CN111848322A - Axial chiral oxindole-substituted styrene compound and resolution method and application thereof - Google Patents
Axial chiral oxindole-substituted styrene compound and resolution method and application thereof Download PDFInfo
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Abstract
The invention discloses an axial chiral oxindole-substituted styrene compound and a resolution method and application thereof, wherein the chemical structure of the axial chiral oxindole-substituted styrene compound is shown as a formula 4; taking a compound of a formula 1 and a compound of a formula 2 as reaction raw materials, taking dichloromethane as a solvent, adding
Stirring the molecular sieve to react under the action of a chiral phosphoric acid catalyst, tracking the TLC to react completely, and separating the mixture after filtering, concentrating and purifying to obtain a compound shown in the formula 4; then using the compound of formula 4 as a raw materialThe material is subjected to derivatization to obtain a chiral tertiary amine catalyst 5, and the compound shown in the formula 5 can be used as the chiral tertiary amine catalyst to catalyze the asymmetry [4+2] of p-methylphenyl substituted o-methylene benzoquinone 9 and malononitrile 10]And (4) cyclization reaction. The method has the advantages of mild reaction conditions, wide application range, adoption of various substrates as reactants, obtainment of the compound of the formula 4 with structural diversity and complexity, and high yield.
Description
Technical Field
The invention belongs to the field of organic synthetic chemistry, relates to an axial chiral arylethylene compound, and particularly relates to an axial chiral oxindole-substituted styrene compound, and a resolution method and application thereof.
Background
The axial chiral styrene compound can be used as a ligand and matched with a metal catalyst for use in catalyzing organic chemical reaction. For example, the document angelw.chem.int.ed.2016, 55,2186 reports that the compounds can be used as ligands to catalyze asymmetric allylation of indole and allyl carbonate together with a metal palladium catalyst; the document J.org.chem.2018,83,10060 reports that the compounds can be used as ligands to catalyze the reaction of 2-naphthaldehyde and diethyl zinc together with a metal titanium catalyst.
The axis chiral oxindole-substituted styrene compound has wide application prospect in the field of catalysis, so people urgently need to develop a method for efficiently synthesizing the axis chiral styrene compound. However, the methods reported in the literature for synthesizing axially chiral styrenic compounds are very limited, mainly by the nucleophilic addition reaction of alkynes and the coupling reaction of aryl halides with alkenes to produce an axially chiral backbone. For example, j.am.chem.soc.2018,140,7056 reports the construction of an axial chiral styrene backbone by the nucleophilic addition reaction of o-hydroxyphenylacetylene with sodium benzene sulfinate catalyzed by L-proline; the document angelw.chem.int.ed.2016, 55,2186 reports the construction of an axial chiral styrene backbone using a chiral palladium species catalyzed coupling reaction of aryl halides with hydrazones. Despite these methods, there are still very limited, and therefore there is an urgent need to develop new methods and strategies for synthesizing axially chiral styrenic compounds. At present, the resolution of racemic compounds becomes a simple and efficient method for synthesizing axial chiral compounds, and the research on synthesizing the axial chiral styrene compounds by using the method is blank at home and abroad. Therefore, the synthesis of axially chiral styrenic compounds with novel structures and the development of efficient resolution methods thereof are essential for the development of chiral catalysts with efficient catalytic activity.
Disclosure of Invention
One of the purposes of the invention is to provide an axial chiral oxindole-substituted styrene compound which has a novel structure, so as to fill the blank of the prior art and meet the requirements of the related fields.
The invention also aims to provide the resolution method of the axial chiral oxindole-substituted styrene compound, which has the advantages of mild reaction conditions, low cost and high enantioselectivity.
The invention also aims to provide application of the axial chiral oxindole-substituted styrene compound.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows: an axial chiral oxindole-substituted styrene compound has a chemical structure shown in formula 4:
wherein R is selected from one of hydrogen, C1-C4 alkyl, phenyl, phenethyl, benzyl or substituted benzyl, naphthylbenzyl, benzenesulfonyl or substituted benzenesulfonyl, benzoyl or substituted benzoyl, benzyloxyformyl and C1-C4 alkoxyformyl; r1One selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, ester group and trifluoromethyl; r2One selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, ester group and trifluoromethyl.
The invention also provides a resolution method of the axial chiral oxindole-substituted styrene compound, which comprises the following specific steps:
taking a compound of a formula 1 and a compound of a formula 2 as reaction raw materials, taking dichloromethane as a reaction solvent, adding
Molecular sieve, stirring and reacting under the action of chiral phosphoric acid catalyst,TLC tracking reaction is carried out till the reaction is complete, and the compound of the formula 4 is obtained by filtering, concentrating and purifying; wherein the reaction molar ratio of the compound shown in the formula 1 to the compound shown in the formula 2 is 1: 0.5-1: 0.6; the reaction temperature is 0 to 10 ℃;
the structural formula of the compound of the formula 1 is
Wherein R is selected from one of hydrogen, C1-C4 alkyl, phenyl, phenethyl, benzyl or substituted benzyl, naphthylbenzyl, benzenesulfonyl or substituted benzenesulfonyl, benzoyl or substituted benzoyl, benzyloxyformyl and C1-C4 alkoxyformyl; r1One selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, ester group and trifluoromethyl; r2One selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, ester group and trifluoromethyl.
The structural formula of the compound of the formula 2 is
In the formula, R3One selected from hydrogen, C1-C4 alkyl, phenyl or substituted phenyl, benzyl or substituted benzyl; r4One selected from C1-C4 alkyl, phenyl or substituted phenyl, benzyl or substituted benzyl;
the chiral phosphoric acid catalyst is selected from one or two of binaphthyl skeleton derivatives, octahydrobinaphthyl skeleton derivatives and spiro skeleton derivatives; the structural formula of the binaphthyl skeleton derivative is shown in the specification
Wherein G is selected from 9-anthryl, 9-phenanthryl, 2,4, 6-triisopropylphenyl, 2-naphthyl or 1-naphthyl; the structural formula of the octahydrobinaphthyl skeleton derivative is shown in the specification
Wherein G' is selected from 9-anthryl, 9-phenanthryl, 2,4, 6-triisopropylphenyl, 2-naphthyl or 1-naphthyl; the structural formula of the spiro skeleton derivative is shown in the specification
Wherein G' is selected from 9-anthryl, 9-phenanthryl, 2,4, 6-triisopropylphenyl, 2-naphthyl or 1-naphthyl.
The reaction route is as follows:
preferably, the chiral phosphoric acid catalyst is a compound shown in formula 3, and the structural formula of the compound shown in formula 3 is shown in the specification
Wherein G is selected from 2-naphthyl.
Preferably, the amount of the chiral phosphoric acid catalyst is 10 mol%.
Preferably, the reaction molar ratio of the compound of formula 1 to the compound of formula 2 is 1: 0.58.
Preferably, the reaction temperature is 0 ℃.
Preferably, the purification is silica gel column chromatography, and the eluent is petroleum ether/dichloromethane mixed liquor with the volume ratio of 1: 1.
The invention also provides application of the axial chiral oxoindole-substituted styrene organic micromolecule catalyst in synthesizing a chiral tertiary amine catalyst.
Taking a compound shown in a formula 4a and dichlorosulfurated carbon as raw materials, taking dichloromethane as a reaction solvent, adding pyridine, stirring and reacting at 25 ℃, tracking and reacting by TLC (thin layer chromatography), concentrating, adding (1S,2S) - (+) -N, N-dimethylcyclohexane-1, 2-diamine, taking dichloromethane as a reaction solvent, stirring and reacting at 25 ℃, tracking and reacting by TLC, concentrating and purifying to obtain a compound shown in a formula 5; wherein the reaction molar ratio of the compound of formula 4, dichlorosulfurated carbon to (1S,2S) - (+) -N, N-dimethylcyclohexane-1, 2-diamine is 2:2.4: 3.
The reaction route is as follows:
preferably, the purification is silica gel column chromatography, and the eluent is dichloromethane/methanol mixed solution with the volume ratio of 40: 1.
The compound shown in the formula 5 can be used as a chiral tertiary amine catalyst to catalyze the asymmetric [4+2] cyclization reaction of p-methylphenyl substituted o-methylene benzoquinone 9 and malononitrile 10, so that good yield and extremely high enantioselectivity are obtained.
Compared with the prior art, the method adopts chiral phosphoric acid as a catalyst in the process of synthesizing the axial chiral oxoindole-substituted styrene compound, and well controls the enantioselectivity of the reaction; the reaction condition is conventional, mild reaction condition is realized, the method is more suitable for industrial mass production, and the application range of the method is widened; adopts more kinds of substrates as reactants to obtain products with structural diversity and complexity and high yield.
Detailed Description
The present invention will be described in further detail with reference to specific examples.
The compound of formula 1 can be resolved by the method reported in Synthesis 2016,48, 4548; the compound of formula 2 can be resolved using the method reported in document j.am.chem.soc.2014,136, 17869; the chiral phosphoric acid catalyst and other reagents are commercially available.
The synthetic route of the axially chiral styrene compound 4 is as follows:
in the above reaction, the catalyst chiral phosphoric acid is a compound of formula 3, and the structural formula is as follows:
example 1: to 1 ml of dichloromethane were added 0.1 mmol of the compound of formula 1a and 0.58 mmol of the compound of formula 2a as reactants, 100 mg
Molecular sieves0.01 mmol of chiral phosphoric acid (i.e., the compound of formula 3) as an additive was reacted at 0 ℃ for 5 hours, followed by TLC until the reaction was completed, and then filtered to remove
And (3) washing a filter cake by using ethyl acetate, concentrating the obtained filtrate, and separating by using silica gel column chromatography (the eluent is a mixed solution of petroleum ether and dichloromethane in a volume ratio of 1: 1) to obtain the axially chiral styrene 4a, namely a yellow solid.
The structural characterization data for product 4a is as follows:
yield 44% (19.4 mg); a yellow solid; m.p.130-131 ℃; [ alpha ] to]D20＝+7.1(c 0.18,CHCl3)；1H NMR (400MHz, CDCl3) (ppm) 14.06(s,1H), 7.59-7.47 (m,2H), 7.43-7.33 (m,5H), 7.32-7.27 (m,2H), 7.15-7.11 (m,1H), 7.10-7.03 (m,2H), 7.02-6.96 (m,1H),6.91(d, J ═ 8.0Hz,1H), 6.77-6.68 (m,2H), 6.55-6.44 (m,1H),5.88(d, J ═ 7.7Hz,1H), 5.23-5.10 (m,1H), 5.11-4.98 (m,1H),3.66(s, 2H); 13C NMR (100MHz, CDCl3) (ppm) 168.3,143.6,141.8,141.0,138.7,136.4,136.0,130.0,129.7,128.9,127.9,127.8,127.7,127.3,125.7,125.2,124.1,123.9,122.7,121.8,120.4,120.3,119.4,116.4,114.1,112.6,108.7, 44.0; IR (KBr) 3363,1657,1467,1179,811,745,669 cm-1; ESI FTMS exact mass calcd for (C30H23N3O + Na) + requires m/z 464.1733, found m/z 464.1731; enantiomeric excess ratio 96%, defined by HPLC (Daicel Chiralpak IC, n-hexane/isopropanol 70/30, flow rate1.0mL/min, T30 ℃,254nm), tR 4.803(minor), tR 5.740(major)
The reaction schemes for examples 1-20 are shown below:
the reaction raw materials, reaction conditions and yields are shown in table 1:
TABLE 1
*0.1 mmol of the compound of formula 1 and 0.58 mmol of the compound of formula 2 as reactants, 0.0l of chiral phosphoric acid 3 as catalyst and 1 ml of dichloromethane as solvent.
As can be seen from Table 1, the method of the invention not only can realize the resolution of the axial chiral styrene compound in one step, and has the advantages of high enantioselectivity, high atom economy, environmental friendliness, wide application range, easily available raw materials, simple and safe operation, mild reaction conditions, short reaction time, simple post-treatment and diversified product structures, thereby having great implementation value and potential social and economic benefits.
Example 21
The axial chiral oxindole-substituted styrene compound can be subjected to derivatization and further converted into a chiral tertiary amine catalyst 5, and the synthetic route is as follows:
adding 2.0 mmol of the compound shown in the formula 4a into 15 ml of dichloromethane, then sequentially adding 3.0 mmol of pyridine and 2.4 mmol of dichlorosulfurated carbon, reacting at 25 ℃ for 1 hour, tracing the reaction by TLC till the end, adding 15 ml of dichloromethane and 3.0 mmol of (1S,2S) - (+) -N, N-dimethylcyclohexane-1, 2-diamine after concentration, reacting at 25 ℃ for 0.5 hour, tracing the reaction by TLC till the end, separating by silica gel column chromatography (eluent is mixed solution of dichloromethane and methanol with volume ratio of 40: 1) after concentration, and obtaining the compound shown in the formula 5.
The structural characterization data for the compound of formula 5 is as follows:
yield 52% (650 mg); a yellow solid; m.p.130-131 ℃; [ alpha ] to]D 20＝+104.4(c 0.16,Acetone)；1H NMR(400MHz,CDCl3)13.92(s,1H),8.14–8.02(m,1H),7.99–7.74(m,1H),7.65–7.60(m,1H),7.50–7.29(m,9H),7.26–7.18(m,2H),7.03–6.95(m,2H),6.66(d,J＝7.8Hz,1H),6.63–6.56(m,1H),6.41(s,1H),5.75–5.61(m,1H),5.11–4.99(m,2H),4.08(s,1H),2.85(s,1H),2.20(s,6H),1.85(s,1H),1.75–1.62(m,2H),1.47–1.35(m,1H),1.15–0.96(m,3H),0.77–0.48(m,1H)；13C NMR(100MHz,CDCl3)180.8,167.9,141.0,140.3,138.3,136.3,135.7,134.2,129.9,129.0,128.8,127.7,127.5,127.4,127.3,127.1,126.7,125.4,123.8,123.6,122.2,121.6,120.6,120.0,114.1,112.4,108.6,65.8,54.6,43.8,39.1,31.4,24.2,23.9,22.4；IR(KBr):3565,3054,1539,1506,1455,1344,788,697cm-1；ESI FTMS exact mass calcd for(C39H39N5OS+Na)+requires m/z 648.2768,foundm/z 648.2762.
The compound shown in the formula 5 can be used as a chiral tertiary amine catalyst to catalyze the asymmetric [4+2] cyclization reaction of p-methoxyphenyl substituted o-methylenebenzoquinone 9 and malononitrile 10, so that good yield and extremely high enantioselectivity are obtained. The catalytic effect is superior to that of the similar chiral tertiary amine catalyst sold in the market by 6-8. The reaction formula is as follows:
example 22
To 1 ml of toluene were added 0.1 mmol of methylphenyl-substituted o-methylenequinone 9 and 0.006 mmol of the compound of formula 5, and the temperature was reduced to-50 ℃. Adding 0.1 mmol of malononitrile 10, reacting at-50 ℃ for 4 hours, tracking the reaction by TLC until the reaction is finished, concentrating, and separating by silica gel column chromatography (the eluent is a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 2: 1) to obtain the compound of the formula 11.
The structural characterization data for product 11 is as follows:
yield: 90% (29.0 mg); yellow solid, m.p.102-103 ℃; [ alpha ] to]D 20＝-39.5(c 0.35,Acetone)；1H NMR(400MHz,CDCl3)7.10(d,J＝8.6Hz,2H),6.85(d,J＝8.6Hz,2H),6.50(s,1H),6.34(s,1H),5.92(s,1H),5.89(s,1H),4.58(s,1H),4.54(s,2H),3.78(s,3H)；13C NMR(100MHz,CDCl3)159.0,158.9,147.2,144.9,143.0,136.9,129.0,120.0,115.3,114.3,107.9,101.7,97.9,60.9,55.4,40.5；IR:2924,2189,1684,1507,1397,1245,1035,772cm-1；ESI FTMS exact mass calcd for(C18H14N2O4+Na)+requires m/z 345.0846,found m/z345.0857.The enantiomeric excess:91％,determined by HPLC(Daicel Chiralpak OD-H,hexane/isopropanol＝70/30,flow rate 0.7mL/min,T＝30℃,254nm):tR＝11.173min(major),tR＝16.023min(minor).
The latent application of the resolution axial chiral oxindole-substituted styrene compound is as a chiral tertiary amine catalyst. In addition, the derivative of the compound is further converted into a chiral tertiary amine catalyst, and the result shows that the asymmetric [4+2] cyclization reaction of p-methoxyphenyl-substituted o-methylenebenzoquinone and malononitrile has a certain catalytic effect, and the catalytic effect is superior to that of a similar chiral tertiary amine catalyst sold in the market.
The method for splitting the axial chiral oxoindole-substituted styrene compound is an asymmetric addition reaction under the catalysis of a small organic molecule, and the axial chiral oxoindole-substituted styrene compound is split from a racemic raw material, so that the method is simple and convenient to operate, mild in reaction conditions, economic and easily available in raw materials, and the optical purity of the split oxoindole-substituted axial chiral styrene compound is high (the ee value is up to 96%). The oxindole-substituted axial chiral styrene compound obtained by resolution is expected to be widely applied to the field of asymmetric catalysis.
Claims (9)
1. An axial chiral oxindole-substituted styrene compound is characterized in that the chemical structure is shown as formula 4:
wherein R is selected from hydrogen, C1-C4 alkyl, phenyl, phenethyl, benzyl or substituted benzyl, naphthylbenzyl, phenylsulfonyl or substituted phenylsulfonyl, benzoyl or substituted benzoyl, benzyloxyformyl, C1-C4 alkaneOne of the oxoformyl groups; r1One selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, ester group and trifluoromethyl; r2One selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, ester group and trifluoromethyl.
2. The resolution method of the axial chiral oxoindole-substituted styrene compound as claimed in claim 1, which is characterized by comprising the following steps:
taking a compound of a formula 1 and a compound of a formula 2 as reaction raw materials, taking dichloromethane as a solvent, adding
Stirring the molecular sieve to react under the action of a chiral phosphoric acid catalyst, tracking the TLC to react completely, and separating the mixture after filtering, concentrating and purifying to obtain a compound shown in the formula 4; wherein the reaction molar ratio of the compound shown in the formula 1 to the compound shown in the formula 2 is 1: 0.5-1: 0.6; the reaction temperature is 0 to 10 ℃;
the structural formula of the compound of the formula 1 is
Wherein R is selected from one of hydrogen, C1-C4 alkyl, phenyl, phenethyl, benzyl or substituted benzyl, naphthabenzyl, benzenesulfonyl or substituted benzenesulfonyl, benzoyl or substituted benzoyl, benzyloxyformyl and C1-C4 alkoxyformyl; r1One selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, ester group and trifluoromethyl; r2One selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, ester group and trifluoromethyl;
the structural formula of the compound of the formula 2 is
In the formula, R3One selected from hydrogen, C1-C4 alkyl, phenyl or substituted phenyl, benzyl or substituted benzyl; r4One selected from C1-C4 alkyl, phenyl or substituted phenyl, benzyl or substituted benzyl;
the chiral phosphoric acid catalyst is selected from one or two of binaphthyl skeleton derivatives, octahydrobinaphthyl skeleton derivatives and spiro skeleton derivatives; the structural formula of the binaphthyl skeleton derivative is shown in the specification
Wherein G is selected from 9-anthryl, 9-phenanthryl, 2,4, 6-triisopropylphenyl, 2-naphthyl or 1-naphthyl; the structural formula of the octahydrobinaphthyl skeleton derivative is shown in the specification
Wherein G' is selected from 9-anthryl, 9-phenanthryl, 2,4, 6-triisopropylphenyl, 2-naphthyl or 1-naphthyl; the structural formula of the spiro skeleton derivative is shown in the specification
Wherein G' is selected from 9-anthryl, 9-phenanthryl, 2,4, 6-triisopropylphenyl, 2-naphthyl or 1-naphthyl.
3. The method for resolving axial chiral oxoindole-substituted styrene compound as claimed in claim 2, wherein the chiral phosphoric acid catalyst is a compound of formula 3, and the compound of formula 3 has a structural formula
Wherein G is selected from 2-naphthyl.
4. The method for resolving an axial chiral oxoindole-substituted styrene compound as claimed in claim 2, wherein the amount of said chiral phosphoric acid catalyst is 10 mol%.
5. The method for resolving an axial chiral oxoindole-substituted styrene compound as claimed in claim 2, wherein the reaction molar ratio of the compound of formula 1 to the compound of formula 2 is 1: 0.58.
6. The method for resolving an axial chiral oxoindole-substituted styrene compound as claimed in claim 2, wherein the reaction temperature is 0 ℃.
7. The method for resolving the axial chiral oxoindole-substituted styrene compound as claimed in claim 2, wherein the purification is performed by silica gel column chromatography, and the eluent is petroleum ether/dichloromethane mixed solution with a volume ratio of 1: 1.
8. The application of the axial chiral oxoindole-substituted styrene compound in the synthesis of the chiral tertiary amine catalyst as claimed in claim 1, which is characterized in that a compound shown in formula 4a and dichlorocarbon sulfide are used as raw materials, dichloromethane is used as a reaction solvent, pyridine is added, stirring reaction is carried out at 25 ℃, TLC tracking reaction is carried out till the end, after concentration, (1S,2S) - (+) -N, N-dimethylcyclohexane-1, 2-diamine is added, dichloromethane is used as a reaction solvent, stirring reaction is carried out at 25 ℃, TLC tracking reaction is carried out till the end, concentration and purification are carried out, and then a compound shown in formula 5 is obtained; wherein the reaction molar ratio of the compound of formula 4, dichlorosulfurated carbon to (1S,2S) - (+) -N, N-dimethylcyclohexane-1, 2-diamine is 2:2.4: 3.
9. The use of claim 8, wherein the purification is silica gel column chromatography, and the eluent is a dichloromethane/methanol mixture with a volume ratio of 40: 1.
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| CN112264091A (en) * | 2020-11-27 | 2021-01-26 | 江苏师范大学 | Axial chiral styrene tertiary amine thiourea catalyst and preparation method and application thereof |
| CN114751866A (en) * | 2022-04-28 | 2022-07-15 | 南昌航空大学 | 3,3' -biquinazolinone compound containing N-N chiral axis |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104557957A (en) * | 2013-10-09 | 2015-04-29 | 华东师范大学 | Synthetic method of spiro-oxoindole ethylene oxide derivative |
| CN105693737A (en) * | 2014-11-28 | 2016-06-22 | 中国科学院大连化学物理研究所 | Dipyridine ligands with axial chirality and synthetic method thereof |
| CN107501163A (en) * | 2017-09-07 | 2017-12-22 | 南方科技大学 | A kind of method that chiral phosphoric acid catalyzes and synthesizes axial chirality aniline indoles |
| CN108586284A (en) * | 2018-04-24 | 2018-09-28 | 杭州师范大学 | A kind of axial chirality aryl olefin compound and its synthetic method |
| CN110041174A (en) * | 2019-04-28 | 2019-07-23 | 南方科技大学 | A kind of EBINOL axial chirality compound and its synthetic method and application |
| CN110452150A (en) * | 2019-08-22 | 2019-11-15 | 江苏师范大学 | A kind of axial chirality indoles-naphthalene compounds and preparation method thereof |
| CN110467555A (en) * | 2019-08-22 | 2019-11-19 | 江苏师范大学 | A kind of axial chirality aryl-indole compounds and its synthetic method |
-
2020
- 2020-08-05 CN CN202010777413.6A patent/CN111848322B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104557957A (en) * | 2013-10-09 | 2015-04-29 | 华东师范大学 | Synthetic method of spiro-oxoindole ethylene oxide derivative |
| CN105693737A (en) * | 2014-11-28 | 2016-06-22 | 中国科学院大连化学物理研究所 | Dipyridine ligands with axial chirality and synthetic method thereof |
| CN107501163A (en) * | 2017-09-07 | 2017-12-22 | 南方科技大学 | A kind of method that chiral phosphoric acid catalyzes and synthesizes axial chirality aniline indoles |
| CN108586284A (en) * | 2018-04-24 | 2018-09-28 | 杭州师范大学 | A kind of axial chirality aryl olefin compound and its synthetic method |
| CN110041174A (en) * | 2019-04-28 | 2019-07-23 | 南方科技大学 | A kind of EBINOL axial chirality compound and its synthetic method and application |
| CN110452150A (en) * | 2019-08-22 | 2019-11-15 | 江苏师范大学 | A kind of axial chirality indoles-naphthalene compounds and preparation method thereof |
| CN110467555A (en) * | 2019-08-22 | 2019-11-19 | 江苏师范大学 | A kind of axial chirality aryl-indole compounds and its synthetic method |
Non-Patent Citations (1)
| Title |
|---|
| JING LIANG等: "An Efficient Synthesis of Functionalized 2-Oxoindole Derivatives by Organocatalytic Z / E -Selective Benzylic Functionalization of (o -Aminobenzyl)indoles with Isatins", 《SYNTHESIS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112264091A (en) * | 2020-11-27 | 2021-01-26 | 江苏师范大学 | Axial chiral styrene tertiary amine thiourea catalyst and preparation method and application thereof |
| CN114751866A (en) * | 2022-04-28 | 2022-07-15 | 南昌航空大学 | 3,3' -biquinazolinone compound containing N-N chiral axis |
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