CN111686798A - BINOL axis chiral thiourea organic catalyst for preparing spiro tetrahydrothiophene - Google Patents
BINOL axis chiral thiourea organic catalyst for preparing spiro tetrahydrothiophene Download PDFInfo
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Abstract
The invention discloses a BINOL axial chiral thiourea organic catalyst for preparing spirotetrahydrothiophene, which comprises the following starting materials: 3-hydroxy-2-naphthoic acid, which is a chiral BINOL-3,3' -dicarboxylic acid compound prepared by taking 3-hydroxy-2-naphthoic acid as an initial raw material through esterification, oxidative coupling, de-esterification hydrolysis and resolution of a racemic compound. Compared with other treatment processes, the process is mature, the spirotetrahydrothiophene derivative can be obtained through the reaction with higher yield (80-95%), higher enantioselectivity (86-97%) and diastereoselectivity (>94:6 dr), the reaction substrate is expanded under the optimal condition, the substrate adaptability is better, the synthesized axial chiral BINOL multi-hydrogen bond thiourea small molecular catalyst can effectively catalyze Sulfa-Michael/Aldol reaction, a better result is obtained, and a certain reference is provided for subsequent research.
Description
Technical Field
The invention relates to a catalyst preparation process, in particular to a BINOL axial chiral thiourea organic catalyst for preparing spiro tetrahydrothiophene.
Background
The spirotetrahydrothiophene derivative is a sulfur heterocyclic compound and thioether, is colorless and malodorous liquid at normal temperature, is a five-membered ring structure, is a conjugated photoelectric building material with excellent mechanical properties, is an extremely important antihypertensive intermediate, is applied to the fields of medicines, chemical pesticides, high-molecular building materials and the like, and needs to use a catalyst to catalyze the reaction process in the synthesis process.
The existing catalyst commonly used for synthesizing the spirotetrahydrothiophene derivative comprises the following components: proline derivative organic catalysts and cinchona alkaloid derivative organic catalysts, in 2009, Nikla and the like are used for asymmetric Michael/Aldol condensation reaction of 1, 4-dithiane-2, 5-diol and cinnamaldehyde by using a proline derivative diphenyl prolinol TMS ether/bile acid organic catalytic system to synthesize thiophene derivatives, better yield is obtained, but the enantioselectivity is not high, in 2014, a ZHao group develops a cinchona derivative with low load to catalyze Sulfa-Michael/Aldol tandem reaction between benzylidene-chroman-4-one and 1, 4-dithiane-2, 5-diol by using a cinchona derivative squaramide, simple asymmetric synthesis of chiral spiro tetrahydrothiophene chroman derivatives is realized, and products have three continuous chiral centers, the target product is obtained in better yield and enantioselectivity, but with a smaller substrate range.
The above catalysts have disadvantages such as relatively low yields of thiophene derivatives obtained by the above catalysts, and poor substrate adaptability.
Disclosure of Invention
The purpose of the invention is to solve the defects in the prior art, and provide a BINOL axial chiral thiourea organic catalyst for preparing spirotetrahydrothiophene, the process is mature, the reaction can obtain spirotetrahydrothiophene derivatives with high yield (80-95%), high enantioselectivity (86-97%) and diastereoselectivity (>94:6 dr), the reaction substrate is expanded under the optimal condition, the substrate adaptability is good, the synthesized axial chiral BINOL multi-hydrogen bond thiourea small molecular catalyst can effectively catalyze Sulfa-Michael/Aldol reaction, and a good result is obtained, so that a certain reference is provided for subsequent research.
In order to achieve the purpose, the invention provides the following technical scheme: a BINOL axis chiral thiourea organic catalyst for preparing spirotetrahydrothiophene comprises the following starting materials: 3-hydroxy-2-naphthoic acid.
Preferably, the method comprises the following steps:
synthesis of S1, (R) -BINOL-3, 3' -dicarboxylic acid: taking 3-hydroxy-2-naphthoic acid as an initial raw material, and obtaining a chiral BINOL-3,3' -dicarboxylic acid compound through esterification, oxidative coupling, de-esterification hydrolysis and resolution of a racemic compound;
s2, synthesis of methyl 3-hydroxy-2-naphthoate: dissolving 4.89 g (26 mmol) of 3-hydroxy-2-naphthoic acid in methanol in a 250mL round-bottom flask, slowly adding 5 mL of concentrated sulfuric acid into the flask, heating and refluxing the obtained mixture for 18h, detecting the reaction by TLC, cooling the mixture to room temperature after the reflux is finished, filtering out a solid, concentrating the filtrate, washing the solid with sodium bicarbonate solution until no bubble is generated, extracting with ether solution, distilling the ether layer under reduced pressure, and recrystallizing the distilled solid with methanol to obtain methyl 3-hydroxy-2-naphthoate, wherein the product is yellow needle-shaped solid, and the chemical yield is 96%;
synthesis of S3, methyl 2, 2' -dihydroxy-1, 1' -binaphthalene-3, 3' -dicarboxylate: adding 20g (100mmol) of 3-hydroxy-2-methyl naphthoate into a 500mL three-neck round-bottom flask, sequentially adding 2.3g (10mmol) of CuCl (OH) TMEDA and 300mL of methanol solution, refluxing for 20h under the condition of introducing oxygen, detecting by TLC (thin layer chromatography) until the raw material disappears, removing the solvent by rotary evaporation after the reaction is finished, and purifying by using dichloromethane column chromatography to obtain 18g of light yellow solid with the yield of 90%;
synthesis of S4, 2' -dihydroxy-1, 1' -binaphthalene-3, 3' -dicarboxylic acid: in a 250mL round bottom flask, adding (+/-) 2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid methyl ester 10.05 g (25 mmol) into 80 mL of 2 mol/L sodium hydroxide methanol solution, heating and refluxing the obtained mixed solution for 24h, detecting the reaction by TLC, after the reaction is completed, distilling the obtained mixture under reduced pressure, dissolving the distilled product in 100mL (2 mol/L) of hydrochloric acid solution, adjusting the pH value of the solution to be 1, wherein yellow solid appears in the solution, filtering the solid by a Buchner funnel, washing with water to obtain a wet product, and drying the wet product at 105 ℃. Finally obtaining a dry yellow powder product (+/-) 2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid, wherein the yield is 94%;
resolution of S5, (R) -2, 2' -dihydroxy-1, 1' -binaphthalene-3, 3' -dicarboxylic acid: weighing 10 g of the (+/-) 2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid, dissolving in 250mL of L-leucine methyl ester methanol solution, wherein the solution quickly becomes reddish brown, heating and refluxing the mixed solution for 5 minutes until the solid is completely dissolved, cooling the solution to room temperature, standing for 1 day at 0 ℃, separating out the solid on the bottle wall in the two days, filtering the separated solid through a Buchner funnel, reserving the filtrate, washing the filtered residue with a small amount of methanol, air-drying in a ventilated place to obtain yellow crystals, grinding the yellow crystals into powder in a mortar, pouring into a 250mL round-bottom beaker, adding 80 mL of methanol at the same time, heating the obtained mixed solution, continuously stirring and refluxing for 1 hour, sucking the supernatant by a suction pipe, repeatedly refluxing for 2 times, dissolving undissolved yellow powder by using 2 mol/L NaOH aqueous solution, washing the NaOH aqueous solution dissolved with the yellow powder by using 50mL of diethyl ether, discarding an aqueous phase by using a separating funnel, acidifying the obtained organic phase, adjusting the pH value of the solution to be 1, allowing yellow precipitate to appear in the solution, performing suction filtration by using a Buchner funnel, filtering out a filtrate, washing the obtained filter residue by using water, drying the obtained product at about 110 ℃, and finally obtaining (+) - (R) -2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid product with the chemical yield of 24%;
s6, preparation of acyl chloride: sequentially adding 0.15g (0.4mmol) of (R) -2, 2 '-dihydroxy-1, 1' -binaphthalene-3, 3 '-dicarboxylic acid and 0.1g (0.8mmol) of thionyl chloride into a 100mL single-neck flask, then adding 20mL of purified trichloromethane, gradually heating from room temperature to 70 ℃ under magnetic stirring, carrying out reflux reaction for 6 h until gas is completely released, absorbing tail gas by using a dilute sodium hydroxide solution, detecting by TLC to complete the reaction, and carefully removing excessive thionyl chloride and trichloromethane by rotary evaporation to obtain (R) -2, 2' -dihydroxy-1, 1 '-binaphthalene-3, 3' -dicarboxylic chloride;
s7, preparation of isothiocyanate: 0.1g (1mmol) of potassium thiocyanate, PEG-400 and 20mL of purified dichloromethane are added in sequence into a 50mL single-neck flask with magnetic stirring, the mixture is stirred until the PEG-400 is uniformly dispersed in an organic solvent, all the obtained (R) -2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic chloride is dissolved in 10mL of purified dichloromethane solution, then the solution is slowly dripped into the dichloromethane solution dissolved with the potassium thiocyanate by a constant pressure dropping funnel, the addition is finished for about 5min, the stirring is continued, TLC detection is carried out to remove the acid chloride, the reaction is finished, a precipitate is generated, and the solvent is removed by rotary evaporation to obtain a yellow solid.
S8, preparation of bisacylthiourea: the yellow solid obtained was completely dissolved by adding 20mL THF to a 250mL three-necked flask, 0.11g (0.8mmol) of (R) - (-) -1-phenylpropylamine was added under nitrogen protection, and reacted for 12h under ice bath conditions, after completion of TLC detection, the solvent was removed by rotary evaporation, and purified by column chromatography (eluent: petroleum ether: ethyl acetate =10:1, V/V) to obtain a yellow solid 8a with a yield of 72%. 8b to 8i were synthesized in the same manner.
S9, synthesis of spirotetrahydrothiophene: the asymmetric Sulfa-Michael/Aldol reaction of newly synthesized 9-axial chiral BINOL thiourea organic micromolecule catalysis alpha, beta-unsaturated ketone and 1, 4-dithiane-2, 5-diol is carried out, a compound 2-benzylidene-3, 4-dihydronaphthalene-1 (2H) -ketone (0.13g, 0.4mmol), 1, 4-dithiane-2, 5-diol (7, 0.046g, 0.3mmol) and 8 a-8 i are sequentially added into a 10mL round-bottom flask as catalysts, 2mL THF is added as a solvent, the mixture is stirred for 12H at room temperature, TLC detection reaction is completed, and column chromatography (V stone: V ethylene =10:1) is purified to obtain the spiro tetrahydrothiophene.
The invention has the technical effects and advantages that:
the method is mature in process, the spirotetrahydrothiophene derivative can be obtained through the reaction with high yield (80-95%), high enantioselectivity (86-97%) and diastereoselectivity (>94:6 dr), the reaction substrate is expanded under the optimal condition, the substrate adaptability is good, the synthesized axial chiral BINOL multi-hydrogen bond thiourea small molecular catalyst can effectively catalyze Sulfa-Michael/Aldol reaction, and a good result is obtained, so that a certain reference is provided for subsequent research.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Examples
A BINOL axis chiral thiourea organic catalyst for preparing spirotetrahydrothiophene comprises the following starting materials: 3-hydroxy-2-naphthoic acid.
Preferably, the method comprises the following steps:
synthesis of S1, (R) -BINOL-3, 3' -dicarboxylic acid: taking 3-hydroxy-2-naphthoic acid as an initial raw material, and obtaining a chiral BINOL-3,3' -dicarboxylic acid compound through esterification, oxidative coupling, de-esterification hydrolysis and resolution of a racemic compound;
s2, synthesis of methyl 3-hydroxy-2-naphthoate: dissolving 4.89 g (26 mmol) of 3-hydroxy-2-naphthoic acid in methanol in a 250mL round-bottom flask, slowly adding 5 mL of concentrated sulfuric acid into the flask, heating and refluxing the obtained mixture for 18h, detecting the reaction by TLC, cooling the mixture to room temperature after the reflux is finished, filtering out a solid, concentrating the filtrate, washing the solid with sodium bicarbonate solution until no bubble is generated, extracting with ether solution, distilling the ether layer under reduced pressure, and recrystallizing the distilled solid with methanol to obtain methyl 3-hydroxy-2-naphthoate, wherein the product is yellow needle-shaped solid, and the chemical yield is 96%;
synthesis of S3, methyl 2, 2' -dihydroxy-1, 1' -binaphthalene-3, 3' -dicarboxylate: adding 20g (100mmol) of 3-hydroxy-2-methyl naphthoate into a 500mL three-neck round-bottom flask, sequentially adding 2.3g (10mmol) of CuCl (OH) TMEDA and 300mL of methanol solution, refluxing for 20h under the condition of introducing oxygen, detecting by TLC (thin layer chromatography) until the raw material disappears, removing the solvent by rotary evaporation after the reaction is finished, and purifying by using dichloromethane column chromatography to obtain 18g of light yellow solid with the yield of 90%;
synthesis of S4, 2' -dihydroxy-1, 1' -binaphthalene-3, 3' -dicarboxylic acid: in a 250mL round bottom flask, adding (+/-) 2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid methyl ester 10.05 g (25 mmol) into 80 mL of 2 mol/L sodium hydroxide methanol solution, heating and refluxing the obtained mixed solution for 24h, detecting the reaction by TLC, after the reaction is completed, distilling the obtained mixture under reduced pressure, dissolving the distilled product in 100mL (2 mol/L) of hydrochloric acid solution, adjusting the pH value of the solution to be 1, wherein yellow solid appears in the solution, filtering the solid by a Buchner funnel, washing with water to obtain a wet product, and drying the wet product at 105 ℃. Finally obtaining a dry yellow powder product (+/-) 2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid, wherein the yield is 94%;
resolution of S5, (R) -2, 2' -dihydroxy-1, 1' -binaphthalene-3, 3' -dicarboxylic acid: weighing 10 g of the (+/-) 2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid, dissolving in 250mL of L-leucine methyl ester methanol solution, wherein the solution quickly becomes reddish brown, heating and refluxing the mixed solution for 5 minutes until the solid is completely dissolved, cooling the solution to room temperature, standing for 1 day at 0 ℃, separating out the solid on the bottle wall in the two days, filtering the separated solid through a Buchner funnel, reserving the filtrate, washing the filtered residue with a small amount of methanol, air-drying in a ventilated place to obtain yellow crystals, grinding the yellow crystals into powder in a mortar, pouring into a 250mL round-bottom beaker, adding 80 mL of methanol at the same time, heating the obtained mixed solution, continuously stirring and refluxing for 1 hour, sucking the supernatant by a suction pipe, repeatedly refluxing for 2 times, dissolving undissolved yellow powder by using 2 mol/L NaOH aqueous solution, washing the NaOH aqueous solution dissolved with the yellow powder by using 50mL of diethyl ether, discarding an aqueous phase by using a separating funnel, acidifying the obtained organic phase, adjusting the pH value of the solution to be 1, allowing yellow precipitate to appear in the solution, performing suction filtration by using a Buchner funnel, filtering out a filtrate, washing the obtained filter residue by using water, drying the obtained product at about 110 ℃, and finally obtaining (+) - (R) -2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid product with the chemical yield of 24%;
s6, preparation of acyl chloride: sequentially adding 0.15g (0.4mmol) of (R) -2, 2 '-dihydroxy-1, 1' -binaphthalene-3, 3 '-dicarboxylic acid and 0.1g (0.8mmol) of thionyl chloride into a 100mL single-neck flask, then adding 20mL of purified trichloromethane, gradually heating from room temperature to 70 ℃ under magnetic stirring, carrying out reflux reaction for 6 h until gas is completely released, absorbing tail gas by using a dilute sodium hydroxide solution, detecting by TLC to complete the reaction, and carefully removing excessive thionyl chloride and trichloromethane by rotary evaporation to obtain (R) -2, 2' -dihydroxy-1, 1 '-binaphthalene-3, 3' -dicarboxylic chloride;
s7, preparation of isothiocyanate: 0.1g (1mmol) of potassium thiocyanate, PEG-400 and 20mL of purified dichloromethane are added in sequence into a 50mL single-neck flask with magnetic stirring, the mixture is stirred until the PEG-400 is uniformly dispersed in an organic solvent, all the obtained (R) -2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic chloride is dissolved in 10mL of purified dichloromethane solution, then the solution is slowly dripped into the dichloromethane solution dissolved with the potassium thiocyanate by a constant pressure dropping funnel, the addition is finished for about 5min, the stirring is continued, TLC detection is carried out to remove the acid chloride, the reaction is finished, a precipitate is generated, and the solvent is removed by rotary evaporation to obtain a yellow solid.
S8, preparation of bisacylthiourea: the yellow solid obtained was completely dissolved by adding 20mL THF to a 250mL three-necked flask, 0.11g (0.8mmol) of (R) - (-) -1-phenylpropylamine was added under nitrogen protection, and reacted for 12h under ice bath conditions, after completion of TLC detection, the solvent was removed by rotary evaporation, and purified by column chromatography (eluent: petroleum ether: ethyl acetate =10:1, V/V) to obtain a yellow solid 8a with a yield of 72%. 8b to 8i were synthesized in the same manner.
S9, synthesis of spirotetrahydrothiophene: the asymmetric Sulfa-Michael/Aldol reaction of newly synthesized 9-axial chiral BINOL thiourea organic micromolecule catalysis alpha, beta-unsaturated ketone and 1, 4-dithiane-2, 5-diol is carried out, a compound 2-benzylidene-3, 4-dihydronaphthalene-1 (2H) -ketone (0.13g, 0.4mmol), 1, 4-dithiane-2, 5-diol (7, 0.046g, 0.3mmol) and 8 a-8 i are sequentially added into a 10mL round-bottom flask as catalysts, 2mL THF is added as a solvent, the mixture is stirred for 12H at room temperature, TLC detection reaction is completed, and column chromatography (V stone: V ethylene =10:1) is purified to obtain the spiro tetrahydrothiophene.
In summary, the following steps: compared with other treatment processes, the BINOL axial chiral thiourea organic catalyst for preparing the spirotetrahydrothiophene provided by the invention has the following advantages: the method has the advantages that the process is mature, the spirotetrahydrothiophene derivative can be obtained through the reaction with high yield (80-95%), high enantioselectivity (86-97%) and diastereoselectivity (>94:6 dr), the reaction substrate is expanded under the optimal condition, the substrate adaptability is good, the synthesized axial chiral BINOL multi-hydrogen bond thiourea small molecular catalyst can effectively catalyze the Sulfa-Michael/Aldol reaction, and a good result is obtained, so that a certain reference is provided for subsequent researches.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments or portions thereof without departing from the spirit and scope of the invention.
Claims (2)
1. A BINOL axis chiral thiourea organic catalyst for preparing spiro tetrahydrothiophene is characterized in that: the starting materials are: 3-hydroxy-2-naphthoic acid.
2. The BINOL-axis chiral thiourea organic catalyst of claim 1 for the preparation of spirotetrahydrothiophene, characterized in that: the method comprises the following steps:
synthesis of S1, (R) -BINOL-3, 3' -dicarboxylic acid: taking 3-hydroxy-2-naphthoic acid as an initial raw material, and obtaining a chiral BINOL-3,3' -dicarboxylic acid compound through esterification, oxidative coupling, de-esterification hydrolysis and resolution of a racemic compound;
s2, synthesis of methyl 3-hydroxy-2-naphthoate: dissolving 4.89 g (26 mmol) of 3-hydroxy-2-naphthoic acid in methanol in a 250mL round-bottom flask, slowly adding 5 mL of concentrated sulfuric acid into the flask, heating and refluxing the obtained mixture for 18h, detecting the reaction by TLC, cooling the mixture to room temperature after the reflux is finished, filtering out a solid, concentrating the filtrate, washing the solid with sodium bicarbonate solution until no bubble is generated, extracting with ether solution, distilling the ether layer under reduced pressure, and recrystallizing the distilled solid with methanol to obtain methyl 3-hydroxy-2-naphthoate, wherein the product is yellow needle-shaped solid, and the chemical yield is 96%;
synthesis of S3, methyl 2, 2' -dihydroxy-1, 1' -binaphthalene-3, 3' -dicarboxylate: adding 20g (100mmol) of 3-hydroxy-2-methyl naphthoate into a 500mL three-neck round-bottom flask, sequentially adding 2.3g (10mmol) of CuCl (OH) TMEDA and 300mL of methanol solution, refluxing for 20h under the condition of introducing oxygen, detecting by TLC (thin layer chromatography) until the raw material disappears, removing the solvent by rotary evaporation after the reaction is finished, and purifying by using dichloromethane column chromatography to obtain 18g of light yellow solid with the yield of 90%;
synthesis of S4, 2' -dihydroxy-1, 1' -binaphthalene-3, 3' -dicarboxylic acid: adding 10.05 g (+/-) methyl 2, 2 '-dihydroxy-1, 1' -dinaphthalene-3, 3 '-dicarboxylate (25 mmol) into 80 mL of 2 mol/L sodium hydroxide methanol solution in a 250mL round-bottom flask, heating and refluxing the obtained mixed solution for 24h, detecting the reaction by TLC, distilling the obtained mixture under reduced pressure after the reaction is finished, dissolving the distillation product into 100mL of 2 mol/L hydrochloric acid solution, adjusting the pH value of the solution to be 1, wherein yellow solid appears in the solution, filtering the solid by using a Buchner funnel, washing the solid by using water to obtain a wet product, drying the wet product at 105 ℃, and finally obtaining a dry yellow powder product (+/-) 2, 2' -dihydroxy-1, 1 '-dinaphthalene-3, 3' -dicarboxylic acid, the yield is 94%;
resolution of S5, (R) -2, 2' -dihydroxy-1, 1' -binaphthalene-3, 3' -dicarboxylic acid: weighing 10 g of the (+/-) 2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid, dissolving in 250mL of L-leucine methyl ester methanol solution, wherein the solution quickly becomes reddish brown, heating and refluxing the mixed solution for 5 minutes until the solid is completely dissolved, cooling the solution to room temperature, standing for 1 day at 0 ℃, separating out the solid on the bottle wall in the two days, filtering the separated solid through a Buchner funnel, reserving the filtrate, washing the filtered residue with a small amount of methanol, air-drying in a ventilated place to obtain yellow crystals, grinding the yellow crystals into powder in a mortar, pouring into a 250mL round-bottom beaker, adding 80 mL of methanol at the same time, heating the obtained mixed solution, continuously stirring and refluxing for 1 hour, sucking the supernatant by a suction pipe, repeatedly refluxing for 2 times, dissolving undissolved yellow powder by using 2 mol/L NaOH aqueous solution, washing the NaOH aqueous solution dissolved with the yellow powder by using 50mL of diethyl ether, discarding an aqueous phase by using a separating funnel, acidifying the obtained organic phase, adjusting the pH value of the solution to be 1, allowing yellow precipitate to appear in the solution, performing suction filtration by using a Buchner funnel, filtering out a filtrate, washing the obtained filter residue by using water, drying the obtained product at about 110 ℃, and finally obtaining (+) - (R) -2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic acid product with the chemical yield of 24%;
s6, preparation of acyl chloride: sequentially adding 0.15g (0.4mmol) of (R) -2, 2 '-dihydroxy-1, 1' -binaphthalene-3, 3 '-dicarboxylic acid and 0.1g (0.8mmol) of thionyl chloride into a 100mL single-neck flask, then adding 20mL of purified trichloromethane, gradually heating from room temperature to 70 ℃ under magnetic stirring, carrying out reflux reaction for 6 h until gas is completely released, absorbing tail gas by using a dilute sodium hydroxide solution, detecting by TLC to complete the reaction, and carefully removing excessive thionyl chloride and trichloromethane by rotary evaporation to obtain (R) -2, 2' -dihydroxy-1, 1 '-binaphthalene-3, 3' -dicarboxylic chloride;
s7, preparation of isothiocyanate: sequentially adding 0.1g (1mmol) of potassium thiocyanate, PEG-400 and 20mL of purified dichloromethane into a 50mL single-neck flask with magnetic stirring, stirring until the PEG-400 is uniformly dispersed in an organic solvent, completely dissolving the obtained (R) -2, 2' -dihydroxy-1, 1' -dinaphthalene-3, 3' -dicarboxylic chloride into 10mL of purified dichloromethane solution, slowly dropwise adding the solution into the dichloromethane solution dissolved with the potassium thiocyanate by using a constant-pressure dropping funnel, adding the solution for about 5min, continuously stirring, detecting by TLC (thin layer chromatography) that the acid chloride disappears, completing the reaction, generating a precipitate, and rotationally evaporating the solvent to obtain a yellow solid;
s8, preparation of bisacylthiourea: adding 20mL of THF into a 250mL three-neck flask to completely dissolve the obtained yellow solid, adding 0.11g (0.8mmol) of (R) - (-) -1-phenylpropylamine under the protection of nitrogen, reacting for 12h under the condition of ice bath, detecting by TLC after the reaction is finished, removing the solvent by rotary evaporation, and purifying by column chromatography (eluent: petroleum ether: ethyl acetate =10:1, V/V) to obtain a yellow solid 8a with the yield of 72 percent, and synthesizing 8 b-8 i by the same method;
s9, synthesis of spirotetrahydrothiophene: the asymmetric Sulfa-Michael/Aldol reaction of newly synthesized 9-axial chiral BINOL thiourea organic micromolecule catalysis alpha, beta-unsaturated ketone and 1, 4-dithiane-2, 5-diol is carried out, a compound 2-benzylidene-3, 4-dihydronaphthalene-1 (2H) -ketone (0.13g, 0.4mmol), 1, 4-dithiane-2, 5-diol (7, 0.046g, 0.3mmol) and 8 a-8 i are sequentially added into a 10mL round-bottom flask as catalysts, 2mL THF is added as a solvent, the mixture is stirred for 12H at room temperature, TLC detection reaction is completed, and column chromatography (V stone: V ethylene =10:1) is purified to obtain the spiro tetrahydrothiophene.
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