CN112279743A - Synthesis method of chiral alpha-amino acid ester derivative - Google Patents

Synthesis method of chiral alpha-amino acid ester derivative Download PDF

Info

Publication number
CN112279743A
CN112279743A CN201910668946.8A CN201910668946A CN112279743A CN 112279743 A CN112279743 A CN 112279743A CN 201910668946 A CN201910668946 A CN 201910668946A CN 112279743 A CN112279743 A CN 112279743A
Authority
CN
China
Prior art keywords
chiral
acid ester
amino acid
synthesizing
functional groups
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.)
Granted
Application number
CN201910668946.8A
Other languages
Chinese (zh)
Other versions
CN112279743B (en
Inventor
胡向平
胡信虎
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.)
Dalian Institute of Chemical Physics of CAS
Original Assignee
Dalian Institute of Chemical Physics of CAS
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 Dalian Institute of Chemical Physics of CAS filed Critical Dalian Institute of Chemical Physics of CAS
Priority to CN201910668946.8A priority Critical patent/CN112279743B/en
Publication of CN112279743A publication Critical patent/CN112279743A/en
Application granted granted Critical
Publication of CN112279743B publication Critical patent/CN112279743B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • 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
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
    • C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a method for synthesizing chiral alpha-amino acid ester derivatives, which comprises the following steps: the chiral alpha-amino acid ester derivative is prepared by catalyzing asymmetric hydrogenation of imido ester by taking a complex prepared in situ by reacting a chiral ferrocene skeleton phosphine-phosphoramidite ligand with a metal iridium precursor as a catalyst. Provides a feasible way for synthesizing amino acid. Compared with other methods for synthesizing chiral amino acid ester, the method for synthesizing the hydrogenated chiral ferrocene skeleton phosphine-phosphoramidite ligand is simple, low in price and suitable for kilogram-level production, the iridium/chiral ferrocene skeleton phosphine-phosphoramidite system is high in catalytic activity and enantioselectivity, the enantiomeric excess value (ee value) of the product is up to more than 96%, the hydrogenation reaction is simple to operate, mild in condition and high in atom economy, and the method is suitable for industrial production, has a good result on the synthesis of phenylglycine ethyl ester, achieves the yield of 92% and the enantioselectivity of 91%, and has good industrial practicability.

Description

Synthesis method of chiral alpha-amino acid ester derivative
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of a chiral alpha-amino acid ester derivative, which is suitable for production of unnatural amino acids.
Background
Chiral amino acids and derivatives are important intermediates in chemical, pharmaceutical and biological synthesis, and play an important role in protein and polypeptide research. The simplest and convenient methods for synthesizing chiral amino acid esters include asymmetric hydrogenation of dehydroamino acid esters and asymmetric hydrogenation of alpha-imino acid esters. Wherein, the asymmetric hydrogenation of the alpha-imine acid ester is a green, environment-friendly and efficient method for synthesizing the chiral aromatic amino acid ester. The chiral aromatic amino acid ester compound is prepared by directly hydrogenating an alpha-imino ester substrate with the help of a chiral catalyst and other auxiliary agents. In recent years, there has been great progress on organic small molecule catalyzed asymmetric transfer hydrogenation of α -imidates, while there have been few reports on metal catalyzed asymmetric hydrogenation of α -imidates.
In 2001, the Amii team (H.Abe, H.Amii, K.Unneyama.org.Lett.2001, 3, 313-315;) successfully catalyzed asymmetric hydrogenation of alpha-imidate to chiral amino acid ester derivatives using (R) - (+) -1,1 '-binaphthyl-2, 2' -bisdiphenylphosphine ligands with palladium trifluoroacetate, achieved up to 91% enantioselectivity. However, this method is suitable only for small amounts of substrate.
In 2006, Zhang Mou team (G.Shang, Q.Yang, X.Zhang.Angew.chem.2006,118, 6508-6510; Angew.chem.int.Ed.2006,45,6360-6362) reported asymmetric hydrogenation of aromatic alpha-imino ester, and a chiral alpha-aryl amino acid ester product can be obtained under the catalysis of Rh- (S, S, R, R) -tandPhos, wherein the product yield is more than 93 percent, and the enantioselectivity reaches 95 percent at most.
Therefore, the development of the catalyst with high activity, high stereoselectivity and wide asymmetric reduction range of alpha-imine acid ester applicable to the substrate has very important significance.
Disclosure of Invention
The invention aims to provide a method for synthesizing chiral alpha-amino acid ester derivatives.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a method for synthesizing chiral alpha-amino acid ester derivatives, which adopts chiral catalysts iridium-L and alpha-imino acid ester to prepare chiral amino acid ester derivatives by asymmetric hydrogenation; the chiral catalyst iridium-L is generated by in-situ coordination of an iridium-cyclooctadiene complex and a chiral ferrocene skeleton phosphine-phosphoramidite ligand in a solvent.
A method for synthesizing chiral alpha-amino acid ester derivatives comprises the following steps:
under the protection of nitrogen, dissolving an iridium-cyclooctadiene complex and a chiral ferrocene skeleton phosphine-phosphoramidite ligand in a solvent, stirring for 10 minutes at room temperature, adding a substrate alpha-imino ester and an additive (10 mol%) dissolved in the solvent, placing the mixture into a high-pressure reaction kettle, performing hydrogen replacement for 3 times, introducing hydrogen to 20-100bar, reacting for 1-24 hours at-20-50 ℃, slowly releasing the hydrogen, removing the solvent, and separating by using a silica gel column (eluent: ethyl acetate/petroleum ether ═ 1/10) to obtain the product chiral alpha-amino acid ester derivative.
The solvent is tetrahydrofuran, dioxane, dichloromethane, 1, 2-dichloroethane or toluene; tetrahydrofuran and dioxane are preferred.
The additive is iodine, N-iodosuccinimide, N-bromosuccinimide, N-chlorosuccinimide or tetrabutylammonium iodide; iodine and N-iodosuccinimide are preferred.
In order to achieve the purpose, the technical scheme of the invention is as follows:
Figure BDA0002141026690000011
the imidate and the prepared chiral amino acid ester related by the invention have the following structures:
Figure BDA0002141026690000021
in the formula:
R1is C1～C10Alkyl radicals such as CH3、CH3CH2Etc. C3～C12Cycloalkyl radicals such as cyclopentyl, cyclohexyl, etc., or C containing one or more functional groups of N, S, O, P1～C10Alkyl such as methoxymethyl, ethoxymethyl, etc., or C containing one or more functional groups of N, S, O, P3～C10Cycloalkyl radicals, e.g. 2-tetrahydrofuryl, 4-tetrahydrofuranA group, etc.; or aryl or the like C6-C30Aromatic groups with or without functional groups such as N, S, O, P, e.g. phenyl, 4-methoxyphenyl, etc
R2Is aryl or the like C6-C30Aromatic groups such as phenyl, 4-methoxyphenyl, etc., which may or may not contain N, S, O, P, etc.;
R3is C1～C10Alkyl radicals such as CH3、CH3CH2And the like.
The chiral ferrocene skeleton phosphine-phosphoramidite ligand has the following structure:
Figure BDA0002141026690000022
in the formula, R1、R2Is H; alkyl and cycloalkyl radicals and the like C1～C40Aliphatic groups with or without functional groups such as N, S, O, P; benzyl radical or the like C7-C60A combination of aromatic groups and aliphatic groups, which may or may not contain N, S, O, P functional groups; aryl radicals and the like C6-C60Aromatic groups with or without N, S, O, P functional groups.
Ar is C6-C60Aromatic groups with or without N, S, O, P functional groups.
The X group is: chiral or achiral aliphatic groups with or without functional groups such as N, S, O, P; aromatic groups with or without functional groups such as N, S, O, P; chiral or achiral biphenyl, binaphthyl or tetrahydrobinaphthyl aromatic groups containing or not containing N, S, O, P functional groups.
The iridium-cyclooctadiene complex is: [ Ir (COD) Cl]2、Ir(COD)2BF4Or Ir (COD)2BARF。
The iridium concentration in the reaction system is 0.001-0.01mol/l, and the molar ratio of the chiral ferrocene skeleton phosphine-phosphoramidite ligand to iridium is 1-5: 1; preferably, the iridium concentration is 0.002mol/l and the molar ratio of ligand to iridium is 1: 1.
The molar ratio of the alpha-imidate substrate to the chiral catalyst iridium-L is 50-500: 1; preferably 50-100: 1.
The invention has the beneficial effects that: compared with other methods for synthesizing chiral amino acid ester, the method for synthesizing the hydrogenated chiral ferrocene skeleton phosphine-phosphoramidite ligand is simple, low in price and suitable for kilogram-level production, the iridium/chiral ferrocene skeleton phosphine-phosphoramidite system is high in catalytic activity and enantioselectivity, the enantiomeric excess value (ee value) of the product is up to more than 96%, the hydrogenation reaction is simple to operate, mild in condition and high in atom economy, and the method is suitable for industrial production, has a good result on the synthesis of phenylglycine ethyl ester, achieves the yield of 92% and the enantioselectivity of 91%, and has good industrial practicability.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1: nuclear magnetic resonance hydrogen spectrum of methyl (4-methoxyanilino) phenylacetate prepared in example 1;
FIG. 2: nuclear magnetic resonance carbon spectrum of methyl (4-methoxyanilino) phenylacetate prepared in example 1;
FIG. 3: NMR spectrum of methyl (4-methylphenyl) - (4-methoxyanilino) acetate prepared in example 15;
FIG. 4: NMR spectrum of methyl (4-methylphenyl) - (4-methoxyanilino) acetate prepared in example 15;
FIG. 5: nuclear magnetic resonance hydrogen spectrum of methyl (4-methoxyphenyl) - (4-methoxyanilino) acetate prepared in example 16;
FIG. 6: nuclear magnetic resonance carbon spectrum of methyl (4-methoxyphenyl) - (4-methoxyanilino) acetate prepared in example 16;
FIG. 7: nuclear magnetic resonance hydrogen spectrum of methyl (3-methoxyphenyl) - (4-methoxyanilino) acetate prepared in example 17;
FIG. 8: nuclear magnetic resonance carbon spectrum of methyl (3-methoxyphenyl) - (4-methoxyanilino) acetate prepared in example 17;
FIG. 9: nuclear magnetic resonance hydrogen spectrum of methyl (2-methoxyphenyl) - (4-methoxyanilino) acetate prepared in example 18;
FIG. 10: nuclear magnetic resonance carbon spectrum of methyl (2-methoxyphenyl) - (4-methoxyanilino) acetate prepared in example 18;
FIG. 11: nuclear magnetic resonance hydrogen spectrum of methyl (4-fluorophenyl) - (4-methoxyanilino) acetate prepared in example 19;
FIG. 12: nuclear magnetic resonance carbon spectrum of methyl (4-fluorophenyl) - (4-methoxyanilino) acetate prepared in example 19;
FIG. 13: NMR spectrum of methyl (4-chlorophenyl) - (4-methoxyanilino) acetate prepared in example 20;
FIG. 14: NMR carbon spectrum of methyl (4-chlorophenyl) - (4-methoxyanilino) acetate prepared in example 20;
FIG. 15: NMR spectrum of methyl (3-chlorophenyl) - (4-methoxyanilino) acetate prepared in example 21;
FIG. 16: nuclear magnetic resonance carbon spectrum of methyl (3-chlorophenyl) - (4-methoxyanilino) acetate prepared in example 21;
FIG. 17: NMR spectrum of methyl (4-bromophenyl) - (4-methoxyanilino) acetate prepared in example 22;
FIG. 18: nuclear magnetic resonance carbon spectrum of methyl (4-bromophenyl) - (4-methoxyanilino) acetate prepared in example 22;
FIG. 19: nuclear magnetic resonance hydrogen spectrum of methyl (4-trifluoromethylphenyl) - (4-methoxyanilino) acetate prepared in example 23;
FIG. 20: nuclear magnetic resonance carbon spectrum of methyl (4-trifluoromethylphenyl) - (4-methoxyanilino) acetate prepared in example 23;
FIG. 21: nuclear magnetic resonance hydrogen spectrum of methyl (2-naphthyl) - (4-methoxyanilino) acetate prepared in example 24;
FIG. 22: nuclear magnetic resonance carbon spectrum of methyl (2-naphthyl) - (4-methoxyanilino) acetate prepared in example 24;
FIG. 23: nuclear magnetic resonance hydrogen spectrum of methyl (2-thienyl) - (4-methoxyanilino) acetate prepared in example 25;
FIG. 24: nuclear magnetic resonance carbon spectrum of methyl (2-thienyl) - (4-methoxyanilino) acetate prepared in example 25;
FIG. 25: nuclear magnetic resonance hydrogen spectrum of methyl (cyclohexyl) - (4-methoxyanilino) acetate prepared in example 26;
FIG. 26: nuclear magnetic resonance carbon spectrum of methyl (cyclohexyl) - (4-methoxyanilino) acetate prepared in example 26;
FIG. 27 is a schematic view showing: nuclear magnetic resonance hydrogen spectrum of ethyl phenyl (4-methoxyanilino) acetate prepared in example 27;
FIG. 28: nuclear magnetic resonance carbon spectrum of ethyl phenyl (4-methoxyanilino) acetate prepared in example 27;
FIG. 29: nuclear magnetic resonance hydrogen spectrum of isopropyl phenyl (4-methoxyanilino) acetate prepared in example 28;
FIG. 30: nuclear magnetic resonance carbon spectrum of isopropyl phenyl (4-methoxyanilino) acetate prepared in example 28;
FIG. 31: nuclear magnetic resonance hydrogen spectrum of methyl phenyl (4-methoxyanilino) acetate prepared in example 29;
FIG. 32: NMR carbon spectrum of methyl phenyl (4-methoxyanilino) acetate prepared in example 29.
Detailed Description
The following examples further illustrate the invention but are not intended to limit the invention thereto. NMR was measured by Bruker NMR and High Performance Liquid Chromatography (HPLC) was measured by Agilent 1100 series HPLC.
Example 1
Figure BDA0002141026690000031
Under the protection of nitrogen gas, [ Ir (COD) Cl]2(0.002mmol,0.5 mol%), chiral bisThe cyclopentadienyl iron skeleton phosphine-phosphoramidite ligand (0.0048mmol,1.1 mol%) is dissolved in tetrahydrofuran (1.0mL), stirred at room temperature for 10 minutes, added with a tetrahydrofuran (1.0mL) solution of substrate (4-methoxyphenylimino) methyl phenylacetate (0.4mmol) and 5.1mg iodine, placed in an autoclave, replaced with hydrogen for 3 times, and then charged with hydrogen to 50 atm, and reacted at 25 ℃ for 24 hours. Slowly releasing hydrogen, removing the solvent, and separating by using a silica gel column to obtain the product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 96％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).92％ee was determined by chiral HPLC(Chiralcel OJ-H, n-hexane/i-PrOH＝70/30,0.8ml/min,254nm,40℃):tR(minor)＝26.8min,tR(major)＝29.0min. [α]25 D＝100(c 0.88,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.52–7.44(m,2H),7.39–7.26(m, 3H),6.79–6.65(m,2H),6.60–6.45(m,2H),5.01(s,1H),4.67(s,1H),3.71(s,3H),3.69(s,3H). 13C NMR(101MHz,CDCl3)δ172.58(s),152.54(s),140.21(s),137.81(s),128.88(s),128.30(s), 127.30(s),114.83(d,J＝8.3Hz),77.39(s),77.07(s),76.76(s),61.67(s),55.70(s),52.74(s).
the detection result shows that the product is as follows: (4-Methoxyanilino) phenylacetic acid methyl ester.
Example 2
The reaction conditions H in example 1 were2The pressure was changed to 100 atmospheres, and the remainder was the same as in example 1, and the product was obtained by reaction, and it was detected that the product was (4-methoxyanilino) methyl phenylacetate, the yield was 98%, and the enantioselectivity was 92% ee.
Example 3
The reaction conditions H in example 1 were2The pressure was changed to 20 atmospheres, and the remainder was the same as in example 1, and the reaction yielded a product which was (4-methoxyanilino) methyl phenylacetate, as detected, with a yield of 76% and an enantioselectivity of 90% ee.
Example 4
The reaction conditions in example 1 were changed to 25 ℃ and the reaction was carried out as in example 1 to give a product, which was found to be (4-methoxyanilino) methyl phenylacetate in 93% yield and with an enantioselectivity of 91% ee.
Example 5
The reaction conditions in example 1 were changed to 50 ℃ and the reaction was carried out as in example 1 to obtain a product, which was found to be (4-methoxyanilino) methyl phenylacetate in 95% yield and 80% ee enantioselectivity.
Example 6
The reaction condition additive in example 4 was changed to N-iodosuccinimide, and the rest of the reaction was performed in the same manner as in example 4 to obtain a product, which was detected to be (4-methoxyanilino) methyl phenylacetate, with a yield of 95% and an enantioselectivity of 83% ee.
Example 7
The reaction condition additive in example 4 was changed to N-bromosuccinimide, and the rest of the reaction was performed in the same manner as in example 4 to obtain a product, which was detected to be (4-methoxyanilino) methyl phenylacetate, with a yield of 53% and an enantioselectivity of 67% ee.
Example 8
The reaction condition solvent in example 6 was changed to dichloromethane, and the rest of the reaction was performed in the same manner as in example 6 to obtain a product, which was detected to be (4-methoxyanilino) methyl phenylacetate, with a yield of 93% and an enantioselectivity of 69% ee.
Example 9
The reaction condition solvent in example 6 was changed to dichloroethane, and the rest was the same as in example 6, and the product was obtained by reaction, and it was detected that the product was (4-methoxyanilino) methyl phenylacetate, the yield was 93%, and the enantioselectivity was 67% ee.
Example 10
The reaction condition solvent in example 6 was changed to toluene, and the rest of the reaction was performed in the same manner as in example 6 to obtain a product, which was detected to be (4-methoxyanilino) methyl phenylacetate, with a yield of 94% and an enantioselectivity of 77% ee.
Example 11
Figure BDA0002141026690000051
The reaction conditions in example 6 were changed to 3, 3' -dihydro-substituted ferrocenylphosphine-phosphoramidite, and the rest of the reaction conditions in example 6 were the same as in example 6, and the reaction product was (4-methoxyanilino) methyl phenylacetate, yield was 94%, and enantioselectivity was 63% ee.
Example 12
Figure BDA0002141026690000052
The reaction conditions in example 6 were changed to 3, 3' -methyl-substituted ferrocenylphosphine-phosphoramidite, and the rest of the reaction conditions in example 6 were the same as in example 6, and the reaction product was (4-methoxyanilino) methyl phenylacetate, yield was 95%, and enantioselectivity was 74% ee.
Example 13
Figure BDA0002141026690000053
The reaction conditions in example 6 were changed to 3, 3' -phenyl-substituted ferrocenylphosphine-phosphoramidite, and the rest of the reaction was performed in the same manner as in example 6 to obtain a product, which was methyl (4-methoxyanilino) phenylacetate, yield 43%, and enantioselectivity 51% ee.
Example 14
The substrate to catalyst ratio in example 1 was changed to 1000S/C, i.e.: [ Ir (COD) Cl]2(0.00025mmol,0.05 mol%), chiral phosphine-phosphoramidite ligand (0.00055mmol,0.11 mol%), reaction to obtain product, detection shows that the product is (4-methoxyanilino) methyl phenylacetate, and enantioselectivity is 80% ee.
Example 15
The substrate in example 1 was changed to methyl (4-methylphenyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 96％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).93％ee was determined by chiral HPLC(Chiralcel OJ-H, n-hexane/i-PrOH＝90/10,0.8ml/min,254nm,40℃):tR(major)＝33.8min,tR(minor)＝37.2min. [α]25 D＝100(c 1.02,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.36(d,J＝8.0Hz,2H),7.15(d,J＝ 8.0Hz,2H),6.75–6.66(m,2H),6.58–6.46(m,2H),4.98(s,1H),4.62(s,1H),3.70(s,3H),3.69 (s,3H),2.32(s,3H).13C NMR(101MHz,CDCl3)δ172.75(s),152.49(s),140.29(s),138.08(s), 134.80(s),129.58(s),127.19(s),114.82(d,J＝9.7Hz),77.39(s),77.08(s),76.76(s),61.38(s), 55.70(s),52.69(s),21.16(s).
the detection result shows that the product is as follows: (4-methylphenyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 16
The substrate in example 1 was changed to methyl (4-methoxyphenyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow solid was obtained in 97％yield after purification with column chromatography on silica gel(hexanes/ethyl acetate,10/1).95％ee was determined by chiral HPLC(Chiralcel OJ-H, n-hexane/i-PrOH＝70/30,0.8ml/min,254nm,40℃):tR(minor)＝31.9min,tR(major)＝36.8min. [α]25 D＝82.4(c 0.93,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.39(d,J＝8.7Hz,2H),6.87(d,J＝ 8.7Hz,2H),6.72(d,J＝8.9Hz,2H),6.53(d,J＝8.9Hz,2H),4.96(s,1H),4.61(s,1H),3.78(s, 3H),3.71(s,3H),3.70(s,3H).13C NMR(101MHz,CDCl3)δ172.83(s),159.56(s),152.50(s), 140.26(s),129.74(s),128.43(s),114.82(d,J＝7.7Hz),114.26(s),77.37(s),77.05(s),76.74(s), 61.02(s),55.70(s),55.28(s),52.67(s),29.72(s).
the detection result shows that the product is as follows: (4-methoxyphenyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 17
The substrate in example 1 was changed to methyl (3-methoxyphenyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 95％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).87％ee was determined by chiral HPLC(Chiralpak OJ-H, n-hexane/i-PrOH＝70/30,0.8ml/min,254nm,40℃):tR(minor)＝29.7min,tR(major)＝34.0min. [α]25 D＝83.7(c 1.05,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.26(dd,J＝9.9,5.9Hz,1H),7.05 (dd,J＝14.5,4.9Hz,2H),6.84(dd,J＝8.2,2.4Hz,1H),6.76–6.66(m,2H),6.57–6.47(m,2H), 4.98(s,1H),4.65(s,1H),3.79(s,3H),3.72(s,3H),3.70(s,3H).13C NMR(101MHz,CDCl3)δ 172.47(s),160.00(s),152.54(s),140.21(s),139.42(s),129.86(s),119.64(s),114.82(d,J＝8.7 Hz),113.74(s),112.84(s),77.36(s),77.04(s),76.73(s),61.66(s),55.70(s),55.27(s),52.77(s).
the detection result shows that the product is as follows: (3-methoxyphenyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 18
The substrate in example 1 was changed to methyl (2-methoxyphenyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 93％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).77％ee was determined by chiral HPLC(Chiralpak OJ-H, n-hexane/i-PrOH＝70/30,0.8ml/min,254nm,40℃):tR(minor)＝30.2min,tR(major)＝35.9min. [α]25 D＝82.1(c 1.0,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.34(dd,J＝7.4,1.3Hz,1H),7.30–7.21(m,1H),6.92(t,J＝7.9Hz,2H),6.75–6.66(m,2H),6.67–6.53(m,2H),5.44(s,1H),4.59 (s,1H),3.89(s,3H),3.69(s,3H),3.68(s,3H).13C NMR(101MHz,CDCl3)δ173.09(s),157.14 (s),152.58(s),140.65(s),129.43(s),128.18(s),126.53(s),121.05(s),115.09(s),114.79(s), 111.20(s),77.41(s),77.10(s),76.78(s),55.97–55.58(m),52.54(s).
the detection result shows that the product is as follows: (2-methoxyphenyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 19
The substrate in example 1 was changed to methyl (4-fluorophenyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 92％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).93％ee was determined by chiral HPLC(Chiralpak AD-H, n-hexane/i-PrOH＝80/20,0.8ml/min,254nm,40℃):tR(major)＝11.2min,tR(minor)＝12.6min. [α]25 D＝88.0(c 0.74,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.51–7.41(m,2H),7.09–6.97(m, 2H),6.77–6.66(m,2H),6.55–6.44(m,2H),4.99(s,1H),4.68(s,1H),3.72(s,3H),3.70(s,3H). 13C NMR(101MHz,CDCl3)δ172.33(s),163.86(s),161.40(s),152.62(s),139.94(s),133.57(d, J＝3.1Hz),128.94(d,J＝8.2Hz),115.90(s),115.68(s),114.84(d,J＝8.2Hz),99.99(s),77.36 (s),77.05(s),76.73(s),60.93(s),55.69(s),52.83(s).
the detection result shows that the product is as follows: (4-fluorophenyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 20
The substrate in example 1 was changed to methyl (4-chlorophenyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 98％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).93％ee was determined by chiral HPLC(Chiralpak OJ-H, n-hexane/i-PrOH＝90/10,0.8ml/min,254nm,40℃):tR(major)＝32.2min,tR(minor)＝35.7min. [α]25 D＝112.7(c 0.93,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.43(d,J＝8.5Hz,2H),7.37–7.28 (m,2H),6.81–6.64(m,2H),6.59–6.37(m,2H),4.98(s,1H),4.70(s,1H),3.72(s,3H),3.70(s, 3H).13C NMR(101MHz,CDCl3)δ172.05(s),152.65(s),139.82(s),136.42(s),134.11(s), 129.04(s),128.65(s),114.84(d,J＝9.4Hz),77.37(s),77.05(s),76.73(s),60.99(s),55.69(s), 52.90(s).
the detection result shows that the product is as follows: (4-chlorophenyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 21
The substrate in example 1 was changed to methyl (3-chlorophenyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 95％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).86％ee was determined by chiral HPLC(Chiralpak OJ-H, n-hexane/i-PrOH＝90/10,0.8ml/min,254nm,40℃):tR(minor)＝36.1min,tR(major)＝38.3min. [α]25 D＝85.0(c 0.84,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.50(s,1H),7.38(td,J＝4.6,1.6Hz, 1H),7.32–7.22(m,2H),6.78–6.64(m,2H),6.59–6.39(m,2H),4.97(s,1H),4.72(s,1H),3.73 (s,3H),3.70(s,3H).13C NMR(101MHz,CDCl3)δ171.88(s),152.68(s),140.05(s),139.81(s), 134.78(s),130.10(s),128.52(s),127.46(s),125.47(s),114.85(d,J＝12.2Hz),77.37(s),77.05 (s),76.73(s),61.19(s),55.70(s),52.96(s).
the detection result shows that the product is as follows: (3-chlorophenyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 22
The substrate in example 1 was changed to methyl (4-bromophenyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 97％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).93％ee was determined by chiral HPLC(Chiralpak OJ-H, n-hexane/i-PrOH＝90/10,0.8ml/min,254nm,40℃):tR(major)＝33.6min,tR(minor)＝37.6min. [α]25 D＝94.1(c 1.06,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.52–7.42(m,2H),7.37(d,J＝8.5 Hz,2H),6.78–6.64(m,2H),6.56–6.41(m,2H),4.97(s,1H),4.71(s,1H),3.72(s,3H),3.70(s, 3H).13C NMR(101MHz,CDCl3)δ171.96(s),152.65(s),139.79(s),136.97(s),131.99(s), 129.00(s),122.26(s),114.85(d,J＝9.7Hz),77.38(s),77.07(s),76.75(s),61.05(s),55.69(s), 52.92(s).
the detection result shows that the product is as follows: (4-bromophenyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 23
The substrate in example 1 was changed to methyl (4-trifluoromethylphenyl) - (4-methoxyphenylimino) acetate, and the remainder was changed to
Example 1, the reaction yielded the product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 97％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).92％ee was determined by chiral HPLC(Chiralpak AS-H, n-hexane/i-PrOH＝95/5,0.8ml/min,254nm,40℃):tR(minor)＝11.3min,tR(major)＝15.3min. [α]25 D＝74.5(c 0.86,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.77–7.50(m,4H),6.80–6.63(m, 2H),6.58–6.36(m,2H),5.07(s,1H),4.78(s,1H),3.74(s,3H),3.70(s,3H).13C NMR(101MHz, CDCl3)δ171.66(s),152.73(s),142.01(s),139.65(s),130.66(s),127.69(s),125.82(d,J＝3.7Hz), 114.85(d,J＝14.5Hz),77.35(s),77.03(s),76.71(s),61.27(s),55.67(s),53.03(s).
the detection result shows that the product is as follows: (4-trifluoromethylphenyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 24
The substrate in example 1 was changed to methyl (2-naphthyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 94％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).80％ee was determined by chiral HPLC(Chiralpak AS-H, n-hexane/i-PrOH＝95/5,0.8ml/min,254nm,40℃):tR(major)＝24.1min,tR(minor)＝37.5min. [α]25 D＝84.0(c 0.97,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.95(s,1H),7.87–7.76(m,3H), 7.59(dd,J＝8.5,1.6Hz,1H),7.53–7.38(m,2H),6.75–6.63(m,2H),6.65–6.49(m,2H),5.17 (s,1H),4.81(s,1H),3.70(s,3H),3.67(s,3H).13C NMR(101MHz,CDCl3)δ172.54(s),152.58 (s),140.22(s),135.36(s),133.35(d,J＝11.1Hz),128.77(s),128.09(s),127.74(s),126.62– 126.19(m),125.00(s),114.89(d,J＝3.7Hz),77.41(s),77.09(s),76.78(s),61.85(s),55.70(s), 52.82(s).
the detection result shows that the product is as follows: (2-naphthyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 25
The substrate in example 1 was changed to methyl (2-thienyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 90％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).53％ee was determined by chiral HPLC(Chiralpak AS-H, n-hexane/i-PrOH＝95/5,0.8ml/min,254nm,40℃):tR(major)＝17.7min,tR(minor)＝21.5min. [α]25 D＝31.8(c 1.02,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.26–7.20(m,1H),7.12(d,J＝3.5 Hz,1H),6.97(dd,J＝5.0,3.6Hz,1H),6.78–6.70(m,2H),6.65–6.54(m,2H),5.28(s,1H),4.64 (s,1H),3.77(s,3H),3.71(s,3H).13C NMR(101MHz,CDCl3)δ171.69(s),153.01(s),141.49(s), 139.95(s),127.10(s),125.58(d,J＝11.2Hz),115.27(s),114.87(s),77.40(s),77.08(s),76.76(s), 57.83(s),55.67(s),52.95(s).
the detection result shows that the product is as follows: (2-thienyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 26
The substrate in example 1 was changed to methyl (cyclohexyl) - (4-methoxyphenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 91％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).73％ee was determined by chiral HPLC(Chiralpak AS-H, n-hexane/i-PrOH＝95/5,0.8ml/min,254nm,40℃):tR(minor)＝7.0min,tR(major)＝7.9min. [α]25 D＝-45.2(c 0.88,CH2Cl2).1H NMR(400MHz,CDCl3)δ6.81–6.70(m,2H),6.66–6.51(m, 2H),3.86(d,J＝2.5Hz,1H),3.78(d,J＝6.2Hz,1H),3.73(s,3H),3.68(s,3H),1.86(d,J＝12.5 Hz,1H),1.82–1.59(m,6H),1.34–1.07(m,5H).13C NMR(101MHz,CDCl3)δ174.59(s), 152.66(s),141.58(s),115.14(s),114.89(s),77.37(s),77.05(s),76.73(s),63.39(s),55.73(s), 51.75(s),41.33(s),29.72(s),29.25(s),26.14(d,J＝10.9Hz).
the detection result shows that the product is as follows: (cyclohexyl) - (4-methoxyanilino) acetic acid methyl ester.
Example 27
The substrate in the example 1 is changed into phenyl (4-methoxy phenylimino) ethyl acetate, and the reaction is carried out in the same way as the example 1 to obtain the product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 94％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).93％ee was determined by chiral HPLC(Chiralpak AS-H, n-hexane/i-PrOH＝95/5,0.8ml/min,254nm,40℃):tR(major)＝11.0min,tR(minor)＝12.3min. [α]25 D＝71.7(c 0.96,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.48(d,J＝7.2Hz,2H),7.41–7.19 (m,3H),6.79–6.64(m,2H),6.63–6.38(m,2H),5.00(s,1H),4.76–4.44(m,1H),4.33–4.04(m, 2H),3.69(s,3H),1.20(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ172.06(s),152.48(s), 140.27(s),137.92(s),128.80(s),128.19(s),127.25(s),114.81(d,J＝8.7Hz),77.38(s),77.06(s), 76.74(s),61.72(s),55.70(s),14.06(s).
the detection result shows that the product is as follows: phenyl (4-methoxyanilino) acetic acid ethyl ester.
Example 28
The substrate in the example 1 is changed into phenyl (4-methoxy phenylimino) isopropyl acetate, and the reaction is carried out in the same way as the example 1 to obtain the product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 96％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).96％ee was determined by chiral HPLC(Chiralpak AS-H, n-hexane/i-PrOH＝95/5,0.8ml/min,254nm,40℃):tR(major)＝8.5min,tR(minor)＝9.5min. [α]25 D＝65.9(c 0.94,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.40(d,J＝7.3Hz,2H),7.22(ddd,J ＝15.7,13.9,6.5Hz,3H),6.64(dd,J＝9.6,2.7Hz,2H),6.46(t,J＝6.2Hz,2H),4.94(dt,J＝12.5, 6.3Hz,1H),4.89(s,1H),4.59(s,1H),3.62(s,3H),1.18(d,J＝6.3Hz,3H),0.99(d,J＝6.2Hz, 3H).13C NMR(101MHz,CDCl3)δ171.57(s),152.43(s),140.34(s),137.97(s),128.72(s), 128.09(s),127.17(s),114.80(d,J＝9.7Hz),77.38(s),77.06(s),76.74(s),69.35(s),61.80(s), 55.71(s),21.78(s),21.39(s).
the detection result shows that the product is as follows: isopropyl phenyl (4-methoxyanilino) acetate.
Example 29
The substrate in example 1 was changed to methyl phenyl (4-phenylimino) acetate, and the reaction was carried out in the same manner as in example 1 to obtain a product.
The product was analyzed and the NMR and HPLC data are as follows:
Yellow oil was obtained in 95％yield after purification with column chromatography on silica gel (hexanes/ethyl acetate,10/1).90％ee was determined by chiral HPLC(Chiralcel OD-H, n-hexane/i-PrOH＝99/1,0.8ml/min,254nm,40℃):tR(major)＝32.9min,tR(minor)＝41.2min. [α]D 23＝93.7(c 0.94,CH2Cl2).1H NMR(400MHz,CDCl3)δ7.52–7.45(m,2H),7.39–7.26(m, 3H),7.11(t,J＝7.9Hz,2H),6.69(t,J＝7.3Hz,1H),6.55(d,J＝7.9Hz,2H),5.08(d,J＝5.8Hz, 1H),4.95(d,J＝5.5Hz,1H),3.72(s,3H).13C NMR(101MHz,CDCl3)δ172.36(s),145.96(s), 137.63(s),129.26(s),128.91(s),128.34(s),127.27(s),118.14(s),113.42(s),77.38(s),77.06(s), 76.74(s),60.76(s),52.83(s).
the detection result shows that the product is as follows: phenyl (4-methoxyanilino) acetic acid methyl ester.
Table.Asymmetric hydrogenation ofα-imino estersa)
Figure BDA0002141026690000101
Figure BDA0002141026690000102
Figure BDA0002141026690000111
a)Conditions:5(0.2mmol),[Ir(COD)Cl]2(2μmol),ligand 2d(4.8μmol),H2(50bar),THF (2.0ml),I2(10mol％),24h,0℃.b)Isolated yields.c)Determined by chiral HPLC。

Claims (7)

1. A method for synthesizing chiral alpha-amino acid ester derivatives is characterized in that: the method adopts chiral catalysts iridium-L, alpha-imine acid ester to prepare chiral amino acid ester derivatives through asymmetric hydrogenation; the chiral catalyst iridium-L is generated by in-situ coordination of an iridium-cyclooctadiene complex and a chiral ferrocene skeleton phosphine-phosphoramidite ligand in a solvent.
2. The method of claim 1 for synthesizing a chiral α -amino acid ester derivative, wherein: the method specifically comprises the following steps:
under the protection of nitrogen, dissolving an iridium-cyclooctadiene complex and a chiral ferrocene skeleton phosphine-phosphoramidite ligand in a solvent, stirring for 10 minutes at room temperature, adding a substrate alpha-imino ester and an additive dissolved in the solvent, placing the mixture in a high-pressure reaction kettle, performing hydrogen replacement for 3 times, introducing hydrogen to 20-100bar, reacting for 1-24 hours at-20-50 ℃, slowly releasing the hydrogen, removing the solvent, and separating by using a silica gel column (eluent: ethyl acetate/petroleum ether ═ 1/10) to obtain a product chiral alpha-amino acid ester derivative;
the mole percentage of the additive is 10 mol%;
the solvent is tetrahydrofuran, dioxane, dichloromethane, 1, 2-dichloroethane or toluene;
the additive is iodine, N-iodosuccinimide, N-bromosuccinimide, N-chlorosuccinimide or tetrabutylammonium iodide.
3. The method for synthesizing a chiral α -amino acid ester derivative according to claim 1 or 2, wherein: the substrate alpha-imine acid ester and the prepared chiral amino acid ester derivative respectively have the following structures:
Figure FDA0002141026680000011
in the formula:
R1is C1～C10Alkyl radical, C3～C12Cycloalkyl, or C containing one or more functional groups of N, S, O, P1～C10Alkyl, or C containing one or more functional groups of N, S, O, P3～C10A cycloalkyl group; or aryl or the like C6-C30Aromatic groups with or without functional groups such as N, S, O, P;
R2is aryl or the like C6-C30Aromatic groups with or without functional groups such as N, S, O, P;
R3is C1～C10An alkyl group.
4. The method for synthesizing a chiral α -amino acid ester derivative according to claim 1 or 2, wherein: the structural general formula of the chiral ferrocene skeleton phosphine-phosphoramidite ligand L is as follows:
Figure FDA0002141026680000021
wherein R1 and R2 are H; aliphatic groups containing or not containing functional groups such as N, S, O, P in C1-C40 such as alkyl and cycloalkyl; a combination group of an aromatic group and an aliphatic group, which contains or does not contain functional groups such as N, S, O, P and the like, such as benzyl and the like, C7-C60; aromatic groups containing or not containing functional groups such as N, S, O, P in C6-C60 such as aryl;
ar is an aromatic group containing or not containing functional groups such as N, S, O, P and the like in C6-C60;
the X group is: chiral or achiral aliphatic groups with or without functional groups such as N, S, O, P; aromatic groups with or without functional groups such as N, S, O, P; chiral or achiral biphenyl, binaphthyl or tetrahydrobinaphthyl aromatic groups containing or not containing N, S, O, P functional groups.
5. The method for synthesizing a chiral α -amino acid ester derivative according to claim 1 or 2, wherein: the iridium-cyclooctadiene complex is: [ Ir (COD) Cl]2、Ir(COD)2BF4Or Ir (COD)2BARF。
6. The method for synthesizing a chiral α -amino acid ester derivative according to claim 1 or 2, wherein: the iridium concentration in the reaction system is 0.001-0.01mol/l, and the molar ratio of the chiral ferrocene skeleton phosphine-phosphoramidite ligand to iridium is 1-5: 1.
7. the method for synthesizing a chiral α -amino acid ester derivative according to claim 1 or 2, wherein: the molar ratio of the alpha-imidate substrate to the chiral catalyst iridium-L is 50-500: 1.
CN201910668946.8A 2019-07-24 2019-07-24 Synthesis method of chiral alpha-amino acid ester derivative Active CN112279743B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910668946.8A CN112279743B (en) 2019-07-24 2019-07-24 Synthesis method of chiral alpha-amino acid ester derivative

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910668946.8A CN112279743B (en) 2019-07-24 2019-07-24 Synthesis method of chiral alpha-amino acid ester derivative

Publications (2)

Publication Number Publication Date
CN112279743A true CN112279743A (en) 2021-01-29
CN112279743B CN112279743B (en) 2022-10-18

Family

ID=74419226

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910668946.8A Active CN112279743B (en) 2019-07-24 2019-07-24 Synthesis method of chiral alpha-amino acid ester derivative

Country Status (1)

Country Link
CN (1) CN112279743B (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2361919A1 (en) * 2010-02-15 2011-08-31 AIKAA-Chemicals GmbH Imidazo[1,5-b] pyridazin-amino-phosphorous ligands and their complex compounds

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2361919A1 (en) * 2010-02-15 2011-08-31 AIKAA-Chemicals GmbH Imidazo[1,5-b] pyridazin-amino-phosphorous ligands and their complex compounds

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DENMING XIAO等: "Highly Enantioselective Hydrogenation of Acyclic Imines Catalyzed by Ir ± f-Binaphane Complexes", 《ANGEWNDTE CHEMIE INTERNATIONAL EDITION》 *
GAO SHANG等: "Rh-Catalyzed Asymmetric Hydrogenation of a-Aryl Imino Esters: An Efficient Enantioselective Synthesis of Aryl Glycine Derivatives", 《ANGEWNDTE CHEMIE INTERNATIONAL EDITION》 *

Also Published As

Publication number Publication date
CN112279743B (en) 2022-10-18

Similar Documents

Publication Publication Date Title
Kang et al. Highly enantioselective and diastereoselective cycloaddition of cyclopropanes with nitrones and its application in the kinetic resolution of 2‐substituted cyclopropane‐1, 1‐dicarboxylates
Durand et al. Ionic liquids as a medium for enantioselective catalysis
US20130023662A9 (en) Ruthenium (ii) catalysts for use in stereoselective cyclopropanations
Shen et al. β‐cyclodextrin‐immobilized (4S)‐phenoxy‐(S)‐proline as a catalyst for direct asymmetric aldol reactions
Zhao et al. Asymmetric synthesis of dihydrocoumarins via catalytic sequential 1, 6-addition/transesterification of α-isocyanoacetates with para-quinone methides
Chen et al. Modular Chiral bisoxalamide–copper-catalyzed asymmetric Oxo-Diels–Alder reaction: carbonyl coordination for high enantio-and diastereocontrols
Cheng et al. Asymmetric Hydrogenation of α, β‐Unsaturated Carboxylic Acids Catalyzed by Ruthenium (II) Complexes of Spirobifluorene Diphosphine (SFDP) Ligands
JP4144814B2 (en) Method for producing optically active alcohol compound
Ohta et al. α‐Amino acid: an effective ligand for asymmetric catalysis of transfer hydrogenation of ketones
CN108516937B (en) Method for preparing chiral alpha-hydroxy-beta-keto ester compound by visible light-initiated aerobic Salan-copper catalyst
Dai et al. New efficient P, N, O-tridentate ligands for Ru-catalyzed asymmetric transfer hydrogenation
Ma et al. A New Phosphine‐Amine‐Oxazoline Ligand for Ru‐Catalyzed Asymmetric Hydrogenation of N‐Phosphinylimines
CN102336698A (en) Method for synthesizing chiral indoline through palladium-catalyzed asymmetric hydrogenation
An et al. Isosteviol‐amino Acid Conjugates as Highly Efficient Organocatalysts for the Asymmetric One‐pot Three‐component Mannich Reactions
CN111848322B (en) Axial chiral oxindole-substituted styrene compound and resolution method and application thereof
CN101391960A (en) Method for preparing optically pure 2-hydroxyl-4-aryl-butyric ether
CN112279743B (en) Synthesis method of chiral alpha-amino acid ester derivative
CN113121350B (en) Method for dynamic kinetic resolution of alpha-aryl-alpha-alkyl carboxylate and application thereof
CN112521333A (en) Synthesis method of chiral 2, 3-disubstituted tetrahydroquinoline derivative
CN110551035A (en) Iridium-catalyzed asymmetric reductive amination method for ketone
Diezi et al. Chemo and enantioselective hydrogenation of fluorinated ketones on platinum modified with (R)-1-(1-naphthyl) ethylamine derivatives
CN112824372A (en) Copper-catalyzed asymmetric cyclopropanation method of olefin and application thereof
JP3159661B2 (en) Method for producing optically active alcohols
CN110372514B (en) Method for catalyzing asymmetric Michael addition reaction and catalyst thereof
Fukuzawa et al. Diastereoselective 1, 2‐Addition of Organometallic Reagents to Chiral Formylferrocenes Leading to Enantiomerically Pure Ferrocenyl Amino Alcohols: Application to Asymmetric Dialkylzinc Addition to Aldehydes and Synthesis of Optically Active 1, 2‐Homodisubstituted Ferrocenes

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