CN116554223A - Chiral biphosphine skeleton compound, preparation method and application thereof - Google Patents
Chiral biphosphine skeleton compound, preparation method and application thereof Download PDFInfo
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- CN116554223A CN116554223A CN202210116229.6A CN202210116229A CN116554223A CN 116554223 A CN116554223 A CN 116554223A CN 202210116229 A CN202210116229 A CN 202210116229A CN 116554223 A CN116554223 A CN 116554223A
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- -1 biphosphine skeleton compound Chemical class 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 83
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 24
- 150000001868 cobalt Chemical class 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- 239000003446 ligand Substances 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 238000006467 substitution reaction Methods 0.000 claims description 13
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 229910052738 indium Inorganic materials 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 238000006459 hydrosilylation reaction Methods 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 239000012634 fragment Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 239000002585 base Substances 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- BKFAZDGHFACXKY-UHFFFAOYSA-N cobalt(II) bis(acetylacetonate) Chemical compound [Co+2].CC(=O)[CH-]C(C)=O.CC(=O)[CH-]C(C)=O BKFAZDGHFACXKY-UHFFFAOYSA-N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical group [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 239000010941 cobalt Substances 0.000 claims description 2
- 229910017052 cobalt Inorganic materials 0.000 claims description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical class [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 2
- 150000001924 cycloalkanes Chemical group 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 12
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- GTCCGKPBSJZVRZ-RFZPGFLSSA-N (2r,4r)-pentane-2,4-diol Chemical compound C[C@@H](O)C[C@@H](C)O GTCCGKPBSJZVRZ-RFZPGFLSSA-N 0.000 description 1
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 description 1
- XLQSXGGDTHANLN-UHFFFAOYSA-N 1-bromo-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(Br)C=C1 XLQSXGGDTHANLN-UHFFFAOYSA-N 0.000 description 1
- VEUMANXWQDHAJV-UHFFFAOYSA-N 2-[2-[(2-hydroxyphenyl)methylideneamino]ethyliminomethyl]phenol Chemical compound OC1=CC=CC=C1C=NCCN=CC1=CC=CC=C1O VEUMANXWQDHAJV-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 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 description 1
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5022—Aromatic phosphines (P-C aromatic linkage)
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0896—Compounds with a Si-H linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/505—Preparation; Separation; Purification; Stabilisation
- C07F9/5063—Preparation; Separation; Purification; Stabilisation from compounds having the structure P-H or P-Heteroatom, in which one or more of such bonds are converted into P-C bonds
- C07F9/5072—Preparation; Separation; Purification; Stabilisation from compounds having the structure P-H or P-Heteroatom, in which one or more of such bonds are converted into P-C bonds from starting materials having the structure P-H
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/32—Addition reactions to C=C or C-C triple bonds
- B01J2231/323—Hydrometalation, e.g. bor-, alumin-, silyl-, zirconation or analoguous reactions like carbometalation, hydrocarbation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/845—Cobalt
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a chiral diphosphine skeleton compound, a preparation method and application thereof. The invention provides a compound shown as a formula I, enantiomer or diastereoisomer thereof, wherein m, n, r and t are independently 1, 2 or 3; each R is 1 、R 2 、R 3 And R is 4 Independently C substituted by one or more halogens 1 ‑C 6 Alkyl, methyl or halogen; when R is 1 、R 2 、R 3 And R is 4 When the two are methyl, m, n, R and t are 1, and R 1 、R 2 、R 3 And R is 4 The alignment is positioned at P; r is R 5 Is phenyl, C 1 ‑C 6 Alkyl or C 3 ‑C 6 Cycloalkyl groups. The chiral diphosphine skeleton compound and cobalt salt of the invention are matched to catalyze asymmetryDuring the reaction, the catalytic effect is obvious, the product yield is better, and the product er value is higher.
Description
Technical Field
The invention particularly relates to a chiral diphosphine skeleton compound, a preparation method and application thereof.
Background
Chiral ligands play an extremely important role in asymmetric catalytic synthesis of metal participation. Thus, efforts have been made for the last forty years to develop chiral ligands with high activity and selectivity. So far, chiral ligands with the so-called "dominant structure" (specific references s.—f.zhu, q.— L.Zhou, inPrivilegedChiralLigandsandCatalysts, ed.: q.—l.zhou, wiley-VCH, weinheim,2011, pp.137-170) are widely used. Representative ligand backbones are BINOL, BINAP, bisoxazoline, salen, duPhos, TADDOL, cinchonaalloid, et al. Based on these "dominant structure" ligand backbones, a number of chiral ligands can be extended. Experimental results indicate that most of the ligands can exhibit excellent enantioselectivity in many metal-catalyzed asymmetric catalytic reactions. However, with the progress of the whole asymmetric catalytic reaction and chiral drug development, scientists have found that there are a large number of asymmetric reactions lacking efficient chiral ligands. Therefore, further development of chiral ligands with novel backbones, particularly development of chiral ligands that are inexpensive, easy to obtain and efficient, remains one of the very important and challenging problems. Based on the above characteristics, we intend to develop a novel class of chiral diphosphine ligands.
Disclosure of Invention
The invention aims to solve the technical problem that the structure of a compound for catalyzing asymmetric hydrosilation reaction in the prior art is single, and therefore, the invention provides a chiral diphosphine skeleton compound, a preparation method and application thereof.
The invention provides a compound shown in a formula I, enantiomer or diastereoisomer thereof,
wherein m, n, r and t are independently 1, 2 or 3; r is R 1 、R 2 、R 3 And R is 4 Independently C substituted by one or more halogens 1 -C 6 Alkyl, methyl or halogen; when R is 1 、R 2 、R 3 And R is 4 When the two are methyl, m, n, R and t are 1, and R 1 、R 2 、R 3 And R is 4 The alignment is positioned at P;
R 5 is phenyl, C 1 -C 6 Alkyl or C 3 -C 6 Cycloalkyl groups.
In a preferred embodiment, the compound of formula I, enantiomers or diastereomers thereof; the definition of certain groups may be as follows, and the definition of other groups may be as described in any of the schemes above (hereinafter referred to as "in a preferred scheme"): the compound shown in the formula I is shown in the formula I-a
Wherein R is 1 、R 2 、R 3 、R 4 And R is 5 Is defined as in any one of the present inventions.
In a preferred embodiment, R 1 、R 2 、R 3 And R is 4 Wherein the halogen may independently be fluorine, chlorine, bromine or iodine; such as fluorine.
In a preferred embodiment, R 1 、R 2 、R 3 And R is 4 In said C substituted by one or more halogens 1 -C 6 In the alkyl group, the C 1 -C 6 Alkyl groups can independently be C 1 -C 4 Alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; also for example methyl. The halogen is independently preferably fluorine, chlorine, bromine or iodine; such as fluorine. The plurality is preferably 2 or 3.
In a preferred embodiment, R 5 In the above, the C 1 -C 6 Alkyl can be C 1 -C 4 Alkyl groups, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutylA group, sec-butyl or tert-butyl; also for example methyl.
In a preferred embodiment, R 5 In the above, the C 3 -C 6 Cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclohexyl.
In a preferred embodiment, m is 1.
In a preferred embodiment, n is 1.
In a preferred embodiment, r is 1.
In a preferred embodiment, t is 1.
In a preferred embodiment, R 1 、R 2 、R 3 And R is 4 The same applies.
In a preferred embodiment, R 1 、R 2 、R 3 And R is 4 Independently trifluoromethyl, methyl or fluoro.
In a preferred embodiment, R 1 、R 2 、R 3 And R is 4 And is trifluoromethyl, methyl or fluoro.
In a preferred embodiment, R 5 Is phenyl, cyclohexyl or methyl.
In a certain preferred embodiment, the compound shown in formula I is any one of the following compounds:
the invention also provides a preparation method of the compound shown in the formula I, which comprises the following steps: in a solvent, the compound S-4, the compound S-3 and the compound S-2 are subjected to substitution reaction as shown in the following formula in the presence of alkali;
therein, n, m, r, t, R 1 、R 2 、R 3 、R 4 And R is 5 Is as defined in any one of claims 1 to 5.
In the substitution reaction, the solvent may be a solvent conventional in the art; the solvent can be an ether solvent and/or an amide solvent, and the ether solvent is preferably tetrahydrofuran; the amide solvent is preferably DMF.
In the substitution reaction, the solvent is used in an amount conventional in the art, and the volume molar ratio of the solvent to the compound S-3 can be 1-20mL/mmol; for example 5mL/mmol.
In the substitution reaction, the base may be a base conventional in the art, preferably a metal alkyl compound, more preferably an alkyl lithium, such as n-butyl lithium.
In the substitution reaction, the amount of the base may be an amount conventionally used in the art; the molar ratio of the S-3 compound to the base may be 1 (1-10); for example 1:2.2.
In the substitution reaction, the reaction temperature of the substitution reaction is a reaction temperature conventional in the art; the reaction temperature of the substitution reaction may be less than 20 ℃; for example-78 ℃.
In the substitution reaction, the molar ratio of the compound S-3 to the compound S-2 is a molar ratio conventional in the art, preferably 1 (1-3); for example 1:2.2.
The invention also provides a catalyst composition, which comprises a mixture of the compound shown in the formula I and cobalt salt or a complex formed by the compound shown in the formula I and cobalt salt.
The molar ratio of the compound of formula I to the cobalt salt in the catalyst composition is preferably 1:1.
In the catalyst composition, the cobalt salt may be a cobalt salt conventional in the art, preferably a divalent cobalt salt, such as Co (acac) 2 。
The catalyst composition further comprises indium.
In the catalyst composition, the molar ratio of the compound represented by formula I to the indium may be (1-5): (1-2), preferably 3:1.
The invention provides an application of a compound shown as a formula I in the asymmetric reaction of eneyne as a catalyst ligand;
the asymmetric reaction is an asymmetric hydrosilation reaction.
The asymmetric reaction comprises the following steps: in a solvent in the presence of the compound shown as the formula I and cobalt salt1, 3-eneyne compounds Y of the structural fragment with a composition containing +.>Subjecting compound X of structural fragment to asymmetric hydrosilation to obtain a compound containing +.>The structural fragment of the compound II.
In the asymmetric reaction, the 1,3 eneyne compound Y may be a compound represented by the formula YR 6 Unsubstituted or substituted by one or more R 6-1 Substituted C 6 -C 10 Aryl or 5-to 9-membered heteroaryl; the hetero atom in the heteroaryl is selected from 1, 2 or 3 of O, N and S, and the number of the hetero atoms is 1, 2 or 3; each R is 6-1 Independently C 1 ～C 6 An alkyl group; the C is 6 -C 10 The aryl group is preferably phenyl, and the heteroaryl group of 5 to 9 membered is preferably +.>R 7 Is C 1 ～C 6 Alkyl is preferably methyl.
The compound Y is preferably
In the asymmetric reaction, the compound X may be a silane compound conventional in the art, and the compound X may be a compound represented by the formula XR 8 And R is 9 Independently hydrogen, C 1 ～C 6 Alkyl or unsubstituted or substituted by one or more R 8-1 Substituted C 6 -C 10 Aryl, R 8 And R is 9 Not simultaneously being hydrogen, each R 8-1 Independently C 1 ～C 6 An alkyl group. The compound X is preferably phenylsilane.
In the asymmetric reaction, the compound II can be a compound shown as a formula IIR 6 、R 7 、R 8 And R is 9 Is as defined above; the compound II is preferably +.>
Wherein the conditions and operations of the asymmetric reactions may be those conventional in the art; the following are preferred in the present invention:
the asymmetry reaction is carried out under a gas-protecting condition, and preferably, the gas is nitrogen or argon.
The asymmetric reaction may be carried out in a glove box.
In the asymmetric reaction, the cobalt salt may be used in an amount conventional in the art, and the molar ratio of the cobalt salt to the 1,3 eneyne compound Y may be 1: (1 to 100), for example, 1:20.
in the asymmetric reaction, the molar ratio of the compound shown as the formula I to the 1,3 eneyne compound Y is 1: (1 to 100), for example, 1:20.
in the asymmetric reaction, the molar ratio of the compound X to the 1,3 eneyne compound Y may be (0.2 to 5): 1, a step of; for example, (1 to 1.5): 1, a step of; also for example 1.25:1.
in the asymmetric reaction, the solvent may be a solvent conventional in the art; the solvent may be a cycloalkane, such as cyclohexane.
In the asymmetric reaction, the reaction temperature of the asymmetric reaction is preferably 40 to 70 ℃, for example 50 ℃.
The asymmetric reaction further comprises indium, and the molar ratio of the compound shown as formula I to indium can be (1-5): (1-2), preferably 3:1.
In the asymmetric reaction, the amount of indium may be an amount conventional in the art, and preferably, the molar ratio of indium to the 1,3 eneyne compound Y may be 3:20.
The invention also provides application of the catalyst composition in catalyzing asymmetric reaction of eneyne.
The conditions and operation of the asymmetric reaction are as described in any one of the preceding claims.
The above preferred conditions can be arbitrarily combined on the basis of not deviating from the common knowledge in the art, and thus, each preferred embodiment of the present invention can be obtained.
The term "one or more" or "means 1, 2, 3, 4, 5, 6, 7, 8, 9 or more; for example 1, 2 or 3
The term "comprising" is an open-ended expression, i.e. including what is indicated by the invention, but not excluding other aspects.
The term "substituted" means that any one or more hydrogen atoms on a particular atom is substituted with a substituent, provided that the valence of the particular atom is normal and the substituted compound is stable.
The term "halogen" refers to fluorine, chlorine, bromine or iodine.
The term "alkyl" refers to a straight or branched chain alkyl group having the indicated number of carbon atoms. C (C) 1 -C 6 Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl.
The term "cycloalkyl" refers to a saturated monocyclic group consisting of only carbon atoms, preferably 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
When there is no statement in the exemplified groupsWhere it is stated that it has substituents, such groups are merely unsubstituted. For example when "C 1 ～C 4 Alkyl "not previously" substituted or unsubstituted "refers only to" C 1 ～C 4 Alkyl "as such or" unsubstituted C 1 ～C 4 An alkyl group.
The term "heteroaryl" refers to a cyclic group of a specified number of ring atoms (e.g., 5-9 membered), of a specified number of heteroatoms (e.g., 1, 2, or 3), of a specified heteroatom species (one or more of N, O and S), which is monocyclic or polycyclic, and at least one ring is aromatic (in accordance with the shock rule). Heteroaryl groups are linked to other fragments in the molecule through aromatic or non-aromatic rings.
The reagents and materials used in the present invention are commercially available.
The invention has the positive progress effects that: when the chiral diphosphine skeleton compound and cobalt salt are matched to catalyze asymmetric reaction, the catalytic effect is remarkable, the product yield is good, and the product er value is high.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
Example 1
The general preparation method according to the present invention is described in detail in this example, taking the preparation of compound L1 as an example, as shown in the reaction scheme of the following formula:
a dry 100mL two-necked flask was weighed into activated magnesium turnings (0.38 g,15.5mmol,3.1 eq.) and two elemental iodides, and after three vacuums and nitrogen substitutions 7.5mL diethyl ether was added, followed by cooling the system to 0deg.C. A solution of para-bromobenzotrifluoride (3.38 g,15mmol,3.0 eq.) in diethyl ether (7.5 mL) was added dropwise, the solution was first discolored and then gradually turned dark brown, room temperature was restored and stirred for 2h. The supernatant was transferred to another flask, which had been replaced with nitrogen, and cooled to 0 ℃. Diethyl phosphite (0.69 g,5.0mmol,1.0 eq.) was added dropwise, the system was allowed to return to room temperature and stirred for 18h, then quenched with 2M hydrochloric acid slowly, extracted with ethyl acetate, the organic phases combined and washed with saturated brine, dried over anhydrous sodium sulfate, and after removal of the solvent by spin-on, silica gel column chromatography (PE: ea=4:1 to 2:1) afforded brown solid S-1 (0.98 g,58% yield).
Example 2
This example illustrates in detail the general preparation method according to the invention:
a dried 250mL eggplant-shaped bottle was evacuated and replaced with nitrogen three times, and diisobutylaluminum hydride (1.0M hexane solution, 18mL,17.6mmol,3.0 eq.) was added. The system was cooled to 0deg.C, followed by dropwise addition of a solution of S-1 (1.98 g,5.8mmol,1.0 eq.) in tetrahydrofuran (20 mL). The system was allowed to return to room temperature and stirred for 2h, then 40mL of methyl tert-butyl ether were added in one portion and the system was cooled again to 0 ℃. 24mL of sodium hydroxide solution (3.0M) and 15mL of saturated brine were added in this order, the system was allowed to return to room temperature and stirred for 30min, and allowed to stand for delamination. Separating under nitrogen atmosphere, filtering the organic phase with a short column filled with anhydrous sodium sulfate and diatomaceous earth, vacuum-pumping the solvent, and subjecting to silica gel (2.5X18 cm) flash column chromatography (PE: CH) 2 Cl 2 =25:1) to give colorless liquid S-2 (1.70 g,91% yield).
Example 3
This example illustrates in detail the general preparation method according to the invention:
in a 50mL eggplant-shaped bottle, (2R, 4R) -2, 4-pentanediol (1.04 g,10mmol,1.0 eq.) was weighed in. Dichloromethane (20 mL) and triethylamine (3.1 mL,22.5mmol,2.25 eq.) were added. The system was cooled to 0deg.C and methanesulfonyl chloride (1.7 mL,22mmol,2.2 eq.) was added dropwise and the system was allowed to warm to room temperature and stirred for 2h. The reaction solution was poured into 20ml of 1.0m hydrochloric acid, extracted with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by spinning to give pale yellow liquid S-3 (2.69 g), which was used in the next step without purification.
Example 4
This example illustrates in detail the general preparation method according to the invention:
in the glove box, S-2 (1.70 g,5.3mmol,2.2 eq) was weighed into a 100mL eggplant-shaped bottle, which was capped and removed from the glove box. 12mL of tetrahydrofuran was added and cooled to-78 ℃. N-butyllithium (2.5M hexane solution, 2.1mL,5.3mmol,2.2 eq.) was added dropwise, the solution turned dark red, maintained at-78℃and stirred for 2h. A solution of S-3 (0.63 g,2.4mmol,1.0 eq.) in DMF (8 mL) was added dropwise, followed by slow resumption of the system to room temperature and stirring for 24h until the system changed from dark red to light yellow. Quenching the reaction by adding saturated ammonium chloride solution, extracting with diethyl ether, mixing the organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, and performing silica gel column chromatography (PE: CH) 2 Cl 2 =35:1 to 15:1) to give colorless gum I-1 (494.4 mg,29% yield).
Structural identification data I-1 as shown in the formula I-1.
IR (pure): 2928 (w), 1607 (m), 1462 (w), 1396 (m), 1319(s), 1163 (m), 1119(s), 1058(s), 1015 (m), 828 (m), 697 (m), 598 (m) cm -1 ； 1 HNMR(400MHz,CDCl 3 ):δ7.61–7.45(m,16H),2.63-2.49(m,2H),1.39(p,J＝7.2Hz,2H),1.04(dd,J＝15.2,6.8Hz,6H)； 13 CNMR(100MHz,CDCl 3 ):δ140.7(d,J＝18.3Hz),133.7(dd,J＝19.3,16.2Hz),131.2(qd,J＝32.5,1.7Hz),125.3125.1(m),123.8(qd,J＝272.4,3.3Hz),36.3(t,J＝18.7Hz),26.9(t,J＝11.9Hz),15.5(d,J＝15.2Hz). 19 FNMR(376MHz,CDCl 3 ):δ–62.9(d,J＝9.9Hz)； 31 PNMR(162MHz,CDCl 3 ):δ–0.5；HRMS(ESI + )[M+H] + Theoretical calculation value C 33 H 27 F 12 P 2 713.1391m/z, the actual detection value is 713.1396m/z; optical rotation [ alpha ]] D 20 –67.5(c1.00,CHCl 3 ).
Example 5
Asymmetric hydrosilation of 1,3 eneyne catalyzed by (Co (II)/chiral biphosphine backbone ligand I-1
In this example, chiral diphosphine backbone ligands I-1 and Co (acac) 2 (the complex formed in situ is a chiral catalyst), catalytic asymmetric hydrosilation of 1,3 eneyne is used to exemplify the use of chiral biphosphine backbone compounds in asymmetric catalysis in the present invention.
The operation method comprises the following steps: co (acac) was weighed into a dried 8mL reaction flask in a nitrogen glove box 2 (2.6 mg,0.01mmol,5.0 mol%), I-1 (7.1 mg,0.01mmol,5.0 mol%) and 1mL cyclohexane were stirred at room temperature until homogeneous, and then phenylsilane (27 mg,0.25mmol,1.25 eq.), indium powder (3.4 mg,0.03mmol,15 mol%) and 1a (28.4 mg,0.2mmol,1.0 eq.) were added. The vial cap was screwed on and removed from the glove box, heated to 50 ℃ and reacted for 12h. The reaction was quenched by adding 1mL of saturated ammonium chloride solution, stirred at room temperature for 1h, filtered through a small column filled with silica gel and celite, and rinsed with diethyl ether (3X 8 mL). The solvent was removed from the filtrate on a rotary evaporator and separated by silica gel column chromatography (PE) to give 2a (39.9 mg,80% yield, dr value 93:7; er value 96.5:3.5) as a colourless oil.
Structural identification data of the Compound represented by formula 2a
IR (pure product) 3343 (w), 3018 (m), 2952 (m), 2863 (m), 2115 (m), 1658 (m), 1490 (m), 1405 (m), 1300 (m), 1255 (m), 1111 (m), 994 (m), 882 (m), 836 (m), 754 (m), 692(s) cm -1 ； 1 HNMR(400MHz,CDCl 3 ):δ7.63–7.58(m,2H),7.37–7.27(m,5H),7.22–7.16(m,2H),7.15–7.09(m,1H),7.04(d,J＝2.8Hz,1H),5.15(t,J＝3.6Hz,1H),3.10–2.99(m,1H),1.62(ddd,J＝15.6,8.4,3.2Hz,1H),1.24(d,J＝7.2Hz,3H),0.68(dt,J＝15.6,4.0Hz,1H)； 13 CNMR(100MHz,CDCl 3 ):δ154.9,139.1,138.7,135.4,134.9,129.7,128.4,128.0,126.9,126.6,39.0,24.3,16.8；HRMS(EI + )[M] + Theoretical calculation value C 17 H 18 Si is 250.1172m/z, and the actual detection value is 250.1179m/z; optical rotation [ alpha ]] D 20 45.5(c1.00,CHCl 3 )96.5:3.5e.r.
Example 6
Asymmetric hydrosilation of 1,3 eneyne catalyzed by (Co (II)/chiral biphosphine backbone ligand I-1
In this example, chiral diphosphine backbone ligands I-1 and Co (acac) 2 (the complex formed in situ is a chiral catalyst), catalytic asymmetric hydrosilation of 1,3 eneyne is used to exemplify the use of chiral biphosphine backbone compounds in asymmetric catalysis in the present invention.
The operation method comprises the following steps: co (acac) 2 was weighed into a dried 8mL reaction flask in a nitrogen glove box
(2.6 mg,0.01mmol,5.0 mol%), I-1 (7.1 mg,0.01mmol,5.0 mol%) and 1mL cyclohexane were stirred at room temperature until homogeneous, and then phenylsilane (27 mg,0.25mmol,1.25 eq.), indium powder (3.4 mg,0.03mmol,15 mol%) and 3a (0.2 mmol,1.0 eq.) were added. The vial cap was screwed on and removed from the glove box, heated to 50 ℃ and reacted for 12h. The reaction was quenched by adding 1mL of saturated ammonium chloride solution, stirred at room temperature for 1h, filtered through a small column filled with silica gel and celite, and rinsed with diethyl ether (3X 8 mL). The solvent was removed from the filtrate on a rotary evaporator and separated by silica gel column chromatography (PE) to give 4a (39.9 mg,58% yield, 96.5:3.5 e.r) as a colourless oil.
Structural identification data of the Compound represented by formula 4a
Colourless oil, yield (83.9 mg, 58%); IR (pure product) 2953 (m), 2123 (m), 1598 (m), 1448 (m), 1428 (m), 1292 (m), 1254 (m), 1111 (m), 889 (m), 837 #s),790(m),737(s),698(s)cm -1 ； 1 HNMR(400MHz,CDCl3):δ7.71–7.66(m,2H),7.457.35(m,6H),7.22(ddd,J＝8.0,7.2,1.6Hz,1H),7.13(td,J＝7.2,1.2Hz,1H),6.31–6.26(m,1H),5.15(t,J＝3.6Hz,1H),3.19-3.09(m,1H),1.68(ddd,J＝15.6,8.4,3.2Hz,1H),1.31(d,J＝7.2Hz,3H),0.74(dt,J＝15.6,4.4Hz,1H)； 13 CNMR(100MHz,CDCl3):δ155.6,155.4,154.5,134.9,134.1,130.0,129.2,128.2,127.5,124.1,122.4,120.6,110.7,104.8,39.3,24.1,16.8；HRMS(EI + )[M] + Theoretical value 19H18OSi:290.1121m/z, detection value 290.1122m/z; optical rotation [ alpha ]]D 20 91.8(c1.00,CHCl 3 )。
Comparative example 1
Replacement of the ligand of formula I-1 in example 5 withOther reaction conditions were unchanged, giving a yield of 40% of 2a, dr value 83:17; and an er value of 90:10.
Claims (10)
1. A compound shown in a formula I, enantiomer or diastereoisomer thereof is characterized in that,
wherein m, n, r and t are independently 1, 2 or 3; r is R 1 、R 2 、R 3 And R is 4 Independently C substituted by one or more halogens 1 -C 6 Alkyl, methyl or halogen; when R is 1 、R 2 、R 3 And R is 4 When the two are methyl, m, n, R and t are 1, and R 1 、R 2 、R 3 And R is 4 The alignment is positioned at P;
R 5 is phenyl, C 1 -C 6 Alkyl or C 3 -C 6 Cycloalkyl groups.
2. The compound of formula I, enantiomers or diastereomers thereof, according to claim 1, wherein said compound of formula I satisfies one or more of the following conditions:
(1)R 1 、R 2 、R 3 and R is 4 Wherein the halogen is independently fluorine, chlorine, bromine or iodine; such as fluorine;
(2)R 1 、R 2 、R 3 and R is 4 In said C substituted by one or more halogens 1 -C 6 In the alkyl group, the C 1 -C 6 Alkyl is C 1 -C 4 Alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; also for example methyl;
(3)R 1 、R 2 、R 3 and R is 4 In said C substituted by one or more halogens 1 -C 6 In the alkyl, the halogen is fluorine, chlorine, bromine or iodine; such as fluorine;
(4)R 1 、R 2 、R 3 and R is 4 In said C substituted by one or more halogens 1 -C 6 In the alkyl group, the plurality is 2 or 3;
(5)R 5 in the above, the C 1 -C 6 Alkyl is C 1 -C 4 Alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; also for example methyl;
and (6) R 5 In the above, the C 3 -C 6 Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclohexyl.
3. A compound of formula I, an enantiomer or diastereomer thereof, according to claim 1 or 2, wherein the compound of formula I satisfies one or more of the following conditions:
(1) m is 1;
(2) n is 1;
(3) r is 1;
(4) t is 1;
(5)R 1 、R 2 、R 3 and R is 4 Identical to；
(6)R 1 、R 2 、R 3 And R is 4 Independently trifluoromethyl, methyl or fluoro;
and (7) R 5 Is phenyl, cyclohexyl or methyl.
4. The compound shown in the formula I, enantiomer or diastereoisomer thereof as claimed in claim 3, wherein the compound shown in the formula I is a compound shown in the formula I-a
5. The compound of formula I, enantiomers or diastereomers thereof, as defined in claim 1, wherein R 1 、R 2 、R 3 And R is 4 Simultaneously trifluoromethyl, methyl or fluorine;
preferably, the compound shown in the formula I is any one of the following compounds:
6. a method for preparing a compound shown in a formula I, which is characterized by comprising the following steps: in a solvent, the compound S-4, the compound S-3 and the compound S-2 are subjected to substitution reaction as shown in the following formula in the presence of alkali;
therein, n, m, r, t, R 1 、R 2 、R 3 、R 4 And R is 5 Is as defined in any one of claims 1 to 5;
preferably, the substitution reaction satisfies one or more of the following conditions:
(1) The solvent is an ether solvent and/or an amide solvent, and the ether solvent is tetrahydrofuran preferably; the amide solvent is preferably DMF;
(2) The volume molar ratio of the solvent to the compound S-3 is 1-20mL/mmol; for example 5mL/mmol;
(3) The base is a metal alkyl compound, preferably an alkyl lithium, such as n-butyl lithium;
(4) The molar ratio of the S-3 compound to the alkali is 1 (1-10); for example 1:2.2;
(5) The reaction temperature of the substitution reaction is less than 20 ℃; for example-78 ℃;
and (6) the molar ratio of the compound S-3 to the compound S-2 is 1 (1-3); for example 1:2.2.
7. A catalyst composition comprising a mixture of a compound of formula I and a cobalt salt according to any one of claims 1 to 5, or a complex of a compound of formula I and a cobalt salt according to any one of claims 1 to 5;
preferably, the catalyst composition satisfies one or more of the following conditions:
(1) The molar ratio of the compound shown in the formula I to the cobalt salt is 1:1;
(2) The cobalt salt is a divalent cobalt salt, such as Co (acac) 2 ；
(3) The catalyst composition further comprises indium, preferably the molar ratio of the compound of formula I to indium is (1-5): (1-2), preferably 3:1.
8. Use of a compound of formula I according to any one of claims 1 to 5 as a catalyst ligand in an asymmetric reaction of an eneyne; the asymmetric reaction is an asymmetric hydrosilation reaction;
preferably, in the asymmetric reactionThe method comprises the following steps: in a solvent in the presence of the compound shown as the formula I and cobalt salt1, 3-eneyne compounds Y of the structural fragment with a composition containing +.>Subjecting compound X of structural fragment to asymmetric hydrosilation to obtain a compound containing +.>The structural fragment of the compound II.
9. The use of claim 8; characterized in that the asymmetric reaction satisfies one or more of the following conditions:
(1) The 1,3 eneyne compound Y is a compound shown as a formula YR 6 Unsubstituted or substituted by one or more R 6-1 Substituted C 6 -C 10 Aryl or 5-to 9-membered heteroaryl; the hetero atom in the heteroaryl is selected from 1, 2 or 3 of O, N and S, the number of the hetero atoms is 1, 2 or 3, each R 6-1 Independently C 1 ～C 6 An alkyl group; the C is 6 -C 10 The aryl group is preferably phenyl, and the heteroaryl group of 5 to 9 membered is preferably +.>R 7 Is C 1 ～C 6 Alkyl, preferably methyl; the 1, 3-eneyne compound Y is preferably +.>
(2) The compound X is a compound shown as a formula XR 8 And R is 9 Independently hydrogen, C 1 ～C 6 Alkyl or unsubstituted or substituted by one or more R 8-1 Substituted C 6 -C 10 Aryl, R 8 And R is 9 Not simultaneously being hydrogen, each R 8-1 Independently C 1 ～C 6 An alkyl group; the compound X is preferably phenylsilane;
(3) The compound II is shown as a formula IIR 6 Unsubstituted or substituted by one or more R 6-1 Substituted C 6 -C 10 Aryl or 5-to 9-membered heteroaryl; the hetero atom in the heteroaryl is one or more selected from O, N and S, the number of the hetero atoms is 1, 2 or 3, and each R 6-1 Independently C 1 ～C 6 An alkyl group; the C is 6 -C 10 The aryl group is preferably phenyl, and the heteroaryl group of 5 to 9 membered is preferably +.>R 7 Is C 1 ～C 6 Alkyl, preferably methyl; r is R 8 And R is 9 Independently hydrogen, C 1 ～C 6 Alkyl or unsubstituted or substituted by one or more R 8-1 Substituted C 6 -C 10 Aryl, R 8 And R is 9 Not simultaneously being hydrogen, each R 8-1 Independently C 1 ～C 6 An alkyl group; the compound II is preferably +.>
(4) The asymmetry reaction is carried out under the condition of gas protection, and preferably, the gas is nitrogen or argon;
(5) The asymmetric reaction is carried out in a glove box;
(6) The molar ratio of the cobalt salt to the 1,3 eneyne compound Y is 1: (1 to 100), for example, 1:20, a step of;
(7) The molar ratio of the compound shown in the formula I to the 1,3 eneyne compound Y is 1: (1 to 100), for example, 1:20, a step of;
(8) The molar ratio of the compound X to the 1,3 eneyne compound Y is (0.2-5): 1, a step of; for example, (1 to 1.5): 1, a step of; also for example 1.25:1, a step of;
(9) The solvent is a cycloalkane, such as cyclohexane;
(10) The asymmetric reaction has a reaction temperature of 40-70deg.C, such as 50deg.C;
and (11) the asymmetric reaction further comprises indium, preferably, the molar ratio of the compound of formula I to indium is (1-5): (1-2), preferably 3:1.
10. Use of the catalyst composition of claim 7 for catalyzing an asymmetric reaction of an eneyne;
preferably, the reaction conditions and operation of the asymmetric reaction are as defined in claim 8 or 9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210116229.6A CN116554223A (en) | 2022-01-30 | 2022-01-30 | Chiral biphosphine skeleton compound, preparation method and application thereof |
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