CN109180682A - A kind of chiral aza ring carbene precursor compound and preparation method thereof with bicyclic skeleton - Google Patents
A kind of chiral aza ring carbene precursor compound and preparation method thereof with bicyclic skeleton Download PDFInfo
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- CN109180682A CN109180682A CN201811026359.0A CN201811026359A CN109180682A CN 109180682 A CN109180682 A CN 109180682A CN 201811026359 A CN201811026359 A CN 201811026359A CN 109180682 A CN109180682 A CN 109180682A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2265—Carbenes or carbynes, i.e.(image)
- B01J31/2269—Heterocyclic carbenes
- B01J31/2273—Heterocyclic carbenes with only nitrogen as heteroatomic ring members, e.g. 1,3-diarylimidazoline-2-ylidenes
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Abstract
The present invention discloses a kind of chiral aza ring carbene precursor compound and preparation method thereof with bicyclic skeleton, the present invention is using cheap proline as raw material, it is reacted by 4 easy steps, obtain the chiral aza ring carbene precursor compound that series has bicyclic skeleton, by changing the structure of aromatic amine, the chiral carbone catalyst precursor salt of different structure can be obtained.
Description
Technical field
The present invention relates to organic synthesis fields, and in particular to a kind of chiral aza ring carbene precursor with bicyclic skeleton
Close object and preparation method thereof.
Background technique
The research history of N-heterocyclic carbine (N-heterocyclic carbenes, NHC) will trace back to 1832 earliest,
Wohler and Liebig et al. have found cyanogen root anion (CN?) can be catalyzed benzaldehyde benzoic conden-sation reaction it is subsequent
Lapworth found after studying its mechanism the benzaldehyde of a molecule under the catalysis of cyanogen root anion, carbonylic carbon atom
Electronegativity (i.e. the antipolarity of aldehyde radical is overturn) is changed by traditional electropositivity, and then to the benzaldehyde of another molecule
Nucleophilic addition is carried out, styrax product is finally obtained.And really N-heterocyclic carbine be by Wanzlick andEarly in last
It is reported the sixties in century, but until the isolated free carbenes of the seminars such as Bertrand and Arduengo and is obtained
After obtaining single crystal data, the relevant research in the field NHCs is just attracted wide public concern.NHCs has become non-in current chemical field
Often important ligand is designed to the preparation of metal-organic complex, and then is widely used in homogeneous catalysis, pharmaceutical chemistry, no
Symmetrical synthesis and Material Field.On the other hand, in recent years, NHC directly applies to catalysis as organic micromolecule catalyst
Reaction has also obtained significant progress, has become one of research hotspot of organic chemistry, especially in such catalytic process
Metal participation is not needed, reaction system is environmental-friendly, and price also relative moderate makes it compared with metal carbene chemistry in certain sides
Face has certain superiority.Different according to catalysis substrate type, the organic catalytic reaction that N-heterocyclic carbine participates at present is main
It is each of carbonylic carbon atom, carbonyl alpha-carbon atom, carbonyl β carbon atom, carbonyl gamma carbon and the activation participation of carbonyl δ carbon atom
The electrophilic and necleophilic reaction of kind mainly includes benzoic conden-sation reaction, Stetter reaction, a3-d3Pole reversal reaction, cyclization reaction
With fluorination reaction etc..These reactions provide the construction method of the C-C being simple and efficient, C-N and C-O key for organic synthesis.
Correspondingly, part chirality NHC achieved in asymmetric catalysis as organic micromolecule catalyst it is excellent
Enantioselectivity.Due to the polarity reverse speed characterisstic of N- heterocycle carbine, it constructs the effect of complicated chiral molecules in organic synthesis
Seem further important.Some specific lewis bases and oxidant can induce Cabbeen and carbonyls is formed among Breslow
Body, enolization compound and high enolization compound, these intermediates have further expanded the application range of Cabbeen.The change enumerated below
Conjunction object is in recent years representative chiral azepine carbene precursor salt, they are reacted in asymmetric benzoic conden-sation, Stetter is anti-
It answers, a3-d3Excellent cis-selectivity is embodied in the reaction such as pole reversal reaction, cyclization reaction and fluorination reaction, is achieved
90% or more ee value.
The chiral carbenes as organic micromolecule catalyst are made a general survey of, mostly with the twin nuclei of triazole unit.
Such compound synthesis route is complex, while raw material is relatively expensive, and synthetic route universality is simultaneously bad.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of chiral aza ring carbene precursor chemical combination with bicyclic skeleton
Object and preparation method thereof, so that expanding it applies model in pharmaceutical intermediate synthetic reaction and organic asymmetric catalysis synthesis
Farmland.Specific technical solution is as follows:
A kind of chiral aza ring carbene precursor compound with bicyclic skeleton, which is characterized in that the chirality azacyclo- card
Guest's precursor compound are as follows:
Or its enantiomter:
Wherein, R1Selected from phenyl, substituted aroma group, heteroaromatic, cyclohexyl, benzyl, tert-butyl, isopropyl, methyl and
Isobutyl group, R2Selected from chloride ion, bromide ion, tetrafluoroborate ion and hexafluorophosphoricacid acid ions.
Further, the structure of the compound is selected from:
A kind of preparation method of chirality aza ring carbene precursor compound, which is characterized in that this method comprises the following steps:
(I), will be if general formula (I) compound represented and substitution primary amine are in dicyclohexylcarbodiimide in aprotic solvent
It is reacted under I-hydroxybenzotriazole effect, then collection type (II) compound from reaction product, reaction formula is such as
Under:
(II) reacts the amides compound as shown in general formula (II) with trifluoracetic acid in aprotic solvent,
Then collection type (III) compound, reaction formula are as follows from reaction product:
(III) will react in aprotic solvent such as general formula (III) compound represented and tetrahydrochysene lithium aluminium, then from
Collection type (IV) compound, reaction formula are as follows in reaction product:
(IV), will the chiral diamine as shown in general formula (IV), trimethyl orthoformate or orthoformic acid three in aprotic solvent
Ethyl ester is reacted under lewis acid effect, and then collection type (V) compound, reaction formula are as follows from reaction product:
Further, the step (I) Chinese style (I) compound, substitution primary amine, dicyclohexylcarbodiimide and 1-hydroxyl
The molar ratio of base benzotriazole is 1:1:1.1:1.1, and reaction temperature is 20~30 DEG C, and the reaction time is 5~10 hours.
Further, the reaction temperature of the step (II) is 20~30 DEG C, and the reaction time is 2~5 hours, formula (II)
Compound and trifluoroacetic molar ratio are 1:4.
Further, the reaction temperature of the step (III) is 20~30 DEG C, and the reaction time is 12~24 hours, formula
(III) molar ratio of compound and tetrahydrochysene lithium aluminium is 1:4.
Further, the reaction temperature of the step (IV) is 100~120 DEG C, and the reaction time is 3~12 hours, formula
(IV) compound, orthoformate, lewis acidic molar ratio are 1:1:1~2.
Beneficial effects of the present invention are as follows:
Chiral N-heterocyclic carbine compound with condensed-bicyclic skeleton is urged in Organometallic Chemistry and small organic molecule
Change field plays important role, the chiral carbenes ratio with pyrrolo- imidazoles bicyclic skeleton involved in this project
Rarer, synthetic method also has no document report.The present invention is reacted using cheap proline as raw material by 4 easy steps,
The chiral aza ring carbene precursor compound that series has bicyclic skeleton is obtained, by simply changing the structure of aromatic amine, just
A series of N atoms, which can be obtained, has the different carbone catalysts for replacing functional group.Preparation method designed by the present invention has
Succinctly, efficiently, the features such as controllability is strong, be conducive to its Structure-activity analysis in catalytic process.Because twin nuclei makes
Obtaining such N-heterocyclic carbine chiral centre has rigidity characteristic, and such compound is expected to obtain good answer in asymmetric reaction
With.
Specific embodiment
Below according to preferred embodiment the present invention is described in detail, the objects and effects of the present invention be will become more apparent, with
Under in conjunction with the embodiments, the present invention will be described in further detail.It should be appreciated that specific embodiment described herein is only used
To explain the present invention, it is not intended to limit the present invention.
The representative preparation method (logical method 1) of compound ii:
Under nitrogen protection, 4mmol compound (I) (1 equivalent) is dissolved in dry methylene chloride (40mL), under condition of ice bath
(0 DEG C), sequentially adding 4.4mmol dicyclohexylcarbodiimide (1.1 equivalent) and 4.4mmol1- hydroxybenzotriazole, (1.1 work as
Amount), it is then added dropwise to 4mmol and replaces primary amine.After being stirred at room temperature 5~10 hours, evaporated under reduced pressure, mixture column chromatography point are filtered
Product II is obtained from (PE:EA=8:1).
The representative preparation method (logical method 2) of compound III:
Under nitrogen protection, 8.0mmol trifluoracetic acid (4 equivalent) is added dropwise to 2.0mmol compound (II) (1 equivalent)
Dichloromethane solution (20mL) stirs 2 hours at room temperature, after reaction, 10mL saturated sodium bicarbonate solution and 10mL is added
Dichloromethane solution separates organic layer, through saturated common salt water washing, separates organic layer, filters decompression after anhydrous sodium sulfate is dry
It is evaporated, mixture column chromatography for separation (CH2Cl2: MeOH=30:1) obtain product III.
The representative preparation method (logical method 3) of compounds Ⅳ:
4mmol tetrahydrochysene lithium aluminium is dissolved in tetrahydrofuran solution (10mL), then by nitrogen protection under 0 DEG C of reaction environment
It is added dropwise to the tetrahydrofuran solution (3mL) of 1mmol compound III (1 equivalent) by injection, reacts 24 hours under room temperature,
After reaction, it is cooled to 0 DEG C, water, 15% sodium hydrate aqueous solution and water quenching reaction is sequentially added, steams filtrate after filtering
It is dry, (CH is then separated by silica gel column chromatography2Cl2:CH3OH=20:1 product IV) is obtained.
The representative preparation method (logical method 4) of compound V:
1mmol compounds Ⅳ (1 equivalent), 1mmol triethyl orthoformate (1 equivalent) and 1mmol ammonium tetrafluoroborate are mixed,
It is reacted under 120 DEG C of heating conditions 12 hours, after reaction, by mixture column chromatography for separation (CH2Cl2:CH3OH=50:1
~20:1) obtain product V.
Embodiment 1
The preparation of compound ii -1:
Under nitrogen protection, 861mg compound (I) (4mmol) is dissolved in THF solution (20mL), is sequentially added at 0 DEG C
908mg dicyclohexylcarbodiimide (4.4mmol) and 594mg I-hydroxybenzotriazole (4.4mmol), are then added dropwise to 562 μ
L trimethyl aniline (4mmol), after being stirred at room temperature 5 hours, filtration is evaporated filtrate, separates (PE:EA by silica gel column chromatography
=8:1) obtain product II -1, yield 80%.
Embodiment 2
The preparation of compound ii -2:
Preparation condition is the same as embodiment 1, white solid, yield 86%.
Embodiment 3
The preparation of compound ii -3:
Preparation condition is the same as embodiment 1, white solid, yield 79%.
Embodiment 4
The preparation of compound ii -4:
Preparation condition is the same as embodiment 1, white solid, yield 79%.
Embodiment 5
The preparation of compound ii -5:
Preparation condition is the same as embodiment 1, white solid, yield 79%.
Embodiment 6
The preparation of compound III -1:
Under nitrogen protection, 594 μ L trifluoracetic acids (8mmol) are added dropwise to the two of 664mg compound (II) (2.0mmol)
Chloromethanes solution (20mL) stirs 2 hours at room temperature, after reaction, 10mL saturated sodium bicarbonate solution and 10mL bis- is added
Chloromethanes solution separates organic layer, through saturated common salt water washing, separates organic layer, filtration decompression is steamed after anhydrous sodium sulfate is dry
It is dry, mixture column chromatography for separation (CH2Cl2: MeOH=30:1) obtain product III -1, yield 85%.
Embodiment 7
The preparation and representation of compound III -2:
Preparation condition is the same as embodiment 6, white solid, yield 85%；1H NMR(500MHz,CDCl3)δ:9.14(s,
1H), 7.26 (t, 1H), 7.16 (d, J=7.7Hz, 2H), 3.97 (dd, J=9.2,4.9Hz, 1H), 3.16-3.10 (m, 1H),
3.01 (dd, J=11.3,4.4Hz, 2H), 2.27-2.21 (m, 1H), 2.09 (m, 2H), 1.83 (m, 2H), 1.20 (m, 12H)
Embodiment 8
The preparation and representation of compound III -3:
Preparation condition is the same as embodiment 6, white solid, yield 82%.
Embodiment 9
The preparation of compound III -4:
Preparation condition is the same as embodiment 6, white solid, yield 83%.
Embodiment 10
The preparation of compound III -5:
Preparation condition is the same as embodiment 6, white solid, yield 76%.
Embodiment 11
The preparation and representation of compounds Ⅳ -1:
152mg tetrahydrochysene lithium aluminium (4mmol) is dissolved in tetrahydrofuran solution (10mL) under 0 DEG C of reaction environment by nitrogen protection
In, the tetrahydrofuran solution (5mL) of 232mg compound III -1 (1mmol) is then added dropwise to by injection, under room temperature instead
It answers 24 hours, after reaction, is cooled to 0 DEG C, sequentially add water, 15% sodium hydrate aqueous solution and water quenching reaction, filter
Filtrate is evaporated afterwards, (CH is then separated by silica gel column chromatography2Cl2:CH3OH=20:1 product IV -1) is obtained, yield is
87%；1H NMR(500MHz,CDCl3) δ: 6.76 (s, 2H), 3.94-3.88 (m, 1H), 3.37 (m, 3H), 3.04 (dd, J=
13.8,4.8Hz,1H),2.26(s,6H),2.20(s,3H),2.15–2.12(m,1H),2.02(m,2H),1.78 –1.73(m,
1H).
Embodiment 12
The preparation and representation of compounds Ⅳ -2:
Preparation condition is the same as embodiment 11, white solid, yield 91%；1HNMR(500MHz,CDCl3)δ:7.10–7.07
(m, 2H), 7.04 (dd, J=8.7,6.3Hz, 1H), 3.43-3.36 (m, 1H), 3.35-3.34 (m, 2H), 3.00-2.94 (m,
2H), 2.86 (dd, J=11.7,4.6Hz, 1H), 2.75 (dd, J=11.7,8.3Hz, 1H), 1.92 (m, 1H), 1.85-1.68
(m, 2H), 1.43 (m, 1H), 1.24 (d, J=6.9Hz, 12H)
Embodiment 13
The preparation and representation of compounds Ⅳ -3:
Preparation condition is the same as embodiment 11, white solid, yield 89%；1HNMR(500MHz,CDCl3) δ: 7.15 (t, J=
7.9Hz, 2H), 6.68 (t, J=7.3Hz, 1H), 6.62 (d, J=7.9Hz, 2H), 3.46-3.41 (m, 1H), 3.23 (dd, J=
12.6,4.3Hz, 1H), 3.06 (dd, J=10.1,5.9Hz, 1H), 3.01-2.93 (m, 2H), 1.96-1.91 (m, 1H),
1.85– 1.80(m,1H),1.78–1.71(m,1H),1.55–1.46(m,1H).
Embodiment 14
The preparation and representation of compounds Ⅳ -4:
Preparation condition is the same as embodiment 11, white solid, yield 91%；1H NMR(500MHz,CDCl3)δ:6.85(m,
1H), 6.77(m,1H),6.75–6.72(m,1H),6.68(m,1H),4.08–4.04(m,1H),3.84(s,3H),3.71
(dd, J=14.2,8.0Hz, 1H), 3.51-3.46 (m, 1H), 3.39 (m, 2H), 2.25-2.20 (m, 1H), 2.14-2.09
(m,1H), 2.08–2.03(m,1H),1.89–1.85(m,1H).
Embodiment 15
The preparation and representation of compounds Ⅳ -5:
Preparation condition is the same as embodiment 11, white solid, yield 93%；1HNMR(500MHz,CDCl3)δ:7.14(dd,J
=7.6,1.5Hz, 1H), 7.12-7.07 (m, 1H), 6.72 (td, J=7.4,1.1Hz, 1H), 6.64 (dd, J=8.1,
0.9Hz, 1H), 3.51-3.44 (m, 1H), 3.22 (dd, J=12.0,4.7Hz, 1H), 3.02 (dd, J=12.0,7.9Hz,
1H),2.97– 2.90(m,3H),1.98–1.91(m,1H),1.87–1.79(m,1H),1.77–1.70(m,1H),1.55–
1.47 (m, 1H), 1.26 (d, J=2.5Hz, 3H), 1.25 (d, J=2.5Hz, 3H)
Embodiment 16
The preparation and representation of compound V -1:
By compound 318mg IV -1 (1mmol), 148mg triethyl orthoformate (1mmol) and 126mg ammonium tetrafluoroborate
(1.2mmol) mixing, reacts 12 hours under 120 DEG C of heating conditions, after reaction, by mixture column chromatography for separation
(CH2Cl2:CH3OH=50:1~20:1) obtain product V -1, yield 80%；1H NMR(500MHz,CDCl3)δ: 8.20
(s, 1H), 6.93 (s, 2H), 4.68-4.55 (m, 1H), 4.29-4.24 (m, 1H), 4.16 (t, J=11.5Hz, 1H), 4.00
(dd, J=12.1,6.5Hz, 1H), 3.66-3.59 (m, 1H), 2.40-2.34 (m, 2H), 2.29 (s, 3H), 2.28-2.11
(m,7H),1.91–1.83(m,1H).
Embodiment 17
The preparation and representation of compound V -2:
Preparation condition is the same as embodiment 16, white solid, yield 86%；1HNMR(500MHz,CDCl3)δ:8.22(s,
1H), 7.43 (t, J=7.8Hz, 1H), 7.24-7.21 (m, 2H), 4.71-4.62 (m, 1H), 4.28-4.23 (m, 1H),
4.23-4.16 (m, 1H), 4.00 (dd, J=12.3,6.7Hz, 1H), 3.67-3.62 (m, 1H), 2.90-2.84 (m, 1H),
2.81-2.77 (m, 1H), 2.42 (dd, J=12.4,6.2Hz, 1H), 2.20-2.10 (m, 2H), 1.84-1.79 (m, 1H),
1.28– 1.23(m,12H).
Embodiment 18
The preparation and representation of compound V -3:
Preparation condition is the same as embodiment 16, white solid, yield 83%；1HNMR(500MHz,CDCl3)δ:8.65(s,
1H), 7.39-7.34 (m, 2H), 7.27-7.23 (m, 3H), 4.61-4.53 (m, 1H), 4.40 (t, J=11.1Hz, 1H),
4.23 (dd, J=11.2,8.0Hz, 1H), 4.06-4.00 (m, 1H), 3.63-3.55 (m, 1H), 2.33-2.23 (m, 2H),
1.89–1.81 (m,2H).
Embodiment 19
The preparation and representation of compound V -4:
Preparation condition is the same as embodiment 16, white solid, yield 81%；1H NMR(500MHz,CDCl3)δ:8.61(s,
1H), 7.34-7.30 (m, 2H), 7.03-6.99 (m, 2H), 4.58-4.51 (m, 1H), 4.42 (t, J=11.0Hz, 1H),
4.27 (dd, J=11.2,7.8Hz, 1H), 4.21-4.15 (m, 1H), 3.92 (s, 3H), 3.69-3.62 (m, 1H), 2.39-
2.29(m,2H), 2.17–2.09(m,1H),1.96–1.90(m,1H).
Embodiment 20
The preparation and representation of compound V -5:
Preparation condition is the same as embodiment 16, white solid, yield 88%；1HNMR(500MHz,CDCl3)δ:8.04(s,
1H), 7.41-7.36 (m, 3H), 7.24-7.20 (m, 1H), 4.67-4.60 (m, 1H), 4.31 (t, J=11.3Hz, 1H),
4.10 (dd, J=11.4,8.1Hz, 2H), 3.62-3.54 (m, 1H), 2.96 (dd, J=13.7,6.8Hz, 1H), 2.35-
2.27 (m, 2H), 2.13-2.06 (m, 1H), 1.98-1.91 (m, 1H), 1.25 (d, J=6.8Hz, 3H), 1.22 (d, J=
6.8Hz,3H).
It will appreciated by the skilled person that being not used to limit the foregoing is merely the preferred embodiment of invention
System invention, although invention is described in detail referring to previous examples, for those skilled in the art, still
It can modify to the technical solution of aforementioned each case history or equivalent replacement of some of the technical features.It is all
Within the spirit and principle of invention, modification, equivalent replacement for being made etc. be should be included within the protection scope of invention.
Claims (7)
1. a kind of chiral aza ring carbene precursor compound with bicyclic skeleton, which is characterized in that the chirality N-heterocyclic carbine
Precursor compound are as follows:
Or its enantiomter:
Wherein, R1Selected from phenyl, substituted aroma group, heteroaromatic, cyclohexyl, benzyl, tert-butyl, isopropyl, methyl and isobutyl
Base.R2Selected from chloride ion, bromide ion, tetrafluoroborate ion and hexafluorophosphoricacid acid ions.
2. the chiral aza ring carbene precursor compound according to claim 1 with bicyclic skeleton, which is characterized in that should
The structure of compound is selected from:
3. a kind of preparation method of chiral aza ring carbene precursor compound as described in claim 1, which is characterized in that the party
Method includes the following steps:
(I) in aprotic solvent, will such as general formula (I) compound represented and replace primary amine in dicyclohexylcarbodiimide and
It is reacted under I-hydroxybenzotriazole effect, then collection type (II) compound, reaction formula are as follows from reaction product:
(II) reacts the amides compound as shown in general formula (II) with trifluoracetic acid, then in aprotic solvent
Collection type (III) compound, reaction formula are as follows from reaction product:
(III) will react, then from reaction in aprotic solvent such as general formula (III) compound represented and tetrahydrochysene lithium aluminium
Collection type (IV) compound, reaction formula are as follows in product:
(IV) in aprotic solvent, will chiral diamine, trimethyl orthoformate or triethyl orthoformate as shown in general formula (IV),
It is reacted under lewis acid effect, then collection type (V) compound, reaction formula are as follows from reaction product:
4. preparation method according to claim 3, which is characterized in that described step (I) Chinese style (I) compound, substitution
The molar ratio of primary amine, dicyclohexylcarbodiimide and I-hydroxybenzotriazole is 1:1:1.1:1.1, and reaction temperature is 20~30
DEG C, the reaction time is 5~10 hours.
5. preparation method according to claim 3 or 4, which is characterized in that the reaction temperature of the step (II) is 20
~30 DEG C, the reaction time is 2~5 hours, and formula (II) compound and trifluoroacetic molar ratio are 1:4.
6. preparation method according to claim 5, which is characterized in that the reaction temperature of the step (III) is 20~30
DEG C, the reaction time is 12~24 hours, and the molar ratio of formula (III) compound and tetrahydrochysene lithium aluminium is 1:4.
7. preparation method according to claim 6, which is characterized in that the reaction temperature of the step (IV) be 100~
120 DEG C, the reaction time is 3~12 hours, and formula (IV) compound, orthoformate, lewis acidic molar ratio are 1:1:1~2.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113680385A (en) * | 2021-08-23 | 2021-11-23 | 深圳湾实验室坪山生物医药研发转化中心 | N-heterocyclic carbene-thiourea double-functional group catalyst and preparation method and application thereof |
| CN113731488A (en) * | 2021-08-23 | 2021-12-03 | 深圳湾实验室坪山生物医药研发转化中心 | Nitrogen heterocyclic carbene-urea bifunctional catalyst and preparation method thereof |
| CN113956411A (en) * | 2020-07-20 | 2022-01-21 | 中国石油天然气股份有限公司 | Regulator of conjugated diene and application thereof |
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| CN113956411B (en) * | 2020-07-20 | 2024-03-01 | 中国石油天然气股份有限公司 | Regulator of conjugated diene and application thereof |
| CN113680385A (en) * | 2021-08-23 | 2021-11-23 | 深圳湾实验室坪山生物医药研发转化中心 | N-heterocyclic carbene-thiourea double-functional group catalyst and preparation method and application thereof |
| CN113731488A (en) * | 2021-08-23 | 2021-12-03 | 深圳湾实验室坪山生物医药研发转化中心 | Nitrogen heterocyclic carbene-urea bifunctional catalyst and preparation method thereof |
| CN113680385B (en) * | 2021-08-23 | 2023-05-23 | 深圳湾实验室坪山生物医药研发转化中心 | N-heterocyclic carbene-thiourea bifunctional group catalyst and preparation method and application thereof |
| CN113731488B (en) * | 2021-08-23 | 2023-08-04 | 深圳湾实验室坪山生物医药研发转化中心 | N-heterocyclic carbene-urea difunctional catalyst and preparation method thereof |
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