CN113121587A - Chiral catalyst and heterogeneous chiral catalyst comprising same - Google Patents
Chiral catalyst and heterogeneous chiral catalyst comprising same Download PDFInfo
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- CN113121587A CN113121587A CN202010861876.0A CN202010861876A CN113121587A CN 113121587 A CN113121587 A CN 113121587A CN 202010861876 A CN202010861876 A CN 202010861876A CN 113121587 A CN113121587 A CN 113121587A
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- 239000003054 catalyst Substances 0.000 title claims abstract description 94
- 239000001257 hydrogen Substances 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000011737 fluorine Substances 0.000 claims abstract description 8
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 8
- 239000000758 substrate Substances 0.000 claims description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 239000011787 zinc oxide Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims 1
- 239000013335 mesoporous material Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 193
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 78
- 229910052717 sulfur Inorganic materials 0.000 description 44
- 230000015572 biosynthetic process Effects 0.000 description 42
- 238000003786 synthesis reaction Methods 0.000 description 42
- 238000000605 extraction Methods 0.000 description 39
- 229910052757 nitrogen Inorganic materials 0.000 description 39
- 238000000034 method Methods 0.000 description 35
- 239000003153 chemical reaction reagent Substances 0.000 description 34
- 239000002904 solvent Substances 0.000 description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 239000003921 oil Substances 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 19
- 239000007788 liquid Substances 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 238000006722 reduction reaction Methods 0.000 description 13
- 238000001914 filtration Methods 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 230000003287 optical effect Effects 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000004140 cleaning Methods 0.000 description 8
- 238000011084 recovery Methods 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 238000012856 packing Methods 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 101150026303 HEX1 gene Proteins 0.000 description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229910052681 coesite Inorganic materials 0.000 description 3
- 229910052906 cristobalite Inorganic materials 0.000 description 3
- 229910052682 stishovite Inorganic materials 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- 229910052905 tridymite Inorganic materials 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- IJYPGYBKBODVTO-UHFFFAOYSA-N ClCCC(=O)C1=CC=CC=C1.ClCCC(=O)C1=CC=CC=C1 Chemical compound ClCCC(=O)C1=CC=CC=C1.ClCCC(=O)C1=CC=CC=C1 IJYPGYBKBODVTO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- HTRXGEPDTFSKLI-UHFFFAOYSA-N butanoic acid;ethyl acetate Chemical compound CCCC(O)=O.CCOC(C)=O HTRXGEPDTFSKLI-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- -1 ketone compound Chemical class 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- OBNDGIHQAIXEAO-UHFFFAOYSA-N [O].[Si] Chemical compound [O].[Si] OBNDGIHQAIXEAO-UHFFFAOYSA-N 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- LIVNPJMFVYWSIS-UHFFFAOYSA-N silicon monoxide Chemical class [Si-]#[O+] LIVNPJMFVYWSIS-UHFFFAOYSA-N 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0272—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255
- B01J31/0274—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255 containing silicon
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0272—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255
- B01J31/0275—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255 also containing elements or functional groups covered by B01J31/0201 - B01J31/0269
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
Abstract
A chiral catalyst of formula (I).
In the formula (I), Z ═ Z1Or Z2，Z1And Z2The combination in formula (I) comprises
Or
Or
Y independently comprises hydrogen, fluorine, trifluoromethyl, isopropyl, tert-butyl, CmH2m+1Or OCmH2m+1M is 1 to 10, and n is 1 to 10. The invention further provides a heterogeneous chiral catalyst comprising the chiral catalyst.
Description
Technical Field
The invention relates to a chiral catalyst for enantiomer selective reduction and a heterogeneous chiral catalyst containing the same.
Background
Chiral catalysts (chiral catalysts) are induced to react towards levorotatory or dextrorotatory molecules by utilizing intermolecular forces and steric hindrance, and generally, the success standards of the chiral catalysts in asymmetric synthesis are high optical purity, the chiral catalysts can be recycled, both levorotatory and dextrorotatory isomers can be prepared respectively and the conversion rate is high.
However, in homogeneous reactions, the chiral catalyst eventually mixes with the target product, increasing the difficulty and cost of catalyst recovery.
Disclosure of Invention
According to an embodiment of the present invention, there is provided a chiral catalyst having the formula (I):
in the formula (I), Z ═ Z1Or Z2In combination, comprises
Y independently comprises hydrogen, fluorine, trifluoromethyl, isopropyl, tert-butyl, CmH2m+1Or OCmH2m+1M is 1 to 10, and n is 1 to 10.
According to an embodiment of the present invention, there is provided a heterogeneous chiral catalyst, including: the above chiral catalyst; and a substrate coupled to the chiral catalyst.
Detailed Description
According to an embodiment of the present invention, there is provided a chiral catalyst having the formula (I):
in the formula (I), Z ═ Z1Or Z2In combination, comprises
Y independently comprises hydrogen, fluorine, trifluoromethyl, isopropyl, tert-butyl, CmH2m+1Or OCmH2m+1M is 1 to 10, and n is 1 to 10.
In some embodiments, in formula (I), Y independently comprises hydrogen, CH3Or OCH3And n is 3-8.
In some embodiments, the chiral catalyst of the present invention has the formula (II) or (III):
in the chemical formulas (II) and (III), Y independently comprises hydrogen, fluorine, trifluoromethyl, isopropyl, tert-butyl and CmH2m+1Or OOmH2m+1，m＝1-10, and n-1-10.
In some embodiments, in formulas (II), (III), Y independently comprises hydrogen, CH3Or OCH3And n is 3-8.
In some embodiments, chiral catalysts of the present invention may include the following compounds:
according to an embodiment of the present invention, there is provided a heterogeneous chiral catalyst, including: the above chiral catalyst; and a substrate coupled to the chiral catalyst.
According to an embodiment of the invention, the heterogeneous chiral catalyst has the formula (IV):
in the chemical formula (IV), S is a substrate, and Z ═ Z1Or Z2In combination, comprises
Y independently comprises hydrogen, fluorine, trifluoromethyl, isopropyl, tert-butyl, CmH2m+1Or OCmH2m+1M is 1 to 10, and n is 1 to 10.
In some embodiments, in formula (IV), Y independently comprises hydrogen, CH3Or OCH3And n is 3-8.
In some embodiments, the heterogeneous chiral catalyst of the present invention has the formula (V) or (VI), S is a substrate:
in the chemical formulas (V) and (VI), Y independently comprises hydrogen, fluorine, trifluoromethyl, isopropyl, tert-butyl and CmH2m+1Or OCmH2m+1M is 1 to 10, and n is 1 to 10.
In some embodiments, in formulas (V), (VI), Y independently comprises hydrogen, CH3Or OCH3And n is 3-8.
In some embodiments, the heterogeneous chiral catalyst of the present invention may comprise the following compounds, S being the substrate:
in some embodiments, in chemical formula (IV), the substrate may be surface-modified silicon oxide, titanium oxide, iron oxide, zinc oxide, or aluminum oxide having hydroxyl groups. In some embodiments, the substrate can be a mesoporous (mesoporous) material. In some embodiments, the substrate has a specific surface area of about 10m2A/g to 1,000m2(ii) in terms of/g. In some embodiments, the pore size of the matrix is between about 2nm and 50 nm. In some embodiments, the hydroxy group of S is substituted with Z1Si (OEt)3The groups are linked.In some embodiments, the substrate is bonded to Z1Form silicon-oxygen (-Si-O-) bonds between them. In some embodiments, the average particle size of the matrix may be 5 μm to 500 μm or 30 μm to 300 μm.
Chiral catalyst molecules with 2 to 3 silanized (silation) side chains in the examples of the invention were further reacted with SiO2Forming covalent bond, fixing to SiO2Surface, when solvent and ketone compound (reactant) flow through, reactant and SiO2The chiral catalyst is used for catalytic reaction, and after the reaction is finished, the synthesized chiral alcohol compound (chiral alcohol) is separated along with the flowing of the solvent, so that the separation of the product and the chiral catalyst is facilitated, the recovery and the reuse are convenient, the problem that the chiral catalyst is difficult to recover from the homogeneous reaction can be solved, and the reutilization rate of the chiral catalyst can be improved. And the optical purity and the conversion rate of the product can be effectively increased by the selective reduction method with the chiral catalyst. In addition, the invention can realize continuous reduction reaction, and synthesize chiral alcohol compounds (chiral alcohols) in a more economic and efficient mode.
Example 1
Preparation of chiral catalyst (1)
Reaction step 1
Reaction reagent
Synthesis procedure
Firstly, a 1L double-neck reaction bottle is filled with nitrogen, items 1 to 3 are added into the bottle and stirred until the solution is completely dissolved. Then, the reaction bottle is placed in an ice bath kettle for cooling, nitrogen is introduced, and the temperature in the ice bath kettle is maintained at 0-5 ℃. Then, the solvent of item 4 was slowly dropped, and after dropping, the temperature was naturally returned to room temperature and the mixture was stirred for 2 hours. Thereafter, the product appeared at 14.92min, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5 mL/min. After the reaction is finished, adding300mL H2O, each extraction with 100mL EA and repeated 4 times (total 400mL EA), EA layer was checked using HPLC to find no product in EA layer. Then, the aqueous layer was acidified with 3M HCl aqueous solution to pH 2, extracted with EA, extracted with 100mL EA each time and repeatedly extracted 4 times (total 400mL EA), and the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and concentrated to dryness at 40 ℃. Thereafter, vacuum was applied at room temperature for 12 hours to give 54g of a clear liquid, 89.0% yield, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5mL/min, and the product appeared at 14.70min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 99.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, DMSOd 6): delta 12.63(s, 1H, COOH), 7.36-7.28(m, 5H), 5.10-5.00(m, 3H, OH, PhCH)2O)，4.30-4.19(m，2H)，3.50-3.36(m，2H)，2.21-2.11(m，1H)，1.99-1.81(m，1H)。
Reaction step 2
Reaction reagent
Synthesis procedure
Firstly, a 500mL double-necked reaction flask was purged with nitrogen, and items 1 to 3 were added to the flask and stirred until completely dissolved. Then, the reaction flask is placed in an oil bath pan for cooling, nitrogen is introduced, and the temperature in the oil bath pan is maintained at 40-50 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 11.53min and was complete after 12 hours. After the reaction was completed, the solution was concentrated to leave 20 to 30mL, the aqueous solution of item 4 was added, extraction was performed using EA, extraction was performed with 100mL of EA each time and repeated 3 times (total 300mL of EA), the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and the solvent was concentrated to dryness at 50 ℃ using a rotary concentrator. Thereafter, vacuum was applied at room temperature for 12 hours to obtain 57.8g of a pale yellow transparent liquid in a yield of 79.5% based on Hex: IPA4: 1+ 0.1% TFA, flow rate 1.0mL/min, product was found at 11.507min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 98.0%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.32-7.24(m，5H)，5.18-4.96(m，2H，PhCH2O)，4.51-4.44(m，2H)，3.72-3.59(m，3H)，3.54-3.52(m，2H)，2.32-2.23(m，1H)，2.07-1.80(m，1H)。
Reaction step 3
Reaction reagent
Synthesis procedure
Firstly, a 1L double-neck reaction bottle is filled with nitrogen, items 1 to 4 are added into the bottle and stirred until the solution is completely dissolved. Then, the reaction flask was placed in an oil bath pan to cool, nitrogen was introduced and the temperature in the oil bath pan was maintained at 40 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 18.613min and was complete after 24 hours. After the reaction was complete, 300mL of H was added2O, using DCM for extraction, taking DCM layer with anhydrous magnesium sulfate to remove water, filtering, using a rotary concentrator at 40 degrees C concentration of dry solvent. Thereafter, vacuum was applied at room temperature for 12 hours to give 74.7g of a clear liquid, a yield of 99.2%, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 17.52min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 99.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.32-7.26(m，5H)，5.19-4.98(m，2H，PhCH2O)，4.63-4.58(m，1H)，4.50-4.37(m，2H)，3.83-3.63(m，3H+2H)，3.54-3.41(m，2H)，2.45-2.29(m，1H)，2.14-2.01(m，1H)，1.75-1.62(m，2H)，1.58-1.39(m，4H)。
Reaction step 4
Reaction reagent
Synthesis procedure
First, a 250mL two-necked reaction flask was purged with nitrogen, and item 3 was added to the flask and stirred. After dropping about 10-15mL of item 2, the reaction was started to boil by heating with a blower. Slowly dropping the solution into item 2, placing the reaction flask in an oil bath, and maintaining the internal temperature of the oil bath at 50-60 ℃. Introducing nitrogen into another 500mL double-neck reaction bottle, adding item 1 into the bottle, stirring and cooling to 0-5 ℃. Then, the reaction solution obtained in the above step is slowly dropped into an addition funnel, the internal temperature is maintained at 0-10 ℃, and after dropping, the reaction solution is heated to 40 ℃ for reaction for about 2 hours. After this time, the reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min and the product appeared at 11.98 min. After the reaction was completed, 3M HCl aqueous solution was added to neutralize to pH 6-8, extraction was performed using EA, extraction was performed with 100mL EA each time and extraction was repeated 3 times (total 300mLEA), the EA layer was taken to remove water with anhydrous magnesium sulfate and filtered, and the solvent was concentrated to dryness at 50 ℃ using a rotary concentrator. Then, column (3cm in diameter) packing 40cm (SILICYCLE Silica gel 70-230mesh, pH 7) was taken, impurities were removed by EA: Hex of 1: 10, and then polarity was increased until the product flowed out by EA: Hex of 1: 4, and about 30-50mL of dry solvent was concentrated at 40 ℃ using a rotary concentrator, and the solid was precipitated and filtered. Thereafter, a vacuum was applied at 60 ℃ for 12 hours to give 16.7g of a white solid in 62.3% yield, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 12.053min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 98.5%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.37-7.24(m，15H)，5.10-4.99(m，2H，PhCH2O)，4.40-4.36(d，1H)，3.71-3.66(m，2H+1H)，3.39-3.32(m，1H)，2.23-2.09(m，2H)，1.70-1.69(m，1H)，1.62-1.24(m，8H)。
Reaction step 5
Reaction reagent
| Item | Reactants | Molecular weight | Dosage of | Number of millimoles | Ratio of moles |
| 1 | Reaction step 4 product | 487.59 | 10g | 20.51 | 1 |
| 2 | p-Toluenesulfonic acid (p-Toluenesufonic acid) | 190.22 | 0.04g | 0.205 | 0.01 |
| 3 | Ethyl Acetate (Ethyl Acetate) | - | 50mL | - | - |
| 4 | Methanol (Methanol) | - | 50mL | - | - |
Synthesis procedure
Firstly, introducing nitrogen into a 250mL double-neck reaction bottle, adding items 1-4 into the bottle, stirring, and heating until the internal temperature is 50-60 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 8.947min and was complete over about 4 hours. After the reaction was completed, extraction was performed using EA, 100mL of EA was performed each time and extraction was repeated 3 times (total 300mL of EA), and the EA layer was taken out, dehydrated with anhydrous magnesium sulfate, filtered, and concentrated to dryness at 50 ℃ using a rotary concentrator. Thereafter, a vacuum was applied at 60 ℃ for 12 hours to give 8.3g of a white solid in 99.0% yield, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 8.947min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 88.0%, and the purification was carried out directly to the next step. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.41-7.27(m，15H)，5.18-5.13(m，2H，PhCH2O)，4.97(s，1H)，3.93(s，1H)，3.62-3.59(d，1H)，3.08-3.06(d，1H)，2.20-1.98(m，2H)，1.62-1.60(m，2H)。
Reaction step 6
Reaction reagent
Synthesis procedure
First, a 100mL two-necked reaction flask was purged with nitrogen, and items 1 to 4 were added to the flask and stirred, followed by heating to reflux. Thereafter, the reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 13.24min, which was completed in about 3 days. After the reaction was completed, extraction was performed using EA, 50mL of EA was performed each time and extraction was repeated 3 times (total 150mL of EA), and the EA layer was taken out, dehydrated with anhydrous magnesium sulfate, filtered, and concentrated to dryness at 50 ℃ using a rotary concentrator. Then, column (3cm in diameter) packing 40cm (SILICYCLE Silica gel 70-230mesh, pH 7) was taken, impurities were removed by EA: Hex of 1: 10, and then polarity was increased until the product flowed out by EA: Hex of 1: 4, and about 30-50mL of dry solvent was concentrated at 40 ℃ using a rotary concentrator, and the solid was precipitated and filtered. Thereafter, a vacuum was applied at room temperature for 12 hours to give 2.75g of a clear liquid, a yield of 45.5%, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 13.2min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 94.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.39-7.18(m，15H)，5.11-5.03(m，2H，PhCH2O)，4.87-4.85(m，2H)，4.12-4.07(m，1H)，3.81-3.78(m，6H)，3.71-3.64(m，1H)，3.11-3.05(m，2H)，2.25-2.10(m，2H)，1.60-1.52(m，2H)，1.25-1.16(m，9H)，0.61-0.51(m，2H)。
Reaction step 7
Reaction reagent
Synthesis procedure
First, a 100mL double-necked reaction flask was purged with nitrogenAnd (3) adding the items 1 to 4 into a bottle, stirring, and heating until the internal temperature is 50-60 ℃. Thereafter, the reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 4.787min, which was completed in about 3 hours. Thereafter, the solvent was concentrated to dryness at 50 ℃ using a rotary thickener. Then, column (3cm in diameter) packing 20cm (SILICYCLE Silica gel 70-230mesh, pH 7) is taken, EA: Hex 1: 6 is taken as an eluting solution, impurities are eluted, and then products are eluted by using EA: Hex 1: 1 and are concentrated to dryness. After 12 h of evacuation at room temperature, a clear liquid 0.6g was obtained in 38.0% yield, HPLC was measured at 0.5mL/min with Hex: IPA 4: 1+ 0.1% TFA, and the product appeared at 10.2min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]And the purity is 93.0 percent. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.58-7.53(m，2H)，7.44-7.42(m，2H)，7.30-7.11(m，6H)，5.06(s，1H)，4.90(s，1H)，4.51-4.47(m，1H)，3.82-3.77(m，6H)，3.26-3.22(m，2H)，3.15-3.04(m，2H)，1.63-1.51(m，4H)，1.22-1.19(m，9H)，0.62-0.58(m，2H)。
Reaction step 8
Reaction reagent
Synthesis procedure
Firstly, a 100mL double-neck reaction bottle is filled with nitrogen, items 1 to 3 are added into the bottle and stirred, solid salts are separated out after item 4 is slowly dropped, and the reaction is finished after about 24 hours. After completion of the reaction, extraction was performed using EA, 100mL of EA was used each time and extraction was repeated 3 times (total 150mL of EA), and the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and concentrated to dryness at 35 ℃ using a rotary concentrator. After dissolving with 10mL of Acetone, it was recrystallized with Hexane and the product was filtered using FP-450(Life Sciences) filter paper. Then, vacuum was applied at 40 ℃ for 12 hours to obtain 0.4g of a white solid,yield 77.6%, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5mL/min, the product appeared at 5.427min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 98.9%, and the signal appearing 5 minutes before was solvent EA. Step 8 was found to be reacted by HPLC and the product was 98.9% pure. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3): δ 7.59-7.52(m, 2H), 7.45-7.41(m, 2H), 7.35-7.10(m, 9H), 5.05(s, 1H), 4.94(s, 1H), 4.50-4.45(m, 1H), 3.80-3.75(m, 6H), 3.27-3.30(m, 2H), 3.18-2.93(m, 2H), 1.64-1.51(m, 4H), 1.23-1.18(m, 9H), 0.60-0.57(m, 2H). The target product was measured by mass spectrometry. The data are as follows: HRESI: impact HD Q-TOF mass spectrometer (Bruker, Germany), calcd for C90H120N6O21Si3 ═ 1705.78, found [ M + Na [ ]]+＝1728.75，Na＝22.98。
Example 2
Preparation of heterogeneous chiral catalysts
Reaction step
Reaction reagent
Synthesis procedure
Heterogeneous chiral catalyst (IV)
Firstly, introducing nitrogen into a 100mL double-neck reaction bottle, adding items 1 to 4 into the bottle, stirring, heating to 80 ℃, completing the reaction after about 24 hours, filtering the product by using FP-450(Life Sciences) filter paper, cleaning the solid by using a continuous extraction device, wherein the used solvents are methanol, acetone and dichloromethane, filtering the product by using FP-450(Life Sciences) filter paper after the cleaning is completed, and vacuumizing at 40 ℃ for 12 hours to obtain 2.28 g of white solid. Introducing nitrogen into a 100mL double-neck reaction bottle, adding the product obtained in the step and the item 5-item 7 into the bottle, stirring, heating to 80 ℃, reacting for about 24 hours, filtering the product by using FP-450(Life Sciences) filter paper, cleaning the solid by using a continuous extraction device, wherein the used solvents are methanol, acetone and dichloromethane, filtering the product by using FP-450(Life Sciences) filter paper after cleaning, vacuumizing for 12 hours at 40 ℃ to obtain 2.20 g of white gray solid, and measuring the target product by using IR.
Heterogeneous chiral catalyst (V)
Firstly, introducing nitrogen into a 100mL double-neck reaction bottle, adding items 1 to 4 into the bottle, stirring, heating to 80 ℃, completing the reaction after about 24 hours, filtering the product by using FP-450(Life Sciences) filter paper, cleaning the solid by using a continuous extraction device, wherein the used solvents are methanol, acetone and dichloromethane, filtering the product by using FP-450(Life Sciences) filter paper after the cleaning is completed, and vacuumizing at 40 ℃ for 12 hours to obtain 2.13 g of white solid. Introducing nitrogen into a 100mL double-neck reaction bottle, adding the product obtained in the step and the item 5-item 7 into the bottle, stirring, heating to 80 ℃, reacting for about 24 hours, filtering the product by using FP-450(Life Sciences) filter paper, cleaning the solid by using a continuous extraction device, wherein the used solvents are methanol, acetone and dichloromethane, filtering the product by using FP-450(Life Sciences) filter paper after cleaning, vacuumizing for 12 hours at 40 ℃ to obtain 2.11 g of white gray solid, and measuring the target product by using IR.
IR measurement results
Heterogeneous chiral catalyst (IV): -CH2(2928nm，2854nm，1456nm)、-CONH(1645nm)、3°-OH(1180-1250nm)、-Ph(702-754nm)。
Heterogeneous chiral catalyst (V): -CH2(2927nm，2857nm，1449nm)、-CONH(1643nm)、3°-OH(1162-1245nm)、-Ph(702-753nm)。
Example 3
Application of chiral catalyst in selective reduction reaction
Reaction step
In this example, the chiral catalyst (I), the catalyst (II), and the catalyst (III) are provided to perform the above-described selective reduction reaction, respectively.
Chiral catalyst (I):
catalyst (II):
catalyst (III):
after the reaction was completed, the optical purity and conversion of the product were calculated and the results are shown in Table 1. The optical purity (ee) was calculated as follows:
TABLE 1
As is clear from the results in Table 1, the chiral catalyst (I) having 3 silane-containing side chains of the present invention participated in the selective reduction reaction which was higher than those of the catalysts (II) and (III) in terms of both the optical purity and the conversion of the product.
Example 4
Application of heterogeneous chiral catalyst in selective reduction reaction
Reaction step
In this example, the heterogeneous chiral catalysts (IV) and (V) are provided to perform the above-mentioned selective reduction reaction, respectively.
Heterogeneous chiral catalyst (IV):
heterogeneous chiral catalyst (V):
selective reduction reaction
First, a 0.2M 3-Chloropropiophenone (3-Chloropropiophenone) solution was prepared using toluene as a solvent, a catalyst (IV) in an amount equal to the weight of 3-Chloropropiophenone (3-Chloropropiophenone) was added thereto, the reaction temperature was 25 ℃, the reaction was stirred for 20 minutes, and then a Borane tetrahydrofuran complex solution (1M) was used as a reducing agent, a flow rate of 30 mL/hour was added using 1.5 equivalents, and the reaction was completed at 25 ℃ for 2 hours after completion of dropping, and HPLC was measured, and the mixture ratio of Hexane to IPA was 97: 3, 0.5mL/min, R- (+): 11.80min, S- (-): 13.24 min. High performance liquid chromatography analyzer: multiwavelength Detector: Jasco-MD-2010Plus, Intelligent HPLC Pum: Jasco-PU-980, Column: REGIS Whelk-
-1-(S，S)5μm 
LCColumn 250x 4.6mm。
Catalyst recovery
The solid was filtered through FP-450(Life Sciences) filter paper to recover the catalyst (IV), and the recovered catalyst (IV) was washed with toluene, acetone, and methanol in this order and then vacuum-pumped at 40 ℃ for 8 hours to obtain a white solid.
The selective reduction reaction and catalyst recovery method of the catalyst (V) were tested in the same manner as described above.
After the reaction was completed, the optical purity and conversion of the product were calculated and the results are shown in Table 2.
TABLE 2
From the results shown in Table 2, it can be seen that the selective reduction reaction of the heterogeneous catalyst bonded to a substrate (e.g., silica) according to the present invention can achieve good results in terms of both the optical purity and the conversion rate of the product, even the optical purity of the product can reach 77.2% and the conversion rate can reach 88.3%.
Example 5
Preparation of chiral catalyst (2)
Reaction step 1
Reaction reagent
Synthesis procedure
Firstly, a 1L double-neck reaction bottle is filled with nitrogen, items 1 to 3 are added into the bottle and stirred until the solution is completely dissolved. Then, the reaction bottle is placed in an ice bath kettle for cooling, nitrogen is introduced, and the temperature in the ice bath kettle is maintained at 0-5 ℃. Then, the solvent of item 4 was slowly dropped, and after dropping, the temperature was naturally returned to room temperature and the mixture was stirred for 2 hours. Thereafter, the product appeared at 14.92min, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5 mL/min. After the reaction was complete, 300mL of H was added2O, each extraction with 100mL EA and repeated 4 times (total 400mL EA), EA layer was checked using HPLC to find no product in EA layer. Then, the aqueous layer was acidified to pH 2 with 3M HCl aqueous solution, extracted with EA, extracted with 100mL EA each time and repeatedly extracted 4 times (total 400mL EA), and the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and usedThe solvent was concentrated dry in a rotary thickener at 40 ℃. Thereafter, vacuum was applied at room temperature for 12 hours to give 54g of a clear liquid, 89.0% yield, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5mL/min, and the product appeared at 14.70min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 99.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, DMSOd 6): delta 12.63(s, 1H, COOH), 7.36-7.28(m, 5H), 5.10-5.00(m, 3H, OH, PhCH)2O)，4.30-4.19(m，2H)，3.50-3.36(m，2H)，2.21-2.11(m，1H)，1.99-1.81(m，1H)。
Reaction step 2
Reaction reagent
Synthesis procedure
Firstly, a 500mL double-necked reaction flask was purged with nitrogen, and items 1 to 3 were added to the flask and stirred until completely dissolved. Then, the reaction flask is placed in an oil bath pan for cooling, nitrogen is introduced, and the temperature in the oil bath pan is maintained at 40-50 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 11.53min and was complete after 12 hours. After the reaction was completed, the solution was concentrated to leave 20 to 30mL, the aqueous solution of item 4 was added, extraction was performed using EA, extraction was performed with 100mL of EA each time and repeated 3 times (total 300mL of EA), the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and the solvent was concentrated to dryness at 50 ℃ using a rotary concentrator. Thereafter, a vacuum was applied at room temperature for 12 hours to give 57.8g of a pale yellow transparent liquid in 79.5% yield as measured by Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 11.507min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 98.0%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.32-7.24(m，5H)，5.18-4.96(m，2H，PhCH2O)，4.51-4.44(m，2H)，3.72-3.59(m，3H)，3.54-3.52(m，2H)，2.32-2.23(m，1H)，2.07-1.80(m，1H)。
Reaction step 3
Reaction reagent
Synthesis procedure
Firstly, a 1L double-neck reaction bottle is filled with nitrogen, items 1 to 4 are added into the bottle and stirred until the solution is completely dissolved. Then, the reaction flask was placed in an oil bath pan to cool, nitrogen was introduced and the temperature in the oil bath pan was maintained at 40 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 18.613min and was complete after 24 hours. After the reaction was complete, 300mL of H was added2O, using DCM for extraction, taking DCM layer with anhydrous magnesium sulfate to remove water, filtering, using a rotary concentrator at 40 degrees C concentration of dry solvent. Thereafter, vacuum was applied at room temperature for 12 hours to give 74.7g of a clear liquid, a yield of 99.2%, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 17.52min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 99.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.32-7.26(m，5H)，5.19-4.98(m，2H，PhCH2O)，4.63-4.58(m，1H)，4.50-4.37(m，2H)，3.83-3.63(m，3H+2H)，3.54-3.41(m，2H)，2.45-2.29(m，1H)，2.14-2.01(m，1H)，1.75-1.62(m，2H)，1.58-1.39(m，4H)。
Reaction step 4
Reaction reagent
Synthesis procedure
First, a 250mL two-necked reaction flask was purged with nitrogen, and item 3 was added to the flask and stirred. After dropping about 10-15mL of item 2, the reaction was started to boil by heating with a blower. Slowly dropping the solution into item 2, placing the reaction flask in an oil bath, and maintaining the internal temperature of the oil bath at 50-60 ℃. Introducing nitrogen into another 500mL double-neck reaction bottle, adding item 1 into the bottle, stirring and cooling to 0-5 ℃. Then, the reaction solution obtained in the above step is slowly dropped into an addition funnel, the internal temperature is maintained at 0-10 ℃, and after dropping, the reaction solution is heated to 40 ℃ for reaction for about 2 hours. After this time, the reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min and the product appeared at 11.98 min. After completion of the reaction, 3M HCl aqueous solution was added to neutralize the reaction solution to pH 6 to 8, extraction was performed using EA, extraction was performed with 100mL EA each time and extraction was repeated 3 times (total 300mL EA), the EA layer was taken out, dehydrated with anhydrous magnesium sulfate, filtered, and the solvent was concentrated to dryness at 50 ℃ using a rotary concentrator. Then, column (3cm in diameter) packing 40cm (SILICYCLE Silica gel 70-230mesh, pH 7) was taken, impurities were removed by EA: Hex of 1: 10, and then polarity was increased until the product flowed out by EA: Hex of 1: 4, and about 30-50mL of dry solvent was concentrated at 40 ℃ using a rotary concentrator, and the solid was precipitated and filtered. Thereafter, a vacuum was applied at 60 ℃ for 12 hours to give 16.7g of a white solid in 62.3% yield, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 12.053min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 98.5%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.37-7.24(m，15H)，5.10-4.99(m，2H，PhCH2O)，4.40-4.36(d，1H)，3.71-3.66(m，2H+1H)，3.39-3.32(m，1H)，2.23-2.09(m，2H)，1.70-1.69(m，1H)，1.62-1.24(m，8H)。
Reaction step 5
Reaction reagent
| Item | Reactants | Molecular weight | Dosage of | Number of millimoles | Ratio of moles |
| 1 | Reaction step 4 product | 487.59 | 10g | 20.51 | 1 |
| 2 | p-Toluenesulfonic acid (p-Toluenesufonic acid) | 190.22 | 0.04g | 0.205 | 0.01 |
| 3 | Ethyl Acetate (Ethyl Acetate) | - | 50mL | - | - |
| 4 | Methanol (Methanol) | - | 50mL | - | - |
Synthesis procedure
Firstly, introducing nitrogen into a 250mL double-neck reaction bottle, adding items 1-4 into the bottle, stirring, and heating until the internal temperature is 50-60 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 8.947min and was complete over about 4 hours. After the reaction was completed, extraction was performed using EA, 100mL of EA was performed each time and extraction was repeated 3 times (total 300mL of EA), and the EA layer was taken out, dehydrated with anhydrous magnesium sulfate, filtered, and concentrated to dryness at 50 ℃ using a rotary concentrator. Thereafter, a vacuum was applied at 60 ℃ for 12 hours to give 8.3g of a white solid in 99.0% yield, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 8.947min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 88.0%, and the purification was carried out directly to the next step. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.41-7.27(m，15H)，5.18-5.13(m，2H，PhCH2O)，4.97(s，1H)，3.93(s，1H)，3.62-3.59(d，1H)，3.08-3.06(d，1H)，2.20-1.98(m，2H)，1.62-1.60(m，2H)。
Reaction step 6
Reaction reagent
Synthesis procedure
Firstly, introducing nitrogen into a 100mL double-neck reaction bottle, adding items 1 to 4 into the bottle, stirring,heated to hot reflux. Thereafter, the reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 13.24min, which was completed in about 3 days. After the reaction was completed, extraction was performed using EA, 50mL of EA was performed each time and extraction was repeated 3 times (total 150mL of EA), and the EA layer was taken out, dehydrated with anhydrous magnesium sulfate, filtered, and concentrated to dryness at 50 ℃ using a rotary concentrator. Then, column (3cm in diameter) packing 40cm (SILICYCLE Silica gel 70-230mesh, pH 7) was taken, impurities were removed by EA: Hex of 1: 10, and then polarity was increased until the product flowed out by EA: Hex of 1: 4, and about 30-50mL of dry solvent was concentrated at 40 ℃ using a rotary concentrator, and the solid was precipitated and filtered. Thereafter, a vacuum was applied at room temperature for 12 hours to give 2.75g of a clear liquid, a yield of 45.5%, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 13.2min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 94.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.39-7.18(m，15H)，5.11-5.03(m，2H，PhCH2O)，4.87-4.85(m，2H)，4.12-4.07(m，1H)，3.81-3.78(m，6H)，3.71-3.64(m，1H)，3.11-3.05(m，2H)，2.25-2.10(m，2H)，1.60-1.52(m，2H)，1.25-1.16(m，9H)，0.61-0.51(m.2H)。
Reaction step 7
Reaction reagent
Synthesis procedure
Firstly, introducing nitrogen into a 100mL double-neck reaction bottle, adding items 1-4 into the bottle, stirring, and heating until the internal temperature is 50-60 ℃. Thereafter, the reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 4.787min, which was completed in about 3 hours. Thereafter, the solvent was concentrated to dryness at 50 ℃ using a rotary thickener. Then, column (3cm in diameter) packing 20cm (SILICYCLE Silica gel)70-230mesh, pH 7), using EA: Hex-1: 6 as washing liquid, washing out impurity, using EA: Hex-1: 1 as washing liquid to wash out product, and concentrating. After 12 h of evacuation at room temperature, a clear liquid 0.6g was obtained in 38.0% yield, HPLC was measured at 0.5mL/min with Hex: IPA 4: 1+ 0.1% TFA, and the product appeared at 10.2min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]And the purity is 93.0 percent. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.58-7.53(m，2H)，7.44-7.42(m，2H)，7.30-7.11(m，6H)，5.06(s，1H)，4.90(s，1H)，4.51-4.47(m，1H)，3.82-3.77(m，6H)，3.26-3.22(m，2H)，3.15-3.04(m，2H)，1.63-1.51(m，4H)，1.22-1.19(m，9H)，0.62-0.58(m，2H)。
Reaction step 8
Reaction reagent
Synthesis procedure
Firstly, a 100mL double-neck reaction bottle is filled with nitrogen, items 1 to 3 are added into the bottle and stirred, solid salts are separated out after item 4 is slowly dropped, and the reaction is finished after about 24 hours. After completion of the reaction, extraction was performed using EA, 100mL of EA was used each time and extraction was repeated 3 times (total 150mL of EA), and the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and concentrated to dryness at 35 ℃ using a rotary concentrator. After dissolving with 10mL of Acetone, it was recrystallized with Hexane and the product was filtered using FP-450(Life Sciences) filter paper. Thereafter, a vacuum was applied at 40 ℃ for 12 hours to give 0.46g of a white solid in 80.1% yield, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5mL/min, and the product appeared at 6.46min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 98.6%, and the objective product was measured by NMR. The data are as follows:1H NMR(400MHz，CDCl3)：δ7.58-7.51(m，4H)，7.44-7.38(m，4H)，7.38-7.02(m，18H+3H)，5.11(s，2H)，4.98(s，2H)，4.51-4.46(m，2H)，3.81-3.72(m，12H)，3.38-3.42(m，4H)，3.26-3.31(m，4H)，3.20-2.94(m，4H)，1.69-1.50(m，8H+6H)，1.23-1.16(m，18H)，0.61-0.56(m，4H)。
example 6
Preparation of chiral catalyst (3)
Reaction step 1
Reaction reagent
Synthesis procedure
Firstly, a 1L double-neck reaction bottle is filled with nitrogen, items 1 to 3 are added into the bottle and stirred until the solution is completely dissolved. Then, the reaction bottle is placed in an ice bath kettle for cooling, nitrogen is introduced, and the temperature in the ice bath kettle is maintained at 0-5 ℃. Then, the solvent of item 4 was slowly dropped, and after dropping, the temperature was naturally returned to room temperature and the mixture was stirred for 2 hours. Thereafter, the product appeared at 14.92min, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5 mL/min. After the reaction was complete, 300mL of H was added2O, each extraction with 100mL EA and repeated 4 times (total 400mL EA), EA layer was checked using HPLC to find no product in EA layer. Then, the aqueous layer was acidified with 3M HCl aqueous solution to pH 2, extracted with EA, extracted with 100mL EA each time and repeatedly extracted 4 times (total 400mL EA), and the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and concentrated to dryness at 40 ℃. Thereafter, vacuum was applied at room temperature for 12 hours to give 54g of a clear liquid, 89.0% yield, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5mL/min, and the product appeared at 14.70min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 99.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, DMSOd 6): delta 12.63(s, 1H, COOH), 7.36-7.28(m, 5H), 5.10-5.00(m, 3H, OH, PhCH)2O)，4.30-4.19(m，2H)，3.50-3.36(m，2H)，2.21-2.11(m，1H)，1.99-1.81(m，1H)。
Reaction step 2
Reaction reagent
Synthesis procedure
Firstly, a 500mL double-necked reaction flask was purged with nitrogen, and items 1 to 3 were added to the flask and stirred until completely dissolved. Then, the reaction flask is placed in an oil bath pan for cooling, nitrogen is introduced, and the temperature in the oil bath pan is maintained at 40-50 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 11.53min and was complete after 12 hours. After the reaction was completed, the solution was concentrated to leave 20 to 30mL, the aqueous solution of item 4 was added, extraction was performed using EA, extraction was performed with 100mL of EA each time and repeated 3 times (total 300mL of EA), the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and the solvent was concentrated to dryness at 50 ℃ using a rotary concentrator. Thereafter, a vacuum was applied at room temperature for 12 hours to give 57.8g of a pale yellow transparent liquid in 79.5% yield as measured by Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 11.507min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 98.0%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.32-7.24(m，5H)，5.18-4.96(m，2H，PhCH2O)，4.51-4.44(m，2H)，3.72-3.59(m，3H)，3.54-3.52(m，2H)，2.32-2.23(m，1H)，2.07-1.80(m，1H)。
Reaction step 3
Reaction reagent
Synthesis procedure
Firstly, a 1L double-neck reaction bottle is filled with nitrogen, items 1 to 4 are added into the bottle and stirred until the solution is completely dissolved. Then, the reaction flask was placed in an oil bath pan to cool, nitrogen was introduced and the temperature in the oil bath pan was maintained at 40 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 18.613min and was complete after 24 hours. After the reaction was complete, 300mL of H was added2O, using DCM for extraction, taking DCM layer with anhydrous magnesium sulfate to remove water, filtering, using a rotary concentrator at 40 degrees C concentration of dry solvent. Thereafter, vacuum was applied at room temperature for 12 hours to give 74.7g of a clear liquid, yield 99.2%, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 17.52min [ REGIS (S, S) Whelk-015 μm, 4.6X 150mm]The purity was 99.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.32-7.26(m，5H)，5.19-4.98(m，2H，PhCH2O)，4.63-4.58(m，1H)，4.50-4.37(m，2H)，3.83-3.63(m，3H+2H)，3.54-3.41(m，2H)，2.45-2.29(m，1H)，2.14-2.01(m，1H)，1.75-1.62(m，2H)，1.58-1.39(m，4H)。
Reaction step 4
Reaction reagent
Synthesis procedure
The synthesis was the same as in reaction step 4 of example 1.
Reaction step 5
Reaction reagent
Synthesis procedure
The synthesis was the same as in reaction step 5 of example 1.
Reaction step 6
Reaction reagent
Synthesis procedure
The synthesis was the same as in reaction step 6 of example 1.
Reaction step 7
Reaction reagent
Synthesis procedure
The synthesis was the same as in reaction step 7 of example 1.
Reaction step 8
Reaction reagent
Synthesis procedure
The synthesis was the same as in reaction step 8 of example 1.
Example 7
Preparation of chiral catalyst (4)
Reaction step 1
Reaction reagent
Synthesis procedure
Firstly, a 1L double-neck reaction bottle is filled with nitrogen, items 1 to 3 are added into the bottle and stirred until the solution is completely dissolved. Then, the reaction bottle is placed in an ice bath kettle for cooling, nitrogen is introduced, and the temperature in the ice bath kettle is maintained at 0-5 ℃. Then, the solvent of item 4 was slowly dropped, and after dropping, the temperature was naturally returned to room temperature and the mixture was stirred for 2 hours. Thereafter, the product appeared at 14.92min, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5 mL/min. After the reaction was complete, 300mL of H was added2O, each extraction with 100mL EA and repeated 4 times (total 400mL EA), EA layer was checked using HPLC to find no product in EA layer. Then, the aqueous layer was acidified with 3M HCl aqueous solution to pH 2, extracted with EA, extracted with 100mL EA each time and repeatedly extracted 4 times (total 400mL EA), and the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and concentrated to dryness at 40 ℃. Thereafter, vacuum was applied at room temperature for 12 hours to give 54g of a clear liquid, 89.0% yield, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 0.5mL/min, and the product appeared at 14.70min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 99.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, DMSOd 6): delta 12.63(s, 1H, COOH), 7.36-7.28(m, 5H), 5.10-5.00(m, 3H, OH, PhCH)2O)，4.30-4.19(m，2H)，3.50-3.36(m，2H)，2.21-2.11(m，1H)，1.99-1.81(m，1H)。
Reaction step 2
Reaction reagent
Synthesis procedure
Firstly, a 500mL double-necked reaction flask was purged with nitrogen, and items 1 to 3 were added to the flask and stirred until completely dissolved. Then, the reaction flask is placed in an oil bath pan for cooling, nitrogen is introduced, and the temperature in the oil bath pan is maintained at 40-50 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 11.53min and was complete after 12 hours. After the reaction was completed, the solution was concentrated to leave 20 to 30mL, the aqueous solution of item 4 was added, extraction was performed using EA, extraction was performed with 100mL EA each time and extraction was repeated 3 times (total 300mL EA), the EA layer was taken, dehydrated with anhydrous magnesium sulfate, filtered, and the solvent was concentrated to dryness at 50 ℃ using a rotary concentrator. Thereafter, a vacuum was applied at room temperature for 12 hours to give 57.8g of a pale yellow transparent liquid in 79.5% yield as measured by Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 11.507min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 98.0%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.32-7.24(m，5H)，5.18-4.96(m，2H，PhCH2O)，4.51-4.44(m，2H)，3.72-3.59(m，3H)，3.54-3.52(m，2H)，2.32-2.23(m，1H)，2.07-1.80(m，1H)。
Reaction step 3
Reaction reagent
Synthesis procedure
Firstly, a 1L double-neck reaction bottle is filled with nitrogen, items 1 to 4 are added into the bottle and stirred until the solution is completely dissolved. Then, the reaction flask was placed in an oil bath pan to cool, nitrogen was introduced and the temperature in the oil bath pan was maintained at 40 ℃. The reaction was followed with Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 18.613min and was complete after 24 hours. After the reaction was complete, 300mL of H was added2O, using DCM for extraction, taking DCM layer with anhydrous magnesium sulfate to remove water, filtering, using a rotary concentrator at 40 degrees C concentration of dry solvent. Thereafter, vacuum was applied at room temperature for 12 hours to give 74.7g of a clear liquid, a yield of 99.2%, measured as Hex: IPA 4: 1+ 0.1% TFA at a flow rate of 1.0mL/min, and the product appeared at 17.52min [ REGIS (S, S) Whelk-O15 μm, 4.6X 150mm]The purity was 99.2%. The target product was measured by NMR. The data are as follows: 1H NMR (400MHz, CDCl)3)：δ7.32-7.26(m，5H)，5.19-4.98(m，2H，PhCH2O)，4.63-4.58(m，1H)，4.50-4.37(m，2H)，3.83-3.63(m，3H+2H)，3.54-3.4l(m，2H)，2.45-2.29(m，1H)，2.14-2.01(m，1H)，1.75-1.62(m，2H)，1.58-1.39(m，4H)。
Reaction step 4
Reaction reagent
Synthesis procedure
The synthesis was the same as in reaction step 4 of example 1.
Reaction step 5
Reaction reagent
Synthesis procedure
The synthesis was the same as in reaction step 5 of example 1.
Reaction step 6
Reaction reagent
Synthesis procedure
The synthesis was the same as in reaction step 6 of example 1.
Reaction step 7
Reaction reagent
Synthesis procedure
The synthesis was the same as in reaction step 7 of example 1.
Reaction step 8
Reaction reagent
Synthesis procedure
The synthesis method was the same as in reaction step 8 of example 1 except for the reaction reagents.
Example 8
Recoverable recycling property of heterogeneous chiral catalyst
The heterogeneous chiral catalyst (IV) recovered in example 4 was tested in [ selective reduction reaction ] and [ catalyst recovery ] of example 4, and the reaction and recovery were repeated three times in a cycle to verify the recyclable property of the heterogeneous chiral catalyst (IV).
After the reaction was completed, the optical purity and conversion of the product were calculated and the results are summarized in Table 3.
TABLE 3
Example 9
Recoverable recycling property of heterogeneous chiral catalyst
The heterogeneous chiral catalyst (V) recovered in example 4 was tested in [ selective reduction reaction ] and [ catalyst recovery ] of example 4, and the reaction and recovery were repeated three times in a cycle to verify the recyclable property of the heterogeneous chiral catalyst (V).
After the reaction was completed, the optical purity and conversion of the product were calculated and the results are shown in Table 4.
TABLE 4
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are only exemplary embodiments of the present invention and are not intended to limit the present invention, and any modifications, equivalents, improvements and the like made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (18)
1. A chiral catalyst of formula (I):
wherein Z ═ Z1Or Z2In combination, comprises
Y independently comprises hydrogen, fluorine, trifluoromethyl, isopropyl, tert-butyl, CmH2m+1Or OCmH2m+1M is 1 to 10, and n is 1 to 10.
2. The chiral catalyst of claim 1, wherein Y independently comprises hydrogen, CH3Or OCH3And n is 3-8.
3. The chiral catalyst of claim 1, wherein the chiral catalyst is of formula (II) or (III):
wherein Y independently comprises hydrogen, fluoro, trifluoromethyl, isopropyl, tert-butyl, CmH2m+1Or OCmH2m+1M is 1 to 10, and n is 1 to 10.
4. The chiral catalyst of claim 3, wherein Y independently comprises hydrogen, CH3Or OCH3And n is 3-8.
5. The chiral catalyst of claim 1, wherein the chiral catalyst comprises
6. A heterogeneous chiral catalyst comprising:
a chiral catalyst as in claim 1; and
a substrate attached to the chiral catalyst.
7. The heterogeneous chiral catalyst of claim 6, having formula (IV):
wherein S is a substrate, Z ═ Z1Or Z2In combination, comprises
Y independently comprises hydrogen, fluorine, trifluoromethyl, isopropyl, tert-butyl, CmH2m+1Or OCmH2m+1M is 1 to 10, and n is 1 to 10.
8. The heterogeneous chiral catalyst of claim 7, wherein Y independently comprises hydrogen, CH3Or OCH3And n is 3-8.
9. The heterogeneous chiral catalyst of claim 7, wherein the heterogeneous chiral catalyst is of formula (V) or (VI):
wherein Y independently comprises hydrogen, fluoro, trifluoromethyl, isopropyl, tert-butyl, CmH2m+1Or OCmH2m+1M is 1 to 10, and n is 1 to 10.
10. The heterogeneous chiral catalyst of claim 9, wherein Y independently comprises hydrogen, CH3Or OCH3And n is 3-8.
11. The heterogeneous chiral catalyst of claim 7, wherein the heterogeneous chiral catalyst comprises
12. The heterogeneous chiral catalyst of claim 6, wherein the substrate is surface modified silica, titania, iron oxide, zinc oxide, or alumina having hydroxyl groups.
13. The heterogeneous chiral catalyst of claim 6, wherein the substrate is a mesoporous material.
14. The heterogeneous chiral catalyst of claim 13, wherein the substrate has a specific surface area of between 10m2/g-1，000m2/g。
15. The heterogeneous chiral catalyst of claim 13, wherein the pore size of the substrate is between 2nm and 50 nm.
16. The heterogeneous chiral catalyst of claim 12, wherein the hydroxyl group of the substrate is bonded to Z1Si (OEt)3The groups are linked.
17. The heterogeneous chiral catalyst of claim 16, wherein the substrate is reacted with Z1Form a silicon-oxygen bond therebetween.
18. The heterogeneous chiral catalyst of claim 6, wherein the substrate has an average particle size of 5 μm to 500 μm.
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