CN105949248B - The synthetic method of Josiphos class chiral ferrocene phosphine ligands - Google Patents
The synthetic method of Josiphos class chiral ferrocene phosphine ligands Download PDFInfo
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- CN105949248B CN105949248B CN201610356032.4A CN201610356032A CN105949248B CN 105949248 B CN105949248 B CN 105949248B CN 201610356032 A CN201610356032 A CN 201610356032A CN 105949248 B CN105949248 B CN 105949248B
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- ferrocene
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- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 title claims abstract description 82
- 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 title claims abstract description 61
- 229910000073 phosphorus hydride Inorganic materials 0.000 title claims abstract description 39
- 239000003446 ligand Substances 0.000 title claims abstract description 22
- 238000010189 synthetic method Methods 0.000 title claims abstract description 10
- 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
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- ULNVTMFBEVVUMH-UHFFFAOYSA-N P.[Cl] Chemical compound P.[Cl] ULNVTMFBEVVUMH-UHFFFAOYSA-N 0.000 claims abstract description 8
- 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
- -1 phosphino- Chemical class 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 238000010791 quenching Methods 0.000 claims description 21
- 230000000171 quenching effect Effects 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 12
- AJVBXLXLODZUME-UHFFFAOYSA-N ethenyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=C)C1=CC=CC=C1 AJVBXLXLODZUME-UHFFFAOYSA-N 0.000 claims description 11
- ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 claims description 10
- XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 5
- 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
- 238000000605 extraction Methods 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
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 2
- 239000011261 inert gas Substances 0.000 claims 2
- 229910052742 iron Inorganic materials 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 21
- 230000015572 biosynthetic process Effects 0.000 abstract description 19
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 239000003863 metallic catalyst Substances 0.000 abstract description 2
- 238000006053 organic reaction Methods 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 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
- 239000007789 gas Substances 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 class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000007788 liquid Substances 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- 238000000926 separation method Methods 0.000 description 17
- 238000005292 vacuum distillation Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000000921 elemental analysis Methods 0.000 description 11
- 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
- 238000001914 filtration Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 4
- CRHWEIDCXNDTMO-UHFFFAOYSA-N ditert-butylphosphane Chemical compound CC(C)(C)PC(C)(C)C CRHWEIDCXNDTMO-UHFFFAOYSA-N 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- REJGOFYVRVIODZ-UHFFFAOYSA-N phosphanium;chloride Chemical class P.Cl REJGOFYVRVIODZ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052756 noble gas Inorganic materials 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
- 239000005864 Sulphur Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000003321 amplification Effects 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
- 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
- 150000002431 hydrogen Chemical class 0.000 description 1
- FVMNFVVVDRSINO-UHFFFAOYSA-N iron;phosphane Chemical compound P.[Fe] FVMNFVVVDRSINO-UHFFFAOYSA-N 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
- 238000003199 nucleic acid amplification method Methods 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
- 239000002699 waste material Substances 0.000 description 1
Classifications
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- 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 kind of synthetic methods of Josiphos classes chiral ferrocene phosphine ligand, belong to organic synthesis field.This method is achieved by the steps of：Using ferrocene as starting material, the catalyst of alchlor, with phosphine chlorine compound R2PCl reacts, and Josiphos class chiral ferrocene phosphine ligands are then obtained by the reaction with vinyl diaryl phosphin under the catalytic action of ferric trichloride and D proline.Step is few compared with prior art by the present invention, easy to operate, reduces production cost, is suitble to industrialized production.Josiphos classes chiral ferrocene phosphine ligand obtained can be used as the ligand of metallic catalyst, be catalyzed asymmetric organic reactions, be applied to the fields such as medicine synthesis.
Description
Technical field
The invention belongs to organic synthesis fields, are related to the synthetic method of a kind of organic phosphine compound, more particularly to
The synthetic method of Josiphos class chiral ferrocene phosphine ligands.
Background technology
Josiphos class chiral ferrocene phosphine ligands are a kind of very useful and important ligands, pioneering to be only second to
BINAP ligands can be applied in the reaction of the asymmetry organic synthesis such as the amination of alkene asymmetry hydrogen, Michael additions, in industry
It has been used widely in production, has played an important role in the synthesis of many drugs and fine chemicals.
Currently, the synthesis of Josiphos class chiral ferrocene phosphine ligands mainly passes through chirality 1- ferrocenyl ethyl diformazans
Amine (Ugi amine) is obtained by the reaction as reactive intermediate, although Ugi amine is in synthesis, the separation of optical isomer, highly-solid selectively
Formation keeping when substitution reaction occurs of ortho lithiation and dimethylamine group it is constant etc. there is advantage, but at such
Cumbersome chiral resolution recrystallization process is needed in ligand building-up process, be unfavorable for industrialization amplification (J.Chem.Educ.1972,
49(4),294-296；J.Am.Chem.Soc.1994,116(9),4062-4066；Chimia 1999,53(6),275-280)；
In addition, dimethylamino is intended only as seeking group during the reaction, replaced again by phosphine hydrogen compound in target product, in original
It is a kind of waste in terms of subeconomy；In addition, route needs are used to air-sensitive phosphine hydrogen species compound, brought to operation tired
It is difficult.
In view of the superior catalytic activity of such compound and wide market application prospect, explore more efficient, practicality
The synthetic method of Josiphos class chiral ferrocene phosphine ligands is very necessary.
Invention content
A kind of step is few, and easy to operate, production cost is low present invention aims at providing, and is suitble to industrialized production
The novel synthesis of Josiphos class chiral ferrocene phosphine ligands.
Purpose to realize the present invention, reaction route of the present invention are as follows：
Wherein R is tertiary butyl, cyclohexyl or phenyl；R ' is phenyl or 3,5- 3,5-dimethylphenyls；
Reaction step of the present invention is as follows：
1) under noble gas protection, ferrocene, alchlor and solvent hexane are sequentially added into dry reactor, so
Phosphine chlorine compound R is added dropwise to system at -20-0 DEG C afterwards2Then PCl reacts 2-3 hours at -20-0 DEG C, water is added dropwise into system
It is quenched, by extraction, drying, is recrystallized to give 1- (dialkyl group phosphino-) ferrocene or 1- (diphenylphosphino) ferrocene；
2) under noble gas protection, 1- (dialkyl group phosphino-) ferrocene or 1- (hexichol are sequentially added into dry reactor
Base phosphino-) ferrocene, vinyl diaryl phosphin, ferric trichloride, D-PROLINE and methylene chloride, it is then anti-at 10-30 DEG C
It answers 10-12 hours, water quenching is added into system after reaction and goes out, by extraction, drying, is recrystallized to give Josiphos class hands
Property ferrocene phosphine ligand；
The phosphine chlorine compound R2PCl is di-t-butylchlorophosphine, dicyclohexyl phosphonium chloride or diphenyl phosphine chloride.
The vinyl diaryl phosphin is vinyldiphenylphosphine or vinyl two (3,5- 3,5-dimethylphenyls) phosphine.
Ferrocene, alchlor and the 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 trichloride and vinyl two
The molar ratio of aryl phosphine is 1:0.1-0.2:1-1.3.
The molar ratio 1 of the ferric trichloride and D-PROLINE:1-1.2.
Advantageous effect of the present invention is：1) using ferrocene as starting material, with phosphine chlorine compound alchlor catalysis
Effect is lower to occur Friedel-Crafts reaction, and condition is milder compared with traditional handicraft activates the luxuriant ring of ferrocene using butyl lithium；2) sharp
Use vinyl diaryl phosphin stable in the air as phosphine donor, avoiding makes the phosphine hydrogen species compound of air-sensitive
With operation is simpler；2) using cheap ferric trichloride as catalyst, production cost is reduced, and total recovery reaches
92% or more.The reaction route step is few, easy to operate, it is easier to industrialized production.Two cyclopentadienyl of Josiphos classes chirality obtained
Iron Phosphine ligands can be used as the ligand catalysis asymmetric organic reactions of metallic catalyst, be applied to the fields such as medicine synthesis.
Specific implementation mode
For preferably the present invention is described in detail, an example is as follows：
Embodiment 1
(1) synthesis of 1- (di-t-butyl phosphino-) ferrocene
Under protection of argon gas, sequentially added into dry reactor ferrocene (1mol, 186g), alchlor (1mol,
132g) and 1L n-hexanes, di-t-butylchlorophosphine (1mol, 180g) then is added dropwise to system at -20 DEG C, then at -20 DEG C
It reacts 3 hours, water quenching is added into system and goes out, then liquid separation, organic layer is dry with anhydrous magnesium sulfate, filters, and vacuum distillation removes
Yellow solid is obtained after removing solvent, the lower recrystallizing methanol of argon gas protection obtains 1- (di-t-butyl phosphino-) ferrocene 317g, yield
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；Elemental analysis measured value (meter
Calculation value)/%:C65.45(65.47),H 8.23(8.24).
(2) synthesis of vinyldiphenylphosphine
Under protection of argon gas, diphenyl phosphine chloride (1mol, 220g) and 0.5L tetrahydrofurans are added into dry reactor,
Then the tetrahydrofuran solution (1.1mol, 0.55L) of 2M vinylimidazolium chloride magnesium is added dropwise to system at 0 DEG C, in room after being added dropwise
It is reacted 10 hours under the conditions of temperature, water quenching is added into system and goes out, then liquid separation, organic layer is dry with anhydrous magnesium sulfate, filters, and subtracts
Pressure obtains white solid after solvent is distilled off, and dichloromethane and recrystallizing methanol obtain vinyldiphenylphosphine 201g, yield
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；Elemental 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 protection of argon gas, sequentially added into dry reactor 1- (di-t-butyl phosphino-) ferrocene (0.5mol,
165g), vinyldiphenylphosphine (0.5mol, 106g), ferric trichloride (0.05mol, 8.1g), D-PROLINE (0.05mol,
5.8g) and with 1L dichloromethane, then reacted 12 hours at 25 DEG C, into system be added water quenching go out, then liquid separation, organic layer
With anhydrous magnesium sulfate drying, filtering, vacuum distillation obtains yellow solid after removing solvent, and dichloromethane and recrystallizing methanol obtain
(R)-(-) -1- [(S) -2- (di-t-butyl phosphine) ferrocene] ethyldiphenylphosphine 249g, yield 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. elemental analyses measured values (calculated value)/%:C 70.84
(70.85),H 7.42(7.43).
Embodiment 2
(1) synthesis of 1- (di-t-butyl phosphino-) ferrocene
Under protection of argon gas, sequentially added into dry reactor ferrocene (1mol, 186g), alchlor (1mol,
132g) and 1L n-hexanes, di-t-butylchlorophosphine (0.8mol, 144g) then is added dropwise to system at 0 DEG C, it is then anti-at 0 DEG C
It answers 3 hours, water quenching is added into system and goes out, then liquid separation, organic layer is dry with anhydrous magnesium sulfate, filters, and vacuum distillation removes
Yellow solid is obtained after solvent, the lower recrystallizing methanol of argon gas protection obtains 1- (di-t-butyl phosphino-) ferrocene 258g, yield
98%.
(2) synthesis of vinyl two (3,5- 3,5-dimethylphenyls) phosphine
Under protection of argon gas, into dry reactor be added two (3,5- 3,5-dimethylphenyl) phosphonium chlorides (1mol, 220g) and
Then the tetrahydrofuran solution (1.1mol, 0.55L) of 2M vinylimidazolium chloride magnesium, drop is added dropwise in 0.5L tetrahydrofurans at 0 DEG C to system
It is reacted at ambient temperature after adding 10 hours, water quenching is added into system and goes out, then liquid separation, organic layer anhydrous magnesium sulfate
Dry, filtering, vacuum distillation, which removes, obtains white solid after solvent, dichloromethane and recrystallizing methanol obtain vinyl two (3,
5- 3,5-dimethylphenyls) phosphine 252g, yield 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；Elemental analysis measured value (calculated value)/%: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-dimethylphenyls) phosphine
Under protection of argon gas, sequentially added into dry reactor 1- (di-t-butyl phosphino-) ferrocene (0.5mol,
165g), vinyl two (3,5- 3,5-dimethylphenyl) phosphine (0.5mol, 134g), ferric trichloride (0.1mol, 16g), D-PROLINE
(0.11mol, 12.8g) and with 1L dichloromethane, then reacted 12 hours at 10 DEG C, into system be added water quenching go out, then
Liquid separation, organic layer is dry with anhydrous magnesium sulfate, filters, and vacuum distillation obtains yellow solid, dichloromethane and first after removing solvent
Alcohol is recrystallized to give (R)-(-) -1- [(S) -2- (di-t-butyl phosphine) ferrocene] ethyl two (3,5- 3,5-dimethylphenyl) phosphine 278g,
Yield 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. elemental analyses measured values (calculate
Value)/%:C 72.11(72.12),H 7.42(7.40).
Embodiment 3
(1) synthesis of 1- (dicyclohexyl phosphino-) ferrocene
Under protection of argon gas, sequentially added into dry reactor ferrocene (1mol, 186g), alchlor (1mol,
132g) and 1L n-hexanes, dicyclohexyl phosphonium chloride (1mol, 232g) then is added dropwise to system at -20 DEG C, then at -20 DEG C
It reacts 3 hours, water quenching is added into system and goes out, then liquid separation, organic layer is dry with anhydrous magnesium sulfate, filters, and vacuum distillation removes
Yellow solid is obtained after removing solvent, the lower recrystallizing methanol of argon gas protection obtains 1- (dicyclohexyl phosphino-) ferrocene 359g, yield
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；Elemental analysis measured value (calculates
Value)/%:C69.11(69.12),H 8.16(8.17).
(2) synthesis of vinyldiphenylphosphine
Under protection of argon gas, diphenyl phosphine chloride (1mol, 220g) and 0.5L tetrahydrofurans are added into dry reactor,
Then the tetrahydrofuran solution (1.1mol, 0.55L) of 2M vinylimidazolium chloride magnesium is added dropwise to system at 0 DEG C, in room after being added dropwise
It is reacted 12 hours under the conditions of temperature, water quenching is added into system and goes out, then liquid separation, organic layer is dry with anhydrous magnesium sulfate, filters, and subtracts
Pressure obtains white solid after solvent is distilled off, and dichloromethane and recrystallizing methanol obtain vinyldiphenylphosphine 199g, yield
94%.
(3) (R)-(-) -1- [(S) -2- (dicyclohexylphosphontetrafluoroborate) ferrocene] ethyldiphenylphosphine
Under protection of argon gas, sequentially added into dry reactor 1- (dicyclohexyl phosphino-) ferrocene (0.5mol,
165g), vinyldiphenylphosphine (0.5mol, 106g), ferric trichloride (0.06mol, 9.7g), D-PROLINE (0.06mol, 7g)
And with 1L dichloromethane, then reacted 12 hours at 25 DEG C, into system be added water quenching go out, then liquid separation, organic layer nothing
Water magnesium sulfate is dry, filters, and vacuum distillation obtains yellow solid after removing solvent, and dichloromethane and recrystallizing methanol obtain (R)-
(-) -1- [(S) -2- (dicyclohexylphosphontetrafluoroborate) ferrocene] ethyldiphenylphosphine 276g, yield 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. elemental analyses measured values (calculated value)/%:C 72.58(72.60),H 7.61
(7.62).
Embodiment 4
(1) synthesis of 1- (dicyclohexyl phosphino-) ferrocene
Under protection of argon gas, sequentially added into dry reactor ferrocene (1mol, 186g), alchlor (1mol,
132g) and 1L n-hexanes, dicyclohexyl phosphonium chloride (0.9mol, 209g) then is added dropwise to system at -10 DEG C, then -10
DEG C reaction 3 hours, into system water quenching is added goes out, then liquid separation, and organic layer is dry with anhydrous magnesium sulfate, filtering, vacuum distillation
Yellow solid is obtained after removing solvent, the lower recrystallizing methanol of argon gas protection obtains 1- (dicyclohexyl phosphino-) ferrocene 330g, produces
Rate 96%.
(2) synthesis of vinyl two (3,5- 3,5-dimethylphenyls) phosphine
Under protection of argon gas, into dry reactor be added two (3,5- 3,5-dimethylphenyl) phosphonium chlorides (1mol, 220g) and
Then the tetrahydrofuran solution (1.1mol, 0.55L) of 2M vinylimidazolium chloride magnesium, drop is added dropwise in 0.5L tetrahydrofurans at 0 DEG C to system
It is reacted at ambient temperature after adding 10 hours, water quenching is added into system and goes out, then liquid separation, organic layer anhydrous magnesium sulfate
Dry, filtering, vacuum distillation, which removes, obtains white solid after solvent, dichloromethane and recrystallizing methanol obtain vinyl two (3,
5- 3,5-dimethylphenyls) phosphine 252g, yield 94%.
(3) (R)-(-) -1- [(S) -2- (dicyclohexylphosphontetrafluoroborate) ferrocene] ethyl two (3,5- 3,5-dimethylphenyls) phosphine
Under protection of argon gas, sequentially added into dry reactor 1- (dicyclohexyl phosphino-) ferrocene (0.5mol,
165g), vinyl two (3,5- 3,5-dimethylphenyl) phosphine (0.6mol, 161g), ferric trichloride (0.06mol, 9.7g), D-PROLINE
(0.07mol, 8g) and with 1L dichloromethane, then reacted 12 hours at 25 DEG C, into system be added water quenching go out, then divide
Liquid, organic layer is dry with anhydrous magnesium sulfate, filters, and vacuum distillation obtains yellow solid, dichloromethane and methanol after removing solvent
It is recrystallized to give (R)-(-) -1- [(S) -2- (dicyclohexylphosphontetrafluoroborate) ferrocene] ethyl two (3,5- 3,5-dimethylphenyl) base phosphine 299g,
Yield 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. elemental analyses measured values (calculated value)/%:C 73.82
(73.84),H 8.05(8.06).
Embodiment 5
(1) synthesis of 1- (diphenylphosphino) ferrocene
Under protection of argon gas, sequentially added into dry reactor ferrocene (1mol, 186g), alchlor (1mol,
132g) and 1L n-hexanes, diphenyl phosphine chloride (1mol, 220g) then is added dropwise to system at -20 DEG C, it is then anti-at -20 DEG C
It answers 3 hours, water quenching is added into system and goes out, then liquid separation, organic layer is dry with anhydrous magnesium sulfate, filters, and vacuum distillation removes
Yellow solid is obtained after solvent, the lower recrystallizing methanol of argon gas protection obtains 1- (diphenylphosphino) ferrocene 351g, yield 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；Elemental analysis measured value (calculates
Value)/%:C71.36(71.38),H 5.16(5.17).
(2) synthesis of vinyldiphenylphosphine
Under protection of argon gas, diphenyl phosphine chloride (1mol, 220g) and 0.5L tetrahydrofurans are added into dry reactor,
Then the tetrahydrofuran solution (1.1mol, 0.55L) of 2M vinylimidazolium chloride magnesium is added dropwise to system at 0 DEG C, in room after being added dropwise
It is reacted 10 hours under the conditions of temperature, water quenching is added into system and goes out, then liquid separation, organic layer is dry with anhydrous magnesium sulfate, filters, and subtracts
Pressure obtains white solid after solvent is distilled off, and dichloromethane and recrystallizing methanol obtain vinyldiphenylphosphine 201g, yield
95%.
(3) (R)-(-) -1- [(S) -2- (diphenylphosphine) ferrocene] ethyldiphenylphosphine
Under protection of argon gas, sequentially added into dry reactor 1- (diphenylphosphino) ferrocene (0.5mol, 186g),
Vinyldiphenylphosphine (0.5mol, 106g), ferric trichloride (0.05mol, 8.1g), D-PROLINE (0.05mol, 5.8g) and
It with 1L dichloromethane, is then reacted 12 hours at 25 DEG C, water quenching is added into system and goes out, then liquid separation, the anhydrous sulphur of organic layer
Sour magnesium is dry, filters, and vacuum distillation obtains yellow solid after removing solvent, and dichloromethane and recrystallizing methanol obtain (R)-(-)-
1- [(S) -2- (diphenylphosphine) ferrocene] ethyldiphenylphosphine 271g, yield 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. elemental analyses measured values (meter
Calculation value)/%:C74.10(74.11),H 5.69(5.70).
Embodiment 6
(1) synthesis of 1- (diphenylphosphino) ferrocene
Under protection of argon gas, sequentially added into dry reactor ferrocene (1mol, 186g), alchlor (1mol,
132g) and 1L n-hexanes then react 2 then at 0 DEG C to system dropwise addition diphenyl phosphine chloride (0.9mol, 198g) at 0 DEG C
Hour, into system water quenching is added goes out, then liquid separation, and organic layer is dry with anhydrous magnesium sulfate, filtering, and vacuum distillation removes solvent
After obtain yellow solid, the lower recrystallizing methanol of argon gas protection obtains 1- (diphenylphosphino) ferrocene 323g, yield 97%.
(2) synthesis of vinyl two (3,5- 3,5-dimethylphenyls) phosphine
Under protection of argon gas, into dry reactor be added two (3,5- 3,5-dimethylphenyl) phosphonium chlorides (1mol, 220g) and
Then the tetrahydrofuran solution (1.1mol, 0.55L) of 2M vinylimidazolium chloride magnesium, drop is added dropwise in 0.5L tetrahydrofurans at 0 DEG C to system
It is reacted at ambient temperature after adding 10 hours, water quenching is added into system and goes out, then liquid separation, organic layer anhydrous magnesium sulfate
Dry, filtering, vacuum distillation, which removes, obtains white solid after solvent, dichloromethane and recrystallizing methanol obtain vinyl two (3,
5- 3,5-dimethylphenyls) phosphine 252g, yield 94%.
(3) (R)-(-) -1- [(S) -2- (diphenylphosphine) ferrocene] ethyl two (3,5- 3,5-dimethylphenyls) base phosphine
Under protection of argon gas, sequentially added into dry reactor 1- (diphenylphosphino) ferrocene (0.5mol, 186g),
Vinyl two (3,5- 3,5-dimethylphenyl) base phosphine (0.65mol, 174g), ferric trichloride (0.05mol, 8.1g), D-PROLINE
(0.05mol, 5.8g) and with 1L dichloromethane, then reacted 12 hours at 25 DEG C, into system be added water quenching go out, then divide
Liquid, organic layer is dry with anhydrous magnesium sulfate, filters, and vacuum distillation obtains yellow solid, dichloromethane and methanol after removing solvent
It is recrystallized to give (R)-(-) -1- [(S) -2- (diphenylphosphine) ferrocene] ethyl two (3,5- 3,5-dimethylphenyl) base phosphine 303g, is produced
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. elemental analyses measured values (calculated value)/%:C 75.11(75.12),H 6.45
(6.46).。
Claims (4)
1. the synthetic method of structural formula Josiphos classes chiral ferrocene phosphine ligand as shown in (I), which is characterized in that logical
Cross following steps realization：
Wherein R is tertiary butyl, cyclohexyl or phenyl；R ' is phenyl or 3,5- 3,5-dimethylphenyls；
1）Under inert gas protection, ferrocene, alchlor and solvent hexane are sequentially added into dry reactor, so
Phosphine chlorine compound R is added dropwise to system at -20-0 DEG C afterwards2Water quenching is added dropwise into system after being reacted 2-3 hours at -20-0 DEG C by PCl
It goes out, by extraction, drying, is recrystallized to give 1- (dialkyl group phosphino-) ferrocene or 1- (diphenylphosphino) ferrocene；
2）Under inert gas protection, 1- (dialkyl group phosphino-) ferrocene or 1- (hexichol are sequentially added into dry reactor
Base phosphino-) ferrocene, vinyl diaryl phosphin, ferric trichloride, D-PROLINE and and methylene chloride, then in 10-30
DEG C reaction 10-12 hour, after reaction into system addition water quenching go out, by extraction, drying, be recrystallized to give Josiphos
Class chiral ferrocene phosphine ligand；
The phosphine chlorine compound R2PCl is di-t-butylchlorophosphine, dicyclohexyl phosphonium chloride or diphenyl phosphine chloride；
The vinyl diaryl phosphin is vinyldiphenylphosphine or vinyl two (3,5- 3,5-dimethylphenyls) phosphine.
2. the synthetic method of Josiphos classes chiral ferrocene phosphine ligand as described in claim 1, which is characterized in that described
Ferrocene, alchlor and phosphine chlorine compound R2The molar ratio of PCl is 1: 1 : 0.8-1.0.
3. the synthetic method of Josiphos classes chiral ferrocene phosphine ligand as described in claim 1, which is characterized in that described
1- (dialkyl group phosphino-) ferrocene or 1- (diphenylphosphino) ferrocene, ferric trichloride and vinyl diaryl phosphin feeds intake
Molar ratio is 1: 0.1-0.2 : 1-1.3.
4. the synthetic method of Josiphos classes chiral ferrocene phosphine ligand as described in claim 1, which is characterized in that trichlorine
The molar ratio for changing iron and D-PROLINE is 1: 1-1.2.
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| CN101479284A (en) * | 2006-06-30 | 2009-07-08 | 索尔维亚斯股份公司 | Diphosphine ligands |
| CN101570550A (en) * | 2009-06-09 | 2009-11-04 | 武汉理工大学 | Method for synthesizing chiral ferrocene diphosphine ligand |
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| CN101479284A (en) * | 2006-06-30 | 2009-07-08 | 索尔维亚斯股份公司 | Diphosphine ligands |
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