CN114539319B - Chiral phosphine-dicyclophosphoramidite ligand and preparation method and application thereof - Google Patents

Chiral phosphine-dicyclophosphoramidite ligand and preparation method and application thereof Download PDF

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CN114539319B
CN114539319B CN202011326211.6A CN202011326211A CN114539319B CN 114539319 B CN114539319 B CN 114539319B CN 202011326211 A CN202011326211 A CN 202011326211A CN 114539319 B CN114539319 B CN 114539319B
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phenyl
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dicyclophosphamide
acetamide
chiral phosphine
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CN114539319A (en
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胡向平
杜洪泉
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Dalian Institute of Chemical Physics of CAS
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
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    • 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
    • B01J31/2495—Ligands comprising a phosphine-P atom and one or more further complexing phosphorus atoms covered by groups B01J31/1845 - B01J31/1885, e.g. phosphine/phosphinate or phospholyl/phosphonate ligands
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    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/645—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of C=C or C-C triple bonds
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Abstract

The invention provides a novel chiral phosphine-dicyclophosphoramidite ligand, a preparation method and application thereof. The preparation of the novel chiral phosphine-dicyclophosphamide ester ligand adopts chiral phosphine amine intermediate (R) -or (S) -DPPNH 2 And bisphenol ketone compound as raw materials, generating imine by condensation, reducing by lithium aluminum tetrahydroide to obtain secondary amine compound, and finally reacting with PBr 3 Reacting in a chloroform solution of triethylamine to obtain the target chiral phosphine-dicyclophosphamide ester ligand. The chiral phosphine-dicyclophosphamide ester ligand provided by the invention has the characteristics of wide raw material sources, simple and convenient synthesis, stable property, adjustable space structure and electronic property, excellent activity and enantioselectivity in catalyzing asymmetric hydrogenation reaction, and the like.

Description

Chiral phosphine-dicyclophosphoramidite ligand and preparation method and application thereof
Technical Field
The invention belongs to the field of chiral phosphine-dicyclophosphamide ester ligand synthesis, and in particular relates to a chiral phosphine-dicyclophosphamide ester ligand, a preparation method and application thereof.
Background
Catalytic asymmetric hydrogenation is a core technology in asymmetric synthesis, and is one of the most effective methods for synthesizing optically pure chiral drugs, pesticides, food additives and fragrances, and the design synthesis of chiral ligands is a key factor for realizing the core technology. Asymmetric catalytic hydrogenation has been attracting attention because of its high atom economy, and has become one of the most direct and efficient methods for obtaining chiral compounds. During the development of asymmetric catalytic hydrogenation, the design and synthesis of chiral phosphine ligands takes a very important role [ (a) born a. Phosphorus Ligands in Asymmetric Catalysis, wiley-VCH, weinheim,2008; (b) Zhou, q. -l.privileged Chiral Ligands and Catalysts, wiley-VCH, weinheim,2011 (c) Tang, w. -j; zhang, x. -m.new Chiral Phosphorus Ligands for Enantioselective Hydrogenation, chem.rev.2003,103,3029-3069 ]. The development of chiral ligands remains the heart of research on asymmetric catalytic hydrogenation.
Recent studies have shown that asymmetric hybridized chiral phosphine-phosphoramidite ligands exhibit even more excellent activity and optical selectivity [ (d) Chen, s. -s. ] in many asymmetric catalytic reactions compared to C2 symmetric chiral biphosphine ligands; hou, c. -j; hu, x. -p.chiral phosphine-phosphoramidite ligands in asymmetric catalysis, synth.commun.2016,46,917; (e) Hou Chuanjin, liu Xiaoning, xia Ying, hu Xiangping, progress in the use of asymmetric hybridized chiral phosphine-phosphoramidite ligands in asymmetric catalytic reactions, < < organic chemistry > >,2012,32,2239 > ]. Most of the chiral phosphine-phosphoramidite ligands have binaphthyl chiral monocyclic phosphoramidite skeleton, while chiral phosphine-dicyclic phosphoramidite skeleton ligands with higher rigidity structures are not reported in the literature. The invention aims to develop a chiral phosphine-phosphoramidite ligand with a dicyclophosphamide ester skeleton, which has excellent activity and stereoselectivity in asymmetric catalytic hydrogenation reaction.
Disclosure of Invention
In order to solve the defects in the prior art, the invention provides a chiral phosphine-dicyclophosphoramidite ligand and a preparation method thereof, wherein the method uses chiral phosphine amine intermediate (R) -or (S) -DPPNH 2 And bisphenol ketone compound as raw materials, generating imine by condensation, reducing by lithium aluminum tetrahydroide to obtain secondary amine compound, and finally reacting with PBr 3 Reacting in a chloroform solution of triethylamine to obtain the target chiral phosphine-dicyclophosphamide ester ligand.
To achieve the above object, the present invention provides chiral phosphine-dicyclophosphamide ester ligands having the following structural formula I or II:
i and II are enantiomers of each other
Wherein:
ar is phenyl or substituted phenyl, naphthyl or substituted naphthyl, heterocyclic aromatic group or substituted heterocyclic aromatic group; the substituted phenyl,The substituent of the substituted naphthyl and the substituted heterocyclic aromatic group is selected from C 1 -C 40 Alkyl, C 1 -C 40 One or more of alkoxy, halogen, nitro, ester, or cyano; the heterocyclic aromatic group refers to five-membered or six-membered aromatic groups containing one or more N, O, S and other heteroatoms;
r is selected from hydrogen, C 1 -C 40 Alkyl, C 1 -C 40 Alkoxy, C 3 -C 12 One or more of cycloalkyl, phenyl, benzyl, phenoxy, halogen, nitro, amido, hydroxyl, carboxyl, ester or cyano, etc., wherein the number of the substituents is 1-5;
R 1 is C 1 -C 40 Alkyl, C 3 -C 12 Cycloalkyl, phenyl or substituted phenyl, naphthyl or substituted naphthyl, a heterocyclic aromatic group or a substituted heterocyclic aromatic group; the substituent of the substituted phenyl, substituted naphthyl and substituted heterocyclic aromatic group is selected from C 1 -C 40 Alkyl, C 1 -C 40 One or more of alkoxy, halogen, nitro, ester, or cyano; the heterocyclic aromatic group refers to five-membered or six-membered aromatic groups containing one or more N, O, S and other heteroatoms;
the invention provides a preparation method of chiral phosphine-dicyclophosphamide ester ligand, which comprises the following steps:
(1) Chiral phosphane intermediates such as (R) -or (S) -DPPNH 2 (III) with bisphenol ketone compound (IV) to form imine (V): dissolving chiral phosphine amine intermediate and bisphenol ketone compound in toluene solution in a round bottom flask, adding catalytic amount of trifluoroacetic acid (TFA), refluxing and separating water for 6-24 hours, removing solvent, and performing column chromatography on the residue to obtain imine (V).
(2) Reduction of imine (V) to secondary amine (VI): the imine (V) is dissolved in dry tetrahydrofuran, 3-6 equivalents of lithium aluminum hydride are added in batches, the reaction is carried out for 12-24 hours at room temperature, then a proper amount of ethyl acetate and water are added successively, the separated liquid is extracted, and anhydrous sodium sulfate is dried to obtain the corresponding secondary amine (VI).
(3) Preparation of chiral phosphine-dicyclophosphamide ester ligand I or II: dissolving secondary amine in degassed chloroform solution under nitrogen protection, adding 3-6 equivalents of triethylamine under ice water bath condition, adding 1-2 equivalents of phosphorus tribromide, stirring at room temperature for 12-24 hours, removing solvent, and subjecting the residue to column chromatography to obtain I or II.
In the step of condensing to generate imine, the chiral phosphane intermediate: bisphenol ketone compound: TFA molar ratio of 1-1.2:1:0.01-0.001. The preferred ratio is 1:1.1:0.01.
in the step (2) of the reduction to give the secondary amine (V) according to the present invention, lithium aluminum hydride is used in an amount of 3 to 6 equivalents, preferably 3 equivalents. The reaction time is preferably 24 hours.
In said step (3) of the present invention, the reaction medium is selected from one or more of dichloroethane, chloroform and dichloromethane; the reaction yield is higher especially when the reaction medium is chloroform.
In the present invention, the chiral phosphine-amine intermediate III has the following structure:
wherein Ar and R 1 Ar and R as described in structures I and II 1 Is an equivalent group.
Ar is preferably of the structure:
R 1 preferred structures are methyl and isopropyl.
The bisphenol ketone compound (IV) has the following structural formula:
wherein R and structures I and II are equivalent groups.
The bisphenol ketone compound has the preferable structure as follows:
chiral phosphine-dicyclophosphamide ester ligand is synthesized according to the following route in the invention:
wherein Ar, R and R 1 Ar, R and R are as described in structures I and II 1 Is an equivalent group.
The invention also relates to the use of the ligands described above in asymmetric hydrogenation of c=c double bonds.
The chiral phosphine-dicyclophosphamide ester ligand provided by the invention can be used in asymmetric hydrogenation reaction in C=C bond, the chiral phosphine-dicyclophosphamide ester ligand and Pt, pd, ir, ru or Rh are combined into a catalyst according to the mol ratio of 1.1:1-2.2:1, and the ratio of a reaction substrate to the catalyst is 100-10000:1, the reaction time is 0.1-24 hours.
The asymmetric hydrogenation reaction is a catalytic asymmetric hydrogenation reaction of the following substrates:
(1) Catalytic asymmetric hydrogenation of alpha-dehydroamino acids;
(2) Catalytic asymmetric hydrogenation of beta-dehydroamino acids;
(3) Catalytic asymmetric hydrogenation of itaconate and beta-substituted itaconate compounds;
(4) Catalytic asymmetric hydrogenation of alpha-acyclic and cyclic enamides;
(5) Catalytic asymmetric hydrogenation of alpha-acyclic and cyclic enol esters;
(6) Catalytic asymmetric hydrogenation of 1, 1-disubstituted aryl olefins.
The invention has the beneficial effects that:
the chiral phosphine-dicyclophosphamide ester ligand is a structural ligand, and has the characteristics of wide raw material sources, simple and convenient synthesis, stable property, adjustable space structure and electronic property, excellent activity and enantioselectivity in catalyzing asymmetric hydrogenation reaction and the like; the catalyst formed by the catalyst and the metal precursors such as Pt, pd, ir, ru or Rh has stable property, good tolerance to air and humidity, mild reaction conditions of the participating asymmetric hydrogenation, capability of reacting at room temperature, wide application range of hydrogen pressure and no influence on the activity and stereoselectivity of the catalyst from normal pressure to high pressure. The asymmetric hydrogenation reaction of the catalyst formed by the chiral phosphine-dicyclophosphamide ester ligand and the metal precursor on C=C double bond can obtain the enantioselectivity of 99%ee; the catalyst has high activity, TON is up to 10000.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 nuclear magnetic resonance hydrogen spectrum of chiral phosphine-dicyclophosphamide ester ligand compound I-1;
FIG. 2 nuclear magnetic resonance spectrum of chiral phosphine-dicyclophosphamide ester ligand compound I-1;
FIG. 3 nuclear magnetic resonance spectrum of chiral phosphine-dicyclophosphamide ester ligand compound I-1;
FIG. 4 nuclear magnetic resonance hydrogen spectrum of chiral phosphine-dicyclophosphamide ester ligand compound I-2;
FIG. 5 nuclear magnetic resonance spectrum of chiral phosphine-dicyclophosphamide ester ligand compound I-2;
FIG. 6 nuclear magnetic resonance spectrum of chiral phosphine-dicyclophosphamide ester ligand compound I-2;
FIG. 7 nuclear magnetic resonance hydrogen spectrum of chiral phosphine-dicyclophosphamide ester ligand compound I-3;
FIG. 8 nuclear magnetic resonance spectrum of chiral phosphine-dicyclophosphamide ester ligand compound I-3;
FIG. 9 nuclear magnetic resonance spectrum of chiral phosphine-dicyclophosphamide ester ligand compound I-3;
FIG. 10 is a nuclear magnetic resonance hydrogen spectrum of the hydrogenated product N- (2- (1-phenethyl) phenyl) acetamide;
FIG. 11 nuclear magnetic resonance carbon spectrum of hydrogenated product N- (2- (1-phenethyl) phenyl) acetamide;
Detailed Description
Synthesis of chiral ligands
Chiral phosphine-dicyclophosphamide ester ligand is prepared by first preparing chiral phosphine amine intermediate such as (R) -or (S) -DPPNH 2 Generating imine with bisphenol ketone compound, reducing with lithium aluminum hydride to obtain secondary amine compound, and finally reacting with PBr 3 The reaction was carried out in a chloroform solution of triethylamine.
The present invention will be described in detail with reference to the following examples, but the present invention is not limited to the examples. Nuclear magnetic resonance is measured by Bruker Nuclear magnetic resonance, and High Performance Liquid Chromatography (HPLC) is measured by Agilent 1100 series high performance liquid chromatography.
Preparation of chiral phosphine-dicyclophosphamide ester ligand
Example 1
Preparation of chiral phosphine-dicyclophosphamide ester ligand I-1
(S) -DPPNH 2 (III-1) 1.28mmol of bis (3, 5-di-tert-butyl-2-hydroxyphenyl) methanone (IV-1) each was dissolved in a 50mL round-bottomed flask containing 20mL of toluene, and a catalytic amount of trifluoroacetic acid (TFA) 38uL was added by microinjection and water was separated under reflux for 24 hours. After the reaction, the solvent was removed in vacuo, and petroleum ether column chromatography was performed to obtain 0.68g of an imine compound in a yield of 70%.
Under the protection of nitrogen, the obtained imine compound is dissolved in 10mL of dry tetrahydrofuran solution, 0.12g of lithium aluminum hydride is added in batches, after stirring for 24 hours at room temperature, 10mL of ethyl acetate and 10mL of water are respectively added for quenching reaction, then the target product is extracted by ethyl acetate, anhydrous sodium sulfate is dried, then the solvent is removed in vacuum, and the secondary amine compound is obtained through column chromatography.
0.63g of the secondary amine compound obtained above was dissolved in 10mL of degassed chloroform solution under nitrogen atmosphere, and 0.36mL of triethylamine (3 equiv) and 80 were added in this orderuL phosphorus tribromide (1 equiv), stirring at room temperature for 4 hours, vacuum removing solvent, and subjecting to petroleum ether column chromatography to obtain the target product chiral phosphine-dicyclophosphamide ester ligand I-1 with a yield of 45%. 1 H NMR(400MHz,CDCl 3 )δ7.48-7.41(m,3H),7.37-7.27(m,5H),7.17(ddd,J＝14.9,8.7,2.1Hz,4H),7.04(d,J＝2.3Hz,1H),7.01-6.93(m,2H),6.82-6.77(m,1H),6.54(t,J＝2.9Hz,1H),6.47(d,J＝2.2Hz,1H),5.33-5.24(m,1H),4.45(d,J＝4.5Hz,1H),1.48(dd,J＝6.7,3.5Hz,3H),1.40(d,J＝4.8Hz,9H),1.37(s,9H),1.23(s,9H),1.16(d,J＝4.1Hz,9H). 13 C NMR(101MHz,CDCl 3 )δ148.5,148.5,148.3,148.2,146.1,146.0,146.0,145.9,143.45,143.3,137.8,137.8,137.3,137.3,137.1,137.0,136.7,136.6,134.5,134.5,134.4,134.3,134.1,133.9,133.,129.2,129.1,128.8,128.8,128.7,128.7,128.6,128.4,127.5,127.4,127.3,127.3,127.0,126.7,126.66,122.9,122.5,122.4,121.8,60.5,57.5,57.3,57.2,57.0,55.5,35.0,34.9,34.4,34.3,31.7,31.6,29.9,29.8,29.8. 31 P NMR(162MHz,CDCl 3 )δ91.23(d,J＝7.4Hz),-17.88(d,J＝7.1Hz).HRMS calc.for C 49 H 60 NO 2 P 2 [M+H] + 756.4094, found:756.4098. The nuclear magnetic hydrogen spectrum, the carbon spectrum and the phosphorus spectrum of the compound I-1 are shown in figures 1, 2 and 3.
Example 2
Preparation of chiral phosphine-dicyclophosphamide ester ligand I-2
The reaction substrate bis (3, 5-di-tert-butyl-2-hydroxyphenyl) methanone IV-1 in example 1 was changed to bis (3, 5-dimethyl-2-hydroxyphenyl) methanone IV-2, and the remainder was the same as in example 1, to obtain chiral phosphine-dicyclophosphamide ester ligand I-2 shown in the following diagram in 56% yield. 1 H NMR(400MHz,CDCl 3 )δ7.51(dd,J＝7.7,4.5Hz,1H),7.45-7.37(m,3H),7.31(d,J＝4.9Hz,3H),7.26-7.09(m,6H),6.89(dd,J＝7.3,4.5Hz,1H),6.75(d,J＝16.3Hz,2H),6.40(s,1H),6.23(s,1H),5.26-5.16(m,1H),4.48(t,J＝9.8Hz,1H),2.20(d,J＝7.2Hz,6H),2.15(d,J＝5.4Hz,6H),1.52(dd,J＝6.6,3.6Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ147.6,147.6,147.4,147.3,144.9,144.8,144.0,143.9,135.9,135.9,135.8,135.8,133.8,133.7,132.9,132.8,132.7,132.6,129.5,129.4,129.3,129.2,128.5,127.8,127.6,127.6,127.5,127.5,127.4,126.4,126.0,126.0,125.9,125.8,125.8,125.3,125.3,125.2,124.1,123.9,55.2,55.0,54.9,54.8,52.6,28.7,25.9,21.8,21.6,19.5,19.5,15.0,14.9. 31 P NMR(162MHz,CDCl 3 )δ96.06(d,J＝8.4Hz),-18.61(d,J＝8.4Hz).HRMS calc.for C 37 H 36 NO 2 P 2 [M+H] + 588.2216, found:588.2221. The nuclear magnetic hydrogen spectrum, carbon spectrum and phosphorus spectrum of the compound I-2 are shown in figures 4, 5 and 6.
Example 3
Preparation of chiral phosphine-dicyclophosphamide ester ligand I-3
The reaction substrate bis (3, 5-di-tert-butyl-2-hydroxyphenyl) methanone IV-1 in example 1 was changed to bis (2-hydroxy-3-methylphenyl) methanone IV-3, and the remainder was the same as in example 1 to obtain chiral phosphine-phosphoramidite ligand I-3 shown in the following figure in 78% yield. 1 H NMR(400MHz,CDCl 3 )δ7.47(dd,J＝7.5,4.6Hz,1H),7.38(p,J＝7.3Hz,3H),7.28(d,J＝5.2Hz,3H),7.25-7.07(m,7H),6.89(ddd,J＝11.7,9.8,5.9Hz,3H),6.67(q,J＝7.2Hz,2H),6.60(d,J＝7.4Hz,1H),6.38(d,J＝7.4Hz,1H),5.27-5.15(m,1H),4.54(d,J＝4.5Hz,1H),2.22(d,J＝9.5Hz,6H),1.50(dd,J＝6.6,3.5Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ148.1,148.0,147.3,147.2,136.9,136.7,136.6,134.9,134.1,134.0,133.9,133.7,129.7,129.5,128.9,128.7,128.6,128.6,128.5,128.5,127.5,127.5,127.4,127.3,127.3,127.2,127.2,126.7,126.6,126.3,124.9,124.7,121.5,121.3,56.3,56.1,56.0,55.8,53.5,22.7,22.5,16.1,16.1. 31 P NMR(162MHz,CDCl 3 )δ95.79(d,J＝9.3Hz),-18.64(d,J＝9.3Hz).HRMS calc.for C 35 H 32 NO 2 P 2 [M+H] + 560.1903, found:560.1908. The nuclear magnetic hydrogen spectrum, carbon spectrum and phosphorus spectrum of the compound I-3 are shown in figures 7, 8 and 9.
2. Asymmetric hydrogenation
Example 4
Under the protection of nitrogen, rh (COD) 2 ]BF 4 (0.00125 mmol,1 mol%) of chiral phosphine-phosphonite amide ligand (I-1) (0.001375 mmol,1.1 mol%) was dissolved in methylene chloride (1.0 mL), stirred at room temperature (25 ℃) for 1 hour, a solution of the substrate N- (2- (1-phenylvinyl) phenyl) acetamide (0.125 mmol) in methylene chloride (1.0 mL) was added, placed in an autoclave, replaced with hydrogen 3 times, then 60bar of hydrogen was introduced, and reacted at room temperature (25 ℃) for 24 hours. Slowly releasing hydrogen, removing solvent, separating with silica gel column to obtain N- (2- (1-phenethyl) phenyl) acetamide product, and converting to>99％。99％ee was determined by chiral HPLC(chiralcel OD-H,n-hexane/i-PrOH＝97/3,0.8mL/min,254nm,40℃):t R (major)＝31.61min,t R (minor)＝35.7min. 1 H NMR(400MHz,CDCl 3 )δ7.69(d,J＝7.6Hz,1H),7.42(d,J＝7.2Hz,1H),7.30(dd,J＝15.4,7.8Hz,3H),7.25-7.19(m,2H),7.16(d,J＝7.4Hz,2H),6.77(s,1H),4.17(dd,J＝13.9,6.9Hz,1H),1.94(s,3H),1.62(d,J＝7.2Hz,3H). 13 C NMR(101MHz,CDCl 3 ) Delta 179.8,168.3,145.3,136.6,135.2,129.1,127.3,127.3,126.8,125.6,124.9,40.8,24.0,21.7. The nuclear magnetic resonance hydrogen spectrum and the carbon spectrum of the product are shown in fig. 10 and 11.
Example 5
The substrate in example 7 was changed to N- (4-fluoro-2- (1-phenylvinyl) phenyl) acetamide, and the remainder was the same as in example 7, whereby chiral N- (4-fluoro-2- (1-phenylethyl) phenyl) acetamide was obtained in a yield of 100% and an enantioselectivity of 93% ee.
Example 6
The substrate of example 7 was changed to N- (4-chloro-2- (1-phenylvinyl) phenyl) acetamide, and the remainder was identical to that of example 7, whereby the chiral N- (4-chloro-2- (1-phenylethyl) phenyl) acetamide was obtained in a yield of 100% and an enantioselectivity of 94% ee.
Example 7
The substrate in example 7 was changed to N- (4-bromo-2- (1-phenylvinyl) phenyl) acetamide, and the remainder was identical to example 7, whereby chiral N- (4-bromo-2- (1-phenylethyl) phenyl) acetamide was obtained in a yield of 100% and an enantioselectivity of 93% ee.
Example 8
The substrate of example 7 was changed to N- (4-methyl-2- (1-phenylvinyl) phenyl) acetamide, and the remainder was the same as in example 7, whereby the chiral N- (4-methyl-2- (1-phenylethyl) phenyl) acetamide was obtained in a yield of 100% and an enantioselectivity of 95%.
Example 9
The substrate of example 7 was changed to N- (4-methoxy-2- (1-phenylvinyl) phenyl) acetamide, and the remainder was the same as in example 7, whereby chiral N- (4-methoxy-2- (1-phenylethyl) phenyl) acetamide was obtained in a yield of 100% and an enantioselectivity of 92% ee.
Example 10
The substrate of example 7 was changed to N- (2- (1- (4- (ethyl) vinyl) phenyl) acetamide, and the remainder was the same as in example 7, whereby chiral N- (2- (1- (4- (ethyl) phenyl) acetamide was obtained in a yield of 100% and an enantioselectivity of 96% ee.

Claims (3)

1. A chiral phosphine-dicyclophosphamide ester ligand characterized by: the chiral phosphine-dicyclophosphamide ester ligand has the following structural formula:
2. a process for the preparation of chiral phosphine-dicyclophosphamide ester ligands as claimed in claim 1, characterized in that: preparation of chiral phosphine-dicyclophosphamide ester ligand I-1:
(S) -DPPNH 2 III-1, bis (3, 5-di-tert-butyl-2-hydroxyphenyl) ketone IV-1 each 1.28mmol was dissolved in a 50mL round bottom flask containing 20mL toluene, a microinjector was added with a catalytic amount of TFA38 uL trifluoroacetic acid, water was separated by reflux for 24 hours, after the reaction was completed, the solvent was removed in vacuo, and petroleum ether column chromatography gave 0.68g of imine compound in 70% yield;
dissolving the obtained imine compound in 10mL of dry tetrahydrofuran solution under the protection of nitrogen, adding 0.12g of lithium aluminum hydride in batches, stirring at room temperature for 24 hours, adding 10mL of ethyl acetate and 10mL of water respectively for quenching reaction, extracting a target product by using ethyl acetate, drying by using anhydrous sodium sulfate, removing a solvent in vacuum, and performing column chromatography to obtain a secondary amine compound;
dissolving 0.63g of the obtained secondary amine compound in 10mL of degassed chloroform solution under the protection of nitrogen, sequentially adding 0.36mL of triethylamine and 80uL of phosphorus tribromide, stirring at room temperature for 4 hours, removing the solvent in vacuum, and carrying out petroleum ether column chromatography to obtain a target product chiral phosphine-dicyclophosphamide ester ligand I-1;
preparation of chiral phosphine-dicyclophosphamide ester ligand I-2:
changing the reaction substrate of the step IV-1 into bis (3, 5-dimethyl-2-hydroxyphenyl) ketone IV-2, and obtaining chiral phosphine-dicyclophosphamide ester ligand I-2, wherein the rest is the same;
preparation of chiral phosphine-dicyclophosphamide ester ligand I-3:
the reaction substrate of bis (3, 5-di-tert-butyl-2-hydroxyphenyl) ketone IV-1 in the above step is changed into bis (2-hydroxy-3-methylphenyl) ketone IV-3, and the rest is the same, so that chiral phosphine-phosphoramidite ligand I-3 is obtained.
3. Use of a chiral phosphine-dicyclophosphamide ester ligand as defined in claim 1 in an asymmetric hydrogenation of c=c double bonds, characterized in that: under nitrogen, 0.00125mmol,1mol% of [ Rh (COD) 2 ]BF 4 0.00137mmol, 1.1mol% of chiral phosphine-phosphonidene amide ligand I-1 is dissolved in 1.0mL of dichloromethane, stirred at room temperature for 1 hour, added with a solution of 0.125mmol of substrate N- (2- (1-phenylvinyl) phenyl) acetamide in 1.0mL of dichloromethane, placed in a high-pressure reaction kettle, replaced by hydrogen for 3 times, then introduced with 60bar of hydrogen, and reacted at room temperature for 24 hours; slowly releasing hydrogen, removing the solvent, and separating by a silica gel column to obtain a product N- (2- (1-phenethyl) phenyl) acetamide; or the substrate in the above step is replaced by N- (4-fluoro-2- (1-phenylvinyl) phenyl) acetamide or N- (4-chloro-2- (1-phenylvinyl) phenyl) ethylAmides, N- (4-bromo-2- (1-phenylvinyl) phenyl) acetamide, N- (4-methyl-2- (1-phenylvinyl) phenyl) acetamide, N- (4-methoxy-2- (1-phenylvinyl) phenyl) acetamide, N- (2- (1- (4- (ethyl) vinyl) phenyl) acetamide, and the obtained products are chiral N- (4-fluoro-2- (1-phenylethyl) phenyl) acetamide, chiral N- (4-chloro-2- (1-phenylethyl) phenyl) acetamide, chiral N- (4-bromo-2- (1-phenylethyl) phenyl) acetamide, chiral N- (4-methyl-2- (1-phenylethyl) phenyl) acetamide, chiral N- (4-methoxy-2- (1-phenylethyl) phenyl) acetamide, and chiral N- (2- (1- (4- (ethyl) phenyl) acetamide in this order.
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CN107073461A (en) * 2015-09-30 2017-08-18 Lg化学株式会社 Carbon monoxide-olefin polymeric for hydroformylation and the hydroformylation process using said composition

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WO2008148202A1 (en) * 2007-06-08 2008-12-11 Kanata Chemical Technologies Inc. Method for the preparation of aminophosphine ligands and their use in metal catalysts
KR101574071B1 (en) * 2014-08-26 2015-12-03 기초과학연구원 Bicyclic Bridgehead Phosphoramidite and Method of Preparation Thereof
CN107073461A (en) * 2015-09-30 2017-08-18 Lg化学株式会社 Carbon monoxide-olefin polymeric for hydroformylation and the hydroformylation process using said composition

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