CN108046995A - A kind of multi-substituted chiral (1- ethoxys) benzene and its method of asymmetric synthesis - Google Patents

A kind of multi-substituted chiral (1- ethoxys) benzene and its method of asymmetric synthesis Download PDF

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CN108046995A
CN108046995A CN201711271014.7A CN201711271014A CN108046995A CN 108046995 A CN108046995 A CN 108046995A CN 201711271014 A CN201711271014 A CN 201711271014A CN 108046995 A CN108046995 A CN 108046995A
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benzene
ethoxys
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CN108046995B (en
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周海峰
刘森生
刘欢
刘祈星
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China Three Gorges University CTGU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/26—Polyhydroxylic alcohols containing only six-membered aromatic rings as cyclic part
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
    • C07C29/145—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones with hydrogen or hydrogen-containing gases
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/26—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydration of carbon-to-carbon triple bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Abstract

The present invention relates to a kind of multi-substituted chiral (1 ethoxy) benzene, concrete structure is as shown in II, while the invention discloses the synthetic methods of the compound a kind of " two step one kettle ways ".The benzene (I) that this method is substituted with polyacetylene base cheap and easy to get is raw material, by step 1)：Using fluorine-containing alcohol and water as solvent, raw hydration reaction generation intermediate ketone is issued in trifluoromethayl sulfonic acid catalysis；Step 2)：It is catalyst that single sulphonyl chiral diamine is directly added in the reaction system with metal Ru or the complex of rhodium or iridium, and add in alkali, it is filled with hydrogen, asymmetric hydrogenation obtains product II, or it is catalyst directly to add in single sulphonyl chiral diamine in the reaction system with metal Ru or the complex of rhodium or iridium, the mixture of sodium formate or formic acid and triethylamine is hydrogen source, and product II is obtained by the reaction through asymmetric transfer hydrogenation.This method is easy to operate, and raw material is easy to get, enantioselectivity and cis-selectivity are all very high.

Description

A kind of multi-substituted chiral (1- ethoxys) benzene and its method of asymmetric synthesis
Technical field
The invention belongs to asymmetric catalytic technology fields, and in particular to a kind of multi-substituted chiral (1- ethoxys) benzene it is not right Claim synthetic method.
Background technology
Multi-substituted chiral (1- ethoxys) benzene is important medicine intermediate.At present by diacetyl benzene or triacetyl benzene It is prepared for raw material by asymmetric reduction, but diacetyl benzene or triacetyl benzene raw materials are difficult to obtain, it is expensive.This Invention main innovation point is that from the benzene of cheap and easily-available polyacetylene base substitution be raw material, using " two step one kettle ways " strategy, hair A kind of Atom economy, green method of step economy for synthesizing multi-substituted chiral (1- ethoxys) benzene, this method tool are opened up There is important application prospect.
The content of the invention
A kind of multi-substituted chiral (1- ethoxys) benzene and its method of asymmetric synthesis, which is characterized in that with cheap and easy to get The benzene (I) of polyacetylene base substitution is raw material, using " two step one kettle ways " strategy, is not required to isolate and purify intermediate；Step 1)：More second The benzene of alkynyl substituted is raw material, and bronsted acid is catalyst, and the mixture of fluorine-containing alcohol and water is solvent, is obtained through hydration reaction Intermediate；
Step 2)：With (R, R)-or (S, S)-N- lists sulphonyl-diaryl chiral ethylenediamine and transition metal ruthenium or rhodium or The complex of iridium is catalyst, under the conditions of alkali is added, is placed in displacement reaction 3 times in autoclave, then adds in hydrogen source and carry out Asymmetric hydrogenation or asymmetric transfer hydrogenation reaction can obtain multi-substituted chiral (1- ethoxys) benzene, and specific reaction equation is such as Under：
Wherein, Ar is selected from
R is hydrogen, C1-C10 alkyl, C1-C10 alkyl oxies, halogenated alkyl, halogen, hydroxyl, amino, nitro, cyano, virtue Any one in base.
The step 1)：The solvent of hydration reaction is the mixture of fluorine-containing alcohol and water, further preferably：1 milliliter of trifluoro Ethyl alcohol and 4-6 equivalent water；
The step 1)：The catalyst of hydration reaction is bronsted acid, further preferably：40-60mol% fluoroforms Sulfonic acid；
The step 1)：The temperature of hydration reaction is 25-100 DEG C；When reaction time is 4-72 small；
The step 2)：Asymmetric hydrogenation or asymmetric transfer hydrogenation used catalyst are single for (R, R)-or (S, S)-N- Sulphonyl-diaryl chiral ethylenediamine and transition metal ruthenium or the complex of rhodium or iridium, general structure such as formula III, formula IV institute Show,
In the general structure III and IV, M Ru, Rh or Ir；
Ar is for phenyl or to methoxyl group, methyl substituted phenyl, naphthalene；
R is-CH3、-CF3、-C6H5、4-CH3C6H4、4-CF3C6H4、4-(t-Bu)-C6H4-、3,4-(CH3)2-C6H3-、 2, 4,6-(CH3)3-C6H2-、2,6-Cl2-C6H3-、2,4,6-(i-Pr)3-C6H2-、C6F5Or naphthalene；
R ' is H, CH3Or i-Pr；
L is benzene, 1,4- dimethyl benzenes, 1- methyl -4- cumenes, 1,3,5- trimethylbenzenes, 1,2,3,4,5- pentamethyls Benzene, 1,2,3,4,5,6- hexamethylbenzenes or pentamethylcyclopentadiene；
X is Cl-、[OTf]-、[PF6]-、[BF4]-、[SbF6]-Or chiral phosphoric acid anion；
Y is C or O.
The step 2)：Asymmetric hydrogenation or asymmetric transfer hydrogenation used catalyst, further preferably, representativeness is urged Agent structure is as follows：
The step 2)：Asymmetric hydrogenation is specially NaOH, KOH, it is necessary to add in alkali, further preferably：1 equivalent KOH；
The step 2)：Asymmetric hydrogenation, hydrogen source are that the purity of 1-10Mpa is more than 99.9% high-purity hydrogen, are preferably： 4MPa；
The step 2)：Asymmetric hydrogenation, reaction temperature are 25-80 DEG C, further preferably：40℃；
The step 2)：Asymmetric transfer hydrogenation, hydrogen source are the formic acid of different proportion and the mixed solution or first of triethylamine Acid sodium aqueous solution；Further preferably：The sodium formate of 10 equivalents and 1 milliliter of water.
The step 2)：Asymmetric transfer hydrogenation, reaction temperature are 25-80 DEG C, further preferably：50℃.
The step 2)：Asymmetric transfer hydrogenation, when the reaction time is 4-72 small.
The invention discloses the synthetic methods of the compound a kind of " two step one kettle ways ".This method is with more second cheap and easy to get The benzene (I) of alkynyl substituted is raw material, by step 1)：Using fluorine-containing alcohol and water as solvent, issued in trifluoromethayl sulfonic acid catalysis Raw hydration reaction generation intermediate ketone；Step 2)：Single sulphonyl chiral diamine and metal Ru or rhodium are directly added in the reaction system Or the complex of iridium is catalyst, and alkali is added in, hydrogen is filled with, asymmetric hydrogenation obtains product II or directly anti- It is catalyst, sodium formate or formic acid and three second to answer and single sulphonyl chiral diamine is added in system with metal Ru or the complex of rhodium or iridium The mixture of amine is hydrogen source, and product II is obtained by the reaction through asymmetric transfer hydrogenation.This method is easy to operate, and raw material is easy to get, mapping Selectivity and cis-selectivity are all very high.
Description of the drawings
Fig. 1 is the HPLC spectrograms of racemic 1,3- bis- (1- ethoxys) benzene.
Fig. 2 is the HPLC spectrograms of (S, S) -1,3- two (1- ethoxys) benzene.
Fig. 3 is the HPLC spectrograms of racemic 1,4- bis- (1- ethoxys) benzene.
Fig. 4 is the HPLC spectrograms of (S, S) -1,4- two (1- ethoxys) benzene.
Fig. 5 is the HPLC spectrograms of racemic 1,3,5- tri- (1- ethoxys) benzene.
Fig. 6 is the HPLC spectrograms of (S, S, S) -1,3,5- three (1- ethoxys) benzene.
Specific embodiment
With reference to specific embodiment, the invention will be further described, but the present invention is not limited to following embodiments.
Chiral catalyst general preparative methods used in the present invention, by taking catalyst B synthesis as an example：0.005mmol(S,S)- N- tolysulfonyl diphenyl chiral ethylenediamines and 0.0025mmol [Ru (cymene)]2Cl2It is dissolved in 0.5 milliliter of dichloromethane In, 0.005mmol triethylamines are added in, are reacted 30 minutes at room temperature, washing, water is mutually extracted 3 times with 1 milliliter of dichloromethane, is merged After be concentrated to dryness to obtain catalyst B, be directly used in catalytic reaction.
Embodiment 1：The asymmetric syntheses of (S, S) -1,3- two (1- ethoxys) benzene
Diacetylene-benzene between 0.5mmol is added in test tube, sequentially adds CF3SO3H (40mol%, 18uL), H2O (4 equvi.,40uL),CF3CH2After OH (1mL), 60 DEG C of reaction 48h, addition 0.005mmol catalyst C, KOH (0.5mmol, 28mg), reaction tube is placed in autoclave, replaced 3 times, the hydrogen of 4Mpa is then charged with, when 40 DEG C of reactions 24 are small.Instead It is washed with water after answering, water is mutually extracted with ethyl acetate 3 times, merges organic phase and is concentrated to dryness, separates yield：86% (petroleum ether： Ethyl acetate=5:1) HPLC measures the enantiomeric excess value of the asymmetric syntheses of product (S, S) -1,3- two (1- ethoxys) benzene For 99%, diastereomeric excess value is 99%, HPLC separation conditions：Chiral column Daicel OJ-H columns, mobile phase：N-hexane/different Propyl alcohol=90:10 (volume ratios), flow velocity：1.0 ml/mins, wavelength：210 nanometers, column temperature：30 degrees Celsius, t1=17.89 points Clock, t2=20.84 minutes, t3=29.93 minutes, t4=32.24 minutes；(racemic product and chiral product HPLC spectrograms difference See Fig. 1 and Fig. 2)；1H NMR(400MHz,CDCl3):δ=7.39-7.37 (m, 1H), 7.33 (dd, J1=8.4Hz, J2= 8.4Hz,1H),7.27-7.23(m,2H),4.86(dd,J1=13.2Hz, J2=13.2Hz, 1H), 2.78 (s, 1H), 1.48 (d, J=6.4Hz, 3H) ppm；13C NMR(100MHz,CDCl3):δ=146.11,146.08,128.55,128.53,124.55, 124.51, 122.49,122.37,70.28,70.25,25.15,25.10ppm.
Table 1 is the HPLC spectral datas of racemic 1,3- bis- (1- ethoxys) benzene
Table 2 is the HPLC spectral datas of (S, S) -1,3- two (1- ethoxys) benzene
Embodiment 2：The asymmetric syntheses of (S, S) -1,3- two (1- ethoxys) benzene
Diacetylene-benzene between 0.5mmol is added in test tube, sequentially adds CF3SO3H (40mol%, 18uL), H2O (4 equvi.,40uL),CF3CH2After OH (1mL), 60 DEG C of reaction 48h, addition 0.005mmol catalyst E, KOH (0.5mmol, 28mg), reaction tube is placed in autoclave, replaced 3 times, the hydrogen of 4Mpa is then charged with, when 40 DEG C of reactions 24 are small.Instead It is washed with water after answering, water is mutually extracted with ethyl acetate 3 times, merges organic phase and is concentrated to dryness, separates yield：62% (oil Ether：Ethyl acetate=5:1) HPLC measures the enantiomeric excess of the asymmetric syntheses of product (S, S) -1,3- two (1- ethoxys) benzene It is worth for 89%, diastereomeric excess value is 91%.
Embodiment 3：The asymmetric syntheses of (S, S) -1,3- two (1- ethoxys) benzene
Diacetylene-benzene between 0.5mmol is added in test tube, sequentially adds CF3SO3H (40mol%, 18uL), H2O (4 equvi.,40uL),CF3CH2After OH (1mL), 60 DEG C of reaction 48h, addition 0.005mmol catalyst F, KOH (0.5mmol, 28mg), reaction tube is placed in autoclave, replaced 3 times, the hydrogen of 4Mpa is then charged with, when 40 DEG C of reactions 24 are small.Instead It is washed with water after answering, water is mutually extracted with ethyl acetate 3 times, merges organic phase and is concentrated to dryness, separates yield：71% (oil Ether：Ethyl acetate=5:1) HPLC measures the enantiomeric excess of the asymmetric syntheses of product (S, S) -1,3- two (1- ethoxys) benzene It is worth for 83%, diastereomeric excess value is 80%.
Embodiment 4：The asymmetric syntheses of (S, S) -1,4- two (1- ethoxys) benzene
The p-diethynylbenzene of 0.5mmol is added in test tube, sequentially adds CF3SO3H (40mol%, 18uL), H2O (4 equvi.,40uL),CF3CH2After OH (1mL), 60 DEG C of reaction 48h, addition 0.005mmol catalyst C, KOH (0.5 mmol, 28mg), reaction tube is placed in autoclave, replaced 3 times, the hydrogen of 4Mpa is then charged with, when 40 DEG C of reactions 24 are small.Instead It is washed with water after answering, water is mutually extracted with ethyl acetate 3 times, merges organic phase and is concentrated to dryness, separates yield：93% (oil Ether：Ethyl acetate=5:1) enantiomeric excess value that HPLC measures product (S, S)-Isosorbide-5-Nitrae-two (1- ethoxys) benzene is 99%, non- Enantiomeric excess value is 90%, HPLC separation conditions：Chiral column Daicel OD-H columns, mobile phase：N-hexane/isopropanol=90: 10 (volume ratios), flow velocity：1.0 ml/mins, wavelength：210 nanometers, column temperature：30 degrees Celsius, t1=12.23 minutes, t2= 13.21 minute, t3=17.05 minutes；(racemic product and chiral product HPLC spectrograms are shown in Fig. 3 and Fig. 4 respectively)；1H NMR (400MHz,CDCl3):δ=7.38 (s, 4H), 4.92 (dd, J1=12.8Hz, J2=12.8Hz, 1H), 2.03 (s, 1H), 1.52 (d, J=5.6Hz, 3H) ppm；13C NMR(100MHz,CDCl3):δ=145.06,125.58,70.18,70.16, 25.15ppm.
The HPLC spectral datas of table 3 racemic 1,4- bis- (1- ethoxys) benzene
The HPLC spectral datas of table 4 (S, S) -1,4- two (1- ethoxys) benzene
Embodiment 5：The asymmetric syntheses of (S, S, S) -1,3,5- three (1- ethoxys) benzene
Three acetylenylbenzenes of 0.5mmol are added in test tube, sequentially add CF3SO3H (60mol%, 27uL), H2O(6 equvi.,60uL),CF3CH2After OH (2mL), 60 DEG C of reaction 72h, addition 0.005mmol catalyst C, KOH (0.5mmol, 28mg), reaction tube is placed in autoclave, replaced 3 times, the hydrogen of 4Mpa is then charged with, when 40 DEG C of reactions 24 are small.Instead It is washed with water after answering, water is mutually extracted with ethyl acetate 3 times, merges organic phase and is concentrated to dryness, separates yield：90% (oil Ether：Ethyl acetate=5:1) enantiomeric excess value that HPLC measures product (S, S, S) -1,3,5- three (1- ethoxys) benzene is 95%, diastereomeric excess value is 99%, HPLC separation conditions：Chiral column Daicel OD-H columns, mobile phase：N-hexane/isopropyl Alcohol=80:20 (volume ratios), flow velocity：1.0 ml/mins, wavelength：254 nanometers, column temperature：30 degrees Celsius, t1=4.89 minutes, t2=5.39 minutes, t3=5.92, t4=6.70, t5=7.84, t6=8.95 minutes；(racemic product and chiral product HPLC Spectrogram is shown in Fig. 5 and Fig. 6 respectively)1H NMR(400MHz,CDCl3):δ=7.43-7.41 (m, 3H), 4.90 (dd, J1=12.8Hz, J2=12.8Hz, 1H), 2.04 (s, 1H), 1.51 (d, J=6.4Hz, 3H) ppm；13C NMR(100MHz,CDCl3):δ= 146.39, 146.38,128.23,128.21,123.07,123.04,122.30,69.96,69.94,25.21,25.19ppm.
Table 5 is the HPLC spectral datas of racemic 1,3,5- tri- (1- ethoxys) benzene
Table 6 is the HPLC spectral datas of (S, S, S) -1,3,5- three (1- ethoxys) benzene；
Embodiment 6：The asymmetric syntheses of (S, S) -1,3- two (1- ethoxys) benzene
Diacetylene-benzene between 0.5mmol is added in test tube, sequentially adds CF3SO3H (40mol%, 18uL), H2O (4 equvi.,40uL),CF3CH2After OH (1mL), 50 DEG C of reaction 4h, 0.005mmol catalyst A, HCOONa (10 is added in Mmol, 680mg), H2O (1mL), when 50 DEG C of reactions 48 are small.It is extracted with ethyl acetate after reaction 3 times, it is dense to merge organic phase It is reduced to dry, separation yield：72% (petroleum ether：Ethyl acetate=5:1) HPLC measures product (S, S) -1,3- two (1- ethoxys) The enantiomeric excess value of the asymmetric syntheses of benzene is 83%, and diastereomeric excess value is 76%.

Claims (10)

  1. A kind of 1. multi-substituted chiral (1- ethoxys) benzene, which is characterized in that the knot of described multi-substituted chiral (1- ethoxys) benzene Structure is as shown in Formula II；
    Wherein, Ar is selected from
    R is in hydrogen, C1-C10 alkyl, C1-C10 alkyl oxies, halogenated alkyl, halogen, hydroxyl, amino, nitro, cyano, aryl Any one.
  2. 2. a kind of method of asymmetric synthesis of multi-substituted chiral described in claim 1 (1- ethoxys) benzene, which is characterized in that
    Step 1)：The benzene of polyacetylene base substitution is raw material, and bronsted acid is catalyst, and the mixture of fluorine-containing alcohol and water is molten Agent obtains intermediate through hydration reaction；
    Step 2)：With (R, R)-or (S, S)-N- lists sulphonyl-diaryl chiral ethylenediamine and transition metal ruthenium or rhodium or iridium Complex is catalyst, under the conditions of alkali is added, is placed in displacement reaction 3 times in autoclave, it is not right then to add in hydrogen source progress Hydrogenation or asymmetric transfer hydrogenation reaction is claimed to can obtain multi-substituted chiral (1- ethoxys) benzene, specific reaction equation is as follows：
  3. 3. the method for asymmetric synthesis of multi-substituted chiral (1- ethoxys) benzene described in claim 2, which is characterized in that described Structural formula I is
    Wherein, Ar is selected from
    R is in hydrogen, C1-C10 alkyl, C1-C10 alkyl oxies, halogenated alkyl, halogen, hydroxyl, amino, nitro, cyano, aryl Any one.
  4. 4. the method for asymmetric synthesis of multi-substituted chiral (1- ethoxys) benzene described in claim 2, which is characterized in that described Using the mixture of fluorine-containing alcohol and water as including trifluoroethanol or hexafluoroisopropanol.
  5. 5. the method for asymmetric synthesis of multi-substituted chiral (1- ethoxys) benzene described in claim 2, which is characterized in that described Bronsted acid catalyst includes trifluoroacetic acid, trifluoromethanesulfonic acid.
  6. 6. the method for asymmetric synthesis of multi-substituted chiral (1- ethoxys) benzene described in claim 2, which is characterized in that described (R, R)-or (S, S)-N- lists sulphonyl-diaryl chiral ethylenediamine are catalysis with transition metal ruthenium or the complex of rhodium or iridium Agent, general structure as shown in formula III, formula IV,
    In the general structure III and IV, M Ru, Rh or Ir；
    Ar is for phenyl or to methoxyl group, methyl substituted phenyl, naphthalene；
    R is-CH3、-CF3、-C6H5、4-CH3C6H4、4-CF3C6H4、4-(t-Bu)-C6H4-、3,4-(CH3)2-C6H3-、2,4,6- (CH3)3-C6H2-、2,6-Cl2-C6H3-、2,4,6-(i-Pr)3-C6H2-、C6F5Or naphthalene；
    R ' is H, CH3Or i-Pr；
    L for benzene, 1,4- dimethyl benzenes, 1- methyl -4- cumenes, 1,3,5- trimethylbenzenes, 1,2,3,4,5- pentamethylbenzenes, 1, 2,3,4,5,6- hexamethylbenzenes or pentamethylcyclopentadiene；
    X is Cl-、[OTf]-、[PF6]-、[BF4]-、[SbF6]-Or chiral phosphoric acid anion；
    Y is C or O.
  7. 7. the method for asymmetric synthesis of multi-substituted chiral (1- ethoxys) benzene described in claim 6, which is characterized in that single sulphonyl Chiral diamine and the concrete structure of metal Ru or the complex of rhodium or iridium are as follows：
    In any one.
  8. 8. the method for asymmetric synthesis of multi-substituted chiral (1- ethoxys) benzene described in claim 2, which is characterized in that described Alkali includes KOH, NaOH.
  9. 9. the method for asymmetric synthesis of multi-substituted chiral (1- ethoxys) benzene described in claim 2, which is characterized in that described Hydrogen source is more than 99.9% hydrogen for purity, adds in during hydrogen to autoclave pressurization to 1-10Mpa, carries out asymmetric hydrogen Change.
  10. 10. the method for asymmetric synthesis of multi-substituted chiral (1- ethoxys) benzene described in claim 2, which is characterized in that described Hydrogen source for different proportion formic acid and triethylamine mixed solution or aqueous sodium formate solution, asymmetric transfer hydrogenation reaction.
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TERUHISA TSUCHIMOTO,TOMOHIRO JOYA,EIJI SHIRAKAWA,YUSUKE KAWAKAMI: "Brønsted Acid-Catalyzed Hydration of Alkynes: A Convenient Route to Diverse Carbonyl Compounds", 《SYNLETT》 *
WENBO LIU, HAINING WANG, AND CHAO-JUN LI: "Metal-Free Markovnikov-Type Alkyne Hydration under Mild Conditions", 《ORGANIC LETTERS》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111704528A (en) * 2020-06-24 2020-09-25 凯特立斯（深圳）科技有限公司 Asymmetric synthesis method of chiral tetraol sugar alcohol compound
CN111704528B (en) * 2020-06-24 2022-07-08 凯特立斯（深圳）科技有限公司 Asymmetric synthesis method of chiral tetraol sugar alcohol compound

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