CN105949248A - Synthesis method of Josiphos chiral ferrocenyl phosphine ligands - Google Patents

Synthesis method of Josiphos chiral ferrocenyl phosphine ligands Download PDF

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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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CN105949248B (en
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陈辉
杨瑞娜
杨振强
段征
周铎
张银龙
赵顺伟
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PUYANG HUICHENG ELECTRONIC MATERIAL Co.,Ltd.
Institute of Chemistry Henan Academy of Sciences Co Ltd
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Institute of Chemistry Henan Academy of Sciences Co Ltd
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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 System
    • 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

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

The synthetic method of Josiphos class chiral ferrocene phosphine ligand
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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