CN113024481B - Preparation method of tartaric acid-derived chiral oxazolidine-2-thioketone - Google Patents
Preparation method of tartaric acid-derived chiral oxazolidine-2-thioketone Download PDFInfo
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Abstract
The invention belongs to the field of chiral compound preparation chemistry, and particularly relates to a preparation method of tartaric acid-derived chiral oxazolidine-2-thione. The method takes tartaric acid as a chiral source, optical pure tartrate reacts with aryl Grignard reagent to prepare chiral 1,1,4, 4-tetraaryl butanetetraol, then the chiral 1,1,4, 4-tetraaryl butanetetraol and thionyl chloride undergo a highly regioselective 2, 3-cyclic sulfitation reaction to generate chiral dichloroaryl cyclic sulfite, then the chiral dichloroaryl cyclic sulfite reacts with alkali liquor under certain conditions to obtain chiral aryl substituted dioxirane, and finally the chiral aryl substituted dioxirane reacts with thiocyanate to prepare chiral oxazolidine-2-thione. The invention takes tartaric acid as a chiral source, is cheap and is easy to obtain; under the condition of no catalyst, stable and low-toxicity thiocyanate and chiral epoxy are subjected to regiospecific reaction to prepare the chiral oxazolidine-2-thione, and the method has the remarkable characteristics of simplicity and convenience in operation, good reaction regioselectivity, easiness in treatment and the like.
Description
Technical Field
The invention belongs to the field of chiral compound preparation chemistry, and particularly relates to a preparation method of tartaric acid-derived chiral oxazolidine-2-thione.
Background
The chiral oxazolidine-2-thioketone as a chiral auxiliary agent is widely applied to the field of asymmetric synthesis, [ (a) Nagao, Y.; yamada, s.; kumagai, t.; ochiai, m.; fujita, e.j.chem.soc., chem.commun.1985,1418, (b) Hsiao, c.n.; liu, l.; miller, m.j.j.org.chem.1987,52,2202.(c) Kazmierczak, f.; helquist, p.j.org.chem.1989,54,3988.(d) Yan, t.h.; lee, h.c.; tan, c.w.tetrahedron lett.1993,34,3559.(e) Yan, t.h.; tan, c.w.; lee, h.c.; huang, t.y.j.am.chem.soc.1993,115,2613.(f) Hsiao, c.n.; liu, l.; miller, m.j.j.org.chem.1995,60,3301.(g) Su, d.w.; wang, y.c.; yan, t.h. tetrahedron lett.1999,40,4197], because it is more easily cleaved after completion of chiral induction than the traditional chiral oxazolidin-2-one (i.e., Evans prosthetic group). In addition, chiral oxazolidine-2-thiones have been found to act as inhibitors of dopamine β -monooxygenase, and the electronic nature and steric hindrance of substituents have a significant effect on inhibitory activity [ Kandatege Wimasasea, D.Shyamali Wimasasea, Silpapathayalage Dharmasena, Donovan C.Haines, Kevin R.Alliston.biochemistry 1997,36,7144-7153 ].
At present, the main method for preparing chiral oxazolidine-2-thione is to start from chiral amino alcohol and react with carbon disulfide to prepare [ Delaunay, d.; toupet, l.; le Corre, M.J.org.chem.1995,60,6604 and 6607 ], carbon disulfide has high toxicity, low flash point and boiling point and low safety of heating reaction. Although improvements have been reported, the expensive reagent 2-chloro-1, 3-dimethylimidazole [ Isobe, t.; ishikawa, T.J.org.chem.1999,64,6986-6992] or thiophosgene with great toxicity [ Crimminsns, M.T.; king, b.w.; tabet, E.A. Chaudhary, K.J.org.chem.2001,66,894-902 ].
Ethylene oxide is a commonly used synthon in organic synthesis and has wide application in the synthesis of complex compounds (oxirans and Oxirenes: monomeric. in Comprehensive Heterocyclic Chemistry III; Katritzky, a.r., Ramsden, c.a., Scriven, e.f.v., Taylor, r.j.k., eds.; Elsevier ltd., 2008; vol.1, pp 173-233.). However, control of regioselective derivatization of 2, 3-disubstituted oxiranes is a great challenge, with regioselective control generally being carried out by Lewis acid catalysts (for regioselective control see review article J. org. chem.2020,85, 13391-13414.). In 2010, TiO (CF) was reported by the Sergio Castillon project group3COO)2Catalyzing the reaction of 1, 2-anhydro sugar and KSCN to prepare oxazolidine-2-thione. It was found that in the presence of conventional Lewis acids such as BF3·OEt2The reaction is carried out in the presence or absence of a catalyst to obtain a complex mixture. (J.org.chem.2010,75, 514-517, Table 1, entries 1-2; product configuration correction see J.org.chem.2012,77,3687-3687)
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide a preparation method of tartaric acid-derived chiral oxazolidine-2-thione. The method has the advantages of cheap and easily-obtained raw materials, simple process, excellent reaction selectivity, higher product yield and high synthesis safety.
The principle of the invention is as follows: the method comprises the following steps of taking tartaric acid as a chiral source, reacting optical pure tartrate with an aryl Grignard reagent to prepare chiral 1,1,4, 4-tetraaryl butanetetraol, carrying out a highly regioselective 2, 3-cyclic sulfitation reaction on the chiral 1,1,4, 4-tetraaryl butanetetraol and thionyl chloride under a certain reaction condition to generate chiral dichloroaryl cyclic sulfite, then reacting the chiral dichloroaryl cyclic sulfite with alkali liquor under a certain condition to obtain chiral aryl substituted ethylene oxide, and finally reacting the chiral aryl substituted ethylene oxide with thiocyanate to prepare chiral oxazolidine-2-thione.
The technical key points provided by the invention are as follows: generating chiral dichloroaryl cyclic sulfite through highly regioselective 2, 3-cyclic sulfitation reaction of chiral 1,1,4, 4-tetraarylbutanetetraol, wherein the chiral dichloroaryl cyclic sulfite attacks a sulfur-oxygen (S-O) bond by alkali under a specific alkaline condition to break the sulfur-oxygen (S-O) bond, and reacting to obtain chiral aryl-substituted bicycloethane; under the condition of no catalyst, chiral aryl substituted ethylene oxide and thiocyanate are subjected to a regiospecific reaction to prepare chiral oxazolidine-2-thioketone, wherein the structural formula of the chiral oxazolidine-2-thioketone is shown as a formula I or a formula II, and Ar in the formula is phenyl, tolyl, ethylphenyl, tert-butylphenyl and p-fluorophenyl:
a preparation method of tartaric acid derived chiral oxazolidine-2-thioketone comprises the following steps:
(1) reacting the optically pure tartrate with an aryl Grignard reagent to prepare chiral 1,1,4, 4-tetraaryl butanetetraol;
(2) in the presence of organic base A, under the condition of-5-36 ℃, chiral 1,1,4, 4-tetraarylbutanetetraol and thionyl chloride generate highly regioselective 2, 3-cyclic sulfitation reaction to prepare chiral dichloroaryl cyclic sulfite;
(3) in a certain organic solvent M at the temperature of minus 10 ℃ to 10 ℃, chiral dichloroaryl cyclic sulfite reacts with an inorganic base B aqueous solution with a certain concentration to prepare chiral aryl substituted bicycloethane;
(4) chiral aryl substituted ethylene oxide reacts with thiocyanate C in a certain organic solvent N at the temperature of 80-120 ℃ to prepare chiral oxazolidine-2-thioketone.
Further, the molar ratio of the optically pure tartrate to the aryl Grignard reagent in the step (1) is 1: 6-8.
Further, the optically pure tartrate in the step (1) is (2R,3R) -tartrate or (2S,3S) -tartrate.
Further, the general formula of the aryl grignard reagent in the step (1) is RMgX, wherein R is phenyl, tolyl, ethylphenyl, tert-butylphenyl, p-fluorophenyl, and X is Cl, Br, I; preferably, in the aryl grignard reagent RMgX in the step (1), R is phenyl, tolyl, or ethylbenzene, and X is Cl or Br; more preferably, the aryl grignard reagent in step (1) is phenyl magnesium bromide or tolyl magnesium bromide.
Further, in the step (2), the organic base A is triethylamine or pyridine.
Further, the molar ratio of the organic base A to the chiral 1,1,4, 4-tetraarylbutanetetraol in the step (2) is (6-30): 1, preferably (20-30): 1.
further, the molar ratio of the thionyl chloride to the chiral 1,1,4, 4-tetraarylbutanetetraol in the step (2) is (2-6): 1, preferably (3-4): 1;
further, the specific operation of step (2) is as follows: adding chiral 1,1,4, 4-tetraarylbutanetetraol and organic base A into a reaction vessel, stirring for 15-30 minutes at-5-10 ℃, dropwise adding thionyl chloride into the mixture, continuously stirring for 30-45 minutes after dropwise adding, heating to 25-36 ℃, continuously stirring for 30-45 minutes, adding water for treatment, and crystallizing to obtain the chiral dichloroaryl cyclic sulfite.
Further, the organic solvent M in step (3) is selected from any one of tetrahydrofuran, dioxane and acetonitrile.
Further, the inorganic base B in the step (3) is NaOH, KOH or Na2S。
Further, the concentration of the inorganic base B aqueous solution in the step (3) is 3-5 mol/L.
Further, the molar ratio of the inorganic base B aqueous solution to the chiral dichloroaryl cyclic sulfite in the step (3) is (6-30): 1, preferably (6-20): 1.
further, the reaction mechanism of the chiral aryl-substituted dioxirane prepared in the step (3) is as follows:
further, the specific operation of the step (3) is as follows: putting the chiral dichloroaryl cyclic sulfite solution dispersed by the organic solvent M and the inorganic base B aqueous solution into a reaction vessel, then reacting for 2-6 hours at the temperature of-10-10 ℃ under stirring, adding water to stop the reaction, and crystallizing to obtain the chiral aryl substituted ethylene oxide.
Further, the reaction temperature in the step (3) is-10-5 ℃; preferably, the reaction temperature in the step (3) is-5 ℃ to 0 ℃; more preferably, the reaction temperature in the step (3) is-5 ℃, and the reaction time is 6 hours; more preferably, the reaction temperature in the step (3) is 0 ℃ and the reaction time is 4 hours.
Further, the organic solvent N in the step (4) is selected from any one of N, N-dimethylformamide, nitromethane and acetonitrile.
Further, the thiocyanate C in the step (4) is NH4SCN or KSCN.
Further, the molar ratio of thiocyanate C to chiral aryl-substituted dioxirane in the step (4) is (2-10): 1, preferably (3-6): 1.
further, the specific operation of step (4) is as follows: putting chiral aryl substituted ethylene oxide, thiocyanate C and an organic solvent N into a reaction vessel, then stirring, reacting for 6-16 hours at 80-120 ℃, adding ethyl acetate into a reaction system, extracting for at least 3 times by using a saturated NaCl aqueous solution, separating to obtain an organic layer, drying, filtering, rotary steaming and carrying out column chromatography to obtain the chiral oxazolidine-2-thioketone.
Preferably, the reaction temperature in the step (4) is 100-120 ℃, and the reaction time is 12-14 hours.
Compared with the prior art, the invention has the advantages and beneficial effects that:
the chiral amino alcohol is artificially synthesized and has high price, and the tartaric acid is used as a chiral source, so the chiral amino alcohol is low in price and easy to obtain. The prior synthesis scheme generally adopts thiophosgene and CS with higher toxicity2And the reagent introduces C ═ S. Preparation by ethylene oxide is currently reportedThe method for preparing oxazolidine-2-thioketone generally needs to realize regioselective synthesis through a catalyst, and the preparation method adopts stable and low-toxicity thiocyanate and chiral bicycloxide to perform regiospecific reaction to prepare the chiral oxazolidine-2-thioketone under the condition of no catalyst, adopts conventional reagent reaction, and has the remarkable characteristics of easily obtained raw materials, simple and convenient operation, good reaction regioselectivity, easy treatment and the like.
Drawings
FIG. 1 is a structural diagram of (5R, 5R') -phenyl substituted chiral oxazolidine-2-thione synthesized in example 1.
Detailed Description
The technical solution of the present invention is further illustrated by the following specific examples.
Example 1: the preparation method of (5R, 5R') -phenyl substituted chiral oxazolidine-2-thioketone comprises the following steps:
step one, preparation of (R, R) -1,1,4, 4-tetraphenylbutanol
Dissolving phenylmagnesium bromide in a tetrahydrofuran solution, dropwise adding (R, R) -diethyl tartrate into a tetrahydrofuran solution of 6 equivalents of phenylmagnesium bromide (namely, the molar ratio of (R, R) -diethyl tartrate to the Grignard reagent is 1:6), reacting for 2 hours, quenching with a saturated ammonium chloride aqueous solution, extracting with diethyl ether, concentrating, and performing silica gel column chromatography (PE/EA is 6: 1) to obtain (R, R) -1,1,4, 4-tetraphenylbutanediol, wherein the yield is as follows: 51 percent. 149: 150 ℃ in m.p.; [ alpha ] to]D 25＝+154.2(c 1.0,CHCl3)；IR(KBr):3436,3058,2916,1598,1492,1447,1063,698；1H-NMR(CDCl3,300MHz):δ7.37–7.13(m,20H,Ar-H)；4.65(d,J＝7.2Hz,2H,OH)4.41(d,J＝4.7Hz,2H,CH)；3.77(d,J＝5.3Hz,2H,OH).13C-NMR(CDCl3,75MHz)δ143.8；142.7；134.6；131.5；129.3；128.3；128.2；127.9；127.5；126.7；125.5；81.3,69.7。
Step two, (4R,5R) -phenyl dichloro-ring sulfite preparation
A round bottom flask was charged with a solution of (R, R) -1,1,4, 4-tetraphenylbutanetetraol in tetrahydrofuran and 30 equivalents of triethylamine (i.e., moles of (R, R) -1,1,4, 4-tetraphenylbutanetetraol and triethylamine)The ratio is 1:30), stirring for 15 minutes at 0 ℃, dropwise adding 3 equivalents of thionyl chloride (namely the molar ratio of (R, R) -1,1,4, 4-tetraphenyl tetraol to thionyl chloride is 1:3), continuously stirring for 30 minutes at 0 ℃ after dropwise adding, recovering to room temperature (25 ℃, the same below), further stirring for 30 minutes, adding water for treatment, and recrystallizing with ethanol to obtain (4R,5R) -phenyl dichlorocyclo sulfite. Yield: and 90 percent. m.p.187-189 ℃; [ alpha ] of]D 20＝+12.5(c 0.5,EA)；1H NMR(CDCl3,300MHz):δ7.43-7.49(m,4H),7.27-7.35(m,10H),7.14-7.18(m,6H),6.06(d,J＝1.2Hz),5.82(d,J＝1.8Hz)；13C NMR(CDCl3,75MHz):δ141.4,140.1,129.2,129.0,128.5,128.2,128.1,127.9,87.5,87.3,78.6。
Step three, preparation of (2R,2R') -phenyl-epoxyethane
A10 mL round-bottomed flask equipped with a magnetic rotor was charged with a THF solution of (4R,5R) -phenyldichlorocyclosulfite, and then a 3mol/L aqueous solution of sodium sulfide [ (R, R) -phenyldichlorocyclosulfite and sodium sulfide at a molar ratio of 1:6]Then reacting for 6 hours under stirring at-5 ℃, adding water to stop the reaction, and recrystallizing ethanol to obtain (2R,2R') -phenyl-oxirane with the yield: 89 percent. m.p. 115-116 ℃; [ alpha ] of]D 20＝+101(c 0.1,EA)；1H-NMR(CDCl3,400MHz):δ7.40-7.44(m,10H),7.13-7.21(m,6H),6.77(d,J＝6.6Hz,4H),3.21(s,2H).13C-NMR(CDCl3,100MHz)δ139.7,137.9,128.7,128.5,128.4,128.2,127.9,127.6,65.8,62.8。
Step four, preparation of (5R, 5R') -phenyl substituted chiral oxazolidine-2-thioketone
Into a 50mL single-neck flask were charged 1mmol of the above chiral (2R,2R') -phenyldioxirane and 6mmol of NH4SCN solid and 10mL nitromethane were heated to 100 ℃ with stirring for 12 hours and the reaction was checked by TLC. After the reaction is finished, adding 15mL of ethyl acetate into a reaction system, extracting for 3 times by using a saturated NaCl aqueous solution, separating to obtain an organic layer, drying, performing suction filtration, performing rotary evaporation, and performing column chromatography (PE/EA is 3: 1) to obtain (5R, 5R') -phenyl substituted chiral oxazolidine-2-thione, wherein the yield is as follows: 92 percent. m.p. 115-116 ℃; [ alpha ] to]D 20＝-272(c 0.1,EA)；1H-NMR(CDCl3,400MHz):δ11.36(s,2H)7.19-7.53(m,20H),5.37(s,2H).13C-NMR(CDCl3,101MHz)δ187.9,142.9,136.9,129.3,129.2,128.8,127.6,125.7,86.1,73.3。
Single crystal data of empirical formula, C30 H24 N2 O2 S2；formula weight,508.65；calculated density,1.256g/cm3；volume(V),
crystal system, Monoclinic; space group, P1211; z is 2; unit cell dimensions, a is 11.3256(17), b is 26.306(4), c is 18.834(3), α is 90b is 103.081(4), γ is 90; h is more than or equal to index ranges-13 and less than or equal to 13, k is more than or equal to-30 and less than or equal to 31, and l is more than or equal to-22 and less than or equal to 21; f (000), 2164; GOF, 0.985. The structure is shown in figure 1.
Example 2: the preparation method of (5R, 5R') -p-tolyl substituted chiral oxazolidine-2-thione comprises the following steps:
step one, (R, R) -1,1,4, 4-tetra-p-tolylbutantetraol preparation
Dissolving phenylmagnesium bromide in tetrahydrofuran solution, dropwise adding (R, R) -diethyl tartrate into 6 equivalents of p-tolylmagnesium bromide (namely, the molar ratio of (R, R) -diethyl tartrate to the Grignard reagent is 1:6) in tetrahydrofuran solution, reacting for 2 hours, quenching with saturated ammonium chloride aqueous solution, extracting with diethyl ether, concentrating, and performing silica gel column chromatography (PE/EA is 6: 1) to obtain (R, R) -1,1,4, 4-tetra-p-tolylbutanetetraol, wherein the yield is as follows: 56 percent. 165: 166 ℃ m.p.;1HNMR(600MHz,Chloroform-d)δ7.17(d,J＝8.3Hz,4H),7.15–7.09(m,8H),7.03(d,J＝8.0Hz,4H),4.70(s,2H),4.35(d,J＝4.5Hz,2H),3.82(d,J＝4.4Hz,2H),2.33(s,6H),2.21(s,6H).13C NMR(151MHz,Chloroform-d)δ141.7,141.2,136.7,136.6,129.2,129.0,125.9,124.8,81.6,77.3,21.1,21.0.
step two preparation of (4R,5R) -p-tolyl dichlorocyclo-sulfite
A round bottom flask was charged with a solution of (R, R) -1,1,4, 4-tetra-p-tolylbutantetraol in tetrahydrofuran and 20 equivalents of triethylamine (i.e., (R, R) -1,1,4, 4-tetra-p-tolylbutantetraol)The molar ratio of the tetraol to the triethylamine is 1:20), stirring for 15 minutes at 0 ℃, dropwise adding 4 equivalents of thionyl chloride (namely the molar ratio of the (R, R) -1,1,4, 4-tetra-p-tolylbutanetetraol to the thionyl chloride is 1:4), continuing stirring at 0 ℃ for 30 minutes after dropwise adding, recovering to room temperature (25 ℃, the same applies below), continuing stirring for 30 minutes, adding water for treatment, and recrystallizing with ethanol to obtain the (4R,5R) -p-tolyldichloro cyclic sulfite. Yield: 90 percent. m.p.179-181 ℃;1H NMR(600MHz,Chloroform-d)δ7.38–7.34(m,2H),7.34–7.30(m,2H),7.16–7.09(m,6H),7.07(d,J＝8.0Hz,2H),6.89(t,J＝8.3Hz,4H),6.00(d,J＝2.1Hz,1H),5.77(d,J＝2.1Hz,1H),2.34(d,J＝9.8Hz,6H),2.27(d,J＝8.2Hz,6H).13C NMR(151MHz,Chloroform-d)δ138.6,138.3,137.9,137.8,137.6,129.0,128.9,128.7,128.6,128.0,127.9,87.6,87.4,21.1,21.0.Anal.calc.for C32H30Cl2O3S:C 67.96,H 5.35；found:C67.93,H 5.31.
step three, preparation of (2R,2R') -p-tolyl-dioxirane
In a 10mL round-bottomed flask equipped with a magnetic rotor, a THF solution of (4R,5R) -p-tolyldichlorocyclsulfite was placed, and a 5mol/L aqueous solution of sodium hydroxide ([ (4R,5R) -p-tolyldichlorocyclsulfite and sodium hydroxide were in a molar ratio of 1:20) was further added,]then, the reaction is carried out for 4 hours under stirring and heating at 0 ℃, water is added to stop the reaction, and ethanol is recrystallized to obtain (2R,2R') -p-tolyl-ethylene oxide, with the yield: 88 percent. m.p. 161-162 ℃;1H NMR(400MHz,Chloroform-d)δ7.31(d,J＝8.1Hz,2H),7.20(d,J＝7.9Hz,2H),6.96(d,J＝7.9Hz,2H),6.66(d,J＝8.1Hz,2H),3.17(s,1H),2.40(s,3H),2.26(s,3H).13C NMR(101MHz,Chloroform-d)δ137.8,137.6,137.0,135.0,129.0,128.9,128.8,127.6,127.4,65.3,62.7,21.2,21.1.Anal.calc.for C32H30O2:C 86.06,H 6.77；found:C 86.01,H 6.73.
step four, (5R, 5R') -p-tolyl substituted chiral oxazolidine-2-thione preparation
A50 mL single-neck flask was charged with 1mmol of the above chiral (2R,2R') -p-tolyl-dioxirane, 6mmol of KSCN solid and 10mL of acetonitrile under stirringThe reaction was heated to 110 ℃ for 12 hours and checked by TLC. After the reaction is finished, adding 15mL ethyl acetate into the reaction system, extracting for 3 times by using a saturated NaCl aqueous solution, separating to obtain an organic layer, drying, filtering, performing rotary evaporation, and performing column chromatography (PE/EA is 3: 1) to obtain (5R, 5R') -p-tolyl substituted chiral oxazolidine-2-thione, wherein the yield is as follows: 87 percent. m.p.>300℃；[α]D 20＝254.5(c 0.1,CHCl3)；1H-NMR(CDCl3,400MHz):δ7.78(brs,2H)7.28-7.21(m,8H),7.04(d,J＝8.0Hz,4H),6.78(d,J＝8.3Hz,4H),5.12(s,2H),2.40(s,6H),2.27(s,6H).13C-NMR(CDCl3,101MHz)δ187.8,140.2,138.8,138.5,134.1,129.8,127.5,125.7,86.2,73.1,21.2,20.9.Anal.calc.for C34H32N2O2S2:C 72.31,H 5.71；found:C 72.27,H 5.68.
The specific embodiments described in this specification are merely illustrative of the present invention. Various modifications or additions may be made to the described embodiments, or alternatives may be employed, by those skilled in the art, without departing from the spirit or ambit of the invention as defined in the appended claims.
Claims (13)
1. A preparation method of tartaric acid-derived chiral oxazolidine-2-thioketone is characterized by comprising the following steps:
(1) reacting the optically pure tartrate with an aryl Grignard reagent to prepare chiral 1,1,4, 4-tetraaryl butanetetraol;
(2) in the presence of organic base, chiral 1,1,4, 4-tetraarylbutanetetraol and thionyl chloride are subjected to highly regioselective 2, 3-cyclic sulfitation reaction at the temperature of-5-36 ℃ to prepare chiral dichloroaryl cyclic sulfite;
(3) in a certain organic solvent at the temperature of 10 ℃ below zero to 10 ℃, chiral dichloroaryl cyclic sulfite reacts with inorganic alkaline water solution with certain concentration for 2 to 6 hours to prepare chiral aryl substituted bicycloethane;
(4) in a certain organic solvent at 80-120 ℃, chiral aryl substituted ethylene oxide reacts with thiocyanate for 6-16 hours to prepare chiral oxazolidine-2-thione;
the general formula of the aryl Grignard reagent in the step (1) is RMgX, wherein R is phenyl, tolyl, ethylphenyl, tert-butylphenyl and p-fluorophenyl; x is Cl, Br or I;
the structural formula of the chiral oxazolidine-2-thione is as follows:
2. the preparation method according to claim 1, wherein the organic base in step (2) is triethylamine or pyridine, and the molar ratio of the organic base to the chiral 1,1,4, 4-tetraarylbutanetetraol is (6-30): 1; the molar ratio of the thionyl chloride to the chiral 1,1,4, 4-tetraarylbutanetetraol is (2-6): 1.
3. the method according to claim 1, wherein the inorganic base in the step (3) is NaOH, KOH or Na2And S, the concentration of the inorganic alkaline water solution is 3-5 mol/L.
4. The method according to claim 3, wherein the molar ratio of the inorganic base to the chiral dichloroaryl cyclic sulfite in the step (3) is (6-30): 1.
5. the method according to claim 1, wherein the organic solvent in step (3) is selected from the group consisting of tetrahydrofuran, dioxane, and acetonitrile.
6. The method according to claim 1, wherein the thiocyanate in step (4) is NH4SCN or KSCN, the molar ratio of thiocyanate to chiral aryl-substituted dioxirane is (2-10): 1.
7. the method according to claim 1, wherein the organic solvent in the step (4) is selected from any one of N, N-dimethylformamide, nitromethane and acetonitrile.
8. The method according to claim 1, wherein the aryl Grignard reagent in the step (1) is phenylmagnesium bromide or tolylmagnesium bromide.
9. The preparation method according to claim 1, wherein the step (3) is specifically performed as follows: putting the chiral dichloroaryl cyclic sulfite solution dispersed by the organic solvent and the inorganic alkaline water solution into a reaction vessel, then reacting for 2-6 hours at the temperature of-10 to 10 ℃ under stirring, adding water to stop the reaction, and crystallizing to obtain the chiral aryl substituted dioxirane.
10. The method according to claim 9, wherein the reaction temperature in the step (3) is-10 ℃ to 5 ℃.
11. The method according to claim 10, wherein the reaction temperature in the step (3) is-5 ℃ to 0 ℃.
12. The preparation method according to claim 1, wherein the step (4) is specifically operated as follows: putting chiral aryl substituted ethylene oxide, thiocyanate and an organic solvent into a reaction vessel, then stirring, reacting for 6-16 hours at 80-120 ℃, adding ethyl acetate into the reaction system, extracting for at least 3 times by using a saturated NaCl aqueous solution, separating to obtain an organic layer, drying, carrying out suction filtration, carrying out rotary evaporation, and carrying out column chromatography to obtain the chiral oxazolidine-2-thioketone.
13. The method as claimed in claim 12, wherein the reaction temperature in the step (4) is 100-120 ℃ and the reaction time is 12-14 hours.
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