[go: up one dir, main page]

CN114085251B - Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof - Google Patents

Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof Download PDF

Info

Publication number
CN114085251B
CN114085251B CN202111287691.4A CN202111287691A CN114085251B CN 114085251 B CN114085251 B CN 114085251B CN 202111287691 A CN202111287691 A CN 202111287691A CN 114085251 B CN114085251 B CN 114085251B
Authority
CN
China
Prior art keywords
reaction
spiro
chiral
ferrocene
biphosphine ligand
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202111287691.4A
Other languages
Chinese (zh)
Other versions
CN114085251A (en
Inventor
聂慧芳
张生勇
李斌
姜茹
张东旭
魏朝
姚琳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fourth Military Medical University FMMU
Original Assignee
Fourth Military Medical University FMMU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fourth Military Medical University FMMU filed Critical Fourth Military Medical University FMMU
Priority to CN202111287691.4A priority Critical patent/CN114085251B/en
Publication of CN114085251A publication Critical patent/CN114085251A/en
Application granted granted Critical
Publication of CN114085251B publication Critical patent/CN114085251B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • B01J31/2442—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring comprising condensed ring systems
    • B01J31/249—Spiro-condensed ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
    • 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
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/827—Iridium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)

Abstract

A chiral ferrocene-spiro framework biphosphine ligand is prepared from chiral ferrocenylamine through ortholithiation, reaction with phosphine trichloride to obtain a dichlorophosphine intermediate, reduction by lithium aluminum hydride to obtain a primary phosphine intermediate, reaction of said intermediate with spiro dibenzyl to generate chiral ferrocene-spiro framework monophosphonic substituted compound, and reaction with different secondary phosphines to obtain ferrocene-spiro framework biphosphine ligand with different chiral centers. The biphosphine ligand not only has the advantages of ferrocene and spiro framework, but also has the advantages of simple synthesis and modularization, and the complex catalyst formed by the biphosphine ligand and metal shows high catalytic activity and stereoselectivity in asymmetric reduction reactions of prochiral olefin, prochiral ketone, prochiral imine and the like.

Description

Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof
Technical Field
The invention relates to a chiral ferrocene-spiro framework biphosphine ligand and a preparation method thereof.
Background
Chiral fine chemical products are widely applied in the fields of medicines, pesticides, fragrances and the like, so that the preparation of the chiral fine chemical products has very important significance. The method for synthesizing the chiral compound mainly comprises chiral source synthesis, racemate resolution, catalytic asymmetric synthesis and the like, and asymmetric catalytic hydrogenation in the catalytic asymmetric synthesis becomes the most ideal method for synthesizing the chiral compound due to the advantages of atom economy, excellent catalytic efficiency, green and clean production process and the like, and is the most mature chiral catalytic technology developed in the current industrial production. The key to asymmetric catalytic hydrogenation is the metal complex catalyst, while the ligand is the core and key to the metal complex catalyst. Therefore, the design of the ligand with novel synthetic structure is always a hot spot for research of asymmetric catalytic hydrogenation reaction and is also the most active field in the research of asymmetric synthesis.
Ferrocene scaffold and spiro scaffold are dominant scaffolds in chiral ligand design, and excellent ligands developed based on these two types of scaffold are not counted, such as Josiphos and SDP, and f-spiroPhos, where two types of scaffold are linked to the same ligand structure, is also an excellent representation. Although tens of thousands of chiral ligands have been reported, many of them exhibit high stereoselectivity, there are few examples of their actual use in industrial production due to low catalytic activity, complicated preparation, difficult modification, and high cost. Therefore, the development of a novel ligand which has high activity, simple synthesis and easy modification has important significance.
The ligand structure mentioned in the above paragraph is as follows:
disclosure of Invention
In order to overcome the defects in the prior art, the invention aims to provide the chiral ferrocene-spiro framework biphosphine ligand and the preparation method thereof, and the ligand not only has the advantages of dominant ferrocene and spiro framework, but also has the advantage of modularization in synthesis, and a complex catalyst formed by the ligand and metal shows high catalytic activity and stereoselectivity in asymmetric reduction reactions of prochiral olefin, prochiral ketone, prochiral imine and the like.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
the chiral ferrocene-spiro framework biphosphine ligand has a molecular structural formula shown in formula 1:
wherein: r is R 1 Is C 1 ～C 6 Alkyl and cycloalkyl aliphatic radicals; c (C) 6 ～C 20 Aromatic groups of (a); r is R 2 Is C 1 ～C 6 Alkyl and cycloalkyl aliphatic radicals; c of benzyl group 7 ～C 20 A combination of an aromatic group and an aliphatic group; c of aryl groups 6 ～C 20 An aromatic group within; the above formula includes stereoisomers thereof.
The synthetic route of the chiral ferrocene-spiro framework biphosphine ligand is as follows:
the preparation method of the chiral ferrocene-spiro framework biphosphine ligand is characterized by comprising the following steps of:
slowly dropwise adding a tert-butyl lithium pentane solution into a methyl tert-butyl ether solution taking (S) -1 or (R) -1 as a raw material at the temperature of-10-30 ℃, wherein the mol ratio of reactants to tert-butyl lithium is 1:1 to 1.2, after the dripping is finished, the mixture is heated to room temperature for reaction; the reaction solution is placed below minus 40 ℃ to minus 80 ℃ again, PCl is slowly added by a syringe 3 Slowly heating to room temperature for reaction for 1-6 h, filtering to remove insoluble substances, and spin-drying the solvent to obtain reddish brown oily matter;
at the temperature of between 10 ℃ below zero and 30 ℃, tetrahydrofuran is dissolved and then is added into LiAlH in a dropwise manner 4 In the methyl tertiary butyl ether solution, the reactant and LiAlH 4 The molar ratio of (2) is 1:2 to 6, reacting for 12 to 24 hours at room temperatureAdding sodium hydroxide solution, stirring, layering, drying, evaporating the solvent to obtain a crude product, and distilling under reduced pressure to obtain a primary phosphine intermediate (S, rp) -2 which is directly used for the next reaction;
weighing NaH, adding into a Schlenk reaction tube, vacuumizing/filling Ar, adding tetrahydrofuran, stirring, adding spiro dibenzyl (R) -3 dissolved in tetrahydrofuran by a syringe, cooling to-40 to-80 ℃, and slowly adding primary phosphine intermediate (S, R) dissolved in tetrahydrofuran p ) And 2, after the addition, naturally heating up for reaction for 12-24 h, then carrying out reflux reaction for 12-24 h, adding saturated sodium bicarbonate solution into the reaction solution for quenching reaction, sequentially washing an organic phase with distilled water and saturated saline water after layering the solution, then drying with anhydrous sodium sulfate, filtering, spin-drying, and separating and purifying by column chromatography (ethyl acetate: petroleum ether: triethylamine=1:20:0.5) to obtain an orange foam product 4.
The transition metal complex catalyst of the chiral diphosphine ligand is prepared from ruthenium (Ru), rhodium (Rh), iridium (Ir), palladium (Pd), platinum (Pt), iron (Fe), cobalt (Co), nickel (Ni) and manganese (Mn).
The transition metal complex catalyst is used for catalyzing asymmetric hydrogenation reaction, hydroformylation reaction, hydrocyanation reaction, hydrosilation reaction, hydroboration reaction, olefin double decomposition reaction, isomerization reaction, diels-Alder reaction, heck reaction, aldol reaction, michael addition reaction and asymmetric epoxidation reaction.
The beneficial effects of the invention are as follows:
the biphosphine ligand not only has the advantages of ferrocene and spiro framework, but also has the advantages of simple synthesis and modularization, and the complex catalyst formed by the biphosphine ligand and metal shows high catalytic activity and stereoselectivity in asymmetric reduction reactions of prochiral olefin, prochiral ketone, prochiral imine and the like.
The chiral ligand is connected with the dominant ferrocene skeleton and the spiro skeleton, and the easily modified side chain phosphine group is introduced, so that compared with f-spiroPhos, the chiral spiro block is less in use, an easily modified site is added, and the synthetic route is very concise and efficient.
Detailed Description
The invention is further described below with reference to examples.
The chiral ferrocene-spiro framework biphosphine ligand has a molecular structural formula shown in formula 1:
wherein: r is R 1 Is C 1 ～C 6 Alkyl and cycloalkyl aliphatic radicals; c (C) 6 ～C 20 Aromatic groups of (a); r is R 2 Is C 1 ～C 6 Alkyl and cycloalkyl aliphatic radicals; c of benzyl group 7 ～C 20 A combination of an aromatic group and an aliphatic group; c of aryl groups 6 ～C 20 An aromatic group within; the above general formula contains stereoisomers thereof, and specific examples of chiral ligands of the invention (L1-L5) are given below
A. Synthesis of ligands
Example 1
To a solution of (S) -1 (2.57 g,10 mmol) in methyl tert-butyl ether was slowly added dropwise a solution of 1.3M tert-butyllithium (8.1 mL,10.5 mmol) in pentane at 0deg.C, and after the addition was completed, the reaction was allowed to proceed to room temperature for 1.5h; the reaction solution was again kept below-78℃and PCl was slowly added by syringe 3 (1.5 g,10.9 mmol) was slowly warmed to room temperature and reacted for 6h, insoluble materials were removed by filtration, and the solvent was dried by spinning to give a reddish brown oil. At 0 ℃, tetrahydrofuran is dissolved and then is added to LiAlH in a dropwise manner 4 (0.95 g,25 mmol) methyl tertiary butyl ether solution, reacting overnight at room temperature, adding 15% sodium hydroxide solution, stirring for 2h, layering, drying, evaporating the solvent to obtain a crude product, and distilling under reduced pressure to obtain a primary phosphine intermediate (S, rp) -2, which is directly used for the next reaction.
NaH (320 mg,8 mmol) was weighed into a Schlenk reaction tube10mL of tetrahydrofuran was added with stirring by evacuating/filling Ar, spirodibenzyl (R) -3 (632 mg,2 mmol) dissolved in 5mL of tetrahydrofuran was added by syringe, the temperature was lowered to-78℃and primary phosphine intermediate (S, R) dissolved in 5mL of tetrahydrofuran was slowly added p ) -2 (578 mg,2 mmol), after the addition, naturally heating up and reacting for 20h, refluxing and reacting for 10h, adding saturated sodium bicarbonate solution into the reaction solution to quench the reaction, washing an organic phase with distilled water and saturated saline water sequentially after layering the solution, then drying with anhydrous sodium sulfate, filtering, spin-drying, and separating and purifying by column chromatography (ethyl acetate: petroleum ether: triethylamine=1:20:0.5) to obtain orange foam-like products (S, R) p ,R spiro ) 4810mg, 76% yield. 1 H NMR(400Hz,CDCl 3 )δ7.24–7.18(m,1H),7.18–7.07(m,2H),6.97(d,J＝7.4Hz,1H),6.77(t,J＝7.5Hz,1H),5.87(d,J＝7.5Hz,1H),4.27(s,1H),4.11(dd,J＝6.8,3.0Hz,1H),4.04(s,5H),3.99(s,1H),3.13(s,1H),3.07–2.95(m,2H),2.92–2.78(m,4H),2.76–2.63(m,2H),2.32–2.19(m,2H),2.15(s,6H),2.04–1.92(m,1H),1.92–1.80(m,1H),1.24(d,J＝6.8Hz,3H)； 13 C NMR(101Hz,CDCl 3 )δ148.0(d,J＝4.4Hz),146.5,143.0,142.0,133.6(d,J＝6.5Hz),130.8(d,J＝6.0Hz),129.3,128.3(d,J＝5.4Hz),127.4,125.9,122.5(d,J＝3.0Hz),121.5,96.9(d,J＝22.0Hz),77.3,74.5(d,J＝18.3Hz),71.2(d,J＝5.1Hz),69.4,69.1(d,J＝3.2Hz),66.9,61.3,56.9(d,J＝8.4Hz),39.3,38.6,37.5,30.5(d,J＝17.7Hz),28.4(d,J＝24.4Hz),26.5(d,J＝14.0Hz),7.5； 31 P NMR(162Hz,CDCl 3 )δ-31.99；HRMS(ESI)calcd for C 33 H 37 FeNP[M+H] + :534.2013,Found:534.2103。
Example 2
Primary phosphine intermediate (R, S) was obtained by the same procedure as in example 1 using (R) -1 as the starting material p ) -2. The orange foam-like product (R, S) was obtained in the same manner as in example 1 using spiro dibenzyl (R) -3 as the starting material p ,R spiro ) -4, 73% yield. (ethyl acetate: petroleum ether: triethylamine = 1:20:0.5). 1 H NMR(400Hz,CDCl 3 )δ7.25–7.09(m,4H),7.04(d,J＝7.5Hz,1H),6.98(d,J＝7.6Hz,1H),4.27–4.21(m,2H),4.19(s,5H),4.11(s,1H),4.01(s,1H),3.21–3.12(m,1H),3.12–2.92(m,4H),2.90–2.75(m,3H),2.19(s,6H),2.14–2.02(m,2H),2.02–1.92(m,1H),1.86–1.74(m,1H),1.26(d,J＝2.2Hz,3H)； 13 C NMR(101Hz,CDCl 3 )δ148.3,147.1(d,J＝4.5Hz),143.0,142.9(d,J＝2.7Hz),134.7(d,J＝6.8Hz),132.1(d,J＝5.1Hz),129.4,127.9(d,J＝6.0Hz),127.6(d,J＝3.0Hz),126.6,122.8,122.06(d,J＝3.6Hz),98.0(d,J＝25.0Hz),77.3,76.3(d,J＝27.8Hz),70.5(d,J＝5.9Hz),69.3,68.2,68.0(d,J＝4.2Hz),65.9,61.7,56.6(d,J＝11.0Hz),39.3,37.9,31.5(d,J＝14.3Hz),30.2(d,J＝13.9Hz),27.7(d,J＝25.7Hz),7.7； 31 P NMR(162Hz,CDCl 3 )δ-26.86；HRMS(ESI)calcd for C 33 H 37 FeNP[M+H] + :534.2013,Found:534.2051。
Implementation 3
To the monophosphine intermediate (S, R) p ,R spiro ) A solution of-4 (53 mg,1 mmol) in glacial acetic acid (5 mL) was added to di-tert-butylphosphine (146 mg,1 mmol), the reaction temperature was increased to 82-107 ℃, 31 PNMR monitoring to end of reaction. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and successively with water, saturated NaHCO 3 The solution was washed with saturated NaCl, dried, spin-dried and column chromatographed (ethyl acetate: petroleum ether=1:30) to give the orange bisphosphine ligand L1412 mg, 65% yield. 1 H NMR(400Hz,CDCl 3 )δ7.23–7.06(m,3H),6.99(d,J＝7.4Hz,1H),6.79(t,J＝7.4Hz,1H),6.27(d,J＝7.5Hz,1H),4.24(s,1H),4.14(s,1H),4.19–4.09(m,1H),4.06(s,5H),3.95(s,1H),3.66–3.56(m,1H),,3.39(dd,J＝7.5,2.7Hz,1H),3.09–2.98(m,2H),2.93–2.75(m,3H),2.62(dd,J＝13.5,8.7Hz,1H),2.41–2.15(m,3H),2.05–1.93(m,1H),1.89–1.80(m,3H),1.28(d,J＝10.6Hz,9H),1.17(d,J＝10.7Hz,9H)； 13 C NMR(101Hz,CDCl 3 )δ148.1(d,J＝4.3Hz),146.8(d,J＝31.5Hz),144.0,142.9,141.9,133.9(d,J＝6.8Hz),133.6,131.5(d,J＝5.9Hz),129.7,129.5,128.5(d,J＝5.4Hz),128.2,127.2(d,J＝2.7Hz),125.5(d,J＝64.5Hz),122.4(d,J＝3.1Hz),121.4,102.2(t,J＝24.2Hz),77.3,72.5(dd,J＝21.2,4.3Hz),71.2(d,J＝4.4Hz),69.9(d,J＝3.4Hz),69.4,66.6,61.3,42.6,38.5,38.2(d,J＝126.8Hz),34.6–33.5(m),31.9(d,J＝13.9Hz),31.6(dd,J＝13.2,3.0Hz),30.9–30.3(m),30.1(d,J＝6.7Hz),28.2(dd,J＝24.7,15.0Hz),27.4(d,J＝15.0Hz),17.2(d,J＝2.7Hz)； 31 P NMR(162Hz,CDCl 3 )δ50.61(d,J＝18.5Hz),-35.84(d,J＝17.6Hz)；HRMS(ESI)calcd for C 39 H 49 FeP 2 [M+H] + :635.2659,Found:635.2724。
Example 4
To the monophosphine intermediate (S, R) p ,R spiro ) A solution of-4 (53 mg,1 mmol) in glacial acetic acid (5 mL) was added dicyclohexylphosphine (198 mg,1 mmol), the reaction temperature was raised to 82-107 ℃, 31 p NMR was monitored to end the reaction. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and successively with water, saturated NaHCO 3 The solution was washed with saturated NaCl, dried, spin-dried and column chromatographed (ethyl acetate: petroleum ether=1:30) to give orange bisphosphine ligand L2466 mg, 68% yield. 1 H NMR(400Hz,CDCl 3 )δ7.28–7.08(m,3H),6.99(d,J＝7.3Hz,3H),6.79(t,J＝7.3Hz,1H),6.16(d,J＝7.6Hz,1H),4.21(s,1H),4.15(s,1H),4.07(s,5H),4.00(s,1H),3.50–3.35(m,1H),3.31–3.26(m,1H),3.14–2.61(m,9H),2.40–2.10(m,3H),2.04–1.49(m,21H),1.18(d,J＝8.8Hz,3H)； 13 C NMR(101Hz,CDCl 3 )δ148.1(d,J＝4.1Hz),147.0,146.6,144.0,143.0,141.9,133.6(d,J＝7.2Hz),131.2(d,J＝5.9Hz),129.7,129.5,128.5(d,J＝5.4Hz),128.2,127.3(d,J＝2.7Hz),125.9,125.2,122.5(d,J＝3.0Hz),121.5,100.2(dd,J＝24.2,18.4Hz),77.3,72.3(dd,J＝19.7,3.1Hz),71.1(d,J＝4.7Hz),69.3,68.6(d,J＝3.5Hz),67.0,61.3,42.6,38.8,38.5,37.6,34.1(d,J＝24.1Hz),32.5(d,J＝19.9Hz),31.7(d,J＝18.6Hz),31.1,30.8(d,J＝13.1Hz),30.5(d,J＝15.8Hz),30.2(d,J＝3.0Hz),29.7(d,J＝9.4Hz),28.6(dd,J＝23.8,13.7Hz),28.0(d,J＝14.3Hz),27.8(d,J＝4.5Hz),27.6–26.8(m),26.5(d,J＝2.8Hz),15.3(d,J＝2.6Hz)； 31 P NMR(162Hz,CDCl 3 )δ14.77(d,J＝17.5Hz),-36.08(d,J＝17.5Hz)；HRMS(ESI)calcd for C 43 H 53 FeP 2 [M+H] + :687.2972,Found:687.3026。
Example 5
To the monophosphine intermediate (S, R) p ,R spiro ) A solution of 4 (53 mg,1 mmol) in glacial acetic acid (5 mL) was added to diphenylphosphine (186 mg,1 mmol), the reaction temperature was increased to 82-107 ℃, 31 p NMR was monitored to end the reaction. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and successively with water, saturated NaHCO 3 The solution was washed with saturated NaCl, dried, spin-dried and column chromatographed (ethyl acetate: petroleum ether=1:30) to give 3505 mg of the orange bisphosphine ligand L, 75% yield. 1 H NMR(400Hz,CDCl 3 )δ7.45–7.29(m,10H),7.21(d,J＝7.3Hz,1H),7.18–7.14(m,1H),7.13–7.07(m,1H),7.06–7.02(m,1H),6.91(t,J＝7.4Hz,1H),6.35(d,J＝7.5Hz,1H),4.08(s,5H),3.99(s,1H),3.91–3.83(m,1H),3.69(s,1H),3.17–3.12(m,1H),3.10(s,1H),3.06–2.87(m,4H),2.86–2.78(m,2H),2.72(dd,J＝13.8,7.9Hz,1H),2.28(dd,J＝12.1,6.5Hz,1H),2.19(dd,J＝12.3,6.6Hz,1H),2.06–1.95(m,1H),1.91–1.79(m,1H),1.39–1.32(m,3H)； 13 C NMR(101Hz,CDCl 3 )δ148.1(d,J＝4.1Hz),146.8,143.1(d,J＝2.4Hz),142.1,137.7,135.6(d,J＝20.0Hz),134.6(d,J＝21.6Hz),133.8(d,J＝19.3Hz),133.3(d,J＝6.5Hz),131.8,131.7,130.8(d,J＝5.8Hz),129.6(d,J＝2.9Hz),129.1,128.6–30.0(m),127.7(d,J＝6.9Hz),127.6,126.0,122.7(d,J＝3.2Hz),121.7,98.3(dd,J＝24.8,21.6Hz),77.3,72.3(dd,J＝18.4,3.4Hz),71.0(d,J＝4.6Hz),69.3,69.0,67.4,61.3,38.6,37.6,30.6(d,J＝11.8Hz),29.6(dd,J＝18.7,11.9Hz),28.5(dd,J＝23.2,9.8Hz),27.0(d,J＝13.7Hz),16.0； 31 P NMR(162Hz,CDCl 3 )δ9.12(d,J＝11.0Hz),-36.00(d,J＝10.2Hz)；HRMS(ESI)calcd for C 43 H 41 FeP 2 [M+H] + :675.2033,Found:675.2094。
Example 6
To the monophosphine intermediate (S, R) p ,R spiro ) A solution of-4 (53 mg,1 mmol) in glacial acetic acid (5 mL) was added bis (3, 5-dimethylphenylphosphine (242 mg,1 mmol), the reaction temperature was increased to 82-107 ℃, 31 p NMR was monitored to end the reaction. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and successively with water, saturated NaHCO 3 The solution was washed with saturated NaCl, dried and spin-dried, and column chromatographed (ethyl acetate: petroleum ether=1:30) to give orange bisphosphine ligand L4438 mg, 60% yield. 1 H NMR(400Hz,CDCl 3 )δ7.25–7.14(m,2H),7.10(d,J＝7.3Hz,1H),7.06–6.98(m,4H),6.95–6.84(m,4H),6.36(d,J＝7.5Hz,1H),4.09(s,5H),3.95(s,1H),3.85–3.76(m,1H),3.63(s,1H),3.17–2.97(m,5H),2.96–2.77(m,3H),2.70(dd,J＝13.8,7.9Hz,1H),2.28(d,J＝2.5Hz,13H),2.19(dd,J＝12.4,6.6Hz,1H),2.06–1.95(m,1H),1.91–1.76(m,1H),1.36(t,J＝6.4Hz,3H)； 13 C NMR(101Hz,CDCl 3 )δ148.0(d,J＝4.3Hz),146.7,143.1,142.0,137.7(d,J＝4.7Hz),137.1(d,J＝16.8Hz),136.8(d,J＝7.8Hz),133.9(d,J＝19.8Hz),133.3(d,J＝19.8Hz),130.7,129.8,129.6–129.0(m),128.3(d,J＝5.6Hz),127.5,125.8,122.7(d,J＝3.0Hz),121.7,98.9–97.3(m),77.2,71.9(d,J＝20.5Hz),70.8(d,J＝4.3Hz),69.4,69.2,67.1,61.2,38.5,37.6,30.5(d,J＝11.7Hz),29.3(dd,J＝18.5,11.2Hz),28.4(dd,J＝22.4,9.4Hz),27.0(d,J＝12.4Hz),21.4(d,J＝11.9Hz),16.2； 31 P NMR(162Hz,CDCl 3 )δ9.17(d,J＝7.9Hz),-35.86(d,J＝9.6Hz)；HRMS(ESI)calcd for C 47 H 49 FeP 2 [M+H] + :731.2659,Found:731.2703。
Example 7
To the monophosphine intermediate (S, R) p ,R spiro ) A solution of 4 (53 mg,1 mmol) in glacial acetic acid (5 mL) was added to diphenylphosphine (186 mg,1 mmol), the reaction temperature was increased to 82-107 ℃, 31 p NMR was monitored to end the reaction. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and successively with water, saturated NaHCO 3 The solution was washed with saturated NaCl, dried, spin-dried and column chromatographed (ethyl acetate: petroleum ether=1:30) to give the orange bisphosphine ligand L5492 mg, 73% yield. 1 H NMR(400Hz,CDCl 3 )δ7.46–7.26(m,12H),7.16(d,J＝7.3Hz,1H),7.08–6.97(m,2H),6.88(d,J＝7.1Hz,1H),4.24(s,5H),4.09(s,1H),4.01(t,J＝6.4Hz,1H),3.76(s,1H),3.74(s,1H),3.28–3.11(m,2H),3.06–2.74(m,6H),2.25–2.05(m,2H),2.00–1.85(m,1H),1.85–1.75(m,1H),1.34(t,J＝6.9Hz,3H)； 13 C NMR(101Hz,CDCl 3 )δ148.4,147.0(d,J＝4.7Hz),143.1,142.7(d,J＝2.7Hz),137.9(d,J＝20.1Hz),135.4(d,J＝20.4Hz),134.9–134.4(m),133.8(d,J＝19.6Hz),131.8(d,J＝14.8Hz),129.2(d,J＝29.7Hz),128.4(d,J＝4.4Hz),128.0(d,J＝6.0Hz),127.8(d,J＝7.3Hz),127.6,127.5,126.6,123.0,122.1(d,J＝3.4Hz),98.9(dd,J＝27.9,20.5Hz),77.3,74.7(d,J＝27.1Hz),70.6(d,J＝5.5Hz),69.3,68.9,67.9,38.1,37.8,31.7(t,J＝10.6Hz),30.3(d,J＝9.8Hz),30.6–30.0(m),27.7(d,J＝25.5Hz),16.3； 31 P NMR(162Hz,CDCl 3 )δ9.14(d,J＝24.2Hz),-32.15；HRMS(ESI)calcd for C 43 H 41 FeP 2 [M+H] + :675.2033,Found:675.2090。
B. Catalytic asymmetric hydrogenation
Example 8
Under the protection of nitrogen, the catalyst [ Ir (COD) Cl] 2 (1.68 mg,0.0025 mmol) and ferrocene ligand L3 (3.7 mg,0.0055 mmol) and 1mL tetrahydrofuran were placed in an ampoule, stirred and reacted for 30min, 124mg of imine substrate 7, 40% HBr (0.1 eq. Iv.) were sequentially added, and after three nitrogen substitutions, three substitutions with hydrogen were made, at 50℃and three substitutions with hydrogen were made50atm H 2 The reaction was carried out for 20 hours, the reaction was carried out by filtration through a short silica gel column, and the filtrate obtained by filtration was concentrated to give a product 8, the conversion of the reaction was 97% by GC, and the enantiomeric excess was 90% ee.

Claims (3)

1. The chiral ferrocene-spiro framework biphosphine ligand is characterized in that the molecular structural formula is shown as the formula L1-L5:
2. the chiral ferrocene-spiro framework biphosphine ligand transition metal complex catalyst according to claim 1, wherein the transition metal is iridium (Ir).
3. A chiral ferrocene-spiro backbone biphosphine ligand transition metal complex catalyst according to claim 2 for catalyzing asymmetric reduction reactions of prochiral imines.
CN202111287691.4A 2021-11-02 2021-11-02 Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof Active CN114085251B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111287691.4A CN114085251B (en) 2021-11-02 2021-11-02 Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111287691.4A CN114085251B (en) 2021-11-02 2021-11-02 Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof

Publications (2)

Publication Number Publication Date
CN114085251A CN114085251A (en) 2022-02-25
CN114085251B true CN114085251B (en) 2024-01-19

Family

ID=80298681

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111287691.4A Active CN114085251B (en) 2021-11-02 2021-11-02 Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof

Country Status (1)

Country Link
CN (1) CN114085251B (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000011008A1 (en) * 1998-08-21 2000-03-02 The Penn State Research Foundation Asymmetric catalysis based on chiral phospholanes
CN103193830A (en) * 2013-03-28 2013-07-10 中国人民解放军第四军医大学 Preparation method of chiral ferrocene phosphine ligand
CN108929345A (en) * 2018-07-18 2018-12-04 中国人民解放军第四军医大学 Chiral ferrocene biphosphine ligand and its preparation method and application
CN111116474A (en) * 2019-12-17 2020-05-08 浙江大学 A kind of chiral amine-urea compound based on spiro-dihydroindene skeleton and its preparation method and application

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102153589B (en) * 2011-02-28 2013-01-02 大连多相触媒有限公司 Asymmetric hydrogenation catalyst for imine as well as synthesis method and application thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000011008A1 (en) * 1998-08-21 2000-03-02 The Penn State Research Foundation Asymmetric catalysis based on chiral phospholanes
CN103193830A (en) * 2013-03-28 2013-07-10 中国人民解放军第四军医大学 Preparation method of chiral ferrocene phosphine ligand
CN108929345A (en) * 2018-07-18 2018-12-04 中国人民解放军第四军医大学 Chiral ferrocene biphosphine ligand and its preparation method and application
CN111116474A (en) * 2019-12-17 2020-05-08 浙江大学 A kind of chiral amine-urea compound based on spiro-dihydroindene skeleton and its preparation method and application

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Aminoalkylferrocenyldichlorophosphanes: facile synthesis of versatile chiral starting materials;Steffen Tschirschwitz et al.;《Dalton Transactions》;第S2页 *
Enantioselective Hydrogenation of Diarylmethanimines for Synthesis of Chiral Diarylmethylamines;Duanyang Kong et al.;《J. Org. Chem.》;第81卷;第6641页 *
Highly efficient iridium-catalyzed asymmetric hydrogenation of b-acylamino nitroolefins;Qiaozhi Yan et al.;《Chem. Commun.》;第50卷;第1379-1381页 *
Synthesis of chiral cyclic amines via Ir-catalyzed enantioselective hydrogenation of cyclic imines;Ying Zhang et al.;《Org. Biomol. Chem.》;第15卷;第3006-3012页 *
手性二茂铁双膦配体合成及其不对称氢化反应研究;聂慧芳;《中国优秀硕士学位论文全文数据库 工程科技I辑》(第4期);B014-220 *

Also Published As

Publication number Publication date
CN114085251A (en) 2022-02-25

Similar Documents

Publication Publication Date Title
US5596114A (en) Chiral phospholanes via chiral 1 4-diol cyclic sulfates
JP5389164B2 (en) Novel ruthenium complexes with hybrid amine ligands, their preparation and use
CA2258018A1 (en) Asymmetric synthesis catalyzed by transition metal complexes with cyclic chiral phosphine ligands
KR100384411B1 (en) Chiral ligand in heteroaromatic diphosphine
EP2155767B1 (en) Ruthenium complexes with (p-p)-coordinated ferrocenyldiphosphine ligands, process for preparing them and their use in homogeneous catalysis
US5159093A (en) Iridium-optically active phosphine complex and process for producing optically active alcohols using the same
EP2274313B1 (en) Ruthenium complexes having (p-p)-coordinated disphosphorus donor ligands and processes for preparing them
EP1299401B1 (en) Chiral ligands for asymmetric catalysis
EP2614069A1 (en) Biaryl diphosphine ligands, intermediates of the same and their use in asymmetric catalysis
CN114085251B (en) Chiral ferrocene-spiro framework biphosphine ligand and preparation method thereof
CA2348595A1 (en) Diphosphines
US6727377B2 (en) Asymmetric catalysis based on chiral phospholanes and hydroxyl phospholanes
US20020151735A1 (en) Ligands and their use
CN101023092A (en) Novel bisphosphane catalysts
JP2005523939A (en) Ferrocenyl ligand and method for producing the ligand
US20040249184A1 (en) Novel chiral ligands, transition metal complexes thereof, and the catalytic use of the same
CN115490724B (en) Organophosphine compounds based on cyclophane skeleton and uses thereof
EP2183259B1 (en) Paracyclophane-based ligands, their preparation and use in catalysis
CN114230607B (en) Axis chiral diphosphine ligand and application thereof in asymmetric catalytic reaction
CN101314608A (en) Bidentate organophosphor ligand and uses thereof
CN117946161A (en) A tridentate P, N, N-ligand with phosphinamide structure and its preparation method and application
Lansing Jr Investigations into late transition metal pincer complexes as possible direct partial oxidation catalysts
Pugin et al. Twinphos: A New Family of Chiral Ferrocene Tetra-Phosphine Ligands for Asymmetric Catalytic Transformations
Arda Metallocyclic complexes which contain different heteroatom and their catalitic applications
ITMI20011322A1 (en) MIXED CHIRALITY AMINOPHOSPHITES AS CHIRAL TIMBER FOR STEREO-CONTROLLED HOMOGENEOUS CATALYSIS WITH TRANS METAL COMPLEXES

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant