CN113980053B - Chiral thioether-phosphine compound and preparation method thereof - Google Patents

Chiral thioether-phosphine compound and preparation method thereof Download PDF

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CN113980053B
CN113980053B CN202111312237.XA CN202111312237A CN113980053B CN 113980053 B CN113980053 B CN 113980053B CN 202111312237 A CN202111312237 A CN 202111312237A CN 113980053 B CN113980053 B CN 113980053B
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游歌云
冯彬
彭丽燕
林瑶
李勇刚
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Baise University
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Abstract

The invention discloses a compound which has a structural formula of formula I,in the formula I, R 1 Represents 4-methylphenyl, 4-bromophenyl, 2, 6-dimethylphenyl, 2-methylphenyl, 2-methoxyphenyl, 2-naphthyl, benzyl or tert-butyl, R 2 Represents phenyl or 1,1' -binaphthyl. The invention also discloses a preparation method of the chiral thioether-phosphine compound. The invention also discloses the catalyst and application thereof. According to the invention, a thioether-phosphine ligand library is constructed by thiophenol, chiral amine and phenol, and the prepared chiral thioether-phosphine compound can be used as a chiral ligand for palladium-catalyzed asymmetric allylic alkylation reaction.

Description

Chiral thioether-phosphine compound and preparation method thereof
Technical Field
The invention relates to the technical field of chemistry. More particularly, the present invention relates to a chiral thioether-phosphine compound and a preparation method thereof.
Background
Chiral ligands have been successfully used in industry, and their metal complexes can efficiently realize green synthesis of pharmaceutical intermediates. Nevertheless, there are still a large number of chiral drugs or their chiral intermediates for which synthesis lacks a suitable catalytic system, and thus the development of more efficient, novel chiral ligands and their application in asymmetric synthesis remains a challenging task.
Disclosure of Invention
It is an object of the present invention to solve at least the above problems and to provide at least the advantages to be described later.
It is still another object of the present invention to provide a chiral thioether-phosphine compound and a method for preparing the same, wherein the chiral thioether-phosphine compound is prepared by using thiophenol, chiral amine and phenol to construct a thioether-phosphine ligand library, and the prepared chiral thioether-phosphine compound can be used as a chiral ligand for palladium-catalyzed asymmetric allylic alkylation reaction.
To achieve these objects and other advantages and in accordance with the purpose of the invention, there is provided a chiral thioether-phosphine compound having the structural formula I,
in the formula I, R 1 Represents 4-methylphenyl, 4-bromophenyl, 2, 6-dimethylphenyl, 2-methylphenyl, 2-methoxyphenyl, 2-naphthyl, benzyl or tert-butyl, R 2 Represents phenyl or 1,1' -binaphthyl.
The preparation method of the chiral thioether-phosphine compound comprises the following steps:
step one, reacting 2-fluorobenzaldehyde with thiophenol or mercaptan to obtain thioether benzaldehyde;
the structural formula of the 2-fluorobenzaldehyde is shown in the formula II,
the structural formula of the thiophenol or the thiol is shown in a formula III,
the structural formula of the thioether benzaldehyde is shown in a formula IV,
step two, reductive amination of thioether benzaldehyde and (R) - (+) -alpha-methylbenzylamine to obtain an intermediate;
the structural formula of the (R) - (+) -alpha-methylbenzylamine is shown as a formula V,
the structural formula of the intermediate is shown in a formula VI,
step three, reacting the intermediate with a phenolic compound to obtain a chiral thioether-phosphine compound I,
the structural formula of the phenolic compound is shown in a formula VII,
preferably, the method comprises the steps of:
step one, preparing 1.0 equivalent of 2-fluorobenzaldehyde II, 1.0 equivalent of thiophenol or mercaptan III and 2.0 equivalent of potassium carbonate, taking dimethyl sulfoxide as a solvent, reacting for 2-10 hours at 100 ℃, filtering to remove the solvent after the reaction is finished, washing a filter cake by ethyl acetate, adding a saturated ammonium chloride solution into filtrate, separating liquid, extracting an aqueous phase by ethyl acetate, mixing an organic phase with anhydrous sodium sulfate, drying, filtering, mixing the filtrate with silica gel powder, removing the solvent under reduced pressure, passing through a silica gel column, separating by column chromatography according to the volume ratio petroleum ether/ethyl acetate=50:1, and obtaining thioether benzaldehyde IV after removing chromatographic liquid;
step two, preparing 1.0 equivalent of thioether benzaldehyde IV and 1.2 equivalent of (R) - (+) -alpha-methylbenzylamine V, reacting in methanol for 10min, adding 2.0 equivalent of sodium borohydride, stirring until the sodium borohydride is completely dissolved, removing the methanol by desolventizing and concentrating, adding saturated ammonium chloride solution, extracting with methylene dichloride for 3 times, combining organic phases, drying with anhydrous sodium sulfate, carrying out suction filtration, stirring filtrate with silica gel powder, removing the solvent under reduced pressure, passing through a silica gel column, carrying out column chromatography separation according to the volume ratio petroleum ether/ethyl acetate=20:1, and obtaining an intermediate VI after removing chromatographic liquid;
thirdly, preparing 1.0 equivalent of amine intermediate VI, reacting with 1.0 equivalent of phosphorus trichloride in tetrahydrofuran to obtain light yellow turbid liquid, adding 1.0 equivalent of triethylamine, stirring for 30min, dissolving 1.1 equivalent of phenolic compound VII in tetrahydrofuran, dropwise adding the system at 0 ℃, detecting by a dot plate until the reaction is completed, quenching by saturated sodium chloride solution, separating liquid, combining organic phases, drying, stirring silica gel powder, removing solvent, passing through a silica gel column, and separating by column chromatography according to the volume ratio of petroleum ether/ethyl acetate of 30:1 to obtain chiral thioether-phosphine compound I.
A catalyst which is a complex formed by the reaction of the chiral thioether-phosphine compound of claim 1 with an allyl palladium chloride dimer.
Preferably, the chiral thioether-phosphine compound and the allyl palladium chloride dimer are mixed and dissolved in an organic solvent in a molar ratio of 4-6:1, and the complex formed by stirring and reacting at room temperature is formed.
The use of a catalyst, wherein the complex formed by the reaction of the chiral thioether-phosphine compound and the allyl palladium chloride dimer is used as a palladium-catalyzed asymmetric allyl alkylation catalyst.
The invention at least comprises the following beneficial effects:
the preparation method has the advantages of simplicity and high yield, can quickly construct various chiral ligand libraries, has good catalytic activity on catalyzing asymmetric allylic alkylation by a complex formed by the prepared compound and allyl palladium chloride dimer, can be used as a ligand for palladium-catalyzed asymmetric allylic alkylation, and can be directly used for preparing various allylic alkylation compounds.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Drawings
FIG. 1 is a schematic illustration of the reaction scheme of the present invention;
FIG. 2 is a schematic illustration of an asymmetric allylic alkylation reaction scheme of the present invention.
Detailed Description
The present invention is described in further detail below with reference to examples to enable those skilled in the art to practice the invention by reference to the specification.
It will be understood that terms, such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.
The experimental methods described in the following embodiments are conventional methods unless otherwise indicated, and the reagents and materials are commercially available.
< example 1>
Chiral thioether-phosphine compound has the structural formula I-1.
Dissolving 2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and 4-methylbenzothiool (50 mmol) in 50mL of dimethyl sulfoxide solution at room temperature, heating to 100 ℃, performing suction filtration after the reaction is completed, washing a filter cake with ethyl acetate (3X 20 mL), adding 100mL of saturated ammonium chloride solution into filtrate, transferring into a separating funnel for separating liquid, collecting an organic phase, washing a water phase with ethyl acetate (3X 20 mL), combining the organic phases, drying anhydrous sodium sulfate, performing suction filtration, removing a solvent from the filtrate with silica gel powder under reduced pressure, passing through a silica gel column, performing column chromatography separation with petroleum ether/ethyl acetate (50:1), and performing vacuum removal of a chromatographic liquid to obtain an intermediate IV-1, wherein the compound is a light yellow solid with the yield of 85%;
intermediate IV-1 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol, stirred until IV-1 completely disappeared, cooled to 0℃and sodium borohydride (20 mmol) was added in portions to the reaction system, and stirred until complete reaction was achieved. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-1 with yield of 87%;
intermediate VI-1 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, then (R) -binaphthol (5.5 mmol) was dissolved in tetrahydrofuran, zero degrees Celsius was added dropwise to the system, and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is completed, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel to separate liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-1, wherein the yield is 76 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,Chloroform-d)δ7.93(dd,J＝26.8,8.5Hz,2H),7.79-7.09(m,18H),7.07-6.99(m,2H),6.92-6.75(m,5H),4.31-4.02(m,2H),3.91-3.69(m,2H),2.27(s,3H),1.77(d,J＝2.4Hz,3H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(100MHz,CDCl 3 )δ150.06,150.01,149.44,143.05,143.03,139.50,136.57,134.35,132.76,132.31,132.11,131.82,131.34,130.86,130.70,130.63,130.12,130.09,129.79,128.77,128.31,128.24,128.05,127.62,127.60,127.43,127.39,127.20,127.02,126.79,125.96,125.83,124.73,124.28,124.19,124.14,122.22,122.20,121.52,58.11(d,J＝24Hz),45.78,22.50(d,J＝24Hz),21.08.
the nuclear magnetic resonance phosphorus spectrum data are: 31 P NMR(162MHz,CDCl 3 )δ144.74.
< example 2>
Chiral thioether-phosphine compound has the structural formula of I-2.
Dissolving 2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and 4-bromothiophenol (50 mmol) in 50mL of dimethyl sulfoxide solution at room temperature, heating to 100 ℃, performing suction filtration after the reaction is completed, washing a filter cake with ethyl acetate (3X 20 mL), adding 100mL of saturated ammonium chloride solution into filtrate, transferring into a separating funnel for separating liquid, collecting an organic phase, washing a water phase with ethyl acetate (3X 20 mL), combining the organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing a solvent from the filtrate with silica gel powder under reduced pressure, passing through a silica gel column, performing column chromatography separation with petroleum ether/ethyl acetate (50:1), and performing vacuum removal of a chromatographic liquid to obtain an intermediate IV-2, wherein the compound is a light yellow solid with the yield of 87%;
intermediate IV-2 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol and stirred until IV-2 completely disappeared, and cooled to 0deg.C. Sodium borohydride (20 mmol) was then added in portions to the reaction system and stirred until complete reaction. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-2 with a yield of 86%;
intermediate VI-2 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL of tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, then (R) -binaphthol (5.5 mmol) was dissolved in tetrahydrofuran, zero degrees celsius was added dropwise to the system, and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is completed, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel, separating the liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating the mixture by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-2, wherein the yield is 72 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ7.97(d,J＝8.7Hz,1H),7.90(d,J＝8.2Hz,1H),7.75(d,J＝8.2Hz,1H),7.65-7.52(m,3H),7.47-7.15(m,13H),7.15-7.04(m,3H),6.77(d,J＝8.8Hz,1H),6.57(d,J＝8Hz 2H),4.08(dd,J＝15.3,7.5Hz,1H),3.83-3.67(m,2H),1.76(d,J＝7.4Hz,3H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(100MHz,CDCl 3 )δ149.95,149.90,149.36,142.95,142.93,141.44,136.14,134.53,132.77,132.75,132.21,131.85,131.51,131.37,130.56,130.17,129.99,129.69,129.01,128.64,128.35,128.29,128.25,127.54,127.51,127.45,127.02,126.68,126.02,125.93,124.80,124.48,124.13,122.20,122.18,122.16,122.14,121.41,119.63,58.19(d,J＝24Hz),45.80,22.63(d,J＝25Hz).
the nuclear magnetic resonance phosphorus spectrum data are: 31 P NMR(162MHz,CDCl 3 )δ144.14.
< example 3>
Chiral thioether-phosphine compounds have the structural formula I-3.
2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and 2-methylbenzothiool (50 mmol) are dissolved in 50mL of dimethyl sulfoxide solution at room temperature, heated to 100 ℃, filtered by suction after the reaction is completed, filter cakes are washed by ethyl acetate (3X 20 mL), 100mL of saturated ammonium chloride solution is added into filtrate and transferred into a separating funnel for separating, an organic phase is collected, an aqueous phase is washed by ethyl acetate (3X 20 mL), anhydrous sodium sulfate is dried after the organic phase is combined, then filtered by suction, the filtrate is stirred with silica gel powder to remove a solvent under reduced pressure, a silica gel column is used for column chromatography separation by petroleum ether/ethyl acetate (50:1), and an intermediate IV-3 is obtained after the chromatographic liquid is removed under reduced pressure, and the compound is a light yellow solid with the yield of 81 percent.
Intermediate IV-3 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol and stirred until IV-3 completely disappeared, and cooled to 0deg.C. Sodium borohydride (20 mmol) was then added in portions to the reaction system and stirred until complete reaction. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-3 with a yield of 89%;
intermediate VI-3 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, then (R) -binaphthol (5.5 mmol) was dissolved in tetrahydrofuran, zero degrees Celsius was added dropwise to the system, and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is finished, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel to separate liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-3, wherein the yield is 75 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ7.97(d,J＝8.8Hz,1H),7.90(d,J＝8.2Hz,1H),7.74(d,J＝8.2Hz,1H),7.64-7.55(m,3H),7.53-7.08(m,14H),7.09-6.95(m,2H),6.93(d,J＝7.8Hz,1H),6.82-6.72(m,2H),6.65(d,J＝7.8Hz,1H),4.10(dd,J＝15.5,7.5Hz,1H),3.85-3.60(m,2H),2.09(s,3H),1.76(d,J＝7.3Hz,3H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(100MHz,CDCl 3 )δ150.01,149.96,149.44,143.10,139.48,138.17,134.32,133.36,132.78,132.32,131.70,131.36,130.59,130.57,130.18,130.13,130.10,128.33,128.24,128.17,127.64,127.62,127.42,127.40,127.29,127.04,126.91,126.75,126.47,125.96,125.83,124.75,124.26,124.22,124.16,122.22,122.14,121.38,58.24(d,J＝24Hz),45.79(d,J＝2Hz),22.66(d,J＝13Hz),20.13.
the nuclear magnetic resonance phosphorus spectrum data are: 31 P NMR(162MHz,CDCl 3 )δ144.40.
< example 4>
Chiral thioether-phosphine compounds have the structural formula I4.
Dissolving 2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and 2-methoxythiophenol (50 mmol) in 50mL of dimethyl sulfoxide solution at room temperature, heating to 100 ℃, performing suction filtration after the reaction is completed, washing a filter cake with ethyl acetate (3X 20 mL), adding 100mL of saturated ammonium chloride solution into filtrate, transferring into a separating funnel for separating liquid, collecting an organic phase, washing a water phase with ethyl acetate (3X 20 mL), combining the organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing a solvent from the filtrate with silica gel powder under reduced pressure, passing through a silica gel column, performing column chromatography separation with petroleum ether/ethyl acetate (50:1), and performing vacuum removal of a chromatographic liquid to obtain an intermediate IV-4, wherein the compound is a light yellow solid with the yield of 90%;
intermediate IV-4 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol and stirred until IV-4 completely disappeared, and cooled to 0deg.C. Sodium borohydride (20 mmol) was then added in portions to the reaction system and stirred until complete reaction. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-4 with a yield of 90%;
intermediate VI-4 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, then (R) -binaphthol (5.5 mmol) was dissolved in tetrahydrofuran, zero degrees Celsius was added dropwise to the system, and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is completed, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel, separating the liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating the mixture by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-4, wherein the yield is 80 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ7.93(dd,J＝29.8,8.5Hz,2H),7.71(d,J＝8.2Hz,1H),7.68-7.44(m,5H),7.42-7.00(m,14H),6.77(t,J＝7.1Hz,2H),6.49-6.38(m,2H),4.21-4.08(m,1H),3.95-3.78(m,2H),3.74(s,3H),1.74(d,J＝8.0Hz,3H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(100MHz,CDCl 3 )δ156.63,149.99,149.94,149.42,143.04,140.88,133.30,132.75,132.27,131.34,130.53,130.11,130.09,129.91,128.54,128.38,128.24,127.94,127.65,127.54,127.34,127.28,127.04,126.70,125.94,125.78,124.73,124.47,124.20,122.22,122.03,121.43,121.11,110.72,57.96(d,J＝24Hz),55.80,45.69,22.48(d,J＝24Hz).
the nuclear magnetic resonance phosphorus spectrum data are: 331 P NMR(162MHz,CDCl 3 )δ144.43.
< example 5>
Chiral thioether-phosphine compounds have the structural formula I5.
Dissolving 2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and 2, 6-dimethylbenzenesulfide (50 mmol) in 50mL of dimethyl sulfoxide solution at room temperature, heating to 100 ℃, carrying out suction filtration after the reaction is completed, washing a filter cake with ethyl acetate (3X 20 mL), adding 100mL of saturated ammonium chloride solution into filtrate, transferring into a separating funnel for separating liquid, collecting an organic phase, washing a water phase with ethyl acetate (3X 20 mL), combining the organic phases, drying with anhydrous sodium sulfate, carrying out suction filtration, removing a solvent from the filtrate with silica gel powder under reduced pressure, passing through a silica gel column, carrying out column chromatography separation with petroleum ether/ethyl acetate (50:1), and carrying out reduced pressure removal of a chromatographic liquid to obtain an intermediate IV-5, wherein the compound is a light yellow solid with the yield of 86%;
intermediate IV-5 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol and stirred until IV-5 completely disappeared, and cooled to 0deg.C. Sodium borohydride (20 mmol) was then added in portions to the reaction system and stirred until complete reaction. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-5 with a yield of 88%;
intermediate VI-5 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, then (R) -binaphthol (5.5 mmol) was dissolved in tetrahydrofuran, zero degrees Celsius was added dropwise to the system, and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is completed, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel, separating the liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating the mixture by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-5, wherein the yield is 71 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,Chloroform-d)δ8.03-7.87(m,2H),7.82-7.74(m,2H),7.65-7.55(m,3H),7.54-7.01(m,13H),6.95-6.80(m,2H),6.21(d,J＝8Hz,1H),4.30-4.16(m,1H),3.74(q,J＝12Hz,2H),2.04(d,J＝2.8Hz,6H),1.85(d,J＝3.1Hz,3H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(100MHz,CDCl 3 )δ150.16,150.11,149.51,143.89,143.24,136.15,135.01,132.79,132.43,131.34,130.77,130.22,130.15,130.10,129.05,128.45,128.27,128.18,127.66,127.55,127.01,126.80,125.98,125.89,124.73,124.43,124.35,124.18,124.12,122.31,122.24,121.62,58.41(d,J＝23Hz),45.69,22.81(d,J＝27Hz),21.42.
the nuclear magnetic resonance phosphorus spectrum data are: 31 P NMR(162MHz,CDCl 3 )δ145.34.
< example 6>
Chiral thioether-phosphine compounds have the structural formula I6.
Dissolving 2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and 2-naphthalene thiophenol (50 mmol) in 50mL of dimethyl sulfoxide solution at room temperature, heating to 100 ℃, performing suction filtration after the reaction is completed, washing a filter cake with ethyl acetate (3X 20 mL), adding 100mL of saturated ammonium chloride solution into filtrate, transferring into a separating funnel for separating liquid, collecting an organic phase, washing a water phase with ethyl acetate (3X 20 mL), combining the organic phases, drying anhydrous sodium sulfate, performing suction filtration, stirring the filtrate with silica gel powder, removing a solvent under reduced pressure, passing through a silica gel column, performing column chromatography separation by petroleum ether/ethyl acetate (50:1), and performing vacuum removal of a chromatographic liquid to obtain an intermediate IV-6, wherein the compound is a light yellow solid with the yield of 78%;
intermediate IV-6 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol and stirred until IV-6 completely disappeared, and cooled to 0deg.C. Sodium borohydride (20 mmol) was then added in portions to the reaction system and stirred until complete reaction. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-6 with a yield of 89%;
intermediate VI-6 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, then (R) -binaphthol (5.5 mmol) was dissolved in tetrahydrofuran, zero degrees Celsius was added dropwise to the system, and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is completed, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel, separating the liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating the mixture by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-6, wherein the yield is 73 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ7.96(d,J＝8.8Hz,1H),7.89(d,J＝8.2Hz,1H),7.78-7.71(m,1H),7.66-7.14(m,21H),7.09(q,J＝7.5Hz,2H),6.88(d J＝8.6Hz,1H),6.70(d,J＝8.8Hz,1H),4.11(dd,J＝15.6,7.5Hz,1H),3.87-3.70(m,2H),1.77(dd,J＝7.4,2.6Hz,3H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(100MHz,CDCl 3 )δ149.40,142.96,140.74,133.82,133.70,132.76,132.74,132.19,131.84,131.34,130.51,130.12,129.99,128.55,128.40,128.33,128.23,128.10,127.76,127.55,127.51,127.36,127.17,127.08,127.01,126.60,126.51,125.96,125.79,125.74,124.74,124.26,124.22,122.19,121.38,58.21(d,J＝21Hz),45.89,26.93(d,J＝8.8Hz,1H),22.60(d,J＝26Hz).
the nuclear magnetic resonance phosphorus spectrum data are: 31 P NMR(162MHz,CDCl 3 )δ144.54.
< example 7>
Chiral thioether-phosphine compounds have the structural formula I7.
Dissolving 2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and benzyl mercaptan (50 mmol) in 50mL of dimethyl sulfoxide solution at room temperature, heating to 100 ℃, carrying out suction filtration after the reaction is completed, washing a filter cake with ethyl acetate (3X 20 mL), adding 100mL of saturated ammonium chloride solution into filtrate, transferring into a separating funnel for separating liquid, collecting an organic phase, washing a water phase with ethyl acetate (3X 20 mL), combining the organic phases, drying with anhydrous sodium sulfate, carrying out suction filtration, stirring the filtrate with silica gel powder, removing a solvent under reduced pressure, passing through a silica gel column, carrying out column chromatography separation by petroleum ether/ethyl acetate (50:1), and carrying out reduced pressure removal of chromatographic liquid to obtain an intermediate IV-7, wherein the compound is a light yellow solid, and the yield is 77%;
intermediate IV-7 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol and stirred until IV-7 completely disappeared, and cooled to 0deg.C. Sodium borohydride (20 mmol) was then added in portions to the reaction system and stirred until complete reaction. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-7 with a yield of 92%;
intermediate VI-7 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, then (R) -binaphthol (5.5 mmol) was dissolved in tetrahydrofuran, zero degrees Celsius was added dropwise to the system, and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is completed, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel, separating the liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating the mixture by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-7, wherein the yield is 80 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ7.96(d,J＝8.8Hz,1H),7.88(d,J＝8.2Hz,1H),7.69(t,J＝7.8Hz,2H),7.58(d,J＝8.8Hz,1H),7.54-7.47(m,3H),7.46-7.03(m,14H),7.01-6.95(m,1H),6.88(dd,J＝8.8,1.4Hz,1H),6.85-6.77(m,2H),4.15-3.95(m,1H),3.79(s,2H),3.32(q,J＝16Hz,1H),1.78(d,J＝7.4Hz,3H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(100MHz,CDCl 3 )δ150.10,150.05,149.50,143.14,143.13,139.53,137.01,133.89,132.75,132.73,132.39,131.55,131.33,130.61,130.15,128.62,128.38,128.25,128.10,127.65,127.63,127.48,127.45,127.13,126.95,126.84,126.74,126.72,126.00,125.95,124.74,124.46,124.07,124.02,122.40,122.38,122.20,122.18,121.66,58.20(d,J＝24Hz),45.70,38.52,22.63(d,J＝13Hz).
the nuclear magnetic resonance phosphorus spectrum data are: 31 P NMR(162MHz,CDCl 3 )δ145.05.
< example 8>
Chiral thioether-phosphine compounds have the structural formula I8.
Dissolving 2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and tert-butyl mercaptan (50 mmol) in 50mL of dimethyl sulfoxide solution at room temperature, heating to 100 ℃, carrying out suction filtration after the reaction is completed, washing a filter cake with ethyl acetate (3X 20 mL), adding 100mL of saturated ammonium chloride solution into filtrate, transferring into a separating funnel for separating liquid, collecting an organic phase, washing an aqueous phase with ethyl acetate (3X 20 mL), combining the organic phases, drying anhydrous sodium sulfate, carrying out suction filtration, stirring the filtrate with silica gel powder, removing a solvent under reduced pressure, passing through a silica gel column, carrying out column chromatography separation by petroleum ether/ethyl acetate (50:1), and carrying out reduced pressure removal of a chromatographic liquid to obtain an intermediate IV-8, wherein the compound is a light yellow solid, and the yield is 88%;
intermediate IV-8 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol and stirred until IV-8 completely disappeared, and cooled to 0deg.C. Sodium borohydride (20 mmol) was then added in portions to the reaction system and stirred until complete reaction. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-8 with a yield of 80%;
intermediate VI-8 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, then (R) -binaphthol (5.5 mmol) was dissolved in tetrahydrofuran, zero degrees Celsius was added dropwise to the system, and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is completed, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel, separating the liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating the mixture by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-8, wherein the yield is 78 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ7.97(d,J＝8.8Hz,1H),7.90(d,J＝8.2Hz,1H),7.76(t,J＝8.6Hz,2H),7.60(t,J＝8.3Hz,2H),7.51-7.18(m,12H),7.17-7.04(m,2H),6.87(d,J＝8.8Hz,1H),4.10-3.76(m,2H),3.86(d,J＝16.4Hz,1H),1.77(d J＝7.5Hz,3H),0.61(s,9H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(100MHz,CDCl 3 )δ150.13,150.09,149.60,144.01,143.10,143.08,138.82,132.76,132.74,132.50,131.60,131.35,130.75,130.14,130.10,129.14,128.31,128.26,128.17,127.94,127.68,127.66,127.39,126.98,126.73,126.23,125.97,125.86,124.72,124.35,122.44,122.26,122.24,121.78,57.42(d,J＝25Hz),46.98,46.73(d,J＝5Hz),30.23,22.46(d,J＝26Hz).
the nuclear magnetic resonance phosphorus spectrum data are: 31 P NMR(162MHz,CDCl 3 )δ145.23.
< example 9>
Chiral thioether-phosphine compounds have the structural formula I9.
Dissolving 2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and 4-methylbenzothiool (50 mmol) in 50mL of dimethyl sulfoxide solution at room temperature, heating to 100 ℃, performing suction filtration after the reaction is completed, washing a filter cake with ethyl acetate (3X 20 mL), adding 100mL of saturated ammonium chloride solution into filtrate, transferring into a separating funnel for separating liquid, collecting an organic phase, washing a water phase with ethyl acetate (3X 20 mL), combining the organic phases, drying anhydrous sodium sulfate, performing suction filtration, removing a solvent from the filtrate with silica gel powder under reduced pressure, passing through a silica gel column, performing column chromatography separation with petroleum ether/ethyl acetate (50:1), and performing vacuum removal of a chromatographic liquid to obtain an intermediate IV-1, wherein the compound is a light yellow solid with the yield of 85%;
intermediate IV-1 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol and stirred until IV-1 completely disappeared, and cooled to 0deg.C. Sodium borohydride (20 mmol) was then added in portions to the reaction system and stirred until complete reaction. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-1 with yield of 85%;
intermediate VI-1 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, then (S) -binaphthol (5.5 mmol) was dissolved in tetrahydrofuran, the system was added dropwise at 0℃and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is completed, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel, separating the liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating the mixture by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-9, wherein the yield is 74 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ7.95(d,J＝8.8Hz,1H),7.89(d,J＝8.2Hz,1H),7.77(dd,J＝16.4,8.0Hz,2H),7.66(d,J＝8.8Hz,1H),7.55(d,J＝8.7Hz,1H),7.41-7.16(m,12H),7.15-7.07(m,2H),7.00-6.82(m,5H),4.67-4.48(m,1H),4.09(dd,J＝16.9,5.3Hz,1H),3.86(dd,J＝16.9,5.3Hz,1H),2.26(s,3H),1.49(d,J＝8.4Hz,3H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(100MHz,CDCl 3 )δ149.86,149.80,149.26,141.99,141.04,136.49,133.42,132.74,132.47,132.43,131.96,131.34,130.56,130.25,130.17,129.84,129.70,128.97,128.26,128.17,128.15,127.90,127.44,127.27,127.20,127.03,126.95,125.97,125.86,124.75,124.36,124.12,124.07,122.20,121.99,121.56,56.09(d,J＝25Hz),44.47(d,J＝6Hz),21.04,20.52(d,J＝13Hz).
the nuclear magnetic resonance phosphorus spectrum data are: 31 P NMR(162MHz,CDCl 3 )δ146.01.
< example 10>
Chiral thioether-phosphine compounds have the structural formula I10.
Dissolving 2-fluorobenzaldehyde (50 mmol), potassium carbonate (100 mmol) and 2-methoxythiophenol (50 mmol) in 50mL of dimethyl sulfoxide solution at room temperature, heating to 100 ℃, performing suction filtration after the reaction is completed, washing a filter cake with ethyl acetate (3X 20 mL), adding 100mL of saturated ammonium chloride solution into filtrate, transferring into a separating funnel for separating liquid, collecting an organic phase, washing a water phase with ethyl acetate (3X 20 mL), combining the organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing a solvent from the filtrate with silica gel powder under reduced pressure, passing through a silica gel column, performing column chromatography separation with petroleum ether/ethyl acetate (50:1), and performing vacuum removal of a chromatographic liquid to obtain an intermediate IV-5, wherein the compound is a light yellow solid with the yield of 90%;
intermediate IV-5 (10 mmol) and (R) - (+) -alpha-methylbenzylamine V (12 mmol) were dissolved in 100mL of methanol and stirred until IV-5 completely disappeared, and cooled to 0deg.C. Sodium borohydride (20 mmol) was then added in portions to the reaction system and stirred until complete reaction. Removing methanol under reduced pressure, adding 100mL of saturated ammonium chloride, extracting with dichloromethane for three times, mixing organic phases, drying with anhydrous sodium sulfate, performing suction filtration, removing solvent from filtrate with silica gel powder under reduced pressure, separating with petroleum ether/ethyl acetate (20:1) by column chromatography, removing chromatographic liquid to obtain intermediate VI-5 with yield of 85%;
intermediate VI-5 (5 mmol) and phosphorus trichloride (5 mmol) were dissolved in 10mL of tetrahydrofuran, triethylamine (5 mmol) was added dropwise, the reaction was carried out at room temperature for three hours, phenol (11 mmol) was then dissolved in tetrahydrofuran, zero degrees celsius was added dropwise to the system, and then triethylamine (10 mmol) was added. The reaction was checked by TLC. After the reaction is completed, adding saturated ammonium chloride solution to quench the reaction, transferring the system to a separating funnel to separate liquid, collecting an organic phase, adding methylene dichloride into a water phase to extract for three times (3X 5 mL), combining the organic phase, drying the organic phase by anhydrous sodium sulfate, stirring the organic phase with silica gel powder, removing the solvent under reduced pressure, passing the mixture through a silica gel column, and separating by column chromatography by petroleum ether/ethyl acetate (30:1) to obtain the target compound shown in the formula I-10, wherein the yield is 56 percent.
The nuclear magnetic resonance hydrogen spectrum data are: 1 H NMR(400MHz,CDCl 3 )δ7.58-7.49(m,1H),7.37-7.11(m,13H),7.09-6.89(m,4H),6.97-6.73(m,5H),4.78-4.61(m,2H),4.52-4.32(m,1H),3.85(s,3H),1.58(d,J＝5.9Hz,3H).
the carbon-13 nuclear magnetic resonance data were: 13 C NMR(101MHz,CDCl 3 )δ156.57,142.46,142.12,142.10,134.22,131.57,129.49,129.44,129.09,128.14,128.08,127.72,127.42,127.31,126.94,125.09,122.89,122.84,121.29,120.20,120.11,120.07,119.98,110.71,55.85,55.63,44.46(d,J＝11Hz),21.03(d,J＝5Hz).
the nuclear magnetic resonance phosphorus spectrum data are: 31 P NMR(162MHz,CDCl 3 )δ139.12.
< test for verifying catalytic activity >
Under the protection of nitrogen, 0.01mmol of allyl palladium chloride dimer and 0.044mmol of ligand are dissolved in 2mL of dichloromethane and stirred at room temperature for one hour, then 0.2mmol of allyl acetate and 0.6mmol of cesium carbonate are added into the system, the temperature is raised to 40 ℃ and stirred for 10 minutes, and 0.3mmol of dimethyl malonate is added into the system for reaction, and the reaction is stirred until the reaction is complete. Adding 10mL of saturated ammonium chloride solution to terminate the reaction, extracting with dichloromethane, drying with anhydrous sodium sulfate, filtering, mixing the filtrate with silica gel powder to remove solvent, separating the sample by column chromatography with petroleum ether/ethyl acetate (v/v5:1), and removing the chromatographic liquid under reduced pressure to obtain the allyl alkylated product. Table 1 shows the results of a partial ligand in a palladium catalyzed asymmetric allylation reaction. As can be seen from the following experiments, the complex formed by the compound represented by the formula I and the allyl palladium chloride dimer has good catalytic activity for catalyzing asymmetric allyl alkylation reaction, and the compound I-4 is the best.
Table 1 shows the results of a partial ligand in a palladium catalyzed asymmetric allylation reaction. As can be seen from the following experiments, the complex formed by the compound represented by the formula I and the allyl palladium chloride dimer has good catalytic activity for catalyzing asymmetric allyl alkylation reaction, and the compound I-4 is the best. And has good catalytic effect on various substrates.
TABLE 1 Effect of ligand Effect on allylation reactions a
From the above experiments, it can be seen that the complex formed by the compound represented by formula I and the allyl palladium chloride dimer has good catalytic activity for catalyzing asymmetric allyl alkylation reaction. The compound of the invention can be directly used as a ligand for palladium-catalyzed asymmetric allylic alkylation reaction to prepare various allylic alkylation compounds.
The number of equipment and the scale of processing described herein are intended to simplify the description of the present invention. Applications, modifications and variations of the present invention will be readily apparent to those skilled in the art.
Although embodiments of the present invention have been disclosed above, it is not limited to the details and embodiments shown, it is well suited to various fields of use for which the invention is suited, and further modifications may be readily made by one skilled in the art, and the invention is therefore not to be limited to the particular details and examples shown and described herein, without departing from the general concepts defined by the claims and the equivalents thereof.

Claims (6)

1. The chiral thioether-phosphine compound is characterized in that the structural formula is shown in the formula I,
in the formula I, R 1 Represents 4-methylphenyl, 4-bromophenyl, 2, 6-dimethylphenyl, 2-methylphenyl, 2-methoxyphenyl, 2-naphthyl, benzyl or tert-butyl, R 2 Represents phenyl or 1,1' -binaphthyl.
2. The process for preparing a chiral thioether-phosphine compound according to claim 1, wherein the process comprises:
step one, reacting 2-fluorobenzaldehyde with thiophenol or mercaptan to obtain thioether benzaldehyde;
the structural formula of the 2-fluorobenzaldehyde is shown in the formula II,
thiophenol or thiol of formulaIII，
The structural formula of the thioether benzaldehyde is shown in a formula IV,
step two, reductive amination of thioether benzaldehyde and (R) - (+) -alpha-methylbenzylamine to obtain an intermediate;
the structural formula of the (R) - (+) -alpha-methylbenzylamine is shown as a formula V,
the structural formula of the intermediate is shown in a formula VI,
step three, reacting the intermediate with a phenolic compound to obtain a chiral thioether-phosphine compound I,
the structural formula of the phenolic compound is shown in a formula VII,
3. the process for preparing a chiral thioether-phosphine compound according to claim 2, wherein the process comprises:
step one, preparing 1.0 equivalent of 2-fluorobenzaldehyde II, 1.0 equivalent of thiophenol or mercaptan III and 2.0 equivalent of potassium carbonate, taking dimethyl sulfoxide as a solvent, reacting for 2-10 hours at 100 ℃, filtering to remove the solvent after the reaction is finished, washing a filter cake by ethyl acetate, adding a saturated ammonium chloride solution into filtrate, separating liquid, extracting an aqueous phase by ethyl acetate, mixing an organic phase with anhydrous sodium sulfate, drying, filtering, mixing the filtrate with silica gel powder, removing the solvent under reduced pressure, passing through a silica gel column, separating by column chromatography according to the volume ratio petroleum ether/ethyl acetate=50:1, and obtaining thioether benzaldehyde IV after removing chromatographic liquid;
step two, preparing 1.0 equivalent of thioether benzaldehyde IV and 1.2 equivalent of (R) - (+) -alpha-methylbenzylamine V, reacting in methanol for 10min, adding 2.0 equivalent of sodium borohydride, stirring until the sodium borohydride is completely dissolved, removing the methanol by desolventizing and concentrating, adding saturated ammonium chloride solution, extracting with methylene dichloride for 3 times, combining organic phases, drying with anhydrous sodium sulfate, carrying out suction filtration, stirring filtrate with silica gel powder, removing the solvent under reduced pressure, passing through a silica gel column, carrying out column chromatography separation according to the volume ratio petroleum ether/ethyl acetate=20:1, and obtaining an intermediate VI after removing chromatographic liquid;
thirdly, preparing 1.0 equivalent of amine intermediate VI, reacting with 1.0 equivalent of phosphorus trichloride in tetrahydrofuran to obtain light yellow turbid liquid, adding 1.0 equivalent of triethylamine, stirring for 30min, dissolving 1.1 equivalent of phenolic compound VII in tetrahydrofuran, dropwise adding the system at 0 ℃, detecting by a dot plate until the reaction is completed, quenching by saturated sodium chloride solution, separating liquid, combining organic phases, drying, stirring silica gel powder, removing solvent, passing through a silica gel column, and separating by column chromatography according to the volume ratio of petroleum ether/ethyl acetate of 30:1 to obtain chiral thioether-phosphine compound I.
4. A catalyst, characterized in that it is a complex formed by reacting the chiral thioether-phosphine compound according to claim 1 with an allyl palladium chloride dimer.
5. The catalyst of claim 4, wherein the chiral thioether-phosphine compound is mixed with the allylpalladium chloride dimer in a molar ratio of 4-6:1 in an organic solvent and the resulting complex is reacted at room temperature with stirring.
6. Use of a catalyst, characterized in that the complex formed by the reaction of a chiral thioether-phosphine compound according to claim 1 with an allylpalladium chloride dimer is used as a palladium-catalyzed asymmetric allylalkylation catalyst.
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