CN105949248A - Synthesis method of Josiphos chiral ferrocenyl phosphine ligands - Google Patents
Synthesis method of Josiphos chiral ferrocenyl phosphine ligands Download PDFInfo
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- CN105949248A CN105949248A CN201610356032.4A CN201610356032A CN105949248A CN 105949248 A CN105949248 A CN 105949248A CN 201610356032 A CN201610356032 A CN 201610356032A CN 105949248 A CN105949248 A CN 105949248A
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- ferrocene
- phosphine
- josiphos
- chloride
- vinyl
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- 239000003446 ligand Substances 0.000 title claims abstract description 17
- 238000001308 synthesis method Methods 0.000 title abstract 5
- YLQBEKUKMJWXMC-UHFFFAOYSA-N cyclopenta-1,3-diene cyclopenta-2,4-dien-1-ylphosphane iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.P[c-]1cccc1 YLQBEKUKMJWXMC-UHFFFAOYSA-N 0.000 title abstract 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 80
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims abstract description 55
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 42
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 24
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 19
- 229920002554 vinyl polymer Polymers 0.000 claims abstract description 19
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims abstract description 13
- ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- 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 claims abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 60
- 239000002904 solvent Substances 0.000 claims description 20
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 12
- AJVBXLXLODZUME-UHFFFAOYSA-N ethenyl(diphenyl)phosphane Chemical group C=1C=CC=CC=1P(C=C)C1=CC=CC=C1 AJVBXLXLODZUME-UHFFFAOYSA-N 0.000 claims description 11
- -1 phosphino- Chemical class 0.000 claims description 11
- 238000010189 synthetic method Methods 0.000 claims description 8
- ULNVTMFBEVVUMH-UHFFFAOYSA-N P.[Cl] Chemical compound P.[Cl] ULNVTMFBEVVUMH-UHFFFAOYSA-N 0.000 claims description 7
- XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 6
- WDOKISJWRVNYNS-UHFFFAOYSA-N dicyclohexylphosphanium;chloride Chemical compound Cl.C1CCCCC1PC1CCCCC1 WDOKISJWRVNYNS-UHFFFAOYSA-N 0.000 claims description 4
- MCRSZLVSRGTMIH-UHFFFAOYSA-N ditert-butyl(chloro)phosphane Chemical compound CC(C)(C)P(Cl)C(C)(C)C MCRSZLVSRGTMIH-UHFFFAOYSA-N 0.000 claims description 4
- 229910052756 noble gas Inorganic materials 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 235000021050 feed intake Nutrition 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 21
- 230000015572 biosynthetic process Effects 0.000 abstract description 18
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000006555 catalytic reaction Methods 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 238000006053 organic reaction Methods 0.000 abstract description 2
- NJLHHACGWKAWKL-UHFFFAOYSA-N ClP(Cl)=O Chemical compound ClP(Cl)=O NJLHHACGWKAWKL-UHFFFAOYSA-N 0.000 abstract 1
- 229930182820 D-proline Natural products 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 229910052751 metal Inorganic materials 0.000 abstract 1
- 239000002184 metal Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 48
- 229910052786 argon Inorganic materials 0.000 description 24
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- 239000007787 solid Substances 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- 230000006837 decompression Effects 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 238000004364 calculation method Methods 0.000 description 7
- LUAMIGOADJTNQF-UHFFFAOYSA-N [Mg].[Cl-].C(=C)[N+]1=CNC=C1 Chemical compound [Mg].[Cl-].C(=C)[N+]1=CNC=C1 LUAMIGOADJTNQF-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- WUOIAOOSKMHJOV-UHFFFAOYSA-N ethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(CC)C1=CC=CC=C1 WUOIAOOSKMHJOV-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- USJRLGNYCQWLPF-UHFFFAOYSA-N chlorophosphane Chemical compound ClP USJRLGNYCQWLPF-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group 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
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000006138 lithiation reaction Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000002699 waste material Substances 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
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
-
- 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
- B01J31/2414—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 comprising aliphatic or saturated rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- 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
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0225—Complexes comprising pentahapto-cyclopentadienyl analogues
-
- 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
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
- B01J2531/0263—Planar chiral ligands, e.g. derived from donor-substituted paracyclophanes and metallocenes or from substituted arenes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a synthesis method of Josiphos chiral ferrocenyl phosphine ligands, and belongs to the field of organic synthesis. The method is realized through the following steps of using ferrocene as a starting raw material; using aluminum chloride as a catalyst; taking a reaction with phosphonic chloride compound R2PCl; then, taking a reaction with vinyl diaryl phosphine under the catalysis effect of ferric trichloride and D-proline to obtain the Josiphos chiral ferrocenyl phosphine ligands. Compared with the prior art, the synthesis method has the advantages that the steps are few; the operation is simple; the production cost is reduced; the synthesis method is suitable for industrial production. The prepared Josiphos chiral ferrocenyl phosphine ligands can be used as ligands of metal catalysts for catalyzing an unsymmetrical organic reaction; the synthesis method is applied to the fields of medicine synthesis and the like.
Description
Technical field
The invention belongs to organic synthesis field, relate to the synthetic method of a class organic phosphine compound, particularly relate to
The synthetic method of Josiphos class chiral ferrocene phosphine ligand.
Background technology
Josiphos class chiral ferrocene phosphine ligand is the part that a class is very useful and important, and it is pioneering is only second to
BINAP part, can apply in the asymmetry organic synthesis reactions such as alkene asymmetric hydrogen amination, Michael addition, in industry
Production is used widely, has played an important role in the synthesis of many medicines and fine chemicals.
At present, the synthesis of Josiphos class chiral ferrocene phosphine ligand is mainly by chirality 1-ferrocenyl ethyl diformazan
Amine (Ugi amine) obtains, although Ugi amine is at synthesis, the separation of optical isomer, highly-solid selectively as reactive intermediate reaction
Ortho lithiation and retention of configuration during dimethylamine group generation substitution reaction is constant etc. that aspect has advantage, but at such
Part building-up process needs loaded down with trivial details chiral separation recrystallization process, be unfavorable for industrialization amplify (J.Chem.Educ.1972,
49(4),294-296；J.Am.Chem.Soc.1994,116(9),4062-4066；Chimia 1999,53(6),275-280)；
It addition, dimethylamino is intended only as seeking group in course of reaction, replaced by phosphine hydrogen compound again in target product, former
Subeconomy aspect is a kind of waste；Additionally, this route needs to use air-sensitive phosphine hydrogen species compound, bring tired to operation
Difficult.
In view of the market application foreground that the catalysis that this compounds is superior is active and wide, explore more efficient, practical
The synthetic method of Josiphos class chiral ferrocene phosphine ligand is the most necessary.
Summary of the invention
Present invention aim at providing a kind of step few, simple to operate, production cost is low, is suitable for industrialized production
The novel synthesis of Josiphos class chiral ferrocene phosphine ligand.
For realizing the object of the invention, reaction scheme of the present invention is as follows:
Wherein R is the tert-butyl group, cyclohexyl or phenyl；R ' is phenyl or 3,5-3,5-dimethylphenyl；
Reactions steps of the present invention is as follows:
1) under noble gas is protected, in dry reactor, ferrocene, aluminum chloride and solvent hexane it are sequentially added into, so
After-20-0 DEG C to system drip phosphine chlorine compound R2PCl, then reacts 2-3 hour at-20-0 DEG C, drips water in system
Cancellation, by extracting, be dried, be recrystallized to give 1-(dialkyl group phosphino-) ferrocene or 1-(diphenylphosphino) ferrocene；
2) under noble gas is protected, in dry reactor, 1-(dialkyl group phosphino-) ferrocene or 1-(hexichol it are sequentially added into
Base phosphino-) ferrocene, vinyl diaryl phosphine, ferric chloride, D-PROLINE and methylene chloride, then anti-at 10-30 DEG C
Answering 10-12 hour, reaction terminates to add shrend in backward system and goes out, by extracting, be dried, be recrystallized to give Josiphos class hands
Property ferrocene phosphine part；
Described phosphine chlorine compound R2PCl is di-t-butylchlorophosphine, dicyclohexyl phosphonium chloride or diphenyl phosphine chloride.
Described vinyl diaryl phosphine is vinyldiphenylphosphine or vinyl two (3,5-3,5-dimethylphenyl) phosphine.
Described ferrocene, aluminum chloride and phosphine chlorine compound R2The molar ratio of PCl is 1:1:0.8-1.0.
Described 1-(dialkyl group phosphino-) ferrocene or 1-(diphenylphosphino) ferrocene, ferric chloride and vinyl two
The molar ratio of aryl phosphine is 1:0.1-0.2:1-1.3.
Described ferric chloride and the molar ratio 1:1-1.2 of D-PROLINE.
The present invention has the beneficial effects that: 1) with ferrocene as initiation material, with phosphine chlorine compound in the catalysis of aluminum chloride
There is Friedel-Crafts reaction under effect, utilize with traditional handicraft butyl lithium activation ferrocene luxuriant ring compared with condition gentleer；2) profit
With vinyl diaryl phosphine stable in the air as phosphine donor, it is to avoid to making of the phosphine hydrogen species compound of air-sensitive
With, operate simpler；2) utilize cheap ferric chloride as catalyst, reduce production cost, and total recovery reaches
More than 92%.This reaction scheme step is few, simple to operate, it is easier to industrialized production.Josiphos class chirality two cyclopentadienyl prepared
Ferrum Phosphine ligands can be applied to the fields such as medicine synthesis as the ligand catalysis asymmetric organic reactions of metallic catalyst.
Detailed description of the invention
For preferably the present invention is described in detail, give an actual example as follows:
Embodiment 1
(1) synthesis of 1-(di-t-butyl phosphino-) ferrocene
Under argon shield, be sequentially added in dry reactor ferrocene (1mol, 186g), aluminum chloride (1mol,
132g) and 1L normal hexane, then at-20 DEG C to system dropping di-t-butylchlorophosphine (1mol, 180g), then at-20 DEG C
Reacting 3 hours, add shrend and go out in system, then separatory, organic layer anhydrous magnesium sulfate is dried, filters, and decompression distillation removes
Obtaining yellow solid after removing solvent, under argon shield, methanol is recrystallized to give 1-(di-t-butyl phosphino-) ferrocene 317g, productivity
96%.1H NMR(400MHz,CDCl3), δ: 1.56 (d, J=16.4Hz, 18H), 4.45 (s, 5H), 4.69 (m, 2H), 4.82
(m,2H)；HRMS:[M+H]+Calcd for C18H28FeP 331.1278, Found 331.1276；Elementary analysis measured value (meter
Calculation value)/%:C65.45 (65.47), H 8.23 (8.24).
(2) synthesis of vinyldiphenylphosphine
Under argon shield, in dry reactor, add diphenyl phosphine chloride (1mol, 220g) and 0.5L oxolane,
Then at 0 DEG C of tetrahydrofuran solution (1.1mol, 0.55L) to system dropping 2M vinylimidazolium chloride magnesium, in room after dropping
Reacting 10 hours under the conditions of temperature, add shrend and go out in system, then separatory, organic layer anhydrous magnesium sulfate is dried, filters, subtracts
Pressure obtains white solid, dichloromethane and recrystallizing methanol after solvent is distilled off and obtains vinyldiphenylphosphine 201g, productivity
95%.1H NMR(400MHz,CDCl3),δ:5.49(m,1H),5.77(m,1H),6.50(m,1H),7.16(m,6H),7.28
(m,4H)；HRMS:[M+H]+Calcd for C14H14P 213.0833, Found 213.0832；Elementary analysis measured value (calculates
Value)/%:C 79.21 (79.23), H 6.16 (6.17).
(3) (R)-(-)-1-[(S)-2-(di-t-butyl phosphine) ferrocene] ethyldiphenylphosphine
Under argon shield, be sequentially added in dry reactor 1-(di-t-butyl phosphino-) ferrocene (0.5mol,
165g), vinyldiphenylphosphine (0.5mol, 106g), ferric chloride (0.05mol, 8.1g), D-PROLINE (0.05mol,
5.8g) and and 1L dichloromethane, then 25 DEG C react 12 hours, in system add shrend go out, then separatory, organic layer
Being dried with anhydrous magnesium sulfate, filter, decompression obtains yellow solid, dichloromethane and recrystallizing methanol after solvent is distilled off and obtains
(R)-(-)-1-[(S)-2-(di-t-butyl phosphine) ferrocene] ethyldiphenylphosphine 249g, productivity 92%.1H NMR(400MHz,
CDCl3), δ: 1.06 (dd, J=76.6Hz, J=10.1Hz, 18H), 1.85 (m, 3H), 3.43 (m, 1H), 3.84 (s, 5H, Fc-
H),4.22-4.37(m,3H,Fc-H),7.14-7.35(m,8H,Ph),7.61-7.65(m,2H,Ph).HRMS:[M+H]+:
Calcd forC32H41FeP2543.2033, Found 543.2034. elementary analysis measured value (value of calculation)/%:C 70.84
(70.85),H 7.42(7.43).
Embodiment 2
(1) synthesis of 1-(di-t-butyl phosphino-) ferrocene
Under argon shield, be sequentially added in dry reactor ferrocene (1mol, 186g), aluminum chloride (1mol,
132g) and 1L normal hexane, then at 0 DEG C to system dropping di-t-butylchlorophosphine (0.8mol, 144g), then anti-at 0 DEG C
Answering 3 hours, add shrend and go out in system, then separatory, organic layer anhydrous magnesium sulfate is dried, filters, and decompression is distilled off
Obtaining yellow solid after solvent, under argon shield, methanol is recrystallized to give 1-(di-t-butyl phosphino-) ferrocene 258g, productivity
98%.
(2) synthesis of vinyl two (3,5-3,5-dimethylphenyl) phosphine
Under argon shield, in dry reactor add two (3,5-3,5-dimethylphenyl) phosphonium chloride (1mol, 220g) and
0.5L oxolane, then at 0 DEG C to the tetrahydrofuran solution (1.1mol, 0.55L) of system dropping 2M vinylimidazolium chloride magnesium, drips
React at ambient temperature after adding 10 hours, in system, add shrend go out, then separatory, organic layer anhydrous magnesium sulfate
Be dried, filter, decompression obtain after solvent is distilled off white solid, dichloromethane and recrystallizing methanol obtain vinyl two (3,
5-3,5-dimethylphenyl) phosphine 252g, productivity 94%.1H NMR(400MHz,CDCl3),δ:2.18(s,12H),5.50(m,1H),
5.76(m,1H),6.50(m,1H),7.04-7.26(m,6H)；HRMS:[M+H]+Calcd for C18H22P 269.1459,
Found 269.1458；Elementary analysis measured value (value of calculation)/%:C 80.55 (80.57), H 7.88 (7.89).
(3) (R)-(-)-1-[(S)-2-(di-t-butyl phosphine) ferrocene] ethyl two (3,5-3,5-dimethylphenyl) phosphine
Under argon shield, be sequentially added in dry reactor 1-(di-t-butyl phosphino-) ferrocene (0.5mol,
165g), vinyl two (3,5-3,5-dimethylphenyl) phosphine (0.5mol, 134g), ferric chloride (0.1mol, 16g), D-PROLINE
(0.11mol, 12.8g) and and 1L dichloromethane, then 10 DEG C react 12 hours, in system add shrend go out, then
Separatory, organic layer anhydrous magnesium sulfate is dried, filters, and decompression obtains yellow solid, dichloromethane and first after solvent is distilled off
Alcohol be recrystallized to give (R)-(-)-1-[(S)-2-(di-t-butyl phosphine) ferrocene] ethyl two (3,5-3,5-dimethylphenyl) phosphine 278g,
Productivity 93%.1H NMR(400MHz,CDCl3), δ: 1.07 (dd, J=76.6Hz, J=10.1Hz, 18H), 1.86 (m, 3H),
2.20(s,12H),3.42(m,1H),3.85(s,5H,Fc-H),4.37-4.24(m,3H,Fc-H),7.31-7.62(m,6H,
Ph).HRMS:[M+H]+:Calcdfor C36H49FeP2599.2659, Found 599.2658. elementary analysis measured values (calculate
Value)/%:C 72.11 (72.12), H 7.42 (7.40).
Embodiment 3
(1) synthesis of 1-(dicyclohexyl phosphino-) ferrocene
Under argon shield, be sequentially added in dry reactor ferrocene (1mol, 186g), aluminum chloride (1mol,
132g) and 1L normal hexane, then at-20 DEG C to system dropping dicyclohexyl phosphonium chloride (1mol, 232g), then at-20 DEG C
Reacting 3 hours, add shrend and go out in system, then separatory, organic layer anhydrous magnesium sulfate is dried, filters, and decompression distillation removes
Obtaining yellow solid after removing solvent, under argon shield, methanol is recrystallized to give 1-(dicyclohexyl phosphino-) ferrocene 359g, productivity
94%.1H NMR(400MHz,CDCl3),δ:1.10-1.98(m,22H),4.46(s,5H),4.70(m,2H),4.83(m,2H)；
HRMS:[M+H]+Calcd for C22H32FeP 383.1591, Found 383.1592；Elementary analysis measured value (calculates
Value)/%:C69.11 (69.12), H 8.16 (8.17).
(2) synthesis of vinyldiphenylphosphine
Under argon shield, in dry reactor, add diphenyl phosphine chloride (1mol, 220g) and 0.5L oxolane,
Then at 0 DEG C of tetrahydrofuran solution (1.1mol, 0.55L) to system dropping 2M vinylimidazolium chloride magnesium, in room after dropping
Reacting 12 hours under the conditions of temperature, add shrend and go out in system, then separatory, organic layer anhydrous magnesium sulfate is dried, filters, subtracts
Pressure obtains white solid, dichloromethane and recrystallizing methanol after solvent is distilled off and obtains vinyldiphenylphosphine 199g, productivity
94%.
(3) (R)-(-)-1-[(S)-2-(dicyclohexylphosphontetrafluoroborate) ferrocene] ethyldiphenylphosphine
Under argon shield, be sequentially added in dry reactor 1-(dicyclohexyl phosphino-) ferrocene (0.5mol,
165g), vinyldiphenylphosphine (0.5mol, 106g), ferric chloride (0.06mol, 9.7g), D-PROLINE (0.06mol, 7g)
And and 1L dichloromethane, then 25 DEG C react 12 hours, in system add shrend go out, then separatory, organic layer nothing
Water magnesium sulfate is dried, filters, decompression solvent is distilled off after obtain yellow solid, dichloromethane and recrystallizing methanol obtain (R)-
(-)-1-[(S)-2-(dicyclohexylphosphontetrafluoroborate) ferrocene] ethyldiphenylphosphine 276g, productivity 93%.1H NMR(400MHz,
CDCl3),δ:1.08-1.97(m,22H),1.84(m,3H),3.45(m,1H),3.84(s,5H,Fc-H),4.22-4.38(m,
3H,Fc-H),7.13-7.37(m,8H,Ph),7.61-7.66(m,2H,Ph).HRMS:[M+H]+:Calcd for C36H45FeP2
595.2346, Found 595.2347. elementary analysis measured value (value of calculation)/%:C 72.58 (72.60), H 7.61
(7.62).
Embodiment 4
(1) synthesis of 1-(dicyclohexyl phosphino-) ferrocene
Under argon shield, be sequentially added in dry reactor ferrocene (1mol, 186g), aluminum chloride (1mol,
132g) and 1L normal hexane, then at-10 DEG C to system dropping dicyclohexyl phosphonium chloride (0.9mol, 209g), then-10
DEG C reaction 3 hours, in system add shrend go out, then separatory, organic layer anhydrous magnesium sulfate is dried, filters, decompression distillation
Obtaining yellow solid after removing solvent, under argon shield, methanol is recrystallized to give 1-(dicyclohexyl phosphino-) ferrocene 330g, produces
Rate 96%.
(2) synthesis of vinyl two (3,5-3,5-dimethylphenyl) phosphine
Under argon shield, in dry reactor add two (3,5-3,5-dimethylphenyl) phosphonium chloride (1mol, 220g) and
0.5L oxolane, then at 0 DEG C to the tetrahydrofuran solution (1.1mol, 0.55L) of system dropping 2M vinylimidazolium chloride magnesium, drips
React at ambient temperature after adding 10 hours, in system, add shrend go out, then separatory, organic layer anhydrous magnesium sulfate
Be dried, filter, decompression obtain after solvent is distilled off white solid, dichloromethane and recrystallizing methanol obtain vinyl two (3,
5-3,5-dimethylphenyl) phosphine 252g, productivity 94%.
(3) (R)-(-)-1-[(S)-2-(dicyclohexylphosphontetrafluoroborate) ferrocene] ethyl two (3,5-3,5-dimethylphenyl) phosphine
Under argon shield, be sequentially added in dry reactor 1-(dicyclohexyl phosphino-) ferrocene (0.5mol,
165g), vinyl two (3,5-3,5-dimethylphenyl) phosphine (0.6mol, 161g), ferric chloride (0.06mol, 9.7g), D-PROLINE
(0.07mol, 8g) and and 1L dichloromethane, then 25 DEG C react 12 hours, in system add shrend go out, then divide
Liquid, organic layer anhydrous magnesium sulfate is dried, filters, and decompression obtains yellow solid, dichloromethane and methanol after solvent is distilled off
Be recrystallized to give (R)-(-)-1-[(S)-2-(dicyclohexylphosphontetrafluoroborate) ferrocene] ethyl two (3,5-3,5-dimethylphenyl) base phosphine 299g,
Productivity 92%.1H NMR(400MHz,CDCl3),δ:1.06-1.98(m,22H),1.83(m,3H),2.52(m,12H),3.46
(m,1H),3.84(s,5H,Fc-H),4.22-4.37(m,3H,Fc-H),7.13-7.69(m,6H,Ph).HRMS:[M+H]+:
Calcd forC40H53FeP2651.2972, Found 651.2973. elementary analysis measured value (value of calculation)/%:C 73.82
(73.84),H 8.05(8.06).
Embodiment 5
(1) synthesis of 1-(diphenylphosphino) ferrocene
Under argon shield, be sequentially added in dry reactor ferrocene (1mol, 186g), aluminum chloride (1mol,
132g) and 1L normal hexane, then at-20 DEG C to system dropping diphenyl phosphine chloride (1mol, 220g), then anti-at-20 DEG C
Answering 3 hours, add shrend and go out in system, then separatory, organic layer anhydrous magnesium sulfate is dried, filters, and decompression is distilled off
Obtaining yellow solid after solvent, under argon shield, methanol is recrystallized to give 1-(diphenylphosphino) ferrocene 351g, productivity 95%
。1H NMR(400MHz,CDCl3),δ:4.43(s,5H),4.70(m,2H),4.83(m,2H),7.11-7.69(m,10H,Ph)；
HRMS:[M+H]+Calcd for C22H20FeP 371.0652, Found 371.0653；Elementary analysis measured value (calculates
Value)/%:C71.36 (71.38), H 5.16 (5.17).
(2) synthesis of vinyldiphenylphosphine
Under argon shield, in dry reactor, add diphenyl phosphine chloride (1mol, 220g) and 0.5L oxolane,
Then at 0 DEG C of tetrahydrofuran solution (1.1mol, 0.55L) to system dropping 2M vinylimidazolium chloride magnesium, in room after dropping
Reacting 10 hours under the conditions of temperature, add shrend and go out in system, then separatory, organic layer anhydrous magnesium sulfate is dried, filters, subtracts
Pressure obtains white solid, dichloromethane and recrystallizing methanol after solvent is distilled off and obtains vinyldiphenylphosphine 201g, productivity
95%.
(3) (R)-(-)-1-[(S)-2-(diphenylphosphine) ferrocene] ethyldiphenylphosphine
Under argon shield, be sequentially added in dry reactor 1-(diphenylphosphino) ferrocene (0.5mol, 186g),
Vinyldiphenylphosphine (0.5mol, 106g), ferric chloride (0.05mol, 8.1g), D-PROLINE (0.05mol, 5.8g) and
With 1L dichloromethane, then react 12 hours at 25 DEG C, in system, add shrend go out, then separatory, the anhydrous sulfur of organic layer
Acid magnesium be dried, filter, decompression solvent is distilled off after obtain yellow solid, dichloromethane and recrystallizing methanol obtain (R)-(-)-
1-[(S)-2-(diphenylphosphine) ferrocene] ethyldiphenylphosphine 271g, productivity 93%.1H NMR(400MHz,CDCl3),δ:
1.85(m,3H),3.43(m,1H),3.84(s,5H,Fc-H),4.22-4.37(m,3H,Fc-H),7.14-7.65(m,20H,
Ph).HRMS:[M+H]+:Calcd for C36H33FeP2583.1407, Found 583.1406. elementary analysis measured values (meter
Calculation value)/%:C74.10 (74.11), H 5.69 (5.70).
Embodiment 6
(1) synthesis of 1-(diphenylphosphino) ferrocene
Under argon shield, be sequentially added in dry reactor ferrocene (1mol, 186g), aluminum chloride (1mol,
132g) and 1L normal hexane, then at 0 DEG C to system dropping diphenyl phosphine chloride (0.9mol, 198g), then react 2 at 0 DEG C
Hour, in system, adding shrend go out, then separatory, organic layer anhydrous magnesium sulfate is dried, filters, and decompression is distilled off solvent
After obtain yellow solid, under argon shield, methanol is recrystallized to give 1-(diphenylphosphino) ferrocene 323g, productivity 97%.
(2) synthesis of vinyl two (3,5-3,5-dimethylphenyl) phosphine
Under argon shield, in dry reactor add two (3,5-3,5-dimethylphenyl) phosphonium chloride (1mol, 220g) and
0.5L oxolane, then at 0 DEG C to the tetrahydrofuran solution (1.1mol, 0.55L) of system dropping 2M vinylimidazolium chloride magnesium, drips
React at ambient temperature after adding 10 hours, in system, add shrend go out, then separatory, organic layer anhydrous magnesium sulfate
Be dried, filter, decompression obtain after solvent is distilled off white solid, dichloromethane and recrystallizing methanol obtain vinyl two (3,
5-3,5-dimethylphenyl) phosphine 252g, productivity 94%.
(3) (R)-(-)-1-[(S)-2-(diphenylphosphine) ferrocene] ethyl two (3,5-3,5-dimethylphenyl) base phosphine
Under argon shield, be sequentially added in dry reactor 1-(diphenylphosphino) ferrocene (0.5mol, 186g),
Vinyl two (3,5-3,5-dimethylphenyl) base phosphine (0.65mol, 174g), ferric chloride (0.05mol, 8.1g), D-PROLINE
(0.05mol, 5.8g) and and 1L dichloromethane, then 25 DEG C react 12 hours, in system add shrend go out, then divide
Liquid, organic layer anhydrous magnesium sulfate is dried, filters, and decompression obtains yellow solid, dichloromethane and methanol after solvent is distilled off
Be recrystallized to give (R)-(-)-1-[(S)-2-(diphenylphosphine) ferrocene] ethyl two (3,5-3,5-dimethylphenyl) base phosphine 303g, produce
Rate 95%.1H NMR(400MHz,CDCl3),δ:1.81(m,3H),2.43(s,12H),3.42(m,1H),3.86(s,5H,Fc-
H),4.22-4.39(m,3H,Fc-H),7.03-7.72(m,16H,Ph).HRMS:[M+H]+:Calcd for C40H41FeP2
639.2033, Found 639.2035. elementary analysis measured value (value of calculation)/%:C 75.11 (75.12), H 6.45
(6.46).。
Claims (4)
1. the synthetic method of structural formula Josiphos class chiral ferrocene phosphine ligand as shown in (I), it is characterised in that logical
Cross following steps to realize:
Wherein R is the tert-butyl group, cyclohexyl or phenyl；R ' is phenyl or 3,5-3,5-dimethylphenyl；
1) under noble gas is protected, in dry reactor, ferrocene, aluminum chloride and solvent hexane it are sequentially added into, then
Phosphine chlorine compound R is dripped to system at-20-0 DEG C2PCl, after-20-0 DEG C of reaction 2-3 hour, drips shrend in system
Go out, by extracting, be dried, be recrystallized to give 1-(dialkyl group phosphino-) ferrocene or 1-(diphenylphosphino) ferrocene；
2) under noble gas is protected, in dry reactor, 1-(dialkyl group phosphino-) ferrocene or 1-(diaryl phosphine it are sequentially added into
Base) ferrocene, vinyl diaryl phosphine, ferric chloride, D-PROLINE and and methylene chloride, then anti-at 10-30 DEG C
Answering 10-12 hour, reaction terminates to add shrend in backward system and goes out, by extracting, be dried, be recrystallized to give Josiphos class hands
Property ferrocene phosphine part；
Described phosphine chlorine compound R2PCl is di-t-butylchlorophosphine, dicyclohexyl phosphonium chloride or diphenyl phosphine chloride；
Described vinyl diaryl phosphine is vinyldiphenylphosphine or vinyl two (3,5-3,5-dimethylphenyl) phosphine.
2. the synthetic method of Josiphos class chiral ferrocene phosphine ligand as claimed in claim 1, it is characterised in that described
Ferrocene, aluminum chloride and phosphine chlorine compound R2The molar ratio of PCl is 1: 1: 0.8-1.0.
3. the synthetic method of Josiphos class chiral ferrocene phosphine ligand as claimed in claim 1, it is characterised in that described
1-(dialkyl group phosphino-) ferrocene or 1-(diphenylphosphino) ferrocene, ferric chloride feed intake with vinyl diaryl phosphine
Mol ratio is 1: 0.1-0.2: 1-1.3.
4. the synthetic method of Josiphos class chiral ferrocene phosphine ligand as claimed in claim 1, it is characterised in that trichlorine
The molar ratio changing ferrum and D-PROLINE is 1: 1-1.2.
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