol ester, comprising the following steps: methyl 3-methoxybenzoate (83mg, 0.5mmoL) pinacol diboron (254mg, 1mmoL),1, 5-cyclooctadienemethoxyiridium dimer (5mg, 0.0075mmoL, l.5%), thiosilane ligand (4.50mg, 0.015mmoL, 3%, formula L2) and 2-methyltetrahydrofuran (0.5mL) were added to a reaction vessel under argon atmosphere, reacted at 60 ℃ for 22 hours, and after the reaction was completed, the solvent (2-methyltetrahydrofuran) was removed by rotary evaporation (40-50 ℃), and the product was purified by column chromatography (using 300 mesh size silica gel, the silica gel to the substance to be purified at a mass ratio of 100:1, and the eluent was petroleum ether and ethyl acetate at a volume ratio of 20:1) to give yellow methyl 2-formate-4-methoxy-pinacol phenylboronate (113.9mg, 78%, formula (12)), which had a nuclear magnetic spectrum completely identical to the reported nuclear magnetic information.
The arylboronic acid ester compound obtained by the preparation method can be used for synthesizing intermediates of medicines/pesticides. The method can be used for preparing a plurality of similar products, including ethyl formate, isopropyl formate, tert-butyl formate and aromatic rings which can be connected with various substituents, and the ligand is simple and stable, can realize gram level or even kilogram level, and realizes industrial production.
Claims (10)
1. A thiosilane ligand characterized by being a compound of formula L1, L2, or L3:
2. the preparation method of the thiosilane ligand as described in claim 1, characterized in that under the protective atmosphere, 2-bromobenzene thioether compound and n-butyl lithium are subjected to bromine-lithium exchange reaction in tetrahydrofuran at-30 to-80 ℃ to obtain bromine-lithium exchanged thiophenol compound; adding diisopropylchlorosilane into a lithium bromide-exchanged thiophenol compound, carrying out a silanization reaction, and purifying to obtain a thiosilane ligand after the reaction is finished;
wherein the 2-bromobenzene thioether compound is a compound shown as a formula L1 ', L2 ' or L3 ':
3. the process for the preparation of the thiosilane ligand of claim 2, wherein the compound of formula L1' is prepared by: adding 2-bromothioanisole, tert-butyl alcohol and sulfuric acid into water, and reacting to obtain a compound shown as a formula L1';
the compound of formula L2' is prepared by the following process: 2-bromothioanisole, 2-iodoethane and K2CO3And CsCO3Sulfuric acid is added into DMF and reacted at normal temperature to obtain the compound of the formula L2'.
4. The method of claim 2, wherein the reaction time of the lithium bromide exchange reaction is 1 to 2 hours.
5. The method for preparing a thiosilane ligand according to claim 2, wherein the molar ratio of the 2-bromobenzene thioether compound to the n-butyl lithium is 1: (1.1-1.3), the molar ratio of the 2-bromobenzene thioether compound to the diisopropylchlorosilane is 1 (1.3-1.4).
6. The process for the preparation of thiosilane ligands of claim 2, wherein the reaction temperature of the silylation reaction is 0-25 ℃ and the time is 8-12 h.
7. Use of the thiosilane ligand of claim 1 as a catalyst ligand in the preparation of arylboronic acid esters.
8. Use according to claim 7, characterized in that it comprises the following steps: mixing an aryl compound, pinacol ester diboron, (1, 5-cyclooctadiene) (methoxyl) iridium (I) dimer, a thiosilane ligand and a 2-methyltetrahydrofuran solvent under a protective atmosphere, and reacting for 10-48 hours at 30-120 ℃; after the reaction is finished, purifying to obtain arylboronic acid ester;
the structural formulas of the arylboronic acid ester and the aryl compound are respectively shown as a formula (1) and a formula (2):
R1represents an alkyl group, R2Represents a hydrogen atom, an alkyl group, a halogen atom, a nitrogen-dimethyl group, a methoxy group, a carbonyl group, a cyano group, a thioether group or an ester group.
9. The use according to claim 8, wherein the reaction concentration of the aryl compound is 0.1-2mol/L, the pinacol ester of diboronic acid is used in an amount of 0.5-2.5 times the amount of the substance of the aryl compound, the (1, 5-cyclooctadiene) (methoxy) iridium (I) dimer is used in an amount of 0.2-2.5% of the amount of the substance of the aryl compound, and the thiosilane ligand is used in an amount of 2-3 times the amount of the substance of the iridium catalyst.
10. Use according to claim 8, characterized in that the purification is in particular: filtering, decompressing and evaporating 2-methyltetrahydrofuran to dryness, and separating and purifying the obtained crude product by column chromatography, wherein the conditions of the column chromatography are as follows: 200-300 mesh silica gel is used, the mass ratio of the silica gel to the crude product to be purified is (50-100):1, the eluent is mixed liquid of petroleum ether and ethyl acetate or n-pentane, the petroleum ether in the mixed liquid: the volume ratio of the ethyl acetate is (20-50): 1.
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