CN115872872A - Synthesis method and application of chiral o-diamine compound - Google Patents

Synthesis method and application of chiral o-diamine compound Download PDF

Info

Publication number
CN115872872A
CN115872872A CN202111149719.8A CN202111149719A CN115872872A CN 115872872 A CN115872872 A CN 115872872A CN 202111149719 A CN202111149719 A CN 202111149719A CN 115872872 A CN115872872 A CN 115872872A
Authority
CN
China
Prior art keywords
chiral
diamine compound
substituent
phenyl
alkyl
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.)
Pending
Application number
CN202111149719.8A
Other languages
Chinese (zh)
Inventor
胡向平
刘振婷
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 CN202111149719.8A priority Critical patent/CN115872872A/en
Publication of CN115872872A publication Critical patent/CN115872872A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Landscapes

  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a synthetic method and application of a chiral o-diamine compound. The copper catalyst adopted by the method is generated in situ in a reaction medium by a metal copper precursor and a chiral P, N, N-ligand, and the chiral o-diamine compound is obtained at high selectivity through asymmetric propargyl amination reaction and is further converted into a chiral tetranitrogen ligand, and the chiral o-diamine compound is successfully applied to the asymmetric epoxidation reaction of iron-catalyzed olefin. The method has the characteristics of low catalyst cost, simple ligand preparation, high activity, high selectivity, mild reaction conditions, simple and convenient operation and the like.

Description

Synthesis method and application of chiral o-diamine compound
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of a chiral o-diamine compound, and application of a product obtained by the method in an iron-catalyzed asymmetric epoxidation reaction of olefin after being further converted into a chiral tetranitrogen ligand.
Background
Nitrogen-containing organic compounds are widely present in living bodies and are the basis of life. Major parts constituting a living body, such as proteins, enzymes that achieve physiological activities, alkaloids, DNA fragments for storing genetic information, and urea, which is a metabolic product, are nitrogen-containing compounds. In natural products, the nitrogen element is widely present in various amine compounds, especially many biologically active alkaloids [ Funayama S, cordell G A. Alkalides: A Treasury of Poison and medicines. Academic Press,2015, 73-74 ]. The structures of a plurality of natural products and drug molecules contain a chiral nitrogen heterocyclic ring system of o-diamine, for example, (-) -A-gelastatin A is an inhibitor taking osteopontin as a target and can successfully inhibit the growth and the metastasis of breast cancer cells [ (a) Feldman K.S.; saunders J.C.J.am.chem.Soc.2002,124, 9060-9061; (b) Ichikawa y.; yamaoka t.; nakano k., org.lett.2007,9,2989-2992; (c) When p.m.; du Bois j.angelw.chem., int.ed.2009,48,3802-3805. (R) -Praziquantel drug is a drug that is already on the market for the treatment of fluke disease [ Olliaro p; delgado-Romero P.; keiser j.j.anitimicrob.chemither.2014, 69,863-870. MDM2 inhibitors have been found to be useful in cancer therapy [ (a) Chu x; ding Q.; jiang n.u.s.pat.appl.pub.2012, US20120065210A1 ]. In addition, ortho-diamine derived compounds are also described in coordination chemistry [ (a) Takemura s.; kawakami s.; harada M.Inorg.chem.2014,53,9667-9678.], subject-object identification [ (a) Boiocchi M.; lichelli m.; milani m.inorg.chem.2015,54,47-58 ] and asymmetric catalytic reactions [ (a) Zhou y; yang Q.; shen j.j.org.chem.2015,80,1446-1456; (b) Tong b.m.k.; chiba s.org.lett.2011,13,2948-2951 ] are widely used. In view of the important application of chiral o-diamine compounds in the fields of medicine and catalysis, the simple and efficient construction of chiral o-diamine groups becomes an important research direction in the field of organic synthesis. However, the traditional method for constructing chiral ortho-diamines has great limitations, mainly because the selection of nitrogen source is special and single, which greatly limits the diversity of the synthesis of chiral ortho-diamines. Therefore, the development of an effective synthetic method for constructing the chiral o-diamine compound has important significance for deeply exploring the potential application of the compound.
Alkyne compounds widely exist in nature and are common chemical raw materials. In recent years, transition metal catalyzed asymmetric propargyl amination reactions have been widely developed [ (a) detzr.j., delvillem.m.e.h., hiemstrah, van maarseven j.h., angelw.chem.int.ed.2008, 47,3777-3780; (b) Hattorig, matsuzawa, miyakey, nishibayashiy, angelw.chem.int.ed.2008, 47,3781-3783; (c) Zhangc, wangy-h, hux-h, zhengz, xuj, hux-p, adv.synth.catal.2012,354,2854-2858; (d) Shibatam, nakajimak, nishibayashiy, chem.commun.2014,50,7874-7877; (e) Zhang d. -y., shao l., xu j., hu x. -p., ACS catal.2015,5,5026-5030; (f) Liu Z. -T., wang Y. -H., zhu F. -L., hu X. -P., org.Lett.2016,18,1190-1194.], and provides a simple, quick and effective synthesis way for the preparation of nitrogen-containing compounds, especially nitrogen-containing heterocyclic compounds. The subject group of the inventors has been devoted to the design and development of chiral ligands and the research on the application of the chiral ligands in asymmetric catalytic reactions for many years. The invention successfully realizes asymmetric propargyl 1, 2-diamine reaction by using the chiral catalyst formed by chiral P, N, N-ligand and transition metal copper which are independently researched and developed, obtains chiral o-diamine compound with high selectivity, can be further converted into novel chiral tetranitrogen ligand, and is successfully applied to the asymmetric epoxidation of iron-catalyzed olefin.
Disclosure of Invention
The invention aims to provide a method for synthesizing chiral o-diamine compounds, and the chiral o-diamine compounds are further converted into novel chiral tetranitrogen ligands to be applied to the asymmetric epoxidation reaction of iron-catalyzed olefins, aiming at overcoming the defects in the prior art.
The technical scheme of the invention comprises the following specific steps:
(1) Preparation of chiral copper catalyst: under the protection of nitrogen, copper salt and chiral P, N, N-ligand are stirred in a reaction medium for 0.5 to 2 hours and in-situ coordinated to prepare a chiral copper catalyst;
(2) The synthesis method of the chiral o-diamine compound comprises the following steps: transferring the chiral copper catalyst solution obtained in the step (1) into a low-temperature reaction bath, reducing the temperature to-20-10 ℃, sequentially adding the propargyl compound (III), the 1, 2-diamine compound (II) and the alkali additive, and continuing to react for 12-24 hours. After the reaction is finished, concentrating under reduced pressure until no solvent exists basically, separating by silica gel column chromatography, concentrating under reduced pressure, and drying in vacuum to obtain the chiral ortho-diamine compound (I).
The chiral o-diamine compound (I) has the following structure:
Figure BDA0003286505620000031
in the formula: r is 1 、R 2 H, C1-C10 alkyl, phenyl, substituted phenyl, naphthyl and substituted naphthyl; the substituent is one or more than two of C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5. R 3 Is one or more than two of C1-C3 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkyl with substituent, phenyl and substituted phenyl, naphthyl and substituted naphthyl, benzyl and substituted benzyl, and five-membered or six-membered heterocyclic aromatic groups containing one or more than two oxygen, sulfur and nitrogen atoms; the substituent is one or more than two of C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5.
The 1, 2-diamine compound (II) has the following structure:
Figure BDA0003286505620000041
in the formula: r 1 、R 2 Is represented by the formula I 1 ，R 2 The same groups.
The propargyl compound (III) has the following structure:
Figure BDA0003286505620000042
in the formula: r 3 Is represented by the formula I 3 The same groups. Wherein the leaving group X is fluorine, chlorine, bromine, iodine, alkyl carboxylate, alkylBasic carbonate, alkyl sulfonate, alkyl phosphate, phenyl and substituted phenyl carboxylate, phenyl and substituted phenyl carbonate, phenyl and substituted phenyl sulfonate or phenyl and substituted phenyl phosphate; the substituent on the substituted phenyl is one or more than two of C1-C10 alkyl, C3-C6 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituent is 1-5.
The copper salt is Cu (OAc) 2 ·H 2 O、CuSO 4 ·H 2 O、Cu(OAc) 2 、CuSO 4 、Cu(OTf) 2 、CuCl 2 、CuOAc、CuCl、CuI、CuClO 4 、CuOTf·0.5C 6 H 6 、Cu(CH 3 CN) 4 BF 4 Or Cu (CH) 3 CN) 4 ClO 4 Preferably Cu (OTf) 2 。
The alkali additive is i Pr 2 NEt、NEt 3 、 t BuOK、KOH、NaOH、Na 2 CO 3 、NaHCO 3 、 t BuOK、K 2 CO 3 、Cs 2 CO 3 Or K 3 PO 4 Preferably NEt 3 。
The chiral P, N-ligand has the following structure:
Figure BDA0003286505620000043
in the formula: r 4 、R 5 Is one or more than two of C1-C10 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkyl with substituent, phenyl and substituted phenyl, naphthyl and substituted naphthyl, benzyl and substituted benzyl, and five-membered or six-membered heterocyclic aromatic groups containing one or more than two oxygen, sulfur and nitrogen atoms; the substituent on the C3-C6 naphthenic base, the substituent on the phenyl, the substituent on the naphthyl and the substituent on the benzyl are one or more than two of C1-C10 alkyl, C3-C6 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5;
R 6 is H, C1-C10 alkyl, C3EC6 cycloalkyl or C3-C6 cycloalkyl with substituent, phenyl and substituted phenyl, naphthyl and substituted naphthyl, benzyl and substituted benzyl, and one or more five-membered or six-membered heterocyclic aromatic groups containing one or more than two oxygen atoms, sulfur atoms and nitrogen atoms; the substituent on the C3-C6 naphthenic base, the substituent on the phenyl, the substituent on the naphthyl and the substituent on the benzyl are one or more than two of C1-C10 alkyl, C3-C6 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5;
R 7 is one or more than two of H, halogen, C1-C10 alkyl and C3-C6 cycloalkyl, phenyl and substituted phenyl, alkoxy, phenoxy, acyl, nitro, ester group or cyano.
The reaction medium is at least one of methanol, ethanol, toluene, benzene, xylene, dichloromethane, 1, 2-dichloroethane, diethyl ether, tetrahydrofuran, dimethyl sulfoxide or N, N-dimethylformamide, and is preferably methanol.
The addition molar ratio of the chiral P, N, N-ligand to the copper salt is 1-5;
the molar ratio of the addition amount of the copper catalyst to the addition amount of the propargyl compound (III) is 0.01-1
The molar ratio of the addition amount of the propargyl compound (III) to the addition amount of the 1, 2-diamine compound (II) is 2-4;
the molar ratio of the alkali additive to the addition amount of the 1, 2-diamine compound (II) is 2-4; .
The reaction temperature is 0 ℃;
the reaction time is 12 to 24 hours.
In order to achieve the purpose, the technical scheme of the invention is as follows:
Figure BDA0003286505620000061
the invention has the beneficial effects that:
1. the starting materials are cheap and easy to obtain.
2. The chiral ligand is simple and convenient to synthesize, the catalyst is cheap and easy to obtain, and the dosage is small.
3. The reaction activity is good, the stereoselectivity is high, and the reaction condition is easy to realize;
4. the reaction product can be further converted into a novel chiral tetranitrogen ligand and used in the asymmetric epoxidation reaction of the iron-catalyzed olefin.
Figure BDA0003286505620000062
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention. Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:
FIG. 1 shows chiral N, N prepared in example 1 ’ -diphenyl-N, N ’ -nuclear magnetic resonance hydrogen spectrum of bis (1-phenylprop-2-yne) -1, 2-ethylenediamine;
FIG. 2 shows chiral N, N prepared in example 1 ’ -diphenyl-N, N ’ -nuclear magnetic resonance carbon spectrum of bis (1-phenylprop-2-yne) -1, 2-ethylenediamine;
FIG. 3 shows chiral N, N prepared in example 10 ’ -dimethyl-N, N ’ -nuclear magnetic resonance hydrogen spectrum of bis (1-phenylprop-2-yne) -1, 2-ethylenediamine;
FIG. 4 is chiral N, N prepared in example 10 ’ -dimethyl-N, N ’ Nuclear magnetic resonance carbon spectrum of (1-phenylprop-2-yne) -1, 2-ethanediamine
FIG. 5 shows chiral N, N prepared in example 11 ’ -diphenyl-N, N ’ -nuclear magnetic resonance hydrogen spectrum of bis (1-p-toluenesulfonyl-1H-1, 2, 3-triazole-4-benzyl) -1, 2-ethylenediamine;
FIG. 6 is chiral N, N prepared in example 11 ’ -diphenyl-N, N ’ Nuclear magnetic resonance carbon spectrum of bis (1-p-toluenesulfonyl-1H-1, 2, 3-triazole-4-benzyl) -1, 2-ethylenediamine;
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. The chiral ligand used in the reaction was prepared in the laboratory and purchased commercially.
Example 1
Copper-catalyzed asymmetric propargyl 1, 2-bisamidation: under the protection of nitrogen, metal copper precursor Cu (OTf) 2 (0.015mmol, 5.4mg) and chiral P, N, N-ligand L-1-1 (0.0165mmol, 7.8mg) were placed in a 25mL Hourong tube, 1mL of anhydrous methanol was added, and the mixture was stirred at room temperature for 1 hour, followed by in situ coordination to prepare a chiral copper catalyst. Then, the reaction tube was moved to a constant temperature reaction bath at 0 ℃ to dissolve substrates N, N' -diphenylethylenediamine II-1 (0.3mmol, 63.7mg), propargyl alcohol acetate III-1 (0.66mmol, 115.0mg) and triethylamine (0.78mmol, 110. Mu.L) in 2mL of anhydrous methanol, and the solution was added to the above stirred chiral copper catalyst solution to continue the reaction for 12 hours. After the reaction is finished, concentrating under reduced pressure until no solvent exists basically, separating by silica gel column chromatography (petroleum ether/ethyl acetate = 20)>20:1，>99% ee. The nuclear magnetic resonance hydrogen spectrum and the carbon spectrum of the product are shown in figures 1 and 2: 1 H NMR(400MHz,CDCl 3 ):δ7.55-7.52(m,4H),7.38-7.30(m,6H),7.19-7.12(m,4H),6.79-6.75(m,2H),6.70-6.68(m,4H),5.67(d,J＝2.3Hz,2H),3.50-3.43(m,2H),3.20-3.11(m,2H),2.48(d,J＝2.4Hz,2H)； 13 C NMR(101MHz,CDCl 3 )δ148.0,137.6,129.2,128.6,128.0,128.0,118.6,114.9,81.3,74.9,55.2,45.2.HPLC(ChiralcelAD-H,n-hexane/i-PrOH＝95/5,0.8mL/min,254nm,40℃):t R (minor)＝7.5min,t R (major)＝14.7min.
the structural formula of I-1, II-1, III-1, L-1-1 is as follows:
Figure BDA0003286505620000081
example 2
L-1-2 is used as ligand to react to generate a product I-1
The same procedure as in example 1 was repeated except that ligand L-1-1 in example 1 was replaced with ligand L-1-2. The reaction yielded compound I-1, 99% yield, dr =16, >99% ee.
The structural formula of L-1-2 is as follows:
Figure BDA0003286505620000082
example 3
L-2-1 is used as ligand to react to generate a product I-1
The ligand L-1-1 in example 1 was replaced with ligand L-2-1, and the procedure was otherwise the same as in example 1. The reaction yielded compound I-1, 99% yield, > dr >20, >99% ee.
The structural formula of L-2-1 is as follows:
Figure BDA0003286505620000091
example 4
L-1-3 as ligand to generate product I-1
The ligand L-1-1 in example 1 was replaced with the ligand L-1-3, and the procedure was otherwise the same as in example 1. The reaction yielded compound I-1, 95% yield, > dr >20, >99% ee.
The structural formula of L-1-3 is as follows:
Figure BDA0003286505620000092
/>
example 5
Cu(CH 3 CN) 4 BF 4 And L-1-1 to produce a product I-1
The copper salt Cu (OTf) of example 1 2 With Cu (CH) 3 CN) 4 BF 4 Instead, the rest is the same as example 1. The reaction gave compound I-1, 98% yield, dr =20,>99％ee。
example 6
CuCl and L-1-1 are catalyzed to generate a product I-1
The copper salt Cu (OTf) of example 1 2 Example 1 was followed except that CuCl was used instead. The reaction gave compound I-1, 89% yield, dr =18,>99％ee。
example 7
N, N-diisopropylethylamine is used as an alkali additive to participate in the reaction to generate a product I-1
The base additive triethylamine in example 1 was replaced with N, N-diisopropylethylamine and the rest was the same as in example 1. The reaction yielded compound I-1, 97% yield, dr >20, >99% ee.
Example 8
Alkali-free additive participates in the reaction to generate a product I-1
The base additive triethylamine in example 1 was discarded and the rest was the same as in example 1. The reaction did not yield compound I-1.
Example 9
Absolute ethyl alcohol as reaction medium to participate in the reaction to generate a product I-1
The reaction medium anhydrous methanol in example 1 was replaced by anhydrous ethanol, the remainder being the same as in example 1. The reaction yielded compound I-1, 80% yield, >99% ee.
Example 10
II-2 as a substrate to produce a product I-2
The same procedure used in example 1 except for replacing N, N '-diphenylethylenediamine II-1 with N, N' -dimethylethylenediamine II-2 used in example 1 gave the compound I-2 in a yield of 90% dr>20:1，>99% ee. The hydrogen spectrum and the carbon spectrum of the product nuclear magnetic resonance are shown in figures 3 and 4: 1 H NMR(400MHz,CDCl 3 )δ7.58-7.55(m,4H),7.33-7.23(m,6H),4.78(d,J＝2.2Hz,2H),2.69-2.59(m,4H),2.51(d,J＝2.3Hz,2H),2.16(s,6H)； 13 C NMR(101MHz,CDCl 3 )δ138.4,128.3,128.1,127.5,79.2,75.8,60.1,52.4,38.2,38.2.HPLC(Chiralcel AD-H,n-hexane/i-PrOH＝95/5,0.8mL/min,254nm,40℃):t R (minor)＝25.1min,t R (major)＝30.2min.
the structural formula of I-2, II-2, III-1, L-1-1 is as follows:
Figure BDA0003286505620000101
example 11
Further conversion of I-1 to chiral tetranitrogen ligand L-3-1
I-1 (132.2 mg,0.3 mmol) in example 1, p-toluenesulfonic acid azide (130.2 mg, 0.66mmol) and CuTc (11.4 mg, 0.06mmol) were dissolved in anhydrous toluene and reacted at room temperature for 8 hours. After the reaction was completed, the solvent was removed under reduced pressure, and column chromatography (petroleum ether/ethyl acetate = 10) gave chiral tetranitrogen ligand L-3-1 in 87% yield. The hydrogen spectrum and the carbon spectrum of the product nuclear magnetic resonance are shown in figures 5 and 6: 1 H NMR(400MHz,CDCl 3 )δ7.92-7.86(m,6H),7.35-7.33(m,4H),7.30-7.26(m,6H),7.13-7.10(m,4H),7.02-6.98(m,4H),6.71-6.68(m,2H),6.41-6.39(m,4H),6.12(s,2H),3.32-3.13(m,4H),2.43(s,6H)； 13 c NMR (101MHz, CDCl3) delta 147.7,147.3,138.3,132.9,130.5,129.18,128.7, 128.5,128.0,122.8,118.9, 115.7,60.8,45.9,21.9, the corresponding synthetic schemes, the structural formulae of I-1 and L-3-1 are as follows:
Figure BDA0003286505620000111
example 12
Asymmetric epoxidation reaction of olefin with chiral tetranitrogen ligand L-3-1
Iron-catalyzed asymmetric epoxidation of olefins: under the protection of nitrogen, fe (OTf) 2 (0.01mmol, 3.5mg) and chiral tetranitrogen ligand L-3-1 (0.011mmol, 13.8mg) were placed in a 25mL Hourong tube, and 1mL of anhydrous acetonitrile was added thereto, followed by stirring at room temperature for 1 hour to obtain a chiral iron catalyst solution. Then, the reaction tube was moved to a constant temperature reaction bath at 0 ℃ to add the substrates 1, 2-stilbene (0.2mmol, 36.0 mg) and acetic acid (1.0 mmol,60.0 mg) to the above-mentioned stirred chiral iron catalyst solution, and 50% H was calculated 2 O 2 (0.8mmol, 54. Mu.L) was slowly added by means of a syringe pump, dropwise addition was completed over 1 hour, and the reaction was monitored by TLC (thin layer chromatography). After the reaction is finished, filtering, concentrating under reduced pressure until no solvent exists basically, separating by silica gel column chromatography (petroleum ether/ethyl acetate = 95)92% ee. The product nmr hydrogen and carbon spectra data are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.36(10H,s),3.87(2H,s)； 13 C NMR(100MHz,CDCl 3 )δ137.7,129.2,128.9,126.1,77.9,77.6,77.3,63.4.HPLC(Chiralcel OJ-H,n-hexane/i-PrOH＝90/10,0.5mL/min,254nm,40℃):t R (major)＝16.8min,t R (minor) =20.9min, and the corresponding synthetic route and the structural formula of IV-1 are as follows:
Figure BDA0003286505620000121
/>

Claims (9)

1. a method for synthesizing chiral o-diamine compounds is characterized in that: in a reaction medium, under the catalysis of copper/chiral P, N, N-ligand, under the existence of an alkali additive, the propargyl compound (III) and the 1, 2-diamine compound (II) are subjected to asymmetric propargyl substitution reaction to obtain the chiral o-diamine compound (I).
2. The method for synthesizing chiral o-diamines according to claim 1, wherein said method comprises the steps of:
the method comprises the following specific steps:
(1) Preparation of chiral copper catalyst: under the protection of nitrogen, copper salt and chiral P, N, N-ligand are stirred in a reaction medium for 0.5 to 2 hours to prepare a chiral copper catalyst through in-situ coordination;
(2) Copper-catalyzed asymmetric propargyl 1, 2-bisamidation: transferring the chiral copper catalyst solution obtained in the step (1) into a low-temperature reaction bath, reducing the temperature to-20-10 ℃, sequentially adding a propargyl compound (III), a1, 2-diamine compound (II) and an alkali additive, continuously reacting for 12-24 hours, after the reaction is finished, concentrating the reaction solution under reduced pressure, separating by silica gel column chromatography, concentrating under reduced pressure, and drying under vacuum to obtain the chiral o-diamine compound (I).
3. The method for synthesizing chiral ortho-diamine compound according to claim 1 or 2, wherein:
the chiral o-diamine compound (I) has the following structure:
Figure FDA0003286505610000011
in the formula: r 1 、R 2 H, C1-C10 alkyl, phenyl, substituted phenyl, naphthyl and substituted naphthyl; the substituent is one or more than two of C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5; r 3 Is one or more than two of C1-C3 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkyl with substituent, phenyl and substituted phenyl, naphthyl and substituted naphthyl, benzyl and substituted benzyl, and five-membered or six-membered heterocyclic aromatic groups containing one or more than two oxygen, sulfur and nitrogen atoms; the substituent is one or more than two of C1-C3 alkyl, C1-C3 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5.
4. The method for synthesizing chiral ortho-diamine compound according to claim 1 or 2, wherein:
the 1, 2-diamine compound (II) has the following structure:
Figure FDA0003286505610000021
in the formula: r 1 、R 2 Is represented by the formula I 1 ，R 2 The same group;
the propargyl group-like compound (III) has the following structure:
Figure FDA0003286505610000022
in the formula: r 3 Is represented by the formula I 3 The same group; wherein the leaving group X is fluorineChlorine, bromine, iodine, alkyl carboxylates, alkyl carbonates, alkyl sulfonates, alkyl phosphates, phenyl and substituted phenyl carboxylates, phenyl and substituted phenyl carbonates, phenyl and substituted phenyl sulfonates, or phenyl and substituted phenyl phosphates; the substituent on the substituted phenyl is one or more than two of C1-C10 alkyl, C3-C6 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituent is 1-5.
5. The method for synthesizing chiral ortho-diamine compound according to claim 1 or 2, wherein:
the copper salt is Cu (OAc) 2 ·H 2 O、CuSO 4 ·H 2 O、Cu(OAc) 2 、CuSO 4 、Cu(OTf) 2 、CuCl 2 、CuOAc、CuCl、CuI、CuClO 4 、CuOTf·0.5C 6 H 6 、Cu(CH 3 CN) 4 BF 4 Or Cu (CH) 3 CN) 4 ClO 4 At least one of (1).
6. The method for synthesizing chiral ortho-diamine compound according to claim 1 or 2, wherein:
the chiral P, N-ligand has the following structure:
Figure FDA0003286505610000031
in the formula: r 4 、R 5 Is one or more than two of C1-C10 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkyl with substituent, phenyl and substituted phenyl, naphthyl and substituted naphthyl, benzyl and substituted benzyl, and five-membered or six-membered heterocyclic aromatic groups containing one or more than two oxygen atoms, sulfur atoms and nitrogen atoms; the substituent on the C3-C6 naphthenic base, the substituent on the phenyl, the substituent on the naphthyl and the substituent on the benzyl are one or more than two of C1-C10 alkyl, C3-C6 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5;
R 6 is one or more than two of H, C1-C10 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkyl with substituent, phenyl and substituted phenyl, naphthyl and substituted naphthyl, benzyl and substituted benzyl, and five-membered or six-membered heterocyclic aromatic groups containing one or more than two oxygen atoms, sulfur atoms and nitrogen atoms; the substituent on the C3-C6 naphthenic base, the substituent on the phenyl, the substituent on the naphthyl and the substituent on the benzyl are one or more than two of C1-C10 alkyl, C3-C6 alkoxy, halogen, nitro, ester group or cyano, and the number of the substituents is 1-5;
R 7 is one or more than two of H, halogen, C1-C10 alkyl and C3-C6 cycloalkyl, phenyl and substituted phenyl, alkoxy, phenoxy, acyl, nitro, ester group or cyano.
7. The method for synthesizing chiral ortho-diamine compound according to claim 1 or 2, wherein:
the reaction medium is at least one of methanol, ethanol, toluene, benzene, xylene, dichloromethane, 1, 2-dichloroethane, diethyl ether, tetrahydrofuran, dimethyl sulfoxide or N, N-dimethylformamide, preferably methanol;
the alkali additive is i Pr 2 NEt、NEt 3 、 t BuOK、KOH、NaOH、Na 2 CO 3 、NaHCO 3 、 t BuOK、K 2 CO 3 、Cs 2 CO 3 Or K 3 PO 4 Preferably NEt 3 。
8. The method for synthesizing chiral ortho-diamine compound according to claim 1 or 2, wherein:
the molar ratio of the chiral P, N, N-ligand to the copper salt is 1-5;
the molar ratio of the addition amount of the copper catalyst to the addition amount of the propargyl compound (III) is 0.01-1
The molar ratio of the addition amount of the propargyl compound (III) to the addition amount of the 1, 2-diamine compound (II) is 2-4;
the molar ratio of the alkali additive to the addition amount of the 1, 2-diamine compound (II) is 2-4; .
9. The use of a chiral vicinal diamine compound, as synthesized by the synthesis process of any of claims 1 to 8, wherein: the chiral ortho-diamine compound is further converted into a chiral tetranitrogen ligand and applied to the iron-catalyzed asymmetric epoxidation reaction of olefin.
CN202111149719.8A 2021-09-29 2021-09-29 Synthesis method and application of chiral o-diamine compound Pending CN115872872A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111149719.8A CN115872872A (en) 2021-09-29 2021-09-29 Synthesis method and application of chiral o-diamine compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111149719.8A CN115872872A (en) 2021-09-29 2021-09-29 Synthesis method and application of chiral o-diamine compound

Publications (1)

Publication Number Publication Date
CN115872872A true CN115872872A (en) 2023-03-31

Family

ID=85755990

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111149719.8A Pending CN115872872A (en) 2021-09-29 2021-09-29 Synthesis method and application of chiral o-diamine compound

Country Status (1)

Country Link
CN (1) CN115872872A (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102826947A (en) * 2012-08-22 2012-12-19 中国科学院大连化学物理研究所 Method for catalytic synthesis of chiral propargylamine compound by chiral copper catalyst
CN104693143A (en) * 2013-12-05 2015-06-10 中国科学院大连化学物理研究所 Catalytic asymmetric synthesis method of chiral propargyl amine compounds
CN108059591A (en) * 2016-11-08 2018-05-22 中国科学院大连化学物理研究所 A kind of catalysis method of asymmetric synthesis of chiral alpha-fluoro-beta-acetenyl ketone compound
CN112279779A (en) * 2019-07-24 2021-01-29 中国科学院大连化学物理研究所 Preparation method of chiral aryl oxime ether compound

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102826947A (en) * 2012-08-22 2012-12-19 中国科学院大连化学物理研究所 Method for catalytic synthesis of chiral propargylamine compound by chiral copper catalyst
CN104693143A (en) * 2013-12-05 2015-06-10 中国科学院大连化学物理研究所 Catalytic asymmetric synthesis method of chiral propargyl amine compounds
CN108059591A (en) * 2016-11-08 2018-05-22 中国科学院大连化学物理研究所 A kind of catalysis method of asymmetric synthesis of chiral alpha-fluoro-beta-acetenyl ketone compound
CN112279779A (en) * 2019-07-24 2021-01-29 中国科学院大连化学物理研究所 Preparation method of chiral aryl oxime ether compound

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHENG ZHANG等: "Chiral Tridentate P, N, N Ligands for Highly Enantioselective Copper-Catalyzed Propargylic Amination with both Primary and Secondary Amines as Nucleophiles", 《ADV. SYNTH. CATAL.》, vol. 354, 28 September 2012 (2012-09-28), pages 2854 *

Similar Documents

Publication Publication Date Title
CN104513146B (en) A kind of by the method for beta-keto acid asymmetric synthesis chiral beta-acetenyl ketone
CN106866389B (en) Method for preparing chiral propargyl aryl ether compound
CN105732502B (en) A kind of method for preparing chiral 4,5 pyrazoline class compounds
US7442800B2 (en) Nucleophilic heterocyclic carbene derivatives of Pd(acac)2 for cross-coupling reactions
Prabhakara et al. Ionic liquid-immobilized proline (s) organocatalyst-catalyzed one-pot multi-component Mannich reaction under solvent-free condition
Sanjeevakumar et al. Highly enantioselective Henry reaction catalyzed by a new chiral C2-symmetric N, N′-bis (isobornyl) ethylenediamine–copper complex
CN112279779B (en) Preparation method of chiral aryl oxime ether compound
Karataş et al. N-heterocyclic carbene palladium complexes with different N-coordinated ligands: Comparison of their catalytic activities in Suzuki-Miyaura and Mizoroki-Heck reactions
CN108976241B (en) Synthesis method of chiral 1, 4-dihydropyrano [2,3-c ] pyrazole compound
CN108059591B (en) Catalytic asymmetric synthesis method of chiral α -fluoro- β -ethynyl ketone compound
CN115872872A (en) Synthesis method and application of chiral o-diamine compound
CN109810147B (en) Pyrene-labeled benzimidazole nitrogen heterocyclic carbene palladium metal complex, and preparation and application thereof
CN108101755B (en) Method for preparing chiral 4- (2-propargyl) phenol compound
CN113416173B (en) Method for catalytically synthesizing benzothiazole compounds by using copper complexes
CN104692989A (en) Catalytic asymmetric synthesis method of chiral beta-ethynyl ketone compounds
CN113754604B (en) Nitrogen-containing chiral ligand and application thereof in asymmetric oxidation reaction of thioether
CN114874081A (en) Preparation method of green efficient alpha-functionalized ketone
CN113880781A (en) Method for synthesizing 3-trifluoromethyl substituted 1,2, 4-triazole compound by taking glucose as carbon source
CN112824372A (en) Copper-catalyzed asymmetric cyclopropanation method of olefin and application thereof
CN112824412B (en) Chiral 1 'H-spiro [ indoline-3, 4' -pyrano [2,3-c ] pyrazole ] -2-ketone compound
CN111825509B (en) Catalytic asymmetric synthesis method of chiral 3,4, 4-trisubstituted pyrrolidone compound
CN114957329A (en) Biaryl axial chiral compound and preparation method and application thereof
CN106854125B (en) Method for preparing α -fluoro- β -ethynyl ketone compound containing two chiral centers
CN114539327B (en) Chiral tridentate imine P, N, N-ligand, preparation method and application thereof in Cu-catalyzed asymmetric propargyl conversion
JP5360796B2 (en) Indian derivative and method for producing the same

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