CN112824424B - Chiral ferrocene-imidazole diphosphine ligand and synthesis method and application thereof - Google Patents
Chiral ferrocene-imidazole diphosphine ligand and synthesis method and application thereof Download PDFInfo
- Publication number
- CN112824424B CN112824424B CN201911147195.1A CN201911147195A CN112824424B CN 112824424 B CN112824424 B CN 112824424B CN 201911147195 A CN201911147195 A CN 201911147195A CN 112824424 B CN112824424 B CN 112824424B
- Authority
- CN
- China
- Prior art keywords
- imidazole
- chiral
- substituted
- ferrocene
- chiral ferrocene
- 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
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 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/44—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers
- C07C209/52—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers by reduction of imines or imino-ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
-
- 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
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- 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
-
- 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
- B01J2531/0202—Polynuclearity
- B01J2531/0205—Bi- or polynuclear complexes, i.e. comprising two or more metal coordination centres, without metal-metal bonds, e.g. Cp(Lx)Zr-imidazole-Zr(Lx)Cp
-
- 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
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/827—Iridium
-
- 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
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
-
- 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)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a chiral ferrocene-imidazole diphosphine ligand, a preparation method and application thereof. Specifically, the present invention discloses a synthetic procedure different from the previous reports: dissolving equimolar amount of ferrocenyl chiral alcohol and N, N' -carbonyldiimidazole in anhydrous dichloromethane, and heating and refluxing for reaction for 1 hour to obtain a chiral ferrocene-imidazole intermediate. The chiral ferrocene-imidazole intermediate was dissolved in anhydrous ether, a hexane solution of N-BuLi (1.6M,1.2eq.) was slowly added dropwise, and a mixture of N, N, N ', N' -tetramethylethylenediamine (1.2eq.) and a hexane solution of N-BuLi (1.6M,1.3eq.) was added continuously. And finally, cooling the reaction solution to-15 ℃, slowly adding diethyl ether solution of diphenyl phosphorus chloride (3.0eq.) dropwise, and treating to obtain the target compound chiral ferrocene-imidazole diphosphine ligand. The catalyst formed by the ligand and the iridium metal precursor can catalyze the asymmetric hydrogenation reaction of C ═ N double bonds with high yield and high enantioselectivity.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a chiral ferrocene-imidazole diphosphine ligand, a synthesis method and application of the ligand in iridium-catalyzed asymmetric hydrogenation reaction of C ═ N bonds.
Background
Transition metal asymmetric catalysis is one of the most direct and efficient ways to prepare chiral compounds,is also a popular field of common interest for both academic research and industrial production. The activity and selectivity of the metal catalyst in the asymmetric catalytic reaction can be directly influenced by adjusting the structure of the chiral ligand, so that the chiral ligand with simple design structure, convenient synthesis and high catalytic selectivity also becomes a breakthrough in the transition metal catalytic asymmetric reaction. Thousands of Chiral ligands have been developed to date for use in asymmetric catalytic reactions [ (a) Zhou, q. — l.privilized Chiral ligands and catalysts, Wiley-VCH, Weinheim, 2011; (b) T.P.Yoon, E.N.Jacobsen, Privileged chiral catalysts. science 2003,299, 1691-; (c) family III Design of family III for asymmetry catalyst analysis From C2-symmetric P,P-and N,N-ligands to sterically and electronically nonsymmetrical P,N-ligands.PNAS 2004,101,5723-5726.]Chiral diphosphine ligands are highly representative high-efficiency ligands, especially in asymmetric hydrogenation reactions [ Zhang, w. -c ]; chi, y. -x; zhang, X.M.developing chiral ligands for asymmetric hydrogenation. Acc.chem.Res.2007,40,1278-1290.]. The diphosphine ligands reported now have C2The symmetry is beneficial to simplifying the synthesis steps and reducing the number of reaction transition states, thereby ensuring the high selectivity of the catalyst. Recent studies have shown that diphosphine ligands of asymmetric structure exhibit unique advantages in optimizing the central metal chiral environment, among which the most representative ones are the JosiPhos type ferrocene diphosphine ligands [ (a) Togni, a.; breutel, c.; schnyder, a.; spindler, f.; landert, h.; tijani, A.A novel easy access crystalline transfernyldiphosphine for high activity interactive hydrogenation, and hydrogenation reactions.J.am.chem.Soc.1994,116, 4062-4066; (b) blast, h. -u.; brieden, w.; pugin, b.; spindler, f.; studer, m.; togni, A. Solvias Josiphos Ligands: From discovery to technical applications. Top. Catal.2002,19, 3-16.]. Based on an asymmetric ligand design concept, a novel chiral diphosphine ligand based on a ferrocene-imidazole skeleton is designed and developed, and the novel chiral diphosphine ligand shows excellent catalytic activity and selectivity in asymmetric catalytic hydrogenation reaction. The ligand has wide source of synthetic raw materialsThe preparation method has the characteristics of simple and convenient preparation process, stable property, high enantioselectivity and the like, and has very high industrial application potential.
The method for synthesizing the ligand in the front of the subject group (publication article: org. Lett.2009,11,3226-3229) comprises the following specific steps: esterifying and aminating ferrocenyl chiral alcohol 1 to obtain chiral alpha- (dimethylamino) alkyl or benzyl-ferrocene 2; under the action of n-butyllithium, reacting 2 with diaryl phosphorus chloride to obtain chiral 1- [ (alpha-dimethylamino) alkyl or benzyl ] -2- (diphenylphosphine) ferrocene 3; then, reacting the 3 with imidazole in acetic acid to obtain a chiral ferrocene-imidazole monophosphine intermediate 4; and finally, under the action of n-butyllithium, reacting the 4 with diaryl phosphorus chloride to obtain a target chiral ferrocene-imidazole diphosphine ligand I or II, wherein the reaction process is shown as the following equation:
wherein, a large amount of pyridine and acetic anhydride are needed in the first step of esterification and amination, the post-treatment step is complicated, and acetic acid is needed as a solvent in the third step. Therefore, the synthesis steps are further improved, two steps of esterification amination of chiral alcohol and lithiation and phosphine addition are omitted, the synthesis steps and raw material consumption are greatly reduced, and the total yield is greatly improved.
Disclosure of Invention
The invention aims to provide a chiral diphosphine ligand based on a ferrocene-imidazole skeleton and a synthetic method thereof;
the invention also aims to provide the application of the chiral diphosphine ligand with the ferrocene-imidazole skeleton in asymmetric reaction, in particular to the application in iridium-catalyzed asymmetric hydrogenation reaction of C ═ N bonds.
The structural general formula of the chiral ferrocene-imidazole diphosphine ligand is as follows:
in the formula: i and II are enantiomers of each other.
In the formula: r is H, alkyl in C1-C10, cycloalkyl in C3-C8, phenyl and substituted phenyl, benzyl and substituted benzyl; the substituent on the substituted phenyl or the substituted benzyl is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano;
ar is phenyl and substituted phenyl, naphthyl and substituted naphthyl; the substituent on the substituted phenyl or the substituted naphthyl is one or more than two of C1-C10 alkyl, C1-10 alkoxy, halogen, nitro, ester group or cyano, and the predominant structure is phenyl.
Aiming at the defects that in the prior art (org. Lett.2009,11, 3226-:
the invention provides a synthesis method of a chiral ferrocene-imidazole diphosphine ligand, which comprises the following steps:
(1) heating and reacting chiral ferrocenyl alcohol III or IV and N, N' -carbonyldiimidazole in anhydrous dichloromethane at a molar ratio of 1:1 to obtain a chiral ferrocene-imidazole intermediate V or VI;
(2) under the action of n-butyllithium, the chiral ferrocene-imidazole undergoes two lithiations and reacts with ClPAr to obtain chiral ferrocene-imidazole diphosphine ligand I or II. Wherein the solvent is diethyl ether, and 1-1.2 equivalents of N, N, N ', N' -tetramethylethylenediamine is required to be added in the second lithiation process.
The structural formula of the chiral ferrocene-imidazole intermediate is as follows:
in the formula, R is H, alkyl in C1-C10, cycloalkyl in C3-C8, phenyl and substituted phenyl, benzyl and substituted benzyl; the substituent on the substituted phenyl or the substituted benzyl is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano; ar is phenyl and substituted phenyl, naphthyl and substituted naphthyl; the substituent on the substituted phenyl or the substituted naphthyl is one or more than two of C1-C10 alkyl, C1-10 alkoxy, halogen, nitro, ester group or cyano.
The invention also provides application of the chiral ferrocene-imidazole diphosphine ligand in metal catalysis of asymmetric hydrogenation reaction of C ═ N bond, and the chiral ferrocene-imidazole diphosphine ligand can be used for preparing various chiral amine compounds through a metal catalyst which is pre-coordinated with metal and formed in situ. These chiral amine compounds can also be used as key intermediates in the preparation of chiral compounds having important biological activities, such as the asymmetric synthesis of the chiral herbicide s-metolachlor.
The invention has the beneficial effects that:
compared with the prior art (the publication article: org. Lett.2009,11,3226-3229), the invention omits two steps of esterification and amination of chiral alcohol and phosphine addition by lithiation, greatly reduces the synthesis step and the consumption of raw materials, and greatly improves the total yield.
Detailed Description
While the present invention has been described in connection with the specific embodiments thereof, it is to be understood that these embodiments are merely illustrative and not restrictive of the broad invention, and that this invention not be limited to the specific embodiments disclosed herein.
Example 1
Chiral ligands (R)c,Sp) Preparation of (E) -I-1
Synthesizing a target compound chiral ferrocene-imidazole diphosphine ligand (R) by taking (R) -1-ferrocenyl ethanol (R) -1-1 as a starting materialc,Sp)-I-1。
Under the protection of nitrogen, equimolar amounts of (R) -1-ferrocenyl ethanol 1-1 and N, N' -carbonyldiimidazole are dissolved in anhydrous dichloromethane with the molar ratio of 1:1, and the mixture is heated and refluxed for 1 hour. After the reaction is complete, it is cooled to room temperature, 50mL of diethyl ether are added and the mixture is washed twice with 20% phosphoric acid solution. The aqueous phases were combined, adjusted to PH 5 and extracted twice with dichloromethane. Organic phase anhydrous Na2SO4Drying, concentrating under reduced pressure, and separating by column chromatography (petroleum ether/ethanol 1/1, v: v) to obtain orange red crystal with yield of 85%.
Chiral ferrocene-imidazole (R) -V-1 is dissolved in anhydrous ether under nitrogen, a hexane solution of n-BuLi (1.6M,1.2eq.) is slowly added dropwise over 20 minutes, and the reaction is continued for 1 hour at room temperature. Then, a mixture of N, N' -tetramethylethylenediamine (1.2eq.) and N-BuLi (1.6M,1.3eq.) in hexane was added thereto, the addition was completed for 15 minutes, and the reaction was continued at room temperature for 5 hours. Then, the reaction mixture was cooled to-15 ℃ and a diethyl ether solution of diphenylphosphoryl chloride (3.0eq.) was slowly added dropwise thereto, and the mixture was allowed to naturally warm to room temperature and reacted overnight. After the reaction is finished, adding saturated sodium bicarbonate solution, separating out an organic phase, extracting the aqueous phase with diethyl ether for three times, combining the organic phases, washing with saturated saline solution, and removing anhydrous Na2SO4And (5) drying. Concentrating under reduced pressure, separating the residue by column chromatography (petroleum ether/ethyl acetate: 10/1, v: v), and recrystallizing with n-hexane to obtain orange red crystal (R)c,Sp) -I-1, yield 75%, nmr data as follows:1H NMR(400MHz,CDCl3):δ7.53(m,4H),7.33-7.38(m,5H),7.25(s,1H),7.15(m,3H),7.07(m,3H),6.92(m,3H),6.78(d,J＝2.0Hz,4H),6.57(m,2H),6.43(m,1H),4.69(s,1H),4.43(s,1H),4.06(s,5H),3.91(s,1H),1.62(d,J＝6.8Hz,1H)；13C NMR(100MHz,CDCl3):δ143.7,139.0,137.6,36.2,135.5,134.4,133.4,131.4,130.7,129.2,128.5,128.2,128.0,127.9,127.7,127.4,118.9,93.8,76.5,72.1,70.1,70.0,69.3,51.2,23.0；31P NMR(162MHz,CDCl3):δ-24.12,-35.12.
(R)-1-1，(R)-V-1，(Rc,Sp) The structural formula of I-1 is as follows:
example 2
Chiral ligands (R)c,Sp) Preparation of (E) -I-2
The (R) -1-ferrocenylethanol (R) -1-1 in example 1 was replaced by (R) -1-ferrocenylpropanol (R) -1-2 as the starting material, and the intermediate (R) -V-2 in example 1 was orange red oil (yield 81%) to obtain the target compound chiral ferrocene-imidazole diphosphine ligand (R-imidazole diphosphine ligand)c,Sp) -I-2, reddish brown crystals, yield 50%. The nuclear magnetic resonance data is as follows:1H NMR(400MHz,CDCl3):δ7.57(m,4H),7.4(m,3H),7.20-7.27(m,5H),7.08-7.14(m,3H),7.00(t,J＝6.8Hz,2H),6.86-6.92(m,3H),6.37(t,J＝7.0Hz,2H),6.21(br,1H),4.66(br,1H),4.38(s,1H),3.98(s,5H),3.91(s,1H),2.52(m,1H),2.04(br,1H),0.62(m,3H)；13C NMR(100MHz,CDCl3):δ144.8,139.6,138.0,137.0,136.6,135.8,135.5,134.5,134.3,133.8,133.6,131.3,131.2,129.4,128.7,128.3,128.2,128.1,128.0,127.9,127.6,127.1,119.0,94.9,76.3,72.2,70.0,57.1,29.6,11.6；31P NMR(162MHz，CDCl3):δ-23.86,-37.95.
(R)-1-2，(R)-V-2，(Rc,Sp) -I-2 has the following structural formula:
example 3
Chiral ligand (R)c,Sp) Preparation of (E) -I-3
The (R) -1-ferrocenylethanol (R) -1-1 in the example 1 is replaced by (R) -1-ferrocenylbenzyl alcohol (R) -1-3 as the starting material, and the rest of the method is the same as the example 1, the intermediate (R) -V-3 is orange red oily matter (yield is 82 percent), so that the target compound chiral ferrocene-imidazole diphosphine ligand (R) is obtainedc,Sp) -I-3, brown crystals, yield 70%. The nuclear magnetic resonance data is as follows:1H NMR(400MHz,CDCl3):δ7.60(m,2H),7.45(m,1H),7.36(m,5H),7.15(m,8H),7.04(m,2H),6.97(m,4H),6.89(m,3H),6.82(m,3H),4.42(s,1H),4.39(s,1H),4.05(s,1H),3.85(s,5H)；13C NMR(100MHz,CDCl3):δ144.7,139.9,138.3,137.4,135.6,135.3,133.6,133.4,132.0,130.2,129.3,128.2,128.1,128.0,127.9,127.8,127.7 127.6,120.2,92.8,72.6,71.1,70.4,70.2,59.8,59.6；31P NMR(162MHz,CDCl3):δ-25.30,-33.55.
(R)-1-3，(R)-V-3，(Rc,Sp) -I-3 has the following structural formula:
example 4
Chiral ligands (S)c,Rp) Preparation of (E) -1
The (R) -1-ferrocenylethanol (R) -1-1 in the example 1 is replaced by (S) -1-ferrocenylethanol (S) -1-1 starting material, and the rest of the method is the same as the example 1, and the intermediate (S) -V-1 is orange red oily matter (yield is 80 percent) to obtain the target compound chiral ferrocene-imidazole diphosphine ligand (S)c,Rp) -I-1, brown crystals, yield 72%.
(S)-1-1，(S)-V-1，(Sc,Rp) The structural formula of I-1 is as follows:
example 5
Iridium catalyzed asymmetric hydrogenation of imines
The metal precursor [ Ir (COD) Cl]2And chiral ferrocene-imidazole diphosphine ligand (R)c,Sp) Stirring I-3 in 2L dichloromethane at room temperature for 2h to prepare the chiral iridium catalyst (10) by in-situ coordination-3mol/L). The 200mL autoclave was replaced three times with nitrogen, the freshly prepared imine A1 was injected, and the in situ prepared chiral iridium catalyst Ir- (R) was addedc,Sp)-I-1(S/C＝5×105). The reaction mixture was replaced three times with hydrogen, the pressure was adjusted to 60bar and the reaction was carried out at room temperature for 24 hours. After the reaction, the pressure was released and the reaction vessel was analyzed by GCThe conversion rate is more than 99 percent, the column chromatography separation obtains a hydrogenated product B1 with the yield of 99 percent, and the HPLC analysis obtains 93 percent ee. The detection data of the product, namely the nuclear magnetic resonance hydrogen spectrum and the high performance liquid chromatography, are as follows:1H NMR(400MHz,CDCl3):δ7.20–7.36(m,5H),7.05–7.09(m,2H),6.61–6.65(m,1H),6.48–6.50(m,2H),4.46(q,J＝8.0Hz,1H),4.02(br,1H),1.49(d,J＝8.0Hz,3H).HPLC(OJ-H,n-hexane/i-PrOH＝97/3,1.0mL/min,254nm,40℃):tR(minor)＝20.9min,tR(major)＝25.5min.
the structural formulas of A1 and B1 are as follows:
example 6
The chiral catalyst Ir- (R) in example 5c,Sp) Replacement of-I-1 with Ir- (R)c,Sp) -I-2, otherwise as in example 5, reacted to a reaction conversion of greater than 99% by GC analysis and 80% ee by HPLC analysis.
Example 7
The chiral catalyst Ir- (R) in example 5c,Sp) Replacement of-I-1 with Ir- (R)c,Sp) -I-3, otherwise as in example 5, reacted to a reaction conversion of greater than 99% by GC analysis and 90% ee by HPLC analysis.
Example 8
Imine a1 from example 5 was replaced with a2 as in example 4, the reaction was completed and the product was isolated by column chromatography in 99% yield B2 in 92% ee by HPLC. The detection data of the product of the nuclear magnetic resonance hydrogen spectrum and the high performance liquid chromatography are as follows:1H NMR(400MHz,CDCl3):δ7.28-7.34(m,5H),6.81(d,J＝7.9Hz,1H),6.77(t,J＝7.5Hz,1H),6.66(t,J＝7.7Hz,1H),6.59(d,J＝7.8Hz,1H),4.39(dd,J＝8.6,2.7Hz,1H),4.21(dd,J＝10.6,2.8Hz,1H),3.90-3.95(m,2H).HPLC(OD-H,n-hexane/i-PrOH＝80/20,0.6mL/min,254nm,40℃):tR(minor)＝7.4min,tR(major)＝8.1min.
the structural formulas of A2 and B2 are as follows:
example 9
Imine a1 from example 5 was replaced with methyl 2- (2, 6-dimethylphenylimino) propionate A3, the reaction solvent was dichloroethane, the reaction temperature was 80 ℃, the rest of the examples 5 were followed, the product methyl 2- (2, 6-dimethylphenylamino) propionate B3 was obtained after completion of the reaction by column chromatography, yield 96%, 86% ee was obtained by HPLC analysis. The detection data of the product of the nuclear magnetic resonance hydrogen spectrum and the high performance liquid chromatography are as follows:1H NMR(400MHz,CDCl3):δ6.97(d,J＝7.6Hz,2H),6.81(t,J＝7.6Hz,1H),4.00(q,J＝7.2Hz,1H),3.68(s,3H),2.31(s,6H),1.38(d,J＝7.2Hz,3H)；HPLC(chiralcel OD-H,n-hexane/i-PrOH＝99/1,1.0mL/min,254nm,40℃):tR(minor)＝6.9min,tR(major)＝7.7min.
the structural formulas of A3 and B3 are as follows:
example 10
Imine a1 in example 5 was replaced with s-metolachlor key intermediate a4 (generated from 2-methyl-6-ethyl aniline and methoxy acetone), the reaction solvent was dichloroethane, the reaction temperature was 80 ℃, the rest of example 4, after the reaction was completed, column chromatography was performed to obtain B4 with a yield of 92%, and HPLC analysis gave 90% ee. The detection data of the product of the nuclear magnetic resonance hydrogen spectrum and the high performance liquid chromatography are as follows:1H NMR(400MHz,CDCl3):δ7.02(dd,J＝7.6,15.2Hz,2H),6.89(t,J＝7.6Hz,1H),3.36-3.40(m,6H),2.67(q,J＝7.6Hz,2H),2.31(s,3H),1.25(t,J＝7.6Hz,3H),1.20(d,J＝5.6Hz,3H).HPLC(OJ-H,n-hexane/i-PrOH＝98/2,1.0mL/min,254nm,40℃):tR(minor)＝3.9min,tR(major)＝4.3min.
the structural formulas of A4 and B4 are as follows:
Claims (3)
1. a synthetic method of chiral ferrocene-imidazole diphosphine ligand is characterized by comprising the following steps: the general structural formula is as follows:
in the formula: i and II are enantiomers of each other;
in the formula: r is H, alkyl in C1-C10, cycloalkyl in C3-C8, phenyl and substituted phenyl, benzyl and substituted benzyl; the substituent on the substituted phenyl or the substituted benzyl is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano;
ar is phenyl and substituted phenyl, naphthyl and substituted naphthyl; the substituent on the substituted phenyl or the substituted naphthyl is one or more than two of C1-C10 alkyl, C1-10 alkoxy, halogen, nitro, ester group or cyano;
the preparation method comprises the following steps:
(1) heating chiral ferrocenyl alcohol III or IV and N, N' -carbonyldiimidazole in anhydrous dichloromethane at a molar ratio of 1:1 to react to obtain a chiral ferrocene-imidazole intermediate V or VI;
(2) under the action of n-butyllithium, the chiral ferrocene-imidazole undergoes two lithiations and reacts with ClPAr to obtain chiral ferrocene-imidazole diphosphine ligand I or II.
2. The method for synthesizing chiral ferrocene-imidazole diphosphine ligand according to claim 1, which is characterized in that:
the structural formula of the chiral ferrocene-imidazole intermediate is as follows:
in the formula, R is H, alkyl in C1-C10, cycloalkyl in C3-C8, phenyl and substituted phenyl, benzyl and substituted benzyl; the substituent on the substituted phenyl or the substituted benzyl is one or more than two of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group or cyano; ar is phenyl and substituted phenyl, naphthyl and substituted naphthyl; the substituent on the substituted phenyl or the substituted naphthyl is one or more than two of C1-C10 alkyl, C1-10 alkoxy, halogen, nitro, ester group or cyano.
3. The method for synthesizing chiral ferrocene-imidazole diphosphine ligand according to claim 1, which is characterized in that:
the solvent in the step (2) is diethyl ether, and 1-1.2 equivalents of N, N, N ', N' -tetramethylethylenediamine are required to be added in the second lithiation process.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911147195.1A CN112824424B (en) | 2019-11-21 | 2019-11-21 | Chiral ferrocene-imidazole diphosphine ligand and synthesis method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911147195.1A CN112824424B (en) | 2019-11-21 | 2019-11-21 | Chiral ferrocene-imidazole diphosphine ligand and synthesis method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112824424A CN112824424A (en) | 2021-05-21 |
| CN112824424B true CN112824424B (en) | 2022-07-15 |
Family
ID=75907448
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911147195.1A Active CN112824424B (en) | 2019-11-21 | 2019-11-21 | Chiral ferrocene-imidazole diphosphine ligand and synthesis method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112824424B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110551037A (en) * | 2018-05-31 | 2019-12-10 | 中国科学院大连化学物理研究所 | Method for catalyzing asymmetric hydrogenation of imine by iridium/chiral diphosphine system |
-
2019
- 2019-11-21 CN CN201911147195.1A patent/CN112824424B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110551037A (en) * | 2018-05-31 | 2019-12-10 | 中国科学院大连化学物理研究所 | Method for catalyzing asymmetric hydrogenation of imine by iridium/chiral diphosphine system |
| 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 |
Non-Patent Citations (3)
| Title |
|---|
| Dao-Yong Wang，et al.Enantioselective Rh-Catalyzed Hydrogenation of 3-Aryl-2-phosphonomethylpropenoates by a New Class of Chiral Ferrocenyl Diphosphine Ligands.《ORGANIC LETTERS》.2009,第3226-3227页、SI第2、5-7页. * |
| Enantioselective Rh-Catalyzed Hydrogenation of 3-Aryl-2-phosphonomethylpropenoates by a New Class of Chiral Ferrocenyl Diphosphine Ligands;Dao-Yong Wang，et al;《ORGANIC LETTERS》;20090702;第3226-3227页、SI第2、5-7页 * |
| Simple route to ferrocenyl(alkyl)imidazoles;Alexander A. Simenel，et al;《Journal of Organometallic Chemistry》;20030103;第14页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112824424A (en) | 2021-05-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kurihara et al. | An N‐Linked Bidentate Phosphoramidite Ligand (N‐Me‐BIPAM) for Rhodium‐Catalyzed Asymmetric Addition of Arylboronic Acids to N‐Sulfonylarylaldimines | |
| Lu et al. | Enantioselective alkynylation of aromatic aldehydes catalyzed by new chiral amino alcohol-based ligands | |
| CA2382779C (en) | Chiral ligands, transition-metal complexes thereof and uses thereof in asymmetric reactions | |
| Kurihara et al. | Enantioselective 1, 4-addition of arylboronic acids to α, β-unsaturated carbonyl compounds catalyzed by rhodium (I)-chiral phosphoramidite complexes | |
| CN110551037B (en) | Method for catalyzing asymmetric hydrogenation of imine by iridium/chiral diphosphine system | |
| Liu et al. | Asymmetric transfer hydrogenation of ketones with a polyethylene glycol bound Ru catalyst in water | |
| Fadini et al. | Asymmetric hydroamination of acrylonitrile derivatives catalyzed by Ni (II)-complexes | |
| US20020026064A1 (en) | Ruthenium-diphosphine complexes and their use as catalysts | |
| CN112824422B (en) | Chiral ferrocene-indole diphosphine ligand as well as preparation method and application thereof | |
| Unaleroglu et al. | Synthesis of novel norephedrine-based chiral ligands with multiple stereogenic centers and their application in enantioselective addition of diethylzinc to aldehyde and chalcone | |
| CN111848322B (en) | Axial chiral oxindole-substituted styrene compound and resolution method and application thereof | |
| Lam et al. | An Efficient Approach to Chiral Ferrocene‐Based Secondary Alcohols via Asymmetric Hydrogenation of Ferrocenyl Ketones | |
| Pfaltz | Recent developments in asymmetric catalysis | |
| Chen et al. | Ferrocene-based aminophosphine ligands in the Ru (II)-catalysed asymmetric hydrogenation of ketones: assessment of the relative importance of planar versus carbon-centred chirality | |
| CN112824424B (en) | Chiral ferrocene-imidazole diphosphine ligand and synthesis method and application thereof | |
| Yu et al. | L‐Proline‐based Phosphamides as a New Kind of Organocatalyst for Asymmetric Direct Aldol Reactions | |
| Liu et al. | Synthesis of chiral cyclohexane-backbone P, N-ligands derived from pyridine and their applications in asymmetric catalysis | |
| Zou et al. | New bis (1-ferrocenylethyl) amine-derived monodentate phosphoramidite ligands for highly enantioselective copper-catalyzed 1, 4-conjugate addition | |
| Gonsalves et al. | Pyrrolidine-based amino alcohols: novel ligands for the enantioselective alkylation of benzaldehyde | |
| Šebesta et al. | Influence of structural changes in ferrocene phosphane aminophosphane ligands on their catalytic activity | |
| Dhondge et al. | A pineno-salen type catalyst for the enantioselective Nozaki–Hiyama–Kishi reaction | |
| JP2015172024A (en) | Chiral bicyclic diene ligand having hydrogen bond formation amide group | |
| Xu et al. | trans-(1S, 2S)-1-Substituted-2-(N, N-dialkylamino)-1-indanol derivatives as chiral ligands in the catalytic enantioselective addition of diethylzinc to aldehydes | |
| CN114539319B (en) | Chiral phosphine-dicyclophosphoramidite ligand and preparation method and application thereof | |
| CN112824375B (en) | Method for preparing chiral amine compound by palladium-catalyzed asymmetric hydrogenation of imine |
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 |