CN115160369B - Selenium/sulfur compounds based on TADDOL framework and synthetic method thereof - Google Patents
Selenium/sulfur compounds based on TADDOL framework and synthetic method thereof Download PDFInfo
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- OWVIRVJQDVCGQX-VSGBNLITSA-N [(4r,5r)-5-[hydroxy(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)([C@H]1[C@@H](OC(O1)(C)C)C(O)(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 OWVIRVJQDVCGQX-VSGBNLITSA-N 0.000 title claims abstract description 55
- 238000010189 synthetic method Methods 0.000 title description 6
- 150000003343 selenium compounds Chemical class 0.000 title 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims abstract description 83
- 229910052711 selenium Inorganic materials 0.000 claims abstract description 73
- 239000011669 selenium Substances 0.000 claims abstract description 73
- 150000003464 sulfur compounds Chemical class 0.000 claims abstract description 72
- 229940065287 selenium compound Drugs 0.000 claims abstract description 63
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 31
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 claims abstract description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000001308 synthesis method Methods 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 114
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 45
- 150000003342 selenium Chemical class 0.000 claims description 30
- 229940125773 compound 10 Drugs 0.000 claims description 12
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 12
- 238000004440 column chromatography Methods 0.000 claims description 10
- 229940125904 compound 1 Drugs 0.000 claims description 8
- 229940125782 compound 2 Drugs 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 230000003197 catalytic effect Effects 0.000 claims description 4
- -1 sulphur compound Chemical class 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims 2
- 239000005909 Kieselgur Substances 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 abstract description 9
- 239000003054 catalyst Substances 0.000 abstract description 6
- 239000002879 Lewis base Substances 0.000 abstract description 4
- 150000007527 lewis bases Chemical class 0.000 abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- 238000006555 catalytic reaction Methods 0.000 description 22
- 239000000047 product Substances 0.000 description 15
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 13
- 238000001228 spectrum Methods 0.000 description 11
- 238000004821 distillation Methods 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 229940126214 compound 3 Drugs 0.000 description 7
- 229940125898 compound 5 Drugs 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- RBMPPNCUEPFZNR-UHFFFAOYSA-N P(=O)(N)(N)N.[Se] Chemical compound P(=O)(N)(N)N.[Se] RBMPPNCUEPFZNR-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 125000003944 tolyl group Chemical group 0.000 description 3
- 239000007848 Bronsted acid Substances 0.000 description 2
- 241000790917 Dioxys <bee> Species 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-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
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000008300 phosphoramidites Chemical class 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical group C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 description 1
- WNHPMKYMPWMAIT-UHFFFAOYSA-N 3,4,5,6-tetrahydro-2h-azepine Chemical compound C1CCC=NCC1 WNHPMKYMPWMAIT-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000006668 aldol addition reaction Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/6574—Esters of oxyacids of phosphorus
- C07F9/65744—Esters of oxyacids of phosphorus condensed with carbocyclic or heterocyclic rings or ring systems
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- 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
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
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- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
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- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
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Abstract
The invention discloses a selenium/sulfur compound based on a TADDOL framework and a synthesis method thereof, belonging to the technical field of catalyst synthesis, wherein the selenium/sulfur compound based on the TADDOL framework is shown as a formula (I); the synthesis method of the selenium/sulfur compound based on the TADDOL framework comprises the steps of dissolving chiral TADDOL derivative phosphoramide shown in a formula (II) in an organic solvent, adding selenium powder or sulfur powder, and stirring for reaction to obtain the selenium/sulfur compound. The selenium/sulfur compound based on the TADDOL framework can be used as Lewis base to catalyze more organic synthesis reactions.
Description
Technical Field
The invention belongs to the technical field of catalyst synthesis, and particularly relates to a selenium/sulfur compound based on a TADDOL framework and a synthesis method thereof.
Background
TADDOL [ (4R, 5R) -2,2-dimethyl-alpha, alpha' -tetraphenyl-1,3-dioxolane-4,5-dimethanol]Is a novel Bronsted acid, and the structure of the Bronsted acid can be roughly divided into the following two types: TADDOL having a chiral tartaric acid skeleton structure and TADDOL having a BINOL skeleton structure. TADDOL is used as a ligand in a number of applications including catalytic and Lewis acid mediated enantioselective reactions, including nucleophilic addition to aldehydes as well as ketone and cyanohydrin addition, aldol addition, diels-Alder reactions, (2+2) cycloaddition and olefinic reactions. Chiral and achiral mono-and bidentate phosphites, phosphonates and phosphonates have been used for many different types of transition metal catalyzed reactions, whereas TADDOL is concerned with polar metals (alkali metals, early transition metals), especially titanium and magnesium, as expected from ligands binding to the alcohol oxygen. The principle is as follows: although the distance between two OH groups in the TADDOL is very close, intramolecular hydrogen bonds are not formed, so that the TADDOL is easy to form inclusion compound with a reaction product to form crystalline salt when participating in a catalytic reaction, and the high-melting-point TADDOL is removed through racemization distillation, so that a racemic mixed product is separated, and the TADDOL is used as a Lewis acid to improve the reaction activity, thereby achieving the purpose of chiral catalysis. For example, the prior art is disclosed in publication No. CN 114478337 A, a catalyst 3,3' -disubstituted binaphthyl derivative selenide catalyst for synthesizing axial chiral sulfur-containing diaryl derivatives, shown as formula (IV), and a synthesis method of the catalyst
。
Disclosure of Invention
The invention aims to provide a synthetic method of a selenium/sulfur compound based on a TADDOL framework, which is simple in experimental operation, economical and available in raw materials and mild in reaction conditions, and the prepared compound has a wide application range and good economical efficiency and catalytic performance.
The structural formula of the technical scheme adopted by the invention for realizing the purpose is as follows:
a selenium/sulfur compound based on TADDOL framework is shown in formula (I),
The selenium/sulfur compound based on the TADDOL framework belongs to a catalyst in the field of rich organic micromolecule catalysis, has better economy and catalytic performance, can be used as a Lewis base to catalyze more organic synthesis reactions, has chiral induction capability, achieves the aim of chiral catalysis, and further widens the ligand library of organic catalysis.
Optionally, the selenium/sulfur compound is selected from the following compound 1, compound 2, compound 3, compound 4, compound 5 or compound 6;
the invention also provides a synthesis method of the selenium/sulfur compound based on the TADDOL framework, which comprises the steps of oxidizing chiral TADDOL-derived phosphoramide shown in the formula (II) in an organic solvent by selenium powder or sulfur powder to obtain the selenium/sulfur compound;
The synthesis method realizes the synthesis of the selenium/sulfur compound of the TADDOL-derived phosphoramide for the first time by oxidizing the sulfur powder or the selenium powder of the TADDOL-derived phosphoramide; the synthesis method adopts an economically available TADDOL derived phosphoramidite substrate, the product is prepared by one-step reaction, the reaction operation is simple, the reaction condition is mild, a complex synthesis route is avoided in the process, and the yield of the selenium/sulfur compound based on the TADDOL framework is high and is higher than 80%; the chiral TADDOL derived phosphoramide selenium/sulfur compound synthesized by the synthesis method can be used as Lewis base to catalyze more organic synthesis reactions.
Optionally, the chiral TADDOL derivative phosphoramide shown in the formula (II) is selected from the following compound II-1, compound II-2 or compound II-3;
optionally, the organic solvent is selected from toluene, tetrahydrofuran, dimethyl sulfoxide, cyclohexane, dichloromethane or chloroform.
Optionally, the molar ratio of the chiral TADDOL-derived phosphoramide and selenium powder shown in the formula (II) is 1:2-5, or the molar ratio of the chiral TADDOL-derived phosphoramide and sulfur powder shown in the formula (II) is 1:2-5.
Alternatively, the yield of selenium/sulfur compounds is > 80%.
Optionally, the synthetic route of the selenium/sulfur compound is,
Optionally, the synthetic method of the selenium/sulfur compound comprises the following steps: dissolving chiral TADDOL derivative phosphoramide shown in formula (II) in dichloromethane, adding selenium powder or sulfur powder at room temperature, stirring for reaction, filtering with diatomite, distilling under reduced pressure, and purifying with column chromatography to obtain the compound.
Optionally, reacting for 2-72h.
The invention also provides application of the selenium/sulfur compound in catalysis of chiral compound synthesis reaction.
The invention also provides the selenium/sulfur compound and BF 3 Use of THF in catalysis of chiral compound synthesis reactions.
Optionally, selenium/sulfur compounds and BF 3 THF was used to catalyze the synthesis of chiral compounds 7 and 8 (-)-9；
The selenium/sulfur compound and the chiral isothiourea are used for concerted catalysis of the compound 7 and the compound 8 to synthesize a chiral compound (-) -9, and respective effects can be exerted in the reaction process, so that the chiral compound (-) -9 is obtained.
Optionally, the yield of the chiral compound (-) -9 is more than or equal to 50%.
Optionally, of the chiral compound (-) -9α] D 20 ≤-8.00。
Optionally, the ee of the chiral compound (-) -9 is at least 15%.
The invention also provides a synthetic method of the chiral compound (-) -9, which has the synthetic route of,
Alternatively, a process for the synthesis of the chiral compound (-) -9 comprising reacting compound 7 and compound 8 in an organic solvent with the above selenium/sulfur compound and BF 3 THF reaction gave the chiral compound (-) -9.
Alternatively, the molar ratio of compound 7 to compound 8 is 1.2 to 1.8.
Alternatively, compound 7 and BF 3 The molar ratio of THF is from 1.5 to 1.5.
Optionally, selenium/sulfur compounds and BF 3 The molar ratio of THF was 1:5-15.
Optionally, the organic solvent is selected from toluene, tetrahydrofuran, dimethyl sulfoxide, cyclohexane, dichloromethane or chloroform.
Alternatively, the dosage ratio of the compound 7 to the organic solvent is 1mmol.
Optionally, the reaction temperature is room temperature, and the reaction time is 1-3d.
The invention also provides the application of the selenium/sulfur compound and the chiral compound 10 in the catalytic synthesis reaction of chiral compounds;
。
the invention also provides the selenium/sulfur compound, the chiral compound 10 and BF 3 Use of THF in catalysis of chiral compound synthesis reactions.
Optionally, a selenium/sulfur compound, a chiral compound 10 and BF 3 THF is used for catalyzing compound 7 and compound 8 to synthesize chiral compound (-) -9;
the selenium/sulfur compound and the chiral compound 10 can synergistically catalyze the reaction of the compound 7 and the compound 8, and the specific optical rotation value and the ee value of the chiral compound (-) -9 can be improved.
Optionally, the yield of the chiral compound (-) -9 is more than or equal to 50%.
Optionally, of the chiral compound (-) -9α] D 20 ≤-12.00。
Optionally, the chiral compound (-) -9 has an ee of at least 24%.
The invention also provides a synthetic method of the chiral compound (-) -9, which has the synthetic route of,
Alternatively, a process for the synthesis of the chiral compound (-) -9 comprising reacting the compound 7 and the compound 8 in an organic solvent with the selenium/sulfur compound, the chiral compound 10 and BF described above 3 THF reaction gave the chiral compound (-) -9.
Alternatively, the molar ratio of compound 7 to compound 8 is 1.2 to 1.8.
Alternatively, compound 7 and BF 3 The molar ratio of THF is from 1.5 to 1.5.
Optionally, selenium/sulfur compounds and BF 3 The molar ratio of THF was 1:5-15.
Optionally, the molar ratio of selenium/sulfur compound to chiral compound 10 is 1.2-0.6.
Optionally, the organic solvent is selected from toluene, tetrahydrofuran, dimethylsulfoxide, cyclohexane, dichloromethane, or chloroform.
Alternatively, the amount ratio of the compound 7 to the organic solvent is 1mmol.
Optionally, the reaction temperature is room temperature, and the reaction time is 1-3d.
Compared with the prior art, the invention has the following beneficial effects: the method realizes the synthesis of the selenium/sulfur compound of the TADDOL-derived phosphoramide for the first time by oxidizing the sulfur powder or the selenium powder of the TADDOL-derived phosphoramide; the method adopts an economically available TADDOL derived phosphoramidite substrate, the product is prepared by one-step reaction, the reaction operation is simple, and a complex synthetic route is avoided in the process; the chiral TADDOL-derived phosphoramide selenium/sulfur compound can be used as a Lewis base to catalyze more organic synthesis reactions.
Drawings
FIG. 1 is the NMR spectrum of selenium/sulfur compound obtained in example 1;
FIG. 2 is the NMR spectrum of selenium/sulfur compound obtained in example 1;
FIG. 3 is the NMR spectrum of selenium/sulfur compound obtained in example 2;
FIG. 4 is the NMR spectrum of selenium/sulfur compound obtained in example 2;
FIG. 5 is the NMR spectrum of selenium/sulfur compound obtained in example 3;
FIG. 6 is the NMR spectrum of selenium/sulfur compound obtained in example 3;
FIG. 7 is the NMR spectrum of selenium/sulfur compound obtained in example 4;
FIG. 8 is the NMR C-spectrum of selenium/sulfur compound obtained in example 4;
FIG. 9 is the NMR chart of selenium/sulfur compound obtained in example 5;
FIG. 10 is the NMR spectrum of selenium/sulfur compound obtained in example 5;
FIG. 11 is the NMR spectrum of selenium/sulfur compound obtained in example 6;
FIG. 12 is the NMR spectrum of selenium/sulfur compound obtained in example 6;
FIG. 13 shows the yields of selenium/sulfur compounds from examples 1-6.
Detailed Description
The present invention is described in further detail below with reference to specific embodiments, which are given for the purpose of illustration only and are not intended to limit the scope of the invention. The examples provided below serve as a guide for further modifications by a person skilled in the art and do not constitute a limitation of the invention in any way.
In the following examples, the experimental methods, unless otherwise specified, are conventional. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
In the present embodiment, it is preferred that, nuclear magnetic resonance spectrum of compound ( 1 H NMR、 13 C NMR) was determined from Bruker AVANCE III HD 400, the solvent was deuterated chloroform. Chemical shifts (δ) are quoted in ppm, with tetramethylsilane as internal standard, multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet.
Example 1:
preparation of selenium/sulfur compounds (compound 1) based on TADDOL framework
40 mg chiral (3AR, 8AR) - (-) - (2,2-dimethyl-4,4,8,8-tetraphenyl-tetrahydro- [1,3]Dioxy [4,5-E][1,3,2]Phosphorus dioxide-6-YL) dimethylamine (0.07 mmol, 1.0 equiv) is dissolved in 0.6 mL dichloromethane, selenium powder (17.6 mg, 0.22 mmol, 3.0 equiv) is added into the dichloromethane at room temperature, stirring is carried out at room temperature for reaction overnight, and then reduced pressure distillation and column chromatography purification are carried out to prepare the selenium/sulfur compound (compound 1) based on the TADDOL framework, wherein the yield is 82%, the nuclear magnetic resonance hydrogen spectrum is shown in figure 1, and the nuclear magnetic resonance carbon spectrum is shown in figure 2. 1 H NMR (400 MHz, CDCl 3 ) δ 7.69 – 7.49 (m, 6H), 7.44 – 7.22 (m, 14H), 5.67 (d, J = 7.9 Hz, 1H), 5.20 (d, J = 7.9 Hz, 1H), 2.65 (d, J = 13.2 Hz, 6H), 0.65 (s, 3H), 0.57 (s, 3H); 13 C NMR(101 MHz, CDCl 3 ) δ 144.89, 144.86, 142.55, 141.15, 141.06, 140.24, 140.18, 130.20, 128.69, 128.38, 128.30, 128.25, 128.12, 127.91, 127.70, 127.33, 127.25, 114.25, 92.40, 92.25, 87.36, 87.30, 79.65, 79.63, 78.50, 78.47, 65.99, 37.99, 37.94, 26.89, 26.80, 15.41。
Example 2:
preparation of selenium/sulfur compounds (compound 2) based on TADDOL framework
40 mg chiral (3AR, 8AR) - (-) - (2,2-dimethyl-4,4,8,8-tetraphenyl-tetrahydro- [1,3]Dioxy [4,5-E][1,3,2]Phosphorus dioxide-6-YL) dimethylamine (0.07 mmol, 1.0 equiv) is dissolved in 0.6 mL dichloromethane, sulfur powder (7.1 mg, 0.22 mmol, 3.0 equiv) is added into the dichloromethane at room temperature, the mixture is stirred and reacted for two hours at room temperature, and then the selenium/sulfur compound (compound 2) based on TADDOL framework is prepared by reduced pressure distillation and column chromatography purification, the yield is 99 percent, the nuclear magnetic resonance hydrogen spectrum is shown in figure 3, and the nuclear magnetic resonance carbon spectrum is shown in figure 4. 1 H NMR (400 MHz, CDCl 3 ) δ 7.67 – 7.58 (m, 2H), 7.53 (tt, J = 6.2, 1.5 Hz, 4H), 7.42 – 7.13 (m, 14H), 5.65 (d, J = 7.9 Hz, 1H), 5.15 (d, J = 7.9 Hz, 1H), 2.67 (d, J = 12.7 Hz, 6H), 0.71 (s, 3H), 0.57 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 145.12, 145.08, 143.15, 141.07, 140.97, 140.35, 140.30, 130.12, 128.74, 128.32, 128.18, 127.93, 127.90, 127.85, 127.64, 127.30, 127.25, 127.21, 113.84, 91.24, 91.11, 86.42, 86.36, 79.82, 79.80, 78.47, 78.44, 37.75, 37.70, 26.89, 26.78。
Example 3:
preparation of selenium/sulfur compounds (compound 3) based on TADDOL framework
50 mg chiral 1- [ (3AR, 8AR) -tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxazolo [4,5-E][1,3,2]Diphosphin-6-yl radical]Pyridine (0.09 mmol, 1.0 equiv) is dissolved in 0.5 mL dichloromethane, selenium powder (21.0 mg, 0.27 mmol, 3.0 equiv) is added into the pyridine under the condition of room temperature, the mixture is stirred and reacted for four hours under the condition of room temperature, and then the selenium/sulfur compound (compound 3) based on TADDOL framework is prepared by reduced pressure distillation and column chromatography purification, the yield is 98 percent, the hydrogen spectrum of nuclear magnetic resonance is shown in figure 5, and the carbon spectrum of nuclear magnetic resonance is shown in figure 6. The yield was 98%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.55 – 7.37 (m, 6H), 7.35 – 7.22 (m, 6H), 7.21-7.14 (m, 8H), 5.56 (d, J = 7.9 Hz, 1H), 5.19 (d, J = 7.7 Hz, 1H), 3.26 – 3.05 (m, 2H), 2.98-2.91 (m, 2H), 1.79 – 1.54 (m, 2H), 1.54 – 1.34 (m, 2H), 0.49 (d, J = 20.6 Hz, 6H); 13 C NMR (101 MHz, CDCl 3 ) δ 144.77, 144.75, 142.36, 141.28, 141.18, 140.33, 140.25, 129.85, 128.63, 128.38, 128.30, 128.27, 128.20, 127.91, 127.64, 127.61, 127.23, 127.19, 127.17, 114.56, 91.64, 91.48, 87.80, 87.74, 79.52, 79.50, 78.58, 78.55, 48.37, 48.31, 26.84, 26.70, 26.25, 26.16。
Example 4:
preparation of selenium/sulfur compounds (compound 4) based on TADDOL framework
50 mg chiral 1- [ (3AR, 8AR) -tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxazolo [4,5-E][1,3,2]Diphosphin-6-yl radical]Pyridine (0.09 mmol, 1.0 equiv) is dissolved in 0.5 mL dichloromethane, sulfur powder (8.5 mg, 0.27 mmol, 3.0 equiv) is added into the pyridine under the condition of room temperature, the mixture is stirred and reacted for four hours under the condition of room temperature, and then the selenium/sulfur compound (compound 4) based on TADDOL framework is prepared by reduced pressure distillation and column chromatography purification, the yield is 99 percent, the hydrogen nuclear magnetic resonance spectrum is shown in figure 7, and the carbon nuclear magnetic resonance spectrum is shown in figure 8. 1 H NMR (400 MHz, CDCl 3 ) δ 7.68 – 7.36 (m, 6H), 7.36 – 7.06 (m, 14H), 5.56 (d, J = 7.9 Hz, 1H), 5.13 (d, J = 7.9 Hz, 1H), 3.21-3.15 (m, 2H), 2.98-2.92 (m, 2H), 1.74 – 1.44 (m, 4H), 0.59 (s, 3H), 0.46 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 145.10, 145.07, 143.01, 141.21, 141.11, 140.45, 140.39, 129.88, 128.70, 128.31, 128.15, 128.02, 127.91, 127.60, 127.58, 127.20, 114.11, 90.55, 90.42, 86.80, 86.74, 79.75, 79.72, 78.58, 78.56, 48.03, 47.98, 26.82, 26.75, 26.42, 26.32。
Example 5:
preparation of selenium/sulfur compounds (compound 5) based on TADDOL framework
50 mg chiral 5- ((3AS, 8AS) -2,2-dimethyl-4,4,8,8-tetraphenyltetrahydro- [1,3]Dioxol [4,5-E][1,3,2]Dioxyphosphohept-6-yl) -5H dibenzo [ B, F]Azetiheptene (0.07 mmol, 1.0 equiv) is dissolved in 0.5 mL dichloromethane, selenium powder (17.2 mg, 0.22 mmol, 3.0 equiv) is added into the mixture under room temperature condition, the mixture is stirred and reacted for three days under room temperature, and then the selenium/sulfur compound (compound 5) based on TADDOL framework is prepared by reduced pressure distillation and column chromatography purification, the yield is 99%, the nuclear magnetic resonance hydrogen spectrum is shown in figure 9, and the nuclear magnetic resonance carbon is shown in figure 9The spectra are shown in FIG. 10. 1 H NMR (400 MHz, CDCl 3 ) δ 7.77 – 7.66 (m, 2H), 7.52-7.48 (m, 3H), 7.45-7.39 (m, 5H), 7.38 – 7.20 (m, 11H), 7.20 – 7.11 (m, 1H), 7.08 – 6.96 (m, 3H), 6.94 – 6.83 (m, 2H), 6.57 – 6.44 (m, 3H), 5.65 (d, J = 8.0 Hz, 1H), 4.90 (d, J = 8.0 Hz, 1H), 0.77 (s, 3H), 0.40 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 145.51, 145.46, 142.74, 142.41, 142.29, 141.27, 141.25, 140.69, 140.60, 140.14, 140.10, 136.72, 136.69, 136.43, 136.40, 131.32, 130.66, 130.46, 130.21, 130.18, 129.54, 129.40, 129.39, 129.22, 129.00, 128.97, 128.74, 128.56, 128.55, 128.31, 128.27, 127.96, 127.88, 127.78, 127.76, 127.72, 127.37, 127.24, 127.21, 127.17, 127.03, 126.88, 113.65, 93.00, 92.85, 87.92, 87.86, 79.46, 79.44, 78.65, 78.62, 27.11, 26.52。
Example 6:
preparation of selenium/sulfur compounds (compound 6) based on TADDOL framework
50 mg chiral 5- ((3AS, 8AS) -2,2-dimethyl-4,4,8,8-tetraphenyltetrahydro- [1,3]Dioxaphene [4,5-E][1,3,2]Dioxyphosphohept-6-yl) -5H dibenzo [ B, F]The azacycloheptene (0.07 mmol, 1.0 equiv) is dissolved in 0.5 mL dichloromethane, sulfur powder (7.0 mg, 0.22 mmol, 3.0 equiv) is added into the mixture at room temperature, the mixture is stirred and reacted for eight hours at room temperature, and then the selenium/sulfur compound (compound 6) based on the TADDOL framework is prepared by reduced pressure distillation and column chromatography purification, wherein the yield is 99%, the nuclear magnetic resonance hydrogen spectrum is shown in figure 11, and the nuclear magnetic resonance carbon spectrum is shown in figure 12. 1 H NMR (400 MHz, CDCl 3 ) δ 7.78 – 7.67 (m, 2H), 7.50 (tt, J = 7.9, 1.6 Hz, 3H), 7.43 – 7.33 (m, 6H), 7.40-7.19 (m, 10H), 7.18 – 7.12 (m, 1H), 7.07 (dd, J = 8.4, 6.8 Hz, 2H), 6.98 (td, J = 7.6, 1.8 Hz, 1H), 6.95 – 6.83 (m, 2H), 6.73 – 6.64 (m, 1H), 6.64 – 6.55 (m, 2H), 5.59 (d, J = 8.0 Hz, 1H), 4.86 (d, J = 8.0 Hz, 1H), 0.82 (s, 3H), 0.38 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 145.50, 145.44, 143.24, 142.20, 142.10, 141.46, 141.43, 140.74, 140.64, 140.25, 140.22, 136.69, 136.67, 136.28, 136.24, 131.25, 130.65, 130.46, 130.00, 129.45, 129.39, 129.16, 129.01, 128.84, 128.74, 128.20, 128.11, 127.85, 127.78, 127.67, 127.61, 127.37, 127.15, 127.11, 127.06, 126.83, 113.32, 91.58, 91.46, 87.25, 87.20, 79.56, 78.70, 78.68, 27.20, 26.40。
FIG. 13 is the yield of selenium/sulfur based compounds of examples 1-6, wherein S1 is the selenium/sulfur based compound of example 1, S2 is the selenium/sulfur based compound of example 2, S3 is the selenium/sulfur based compound of example 3, S4 is the selenium/sulfur based compound of example 4, S5 is the selenium/sulfur based compound of example 5, and S6 is the selenium/sulfur based compound of example 6. As can be seen, the yield of selenium/sulfur compound in examples 1-6 was > 80%.
Example 7:
selenium/Sulfur Compound (Compound 1, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
All of Compound 7 (0.05 mmol, 1.0 equiv, cas No.: 2411582-25-5), compound 8 (0.075 mmol, 1.5 equiv, cas No.: 1255094-08-6), BF, and 3 THF (0.05 mmol, 1.0 equiv) and Compound 1 (0.005 mmol, 0.1 equiv) were added to a reaction tube, 1mL of methylene chloride was added thereto, the reaction was stirred at room temperature for two days, and then subjected to distillation under reduced pressure and column chromatography purification to give chiral product (-) -9 in 54% yieldα] D 20 = -15.58 (c = 0.6, CHCl 3 )。 1 H NMR (400 MHz, CDCl 3 ) δ 8.21-8.19 (d, 1H), 7.78-7.69(m, 1H), 7.62-7.51 (m, 3H), 7.40-7.35(m, 1H), 7.31-7.18 (m, 2H), 7.00-6.94(d, 1H), 7.51-6.42(d, 1H), 5.12 (s, 2H)； 13 C NMR (101 MHz, CDCl 3 ) δ 154.46, 153.14, 141.57, 136.22, 133.74, 132.51, 132.11, 131.45, 130.86, 129.14, 128.85, 128.77, 126.25, 125.14, 113.33, 112.54, 109.13, 108.47. Carrying out chiral resolution on the protein by HPLC, wherein the model of a chromatographic Column is Chiralcel Column ID, the temperature of the chromatographic Column is 30 ℃, the mobile phase is n-hexane, i-PrOH =70, the flow rate is 1mL/min, and the secondary retention time is as follows: 11.56 min, main retention time: 9.65 min, er = 35, ee value is 30%.
Example 8:
selenium/Sulfur Compound (Compound 2, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 7 is that the compound used is Compound 2, and the chiral product (-) -9 is obtained in 53% yieldα] D 20 = -9.27 (c = 0.6, CHCl 3 ) And er = 36, the ee value is 28%.
Example 9:
selenium/Sulfur Compounds (Compound 3, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 7 is that the compound used is Compound 3, the yield of the chiral product 9 is 53%, [ 2 ]α] D 20 = -10.15 (c = 0.6, CHCl 3 ) And er = 40, the ee value is 20%.
Example 10:
selenium/Sulfur Compound (Compound 4, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 7 is that the compound used is Compound 4, and the chiral product (-) -9 is obtained in a yield of 50%, [ 2 ]α] D 20 = -8.33 (c = 0.6, CHCl 3 ) And er = 42, the ee value is 16%.
Example 11:
selenium/Sulfur Compound (Compound 5, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 7 is that the compound used is Compound 5, and the chiral product (-) -9 is obtained in 52% yieldα] D 20 = -12.86 (c = 0.6, CHCl 3 ) And er = 40, the ee value is 20%.
Example 12:
selenium/Sulfur Compound (Compound 6, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 7 is that the compound used is Compound 6, and the chiral product (-) -9 is obtained in 51% yieldα] D 20 = -10.40 (c = 0.6, CHCl 3 ) And er = 41, the ee value is 18%.
From examples 7 to 12, it can be seen that the selenium/sulfur compounds of examples 1 to 6 are capable of catalyzing the synthesis of the chiral compound (-) -9 from the compound 7 and the compound 8, the yield of the chiral compound (-) -9 is not less than 50%, and the chiral compound (-) -9 isα] D 20 Less than or equal to-8.00, and ee of the chiral compound (-) -9 is at least 15 percent. This demonstrates that the chiral TADDOL derivatized phosphoramide selenium/sulfur compounds of the invention can be used to catalyze the synthesis of chiral compounds.
Example 13:
selenium/Sulfur Compound (Compound 1, LB), chiral Compound 10 and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
All of Compound 7 (0.05 mmol, 1.0 equiv), compound 8 (0.075 mmol, 1.5 equiv), BF were added 3 THF (0.05 mmol, 1.0 equiv), compound 1 (0.005 mmol, 0.1 equiv) and chiral Compound 10 (0.0025 mmol, 0.05 equiv) were added to a reaction tube, 1mL of dichloromethane was added thereto, the reaction was stirred at room temperature for two days, and then, after distillation under reduced pressure and purification by column chromatography, chiral product (-) -9 was obtained in 56% yieldα] D 20 = -18.17 (c = 0.6, CHCl 3 ) And er = 32,ee value is 36%.
Example 14:
selenium/Sulfur Compound (Compound 2, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 13 is that the compound used is Compound 2, and the chiral product (-) -9 is obtained in 56% yieldα] D 20 = -13.36 (c = 0.6, CHCl 3 ) And er = 33, the ee value is 34%.
Example 15:
selenium/Sulfur Compound (Compound 3, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 13 is that the compound used is Compound 3, the yield of the chiral product 9 is 55%, [ 2 ]α] D 20 = -12.97 (c = 0.6, CHCl 3 ) And er = 35,ee value is 30%.
Example 16:
selenium/Sulfur Compounds (Compound 4, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 13 is that the compound used is Compound 4, and the chiral product (-) -9 is obtained in 53% yieldα] D 20 = -12.04 (c = 0.6, CHCl 3 ) And er = 38, the ee value is 24%.
Example 17:
selenium/Sulfur Compound (Compound 5, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 13 is that the compound used is Compound 5, and the chiral product (-) -9 is obtained in 54% yieldα] D 20 = -15.75 (c = 0.6, CHCl 3 ) And er = 34, the ee value is 32%.
Example 18:
selenium/Sulfur Compound (Compound 6, LB) and BF 3 Use of THF in the catalysis of the synthesis of chiral compounds
The difference from example 13 is that the compound used is Compound 6, and the chiral product (-) -9 is obtained in 52% yieldα] D 20 = -14.86 (c = 0.6, CHCl 3 ) And er = 37,ee value is 26%.
From examples 7 to 12, it can be seen that the selenium/sulfur compounds and the chiral compound 10 of examples 1 to 6 can synergistically catalyze the compound 7 and the compound 8 to synthesize the chiral compound (-) -9, the yield of the chiral compound (-) -9 is not less than 50%, and the chiral compound (-) -9 has the value ofα] D 20 Less than or equal to-12.00, and ee of the chiral compound (-) -9 is at least 24 percent. This shows that the selenium/sulfur compound and the chiral compound 10 of the present invention can synergistically catalyze the reaction of the compound 7 and the compound 8, and can improve the specific optical rotation value and the ee value of the chiral compound (-) -9.
Conventional operations in the operation steps of the present invention are well known to those skilled in the art and will not be described herein.
The embodiments described above are intended to illustrate the technical solutions of the present invention in detail, and it should be understood that the above-mentioned embodiments are only specific embodiments of the present invention, and are not intended to limit the present invention, and any modification, supplement or similar substitution made within the scope of the principles of the present invention should be included in the protection scope of the present invention.
Claims (11)
1. A selenium/sulfur compound based on TADDOL framework, which is selected from the following compound 1 or compound 2;
2. the synthesis method of the selenium/sulfur compounds based on the TADDOL framework, as claimed in claim 1, comprises dissolving chiral TADDOL-derived phosphoramide in dichloromethane, adding selenium powder or sulfur powder at room temperature, continuing stirring for reaction for 2-72h, filtering with diatomaceous earth, distilling under reduced pressure, and purifying with column chromatography to obtain compounds;
the molar ratio of the chiral TADDOL derived phosphoramide to the selenium powder is 1:2-5, or the molar ratio of the chiral TADDOL derived phosphoramide to the sulfur powder is 1:2-5;
the chiral TADDOL derivative phosphoramide is selected from the following compounds II-1:
3. the method for synthesizing selenium/sulfur compounds based on TADDOL framework according to claim 2, characterized in that the yield of selenium/sulfur compounds is > 80%.
4. The selenium/sulfur compound and BF of claim 1 3 The use of THF for the synthesis of chiral compound (-) -9, catalytic compound 7 and compound 8;
5. use according to claim 4, characterized in that the selenium/sulphur compound and BF are applied 3 The molar ratio of THF was 1:5-15.
6. Use according to claim 4, characterized in that the yield of the chiral compound (-) -9 is > 50%.
7. Use according to claim 4, characterized in that the chiral compound (-) -9 has an ee of at least 15%.
8. The selenium/sulfur compound, chiral compound 10 and BF of claim 1 3 The use of THF in catalyzing the synthesis of chiral compound (-) -9 from compound 7 and compound 8;
9. use according to claim 8, characterized in that the selenium/sulphur compound and BF are applied 3 The molar ratio of THF is 1:5-15, the molar ratio of selenium/sulfur compound and chiral compound 10 is 1.
10. Use according to claim 8, characterized in that the yield of the chiral compound (-) -9 is greater than or equal to 50%.
11. Use according to claim 8, characterized in that the chiral compound (-) -9 has an ee of at least 24%.
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