CN114591228B - Chiral styryl pyridyl sulfoxide and synthesis method thereof - Google Patents
Chiral styryl pyridyl sulfoxide and synthesis method thereof Download PDFInfo
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- -1 styryl pyridyl sulfoxide Chemical compound 0.000 title claims abstract description 58
- 238000001308 synthesis method Methods 0.000 title claims description 7
- 239000002994 raw material Substances 0.000 claims abstract description 67
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 239000012298 atmosphere Substances 0.000 claims abstract description 10
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 150000001336 alkenes Chemical class 0.000 claims description 31
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 31
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 11
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims description 11
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003208 petroleum Substances 0.000 claims description 8
- 229910000161 silver phosphate Inorganic materials 0.000 claims description 7
- FJOLTQXXWSRAIX-UHFFFAOYSA-K silver phosphate Chemical compound [Ag+].[Ag+].[Ag+].[O-]P([O-])([O-])=O FJOLTQXXWSRAIX-UHFFFAOYSA-K 0.000 claims description 7
- 229940019931 silver phosphate Drugs 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- 238000012746 preparative thin layer chromatography Methods 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- RAVDHKVWJUPFPT-UHFFFAOYSA-N silver;oxido(dioxo)vanadium Chemical compound [Ag+].[O-][V](=O)=O RAVDHKVWJUPFPT-UHFFFAOYSA-N 0.000 claims description 3
- 150000003462 sulfoxides Chemical class 0.000 abstract description 44
- 238000006243 chemical reaction Methods 0.000 abstract description 25
- 239000003446 ligand Substances 0.000 abstract description 21
- 150000001875 compounds Chemical class 0.000 abstract description 20
- 238000000034 method Methods 0.000 abstract description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract description 12
- 125000005504 styryl group Chemical group 0.000 abstract description 9
- 150000001413 amino acids Chemical class 0.000 abstract description 8
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 abstract description 8
- 125000004076 pyridyl group Chemical group 0.000 abstract description 7
- 229910052763 palladium Inorganic materials 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 238000011084 recovery Methods 0.000 abstract description 5
- 230000000707 stereoselective effect Effects 0.000 abstract description 5
- 238000011914 asymmetric synthesis Methods 0.000 abstract description 4
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 abstract description 3
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 230000006340 racemization Effects 0.000 abstract description 2
- 125000004434 sulfur atom Chemical group 0.000 abstract description 2
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 128
- 239000007858 starting material Substances 0.000 description 44
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 30
- 238000005160 1H NMR spectroscopy Methods 0.000 description 30
- 238000012512 characterization method Methods 0.000 description 30
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 6
- 238000007792 addition Methods 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000004293 19F NMR spectroscopy Methods 0.000 description 4
- ODHCTXKNWHHXJC-GSVOUGTGSA-N 5-oxo-D-proline Chemical compound OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 239000000654 additive Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000011925 1,2-addition Methods 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002160 Celluloid Polymers 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical class OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003608 titanium Chemical class 0.000 description 1
- 150000003609 titanium compounds Chemical class 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
- C07D213/71—Sulfur atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
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- 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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a chiral styryl pyridyl sulfoxide, which belongs to the field of organic synthesis, wherein a sulfur atom is used as a chiral center, one side chain of a sulfinyl group is connected with a styryl group or a substituted styryl group, and the other side chain is connected with a pyridyl group or a substituted pyridyl group; using racemized aryl pyridyl sulfoxide raw material, olefine, palladium catalyst, chiral amino acid ligand and silver salt as reaction raw material, or adding benzoquinone as reaction raw material; and (3) placing the reaction raw materials into an organic solvent, heating the reaction in an air atmosphere, and after the reaction is finished, performing post-treatment on the reaction solution to obtain the chiral styrylpyridyl sulfoxide. The method realizes the first asymmetric synthesis of the chiral styryl pyridyl sulfoxide based on a kinetic resolution strategy, has good universality and good stereoselectivity, and also realizes the stereoselective recovery of S-configuration or R-configuration compounds in the racemization raw materials.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to chiral styryl pyridyl sulfoxide and a synthesis method thereof.
Background
Sulfoxide compounds are widely applied in the fields of organic synthesis, pharmaceutical chemistry and the like, can be used as assistants, ligands, catalysts and the like, and can also be used as pharmacophores, carbonyl organism isosteres or drug molecule modification groups in drug design or development and the like. Chiral sulfoxide structures are widely used in bioactive compounds such as drugs, and are also key structures of prosthetic groups or ligands important in asymmetric synthesis. The traditional method for synthesizing chiral sulfoxide mainly comprises resolution, diastereoselective conversion and biocatalysis, and few methods for synthesizing chiral sulfoxide by adopting a catalytic asymmetric strategy are reported in the current research, especially a method for constructing chiral sulfoxide by utilizing asymmetric hydrocarbon bond activation.
The Chinese patent document with publication number CN111848321A discloses a preparation method of chiral aminated sulfoxide, which takes ligand and iridium complex as catalyst and silver salt is added, thus realizing asymmetric amidation of sulfoxide; the chinese patent publication No. CN101538264a discloses a new method for preparing chiral sulfoxides, which directly oxidizes prochiral thioether into corresponding optically pure or single enantiomer-enriched sulfoxides by hydrogen peroxide derivatives in the presence of chiral titanium complexes prepared from chiral bidentate ligands and titanium compounds.
Chiral sulfoxide containing styryl structure is a very promising bidentate chiral ligand, especially (Jin S S,Wang H,Xu M H.Design of N-Sulfinyl Homoallylic Amines as Novel Sulfinamide-Olefin Hybrid Ligands for Asymmetric Catalysis:Application in Rh-Catalyzed Enantioselective 1,4-Additions.Chemical Communications,2011;Chen G,Gui J,Li L,et al.Chiral Sulfoxide-Olefin Ligands:Completely Switchable Stereoselectivity in Rhodium-Catalyzed Asymmetric Conjugate Additions.Angewandte Chemie International Edition,2011.). is widely applied to rhodium (I) catalyzed asymmetric 1, 4-addition and 1, 2-addition, the synthesis of the bidentate chiral ligand needs to introduce alkenyl through phosphorylation and Horner-Wadsworth-Emmons reaction, the chiral sulfoxide group is introduced through lithium halide exchange and sulfinylation reaction, and stoichiometric chiral sulfinic acid thioester is needed, so the synthesis steps are complicated and the cost is high.
However, the asymmetric synthesis of chiral sulfoxides with pyridine ligand groups and styryl groups has not been reported in the prior art.
Disclosure of Invention
The invention provides a chiral styryl-pyridinyl sulfoxide, which is synthesized by taking racemic aryl-pyridinyl sulfoxide as a starting material and utilizing a palladium-catalyzed asymmetric alkenyl method based on a kinetic resolution strategy, and can be used as a chiral ligand to play an important role in asymmetric catalytic reaction.
The technical scheme adopted is as follows:
A chiral styryl pyridyl sulfoxide has a structural formula shown in formula (I),
Ar 1 is styryl or substituted styryl, and has the structural formula:
Ar 2 is pyridyl or substituted pyridyl, and has the structural formula:
Wherein R 1 is alkyl, alkoxy, hydroxy, halogen or ester; r 2 is alkyl; r is an ester group, an acyl group or an aryl group; * Represents a substitution position;
the chiral styryl pyridyl sulfoxide can be a levorotatory body or a dextrorotatory body with the same chemical general formula.
The compound is characterized in that one side chain of sulfinyl is connected with styryl or substituted styryl, the other side chain is connected with pyridyl or substituted pyridyl, wherein sulfur atoms are chiral centers, and pyridyl, alkenyl and sulfinyl have coordination ability and can easily form a 5-7 membered ring with transition metal, so that the compound can be used as a potential ligand in asymmetric catalysis.
The invention also provides a synthesis method of the chiral styryl pyridyl sulfoxide, which comprises the following steps:
the method comprises the steps of taking a racemized compound shown in a formula (II), olefin, a palladium catalyst, chiral amino acid ligand and silver salt as reaction raw materials, placing the reaction raw materials into an organic solvent, heating the reaction raw materials in an air atmosphere for reaction, and after the reaction is finished, carrying out post-treatment on a reaction solution to obtain a compound shown in the formula (I);
wherein the structural formula of the racemic compound shown in the formula (II) is as follows:
Wherein Ar 3 is phenyl or R 1 substituted phenyl, R 1 and Ar 2 are as defined above.
The invention is based on a kinetic resolution strategy, a racemate shown in a formula (II) is taken as a raw material, the racemate comprises compounds in R-configuration and S-configuration, most of the compounds in R-configuration generate asymmetric alkenyl under the action of chiral amino acid ligand L-pyroglutamic acid, silver salt and palladium catalyst, most of the compounds in S-configuration do not participate in the reaction, and the compounds are left, so that the preparation of chiral styryl pyridyl sulfoxide and the stereoselective recovery of the raw material compounds in S-configuration can be realized; or under the action of chiral amino acid ligand D-pyroglutamic acid, silver salt and palladium catalyst, most S-configuration compounds are subjected to asymmetric alkenyl reaction, and most R-configuration compounds do not participate in the reaction, and the preparation of chiral styrylpyridyl sulfoxide and the stereoselective recovery of R-configuration raw material compounds can be realized.
The reaction raw materials also comprise benzoquinone additives. The addition of benzoquinone catalyst can inhibit the deactivation of the catalyst, thereby improving the yield.
Preferably, the palladium catalyst is palladium acetate.
Preferably, the chiral amino acid ligand is L-pyroglutamic acid or D-pyroglutamic acid.
Preferably, the silver salt comprises silver phosphate or silver metavanadate.
Preferably, the reaction conditions are: the temperature is 55-60 ℃ and the time is 1-48 hours.
Preferably, the molar ratio of the chiral compound shown in the formula (II), the olefin, the palladium catalyst, the chiral amino acid ligand and the silver salt is 1:0.5 to 10:0.01 to 0.5:0.01 to 2:0.5 to 5.
Preferably, the molar ratio of the chiral compound shown in the formula (II) to the additive is 1:0.1 to 3.
Preferably, the ratio of the chiral compound shown in the formula (II) to the organic solvent is 1mol:0.1 to 100L.
Chemoselectivity and stereoselectivity have been key factors in the development of fine organic synthesis, and the site selectivity of the reaction has a close and inseparable relationship with yield and properties of the catalyst, ligand, silver salt, additives and substrate itself.
Preferably, the post-treatment method is thin layer chromatography.
Compared with the prior art, the invention has the beneficial effects that:
(1) The invention provides a method for synthesizing a novel chiral sulfoxide ligand with a (substituted) pyridine group and a (substituted) styryl structure based on a dynamic resolution strategy, which realizes the first asymmetric synthesis of the chiral styryl sulfoxide and is expected to be widely applied to various asymmetric catalytic reactions.
(2) The method disclosed by the invention has good universality, is suitable for synthesizing a series of chiral styrylpyridyl sulfoxide compounds, has good stereoselectivity, not only can prepare the chiral styrylpyridyl sulfoxide, but also can realize the stereoselective recovery of S-configuration or R-configuration compounds in a racemization raw material.
(3) When L-pyroglutamic acid is selected as chiral amino acid ligand, the optical purity of the chiral styryl pyridyl sulfoxide product prepared by the method can reach 99%; the optical purity of the rest S-configuration raw material compound can reach 99 percent; the chiral selectivity (S-factor) is between 9 and 335.
(3) The method has the advantages of simple and controllable operation, mild reaction conditions, wide substrate application range and very good economic value.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of chiral styrylpyridyl sulfoxide product 1a of example 1.
FIG. 2 is a nuclear magnetic resonance chart of chiral styrylpyridyl sulfoxide product 1a of example 1.
FIG. 3 is a high performance liquid chromatography of the racemic styrylpyridyl sulfoxide 1a and the chiral styrylpyridyl sulfoxide product 1a prepared in example 1, wherein A is the racemic styrylpyridyl sulfoxide 1a and B is the chiral styrylpyridyl sulfoxide product 1a prepared in example 1.
FIG. 4 is a high performance liquid chromatography of the racemic arylpyridylsulfoxide starting material and unreacted starting material 2a of example 1, wherein A is the racemic arylpyridylsulfoxide starting material and B is unreacted starting material 2a of S-configuration.
Detailed Description
The invention is further elucidated below in connection with the drawings and the examples. It is to be understood that these examples are for illustration of the invention only and are not intended to limit the scope of the invention.
Example 1
The structural formulas of the arylpyridylsulfoxide feedstock and the olefin feedstock in this example are shown below, respectively:
In a reactor, 0.2 mmol of racemic arylpyridylsulfoxide raw material, 0.2 mmol of olefin, 0.02 mmol of palladium acetate catalyst, 0.04 mmol of L-pyroglutamic acid, 0.4 mmol of silver phosphate, 1.8 ml of isopropyl alcohol and 0.2 ml of toluene are added, and reacted for 12 hours at 55 ℃ under an air atmosphere, cooled and filtered through a layer of kieselguhr, washed and concentrated, and then purified by preparative thin layer chromatography, petroleum ether: ethyl acetate = 4:1 as a developing solvent, the chiral styrylpyridyl sulfoxide product 1a (yield 38%,90% ee) and the unreacted starting material 2a of S-configuration (yield 49%,91% ee) were obtained, and S-factor was 59.
The structural formulas of the product 1a and the unreacted S-configuration raw material 2a are respectively as follows:
Characterization data for product 1a are as follows:
melting point 46.7-47.4 deg.c.
1H NMR(400MHz,CDCl3)δ8.53–8.42(m,2H),8.05(d,J＝7.9Hz,1H),7.94–7.82(m,2H),7.65(d,J＝7.4Hz,1H),7.54–7.39(m,2H),7.28(d,J＝4.4Hz,1H),6.43(dd,J＝15.8,1.2Hz,1H),4.24(t,J＝6.6Hz,2H),1.78–1.66(m,2H),1.51–1.42(m,2H),0.98(t,J＝7.3Hz,3H).
13C NMR(101MHz,CDCl3)δ166.5,165.6,150.0,144.0,139.8,138.1,134.5,131.6,130.8,127.1,125.6,124.7,121.8,119.2,64.8,30.9,19.3,13.9.
HRMS(ESI)m/z:[M+Na]+Calcd.for C18H19NNaO3S:352.0979；found:352.0983。
The nuclear magnetic resonance hydrogen spectrum and the nuclear magnetic resonance carbon spectrum of the chiral styryl pyridyl sulfoxide product 1a are shown in fig. 1 and fig. 2 respectively.
The racemic styrylpyridyl sulfoxide 1a (the preparation method is the same as that of the embodiment, and the difference is that the chiral amino acid ligand is a mixture of L-pyroglutamic acid and D-pyroglutamic acid) and the chiral styrylpyridyl sulfoxide product 1a in the embodiment are tested by adopting a liquid chromatography, in the testing process, a large xylol IJ column is adopted as a stationary phase, the mobile phase is n-hexane/isopropanol=80/20, the flow rate=1.2 mL/min, the detection wavelength is 254nm, the testing results are respectively shown as A and B in fig. 3, and the chiral styrylpyridyl sulfoxide product prepared by the preparation method is mostly in an R-configuration.
Characterization data for unreacted starting material 2a are as follows:
1H NMR(400MHz,CDCl3)δ8.54(dt,J＝4.4,1.5Hz,1H),8.04(dt,J＝8.0,1.1Hz,1H),7.87(td,J＝7.8,1.8Hz,1H),7.83–7.75(m,2H),7.51–7.39(m,3H),7.31–7.27(m,1H).
13C NMR(101MHz,CDCl3)δ165.9,149.9,144.2,138.3,131.3,129.3,125.0,124.8,118.5。
In the liquid chromatography test of the racemic arylpyridylsulfoxide raw material and the recovered unreacted raw material 2a (S-configuration) in this example, in the test process, a large xylonite OJ-H column is used as a stationary phase, normal hexane/isopropanol=90/10 is used as a mobile phase, the flow rate=0.8 mL/min is used, the detection wavelength is 254nm, the test results are respectively shown as A and B in FIG. 4, and the preparation method realizes the stereoselective recovery of the S-configuration raw material.
Examples 2 to 4
In examples 2-4, the aryl pyridinyl sulfoxide starting materials were:
Other raw materials and reaction conditions were the same as in example 1.
Example 2 yields chiral styrylpyridyl sulfoxide product 1b (yield 38%,84% ee) and unreacted starting material 2b in S-configuration (yield 47%,99% ee), S-factor 59, wherein the structural formulae of product 1b and unreacted starting material 2b were:
Characterization data for product 1b are as follows:
Melting point is 52.3-54.1 ℃.
1H NMR(400MHz,CDCl3)δ8.52–8.37(m,2H),8.05(dt,J＝8.0,1.1Hz,1H),7.86(td,J＝7.8,1.8Hz,1H),7.74(d,J＝8.0Hz,1H),7.44(s,1H),7.34–7.21(m,2H),6.41(d,J＝15.8Hz,1H),4.22(t,J＝6.6Hz,2H),2.37(s,3H),1.70(dq,J＝8.6,6.7Hz,2H),1.52–1.39(m,2H),0.96(t,J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ166.5,165.7,149.9,142.1,140.8,139.9,138.0,134.4,131.7,127.7,125.9,124.5,121.6,119.2,64.7,30.8,21.5,19.3,13.9.
HRMS(ESI)m/z:[M+Na]+Calcd.for C19H21NNaO3S:366.1136；found:366.1140。
Characterization data for unreacted starting material 2b are as follows:
1H NMR(400MHz,CDCl3)δ8.58–8.48(m,1H),8.05(dt,J＝7.9,1.1Hz,1H),7.87(td,J＝7.8,1.8Hz,1H),7.76–7.59(m,2H),7.39–7.12(m,3H),2.35(s,3H).
13C NMR(101MHz,CDCl3)δ166.1,149.9,141.9,141.0,138.2,130.0,125.2,124.7,118.5,21.5。
Example 3 yields chiral styrylpyridyl sulfoxide product 1c (yield 40%,92% ee) and unreacted starting material 2c of S-configuration (yield 53%,92% ee), S-factor 79, wherein the structural formulae of product 1c and unreacted starting material 2c are:
Characterization data for product 1c are as follows:
1H NMR(400MHz,CDCl3)δ8.59–8.30(m,2H),8.07(dt,J＝8.0,1.1Hz,1H),7.87(td,J＝7.8,1.7Hz,1H),7.77(d,J＝8.4Hz,1H),7.63(d,J＝2.0Hz,1H),7.50(dd,J＝8.4,2.0Hz,1H),7.32–7.18(m,1H),6.44(d,J＝15.8Hz,1H),4.24(t,J＝6.7Hz,2H),1.82–1.64(m,2H),1.57–1.37(m,2H),1.30(s,9H),0.97(t,J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ166.9,166.0,155.4,150.3,141.1,140.7,138.4,134.4,128.7,126.1,124.9,124.5,121.8,119.6,65.1,35.5,31.5,31.2,19.6,14.2.
HRMS(ESI)m/z:[M+Na]+Calcd.for C22H27NNaO3S:408.1606；found:408.1609。
characterization data for unreacted starting material 2c are as follows:
1H NMR(400MHz,CDCl3)δ8.60–8.51(m,1H),8.07(dt,J＝7.9,1.1Hz,1H),7.88(td,J＝7.7,1.8Hz,1H),7.75–7.63(m,2H),7.52–7.39(m,2H),7.32–7.27(m,1H),1.28(s,9H).
13C NMR(101MHz,CDCl3)δ166.0,154.9,149.9,140.8,138.2,126.4,125.1,124.7,118.7,35.1,31.2.
example 4 yields chiral styrylpyridyl sulfoxide product 1d (yield 43%,88% ee) and unreacted starting material 2d in the S-configuration (yield 45%,99% ee), S-factor 82, the structural formulae of product 1d and unreacted starting material 2d were:
Characterization data for product 1d are as follows:
1H NMR(400MHz,CDCl3)δ8.48(d,J＝4.8Hz,1H),8.44(d,J＝15.8Hz,1H),8.07(d,J＝7.9Hz,1H),7.87(td,J＝7.7,1.5Hz,1H),7.74(d,J＝8.8Hz,1H),7.30–7.22(m,1H),7.10(d,J＝2.6Hz,1H),6.99(dd,J＝8.7,2.6Hz,1H),6.40(d,J＝15.8Hz,1H),4.23(t,J＝6.7Hz,2H),3.84(s,3H),1.71(dq,J＝8.4,6.7Hz,2H),1.54–1.36(m,2H),0.97(t,J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ166.4,165.8,162.1,150.0,139.7,138.0,136.5,135.3,128.3,124.5,122.2,119.3,116.8,112.0,64.8,55.7,30.9,19.3,13.9.
HRMS(ESI)m/z:[M+Na]+Calcd.for C19H21NNaO4S:382.1083；found:382.1089。
characterization data for unreacted starting material 2d are as follows:
1H NMR(400MHz,CDCl3)δ8.53(dt,J＝4.6,1.5Hz,1H),8.07(dt,J＝7.9,1.1Hz,1H),7.89(td,J＝7.7,1.8Hz,1H),7.75–7.63(m,2H),7.32–7.27(m,1H),7.03–6.88(m,2H),3.80(s,3H).
13C NMR(101MHz,CDCl3)δ166.1,162.2,149.9,138.2,135.2,127.4,124.6,118.6,114.9,55.6。
examples 5 to 12
In examples 5-12, the olefin feed had the structural formula:
Other raw materials and reaction conditions were the same as in example 1.
Example 5 provides chiral styrylpyridyl sulfoxide product 1e (37% yield, 82% ee) and unreacted starting material 2a in the S-configuration (42% yield, 98% ee) with S-factor of 46, wherein product 1e has the formula:
characterization data for product 1e are as follows:
1H NMR(400MHz,CDCl3)δ8.49(d,J＝4.7Hz,1H),8.39(d,J＝15.7Hz,1H),8.05(d,J＝7.9Hz,1H),7.93–7.80(m,2H),7.62(dd,J＝7.4,1.7Hz,1H),7.52–7.39(m,2H),7.31–7.21(m,1H),6.34(d,J＝15.7Hz,1H),1.55(s,9H).
13C NMR(101MHz,CDCl3)δ165.3,149.7,138.5,137.8,134.4,131.2,130.3,126.8,125.3,124.4,123.5,119.0,102.3,80.7,59.7,28.0.
HRMS(ESI)m/z:[M+Na]+Calcd.for C18H19NNaO3S:352.0978；found:352.0983。
example 6 yields chiral styrylpyridyl sulfoxide product 1f (yield 49%,88% ee) and unreacted starting material 2a in the S-configuration (yield 50%,97% ee), S-factor 65, wherein the structural formula of product 1f is:
characterization data for product 1f are as follows:
melting point is 121.0-122.3 ℃.
1H NMR(400MHz,CDCl3)δ8.55–8.41(m,2H),8.02(dt,J＝7.9,1.1Hz,1H),7.95–7.81(m,2H),7.62(dd,J＝7.7,1.5Hz,1H),7.53–7.42(m,2H),7.31–7.23(m,1H),6.43(d,J＝15.8Hz,1H),4.42–4.31(m,2H),3.92(d,J＝4.7Hz,2H),2.70(s,1H).
13C NMR(101MHz,CDCl3)δ166.5,165.5,149.9,143.9,140.4,138.3,134.0,131.6,131.1,127.1,125.4,124.9,121.0,119.3,66.5,61.3.
HRMS(ESI)m/z:[M+Na]+Calcd.for C16H15NNaO4S:340.0615；found:340.0619。
Example 7 yields 1g (30% yield, 88% ee) of chiral styrylpyridinium sulfoxide product and 2a (42% yield, 91% ee) of unreacted starting material in the S-configuration, 50 for S-factor, wherein 1g of product has the formula:
Characterization data for product 1g are as follows:
1H NMR(400MHz,CDCl3)δ8.53(d,J＝15.8Hz,1H),8.44(d,J＝4.7Hz,1H),8.04(d,J＝7.9Hz,1H),7.91(dd,J＝7.7,1.6Hz,1H),7.83(td,J＝7.7,1.6Hz,1H),7.64(d,J＝7.4Hz,1H),7.55–7.48(m,1H),7.48–7.40(m,1H),7.30(t,J＝7.8Hz,2H),7.23(dd,J＝7.6,4.8Hz,1H),6.97(dd,J＝11.6,7.7Hz,3H),6.47(d,J＝15.8Hz,1H),4.60(t,J＝4.7Hz,2H),4.28(t,J＝4.7Hz,2H).
13C NMR(101MHz,CDCl3)δ166.6,165.8,159.0,150.3,144.4,140.9,138.4,134.6,131.9,131.3,130.0,127.5,126.0,125.0,121.7,121.4,119.6,115.1,66.4,63.6.
HRMS(ESI)m/z:[M+Na]+Calcd.for C22H19NNaO4S:416.0930；found:416.0932。
Example 8 yields the chiral styrylpyridyl sulfoxide product 1h (yield 44%,90% ee) and unreacted starting material 2a in the S-configuration (yield 51%,92% ee), S-factor 62, wherein the structural formula of product 1h is:
characterization data for product 1h are as follows:
Melting point 165.4-167.1 deg.c.
1H NMR(400MHz,CDCl3)δ8.69(d,J＝15.8Hz,1H),8.52–8.48(m,1H),8.08(dt,J＝8.0,1.0Hz,1H),7.97–7.91(m,1H),7.89(td,J＝7.7,1.8Hz,1H),7.73(dd,J＝7.4,1.7Hz,1H),7.54(dd,J＝7.4,5.7Hz,1H),7.49(dd,J＝7.4,1.7Hz,1H),7.46–7.38(m,2H),7.33–7.23(m,2H),7.23–7.17(m,2H),6.63(d,J＝15.8Hz,1H).
13C NMR(101MHz,CDCl3)δ165.5,164.8,150.9,150.0,144.2,141.8,138.2,134.1,131.7,131.2,129.6,127.3,126.0,125.8,124.7,121.7,120.8,119.2.
HRMS(ESI)m/z:[M+Na]+Calcd.for C20H15NNaO3S:372.0668；found:372.0670。
Example 9 yields chiral styrylpyridyl sulfoxide product 1i (37% yield, 90% de) and unreacted starting material 2a in the S-configuration (46% yield, 99% ee) with S-factor of 99, wherein the structural formula of product 1i is:
characterization data for product 1i are as follows:
1H NMR(400MHz,CDCl3)δ8.53–8.39(m,2H),8.04(dt,J＝7.9,1.1Hz,1H),7.92–7.83(m,2H),7.64(dd,J＝7.5,1.7Hz,1H),7.54–7.39(m,2H),7.32–7.21(m,1H),6.40(d,J＝15.7Hz,1H),4.82(td,J＝10.9,4.4Hz,1H),2.12–2.05(m,1H),1.94(pd,J＝6.9,2.6Hz,1H),1.79(s,1H),1.75–1.66(m,2H),1.60–1.43(m,2H),1.15–1.04(m,2H),0.97–0.92(m,3H),0.91(d,J＝1.5Hz,3H),0.80(d,J＝7.0Hz,3H).
13C NMR(101MHz,CDCl3)δ165.6,165.2,149.6,143.5,139.2,137.8,134.2,131.2,130.4,126.8,125.3,124.4,122.0,119.0,74.4,46.9,40.7,34.1,31.2,26.2,23.4,21.9,20.6,16.3.
HRMS(ESI)m/z:[M+Na]+Calcd.for C24H29NNaO3S:434.1763；found:434.1766。
Example 10 gives chiral styrylpyridyl sulfoxide product 1j (40% yield, 91% de) and unreacted starting material 2a of S-configuration (51% yield, 89% ee) with S-factor of 63, wherein the structural formula of product 1j is:
characterization data for product 1j are as follows:
1H NMR(400MHz,CDCl3)δ8.67(d,J＝15.8Hz,1H),8.49(d,J＝4.6Hz,1H),8.08(d,J＝7.9Hz,1H),7.98–7.90(m,1H),7.91–7.85(m,1H),7.72(dd,J＝7.3,1.8Hz,1H),7.52(pd,J＝7.4,1.6Hz,2H),7.33–7.24(m,1H),7.16(q,J＝8.5Hz,4H),6.61(d,J＝15.8Hz,1H),5.02(d,J＝8.2Hz,1H),4.59(q,J＝6.8Hz,1H),3.72(s,3H),3.21–3.00(m,2H),1.43(s,9H).
13C NMR(101MHz,CDCl3)δ172.4,165.5,164.7,155.2,150.0,149.9,144.2,141.8,138.2,134.1,133.8,131.6,131.2,130.4,127.3,125.7,124.7,121.8,120.7,119.2,80.2,54.5,52.4,37.8,29.8,28.4.
HRMS(ESI)m/z:[M+Na]+Calcd.for C29H30N2NaO7S:573.1663;found:573.1671.
Example 11 yields chiral styrylpyridyl sulfoxide product 1k (yield 36%,90% de) and unreacted starting material 2a of S-configuration (yield 53%,91% ee), S-factor 60, wherein the structural formula of product 1k is:
Characterization data for product 1k are as follows:
1H NMR(400MHz,CDCl3)δ8.66(d,J＝15.8Hz,1H),8.49(dd,J＝5.1,1.6Hz,1H),8.07(dt,J＝7.9,1.1Hz,1H),7.97–7.84(m,2H),7.72(dd,J＝7.3,1.8Hz,1H),7.51(td,J＝7.0,1.7Hz,2H),7.38–7.27(m,2H),6.99–6.89(m,2H),6.62(d,J＝15.8Hz,1H),2.94(dd,J＝9.0,4.2Hz,2H),2.51(dd,J＝18.8,8.6Hz,1H),2.47–2.38(m,1H),2.31(td,J＝10.9,4.1Hz,1H),2.22–1.92(m,4H),1.69–1.41(m,6H),0.92(s,3H).
13C NMR(101MHz,CDCl3)δ165.5,165.1,150.0,148.7,144.2,141.6,138.2,137.6,134.1,131.6,131.2,127.3,126.6,125.8,124.7,121.7,120.8,119.2,118.9,50.5,48.1,44.3,38.1,36.0,31.6,29.5,26.4,25.9,21.7,13.9.
HRMS(ESI)m/z:[M+Na]+Calcd.for C32H31NNaO4S:548.1870；found:548.1871。
Example 12 gives 1l (yield 35%,88% ee) of chiral styrylpyridyl sulfoxide product and 2a (yield 62%,73% ee) of unreacted starting material in S-configuration, S-factor 34, wherein the structural formula of product 1l is:
Characterization data for product 1l are as follows:
melting point is 106.0-107.3 ℃.
1H NMR(400MHz,CDCl3)δ8.46(d,J＝4.7Hz,1H),8.39(d,J＝16.2Hz,1H),8.04(d,J＝7.9Hz,1H),7.97–7.91(m,1H),7.91–7.83(m,1H),7.66(dd,J＝7.6,1.5Hz,1H),7.55–7.48(m,1H),7.46(t,J＝7.4Hz,1H),7.33–7.20(m,1H),6.65(d,J＝16.2Hz,1H),2.80(p,J＝7.6Hz,2H),1.20(t,J＝7.3Hz,3H).
13C NMR(101MHz,CDCl3)δ201.6,150.2,144.3,138.6,138.1,134.8,131.9,131.2,129.8,127.4,125.7,125.1,119.4,33.7,8.7.
HRMS(ESI)m/z:[M+Na]+Calcd.for C16H15NNaO2S:308.0716；found:308.0721。
Example 13
The structural formulas of the arylpyridylsulfoxide feedstock and the olefin feedstock in this example are shown below, respectively:
In a reactor, 0.2 mmol of racemic arylpyridylsulfoxide raw material, 0.2 mmol of olefin raw material, 0.02 mmol of palladium acetate catalyst, 0.04 mmol of L-pyroglutamic acid, 0.4 mmol of silver phosphate, 0.1 mmol of benzoquinone, 1 ml of isopropyl alcohol and 1 ml of toluene are added, and reacted for 12 hours at 60 ℃ under air atmosphere, after cooling, a layer of kieselguhr is filtered, washed, concentrated, and purified by preparative thin layer chromatography to petroleum ether: ethyl acetate = 2:1 as a developing reagent, 1m (yield: 37%,96% ee) of the chiral styrylpyridinium sulfoxide product and 2m (yield: 49%,99% ee) of the S-configuration unreacted starting material were obtained, and S-factor was 259.
The structural formulas of the product 1m and the unreacted S-configuration raw material 2m are respectively as follows:
Characterization data for product 1m are as follows:
Melting point is 95.6-96.5 ℃.
1H NMR(400MHz,CDCl3)δ8.50(dd,J＝4.9,1.7Hz,1H),8.32(d,J＝15.7Hz,1H),8.09(d,J＝7.9Hz,1H),7.92(td,J＝7.8,1.7Hz,1H),7.47(d,J＝8.6Hz,1H),7.35–7.29(m,1H),6.93(d,J＝2.4Hz,1H),6.77(dd,J＝8.6,2.4Hz,1H),6.24(d,J＝15.8Hz,1H),4.20(t,J＝6.7Hz,2H),1.76–1.64(m,2H),1.52–1.35(m,2H),0.95(t,J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ166.5,164.7,160.4,149.9,139.3,138.4,136.9,132.9,129.3,124.9,122.2,119.9,118.7,114.1,64.9,30.8,19.3,13.9..
HRMS(ESI)m/z:[M+Na]+Calcd.for C18H19NNaO4S:368.0928；found:368.0932。
Characterization data for unreacted starting material 2m are as follows:
1H NMR(400MHz,CDCl3)δ8.60–8.51(m,1H),8.13(dt,J＝7.9,1.1Hz,1H),7.95(td,J＝7.8,1.7Hz,1H),7.55–7.45(m,2H),7.44–7.27(m,1H),6.80–6.71(m,2H).
13C NMR(101MHz,CDCl3)δ165.1,159.4,149.5,138.3,133.8,128.1,124.6,118.8,116.4。
Examples 14 to 17
In examples 14-17, the aryl pyridinyl sulfoxide starting materials were:
other raw materials and reaction conditions were the same as in example 13.
Example 14 gives chiral styrylpyridyl sulfoxide product 1n (yield 25%,99% ee) and unreacted starting material 2n of the S-configuration (yield 54%,52% ee), S-factor 335, wherein the structural formulae of product 1n and unreacted starting material 2n are:
characterization data for product 1n are as follows:
melting point is 85.6-86.9 ℃.
1H NMR(400MHz,CDCl3)δ8.48(dd,J＝4.9,1.6Hz,1H),8.43(dd,J＝15.7,1.5Hz,1H),8.05(d,J＝8.0Hz,1H),7.94–7.81(m,2H),7.37–7.24(m,2H),7.14–7.19(m,1H),6.42(d,J＝15.8Hz,1H),4.24(t,J＝6.6Hz,2H),1.70(dq,J＝8.5,6.7Hz,2H),1.57–1.33(m,2H),0.97(t,J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ166.1,165.4,164.4(d,1JC-F＝253.9Hz),150.0,139.6,138.6,138.2,137.0(d,1JC-F＝8.7Hz),128.3(d,3JC-F＝9.5Hz),124.8,122.9,119.1,118.1(d,2JC-F＝22.6Hz),113.9(d,2JC-F＝23.1Hz),65.0,30.8,19.3,13.9.
19F NMR(376MHz,CDCl3)δ-107.78。
HRMS(ESI)m/z:[M+Na]+Calcd.for C18H18FNNaO3S:370.0886；found:370.0889。
Characterization data for unreacted starting material 2n are as follows:
1H NMR(400MHz,CDCl3)δ8.59–8.47(m,1H),8.04(dt,J＝7.9,1.1Hz,1H),7.88(td,J＝7.7,1.8Hz,1H),7.82–7.74(m,2H),7.35–7.28(m,1H),7.18–7.10(m,2H).
13C NMR(101MHz,CDCl3)δ165.4,164.2(d,1JC-F＝252.6Hz),149.6,139.3(d,4JC-F＝2.9Hz),138.0,127.1(d,3JC-F＝8.9Hz),124.6,118.1,116.3(d,2JC-F＝22.7Hz).
19F NMR(376MHz,CDCl3)δ-108.39。
Example 15 provides chiral styrylpyridyl sulfoxide product 1o (yield 25%,97% ee) and unreacted starting material 2o of S-configuration (yield 56%,55% ee), S-factor 114, wherein the structural formulae of product 1o and unreacted starting material 2o are:
Characterization data for product 1o are as follows:
melting point is 110.1-111.6 ℃.
1H NMR(400MHz,CDCl3)δ8.56–8.40(m,2H),8.27(d,J＝1.9Hz,1H),8.10(dt,J＝8.2,1.6Hz,1H),8.07–7.93(m,2H),7.93–7.74(m,1H),7.26(dd,J＝8.5,3.8Hz,1H),6.53(dd,J＝15.8,1.4Hz,1H),5.39–4.95(m,1H),4.25(tt,J＝6.7,1.7Hz,2H),1.72(dd,J＝15.5,8.1Hz,3H),1.50–1.41(m,2H),1.35(d,J＝6.3Hz,6H),0.97(td,J＝7.4,1.4Hz,3H).
13C NMR(101MHz,CDCl3)δ166.3,165.2,164.7,150.0,148.2,139.1,138.3,134.4,133.7,131.2,128.1,125.2,124.9,122.6,119.2,69.5,64.9,30.8,22.0,19.3,13.9.
HRMS(ESI)m/z:[M+Na]+Calcd.for C22H25NNaO5S:438.1348；found:438.1351。
Characterization data for unreacted starting material 2o is as follows:
1H NMR(400MHz,CDCl3)δ8.57–8.52(m,1H),8.15–8.06(m,2H),8.01(dt,J＝7.9,1.1Hz,1H),7.92–7.77(m,3H),7.34–7.28(m,1H),5.30–5.03(m,1H),1.33(d,J＝6.2Hz,6H).
13C NMR(101MHz,CDCl3)δ165.5,165.2,150.0,148.9,138.4,133.5,130.3,125.0,124.7,118.6,69.1,22.0.
example 16 gives chiral styrylpyridyl sulfoxide product 1p (yield 60%,42% ee) and unreacted starting material 2p of the S-configuration (yield 30%,96% ee), S-factor 9, wherein the structural formulae of product 1p and unreacted starting material 2p of the S-configuration are:
characterization data for product 1p are as follows:
1H NMR(400MHz,CDCl3)δ8.52(d,J＝15.8Hz,1H),8.48–8.41(dm,1H),8.18(dt,J＝8.0,1.0Hz,1H),7.87(td,J＝7.7,1.8Hz,1H),7.42–7.32(m,2H),7.29–7.20(m,2H),6.11(d,J＝15.8Hz,1H),4.16(td,J＝6.7,4.4Hz,2H),2.63(s,3H),1.76–1.56(m,2H),1.50–1.34(m,2H),0.96(t,J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ166.0,164.4,149.6,140.5,140.5,139.7,136.9,136.8,132.8,131.7,126.0,123.7,121.5,120.4,64.2,30.5,19.8,18.9,13.6.
HRMS(ESI)m/z:[M+Na]+Calcd.for C19H21NNaO3S:366.1136；found:366.1140。
Characterization data for unreacted starting material 2p are as follows:
1H NMR(400MHz,CDCl3)δ8.51–8.41(m,1H),7.99(dt,J＝8.0,1.1Hz,1H),7.82(td,J＝7.8,1.8Hz,1H),7.76–7.69(m,1H),7.30–7.20(m,3H),7.15(dd,J＝6.7,2.2Hz,1H),2.61(s,3H).
13C NMR(101MHz,CDCl3)δ166.4,149.7,142.9,138.2,137.7,131.2,131.1,127.1,124.7,119.1,19.5.
Example 17 gives chiral styrylpyridyl sulfoxide product 1q (yield 29%,96% ee) and unreacted starting material 2q of the S-configuration (yield 62%,53% ee), S-factor 83, wherein the structural formulae of product 1q and unreacted starting material 2q of the S-configuration are respectively:
characterization data for product 1q are as follows:
1H NMR(400MHz,CDCl3)δ8.72(d,J＝2.2Hz,1H),8.42(d,J＝15.8Hz,1H),8.23(d,J＝8.2Hz,1H),8.11(dd,J＝8.2,2.2Hz,1H),7.74(d,J＝8.1Hz,1H),7.47(d,J＝1.8Hz,1H),7.29(dd,J＝8.2,1.8Hz,1H),6.44(d,J＝15.7Hz,1H),4.24(t,J＝6.6Hz,2H),2.38(s,3H),1.69(dt,J＝8.5,6.8Hz,2H),1.50–1.40(m,2H),0.96(t,J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ170.3,166.5,146.9(q,3JC-F＝4.0Hz),142.6,140.0,139.6,135.4(q,3JC-F＝3.7Hz),134.4,131.8,127.9,127.3(q,2JC-F＝33.7Hz),125.6,121.8,123.0(q,1JC-F＝273.9Hz),118.9,64.8,30.8,21.5,19.3,13.9.
19F NMR(376MHz,CDCl3)δ-64.40。
HRMS(ESI)m/z:[M+Na]+Calcd.for C20H20F3NNaO3S:434.1011;found:434.1014.
Characterization data for unreacted starting material 2q are as follows:
1H NMR(400MHz,CDCl3)δ8.86–8.70(m,1H),8.22(d,J＝8.2Hz,1H),8.11(dd,J＝8.3,2.2Hz,1H),7.78–7.59(m,2H),7.27(d,J＝9.5Hz,1H),2.36(s,3H).
13C NMR(101MHz,CDCl3)δ170.5,146.8(q,3JC-F＝3.9Hz),142.4,140.1,135.5(q,3JC-F＝3.5Hz),130.2,127.8(q,2JC-F＝33.6Hz),125.2,123.0(q,1JC-F＝274.0Hz),118.4,21.6.
19F NMR(376MHz,CDCl3)δ-62.35。
Example 18
The structural formulas of the arylpyridylsulfoxide feedstock and the olefin feedstock in this example are shown below, respectively:
In a reactor, 0.2 mmol of racemic arylpyridylsulfoxide raw material, 0.2 mmol of olefin raw material, 0.02 mmol of palladium acetate catalyst, 0.04 mmol of L-pyroglutamic acid, 0.4 mmol of silver vanadate, 1.8 ml of isopropyl alcohol and 0.2 ml of toluene are added, and reacted for 12 hours at 60 ℃ under an air atmosphere, after cooling, a layer of kieselguhr is filtered, washed and concentrated, and then prepared by preparative thin layer chromatography, petroleum ether: ethyl acetate = 10:1 as a developing solvent, the chiral styrylpyridyl sulfoxide product 1S (yield 31%,91% ee) and unreacted starting material 2a of S-configuration (yield 49%,93% ee) were obtained, and S-factor was 72.
The structural formula of the product 1s is as follows:
Characterization data for product 1s are as follows:
1H NMR(400MHz,CDCl3)δ8.49(d,J＝4.6Hz,1H),8.02(d,J＝7.9Hz,1H),7.94(d,J＝16.1Hz,1H),7.89(dd,J＝7.7,1.6Hz,1H),7.83(td,J＝7.7,1.7Hz,1H),7.70(d,J＝7.6Hz,1H),7.58(d,J＝7.5Hz,2H),7.48–7.43(m,1H),7.40(dd,J＝8.3,6.7Hz,3H),7.34–7.28(m,1H),7.28–7.20(m,1H),7.06(d,J＝16.1Hz,1H).
13C NMR(101MHz,CDCl3)δ149.8,142.1,138.1,137.4,137.1,132.3,131.5,128.9,128.5,128.4,127.2,126.1,125.4,124.7,124.1,119.4,109.3.
HRMS(ESI)m/z:[M+Na]+Calcd.for C19H15NNaOS:328.0766；found:328.0772。
Examples 19 to 21
In examples 19-21, the olefin feed had the structural formula:
other raw materials and reaction conditions were the same as in example 18.
Example 19 gives chiral styrylpyridyl sulfoxide product 1t (yield 33%,90% ee) and unreacted starting material 2a in S-configuration (yield 48%,93% ee.) with S-factor of 65, wherein the structural formula of product 1t is:
characterization data for product 1t are as follows:
melting point 145.9-147.3 ℃.
1H NMR(400MHz,CDCl3)δ8.47(dd,J＝4.7,1.6Hz,1H),8.02(d,J＝7.9Hz,1H),7.96–7.78(m,3H),7.67(dd,J＝7.6,1.6Hz,1H),7.53–7.32(m,6H),7.30–7.21(m,1H),6.99(d,J＝16.1Hz,1H).
13C NMR(101MHz,CDCl3)δ166.4,150.0,142.4,138.4,137.3,135.8,134.3,131.8,131.2,129.4,129.0,128.6,126.4,125.7,125.0,119.6.
HRMS(ESI)m/z:[M+Na]+Calcd.for C19H14ClNNaOS:362.0379；found:362.0382。
Example 20 provides chiral styrylpyridyl sulfoxide product 1u (yield 37%,90% ee) and unreacted starting material 2a in the S-configuration (yield 53%,80% ee), S-factor 47, wherein the structural formula of product 1u is:
characterization data for product 1u are as follows:
1H NMR(400MHz,CDCl3)δ8.51(dd,J＝4.8,1.7Hz,1H),8.05(d,J＝7.9Hz,1H),8.00–7.82(m,3H),7.69(dd,J＝7.5,1.7Hz,1H),7.55(d,J＝1.9Hz,1H),7.51–7.41(m,3H),7.38–7.24(m,3H),7.00(d,J＝16.1Hz,1H).
13C NMR(101MHz,CDCl3)δ166.3,150.0,142.5,139.2,138.5,137.1,135.1,131.8,131.0,130.4,129.2,128.5,127.4,126.5,125.9,125.7,125.5,125.0,119.6.
HRMS(ESI)m/z:[M+Na]+Calcd.for C19H14ClNNaOS:362.0377；found:362.0382。
Example 21 gives chiral styrylpyridyl sulfoxide product 1v (29% yield, 95% ee) and unreacted starting material 2a in S-configuration (51% yield, 72% ee.) S-factor 84, wherein the structural formula of product 1v is:
characterization data for product 1v are as follows:
1H NMR(400MHz,CDCl3)δ8.49(dd,J＝4.9,1.7Hz,1H),8.11–7.99(m,2H),7.94–7.79(m,7H),7.75(dd,J＝7.7,1.4Hz,1H),7.54–7.36(m,4H),7.29–7.15(m,2H).
13C NMR(101MHz,CDCl3)δ166.0,149.8,141.9,138.1,137.3,134.5,133.7,133.4,132.3,131.5,128.6,128.5,128.3,127.9,127.6,126.6,126.4,126.0,125.4,124.7,124.3,123.8,119.4.
HRMS(ESI)m/z:[M+Na]+Calcd.for C23H17NNaOS:378.0924；found:378.0929。
Example 22
The structural formulas of the arylpyridylsulfoxide feedstock and the olefin feedstock in this example are shown below, respectively:
In a reactor, 0.2 mmol of racemic arylpyridylsulfoxide raw material, 0.4 mmol of olefin, 0.01 mmol of palladium acetate catalyst, 0.06 mmol of D-pyroglutamic acid, 0.6 mmol of silver phosphate, 1.8 ml of isopropyl alcohol and 0.4 ml of toluene are added, and reacted for 12 hours at 55 ℃ under air atmosphere, after cooling, a layer of kieselguhr is filtered, washed and concentrated, and then prepared by thin layer chromatography, petroleum ether: ethyl acetate = 4:1 is a developing agent, and the chiral styryl pyridyl sulfoxide product 1a (S-configuration) and the unreacted raw material 2a of R-configuration are obtained.
The structural formulas of the product 1a and the unreacted R-configuration raw material 2a are respectively as follows:
Example 23
The structural formulas of the arylpyridylsulfoxide feedstock and the olefin feedstock in this example are shown below, respectively:
In a reactor, 0.2 mmol of racemic arylpyridylsulfoxide raw material, 0.3 mmol of olefin, 0.06 mmol of palladium acetate catalyst, 0.08 mmol of L-pyroglutamic acid, 0.4 mmol of silver phosphate, 1.6 ml of isopropyl alcohol and 0.8 ml of toluene are added, and reacted for 12 hours at 55 ℃ under air atmosphere, after cooling, a layer of kieselguhr is filtered, washed and concentrated, and then prepared by thin layer chromatography with petroleum ether: ethyl acetate = 4:1 is a developing agent, and the chiral styryl pyridyl sulfoxide product 1a and an unreacted raw material 2a with S-configuration are obtained.
The structural formulas of the product 1a and the unreacted S-configuration raw material 2a are respectively as follows:
While the foregoing embodiments have been described in detail in connection with the embodiments of the invention, it should be understood that the foregoing embodiments are merely illustrative of the invention and are not intended to limit the invention, and any modifications, additions, substitutions and the like made within the principles of the invention are intended to be included within the scope of the invention.
Claims (3)
1. The synthesis method of the chiral styryl pyridyl sulfoxide is characterized by comprising the following steps of:
In a reactor, 0.2 mmol of racemic arylpyridylsulfoxide raw material, 0.2 mmol of olefin, 0.02 mmol of palladium acetate catalyst, 0.04 mmol of L-pyroglutamic acid, 0.4 mmol of silver phosphate, 1.8 ml of isopropyl alcohol and 0.2 ml of toluene are added, and reacted for 12 hours at 55 ℃ under an air atmosphere, cooled and filtered through a layer of kieselguhr, washed and concentrated, and then purified by preparative thin layer chromatography, petroleum ether: ethyl acetate = 4:1 is a developing agent to obtain the chiral styryl pyridyl sulfoxide product;
the structural formulas of the aryl pyridyl sulfoxide raw material and the olefin raw material are respectively The structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
2. The synthesis method of the chiral styryl pyridyl sulfoxide is characterized by comprising the following steps of:
In a reactor, 0.2 mmol of racemic arylpyridylsulfoxide raw material, 0.2 mmol of olefin raw material, 0.02 mmol of palladium acetate catalyst, 0.04 mmol of L-pyroglutamic acid, 0.4 mmol of silver phosphate, 0.1 mmol of benzoquinone, 1 ml of isopropyl alcohol and 1 ml of toluene are added, and reacted for 12 hours at 60 ℃ under air atmosphere, after cooling, a layer of kieselguhr is filtered, washed, concentrated, and purified by preparative thin layer chromatography to petroleum ether: ethyl acetate = 2:1 is a developing agent to obtain the chiral styryl pyridyl sulfoxide product;
the structural formulas of the aryl pyridyl sulfoxide raw material and the olefin raw material are respectively The structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
3. The synthesis method of the chiral styryl pyridyl sulfoxide is characterized by comprising the following steps of:
In a reactor, 0.2 mmol of racemic arylpyridylsulfoxide raw material, 0.2 mmol of olefin raw material, 0.02 mmol of palladium acetate catalyst, 0.04 mmol of L-pyroglutamic acid, 0.4 mmol of silver vanadate, 1.8 ml of isopropyl alcohol and 0.2 ml of toluene are added, and reacted for 12 hours at 60 ℃ under an air atmosphere, after cooling, a layer of kieselguhr is filtered, washed and concentrated, and then prepared by preparative thin layer chromatography, petroleum ether: ethyl acetate = 10:1 is a developing agent to obtain the chiral styryl pyridyl sulfoxide product;
the structural formulas of the aryl pyridyl sulfoxide raw material and the olefin raw material are respectively The structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
Or aryl pyridyl sulfoxide raw material and olefin raw material respectively have the structural formulasThe structural formula of the prepared chiral styryl pyridyl sulfoxide product is
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