CN115368230B - Preparation method of RXR agonist - Google Patents
Preparation method of RXR agonist Download PDFInfo
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- CN115368230B CN115368230B CN202110542312.5A CN202110542312A CN115368230B CN 115368230 B CN115368230 B CN 115368230B CN 202110542312 A CN202110542312 A CN 202110542312A CN 115368230 B CN115368230 B CN 115368230B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- 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
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- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
- C07C2602/28—Hydrogenated naphthalenes
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- 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
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- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention discloses a preparation method of RXR agonist, which comprises the following steps: s1, reacting a compound shown in a formula A with a compound shown in a formula B under the conditions of an aza-carbene copper catalyst, a silicon reagent for providing a hydrogen source, a solvent and an organic base to generate a compound shown in a formula C; s2, reacting a compound shown in a formula C with a compound shown in a formula D under the condition of a Holland-Gellan II catalyst to generate a compound shown in a formula E; s3, removing ethyl from the compound shown in the formula E to generate RXR agonist; wherein R is methyl formate, acetyl, tosyl or trifluoromethanesulfonyl.
Description
Technical Field
The invention relates to the technical field of organic chemical synthesis, in particular to a preparation method of RXR agonist.
Background
The RXR agonist is an orally active and selective RXR agonist with Kd values of 0.4nM,3.6nM and 3.8nM for RXR alpha, RXRbeta and RXRgamma, respectively, and 0.2nM,0.8nM and 0.08nM for EC50, respectively. AGN194204 is inactive against RAR and has anti-inflammatory and anti-cancer effects (J.Med. Chem.2001,44, 2298-2303) and is therefore an important RXR agonist.
The literature reports can be synthesized by the following route:
however, this route step is as long as 11 steps, where the reaction conditions of the multiple steps are severe (e.g., at-78 ℃ C. And the conditions of lithium reagent), and the separation of isomers by HPLC is required, which has a large limit for industrial applications.
Disclosure of Invention
The invention provides a preparation method of RXR agonist, which aims to overcome the defects of more steps and harsh reaction conditions of the synthetic route.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a method of preparing a RXR agonist comprising the steps of:
s1, reacting a compound shown in a formula A with a compound shown in a formula B under the conditions of an aza-carbene copper catalyst, a silicon reagent for providing a hydrogen source, a solvent and an organic base to generate a compound shown in a formula C;
s2, reacting a compound shown in a formula C with a compound shown in a formula D under the condition of a Holland-Gellan II catalyst to generate a compound shown in a formula E;
s3, removing ethyl from the compound shown in the formula E to generate RXR agonist;
wherein R is methyl formate, acetyl, tosyl or trifluoromethanesulfonyl.
The preparation method disclosed by the invention has the advantages of few reaction steps, mild reaction conditions and high yield, and can be suitable for industrial production to prepare the RXR agonist.
Preferably, step s1. The aza-carbene copper catalyst is selected from one of IPrCuCl, SIPrCuCl, IMesCuCl or SIMesCuCl.
Preferably, in the step S1, the aza-carbene copper catalyst is IPrCuCl. When IPrCuCl is selected as the aza-carbene copper catalyst, the yield is higher.
Preferably, the silicon reagent for providing the hydrogen source in the step S1 is selected from one of phenylsilane, triphenylsilane, polymethylhydrosiloxane, tetramethyldisilazane, trimethoxysilane or triethylsilane.
Preferably, step s1. The organic base is selected from the group consisting of lithium tert-butoxide, potassium tert-butoxide or sodium tert-butoxide.
Preferably, the reaction temperature of step S1 is 25-60 ℃.
Preferably, the solvent in the step S1 is one or more of ethylene glycol dimethyl ether, tetrahydrofuran, toluene, dichloromethane, dichloroethane, acetonitrile or 1, 4-dioxane.
Preferably, in S3, the compound of formula E is freed from ethyl groups under the action of an inorganic base.
The inorganic base in step s3 is a common base for promoting the hydrolysis of ester groups, preferably, the inorganic base in step s3 is selected from potassium hydroxide and/or sodium hydroxide.
The compound shown in the formula A can be prepared by a technical scheme which is commercially purchased or disclosed in a literature, and preferably, the compound shown in the formula A is prepared by the following reaction:
the protecting reagent is one of methyl chloroformate, p-toluenesulfonyl chloride, acetic anhydride or trifluoromethanesulfonic anhydride.
As an embodiment, it may be prepared according to the following procedure: the dried flask was taken, and the compound of formula A1 and dried tetrahydrofuran were added and cooled. Ethynyl magnesium bromide was added and warmed to room temperature. And after the reaction is finished, cooling again, and adding an ammonium chloride solution for quenching. The organic phase was extracted with ethyl acetate, dried over sodium sulfate and the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane, cooled, pyridine was added, and methyl chloroformate was added dropwise. After the completion of the dropwise addition, 4-dimethylaminopyridine was added thereto, and the reaction was allowed to warm to room temperature. Hydrochloric acid is added, the organic phase is extracted by dichloromethane, dried by sodium sulfate, and the compound shown in the formula A is obtained by column chromatography separation after the solvent is removed under reduced pressure.
The compounds of formula B can be prepared by commercially available or literature published protocols.
Preferably, the compounds of formula B can be synthesized according to the prior art (Journal of the American Chemical Society,2013, vol.135,24, P.9083-9090).
As an embodiment, it may be prepared according to the following procedure: the dried flask was taken and magnesium turnings were added. After nitrogen substitution, dry tetrahydrofuran and 6-bromo-1, 4-tetramethyl-1, 2,3, 4-tetrahydronaphthalene (compound represented by formula B1) were added. Stirring at room temperature to obtain the Grignard reagent. Another dry flask was taken, replaced with nitrogen, and trimethoxy boron and diethyl ether were added and cooled. The prepared grignard reagent was then added drop-wise to the flask with a syringe and stirring was continued until the reaction was complete. And adding dilute hydrochloric acid, and performing post-treatment to obtain the compound shown in the formula B2. A dry chirek tube was taken, 2-bromopropene, palladium acetate, triphenylphosphine and potassium phosphate were added and nitrogen was replaced. The compound of formula B2 and dried toluene were then added. Heating and stirring was continued. After the reaction is completed, cooling, transferring to a separating funnel, adding water, and performing aftertreatment to obtain the compound shown in the formula B.
The compounds of formula D can be prepared by commercially available or literature published protocols.
Preferably, the compounds of formula D can be synthesized according to the prior art (Organic Letters,2019, vol 21, #1, p.271-274;Journal of Organic Chemistry,2001,vol.66,7,p.2506-2508).
As an embodiment, it may be prepared according to the following procedure: ethyl glyoxylate and 2- (triphenylphosphine) propanal were taken in a flask and dried dichloromethane was added. After cooling, triethylamine was added. After the addition was complete and stirring was continued until the reaction was complete. The solvent is removed under reduced pressure and then the compound shown in the formula D2 is obtained through column chromatography separation. Bromomethyltriphenylphosphine was weighed into another flask, purged with nitrogen, then dried tetrahydrofuran was added and cooled. The n-butyllithium solution was then added dropwise and stirring continued. Another dry flask was taken, and after nitrogen substitution, the compound of formula D2 was placed therein and dissolved by adding dry tetrahydrofuran. After cooling, the reagents prepared above were added dropwise to the flask with a syringe and the reaction was continued until TLC monitored complete reaction of the starting materials. Saturated ammonium chloride solution is added, and then post-treatment is carried out to obtain the compound shown in the formula D.
Compared with the prior art, the invention has the beneficial effects that:
the preparation method of the RXR agonist AGN194204 has the advantages of fewer reaction steps, mild reaction conditions, reduction of the use of dangerous lithium reagents, great improvement of safety performance, and high yield of the prepared AGN194204, and is expected to be used for large-scale industrial production.
Detailed Description
The present invention is further illustrated below with reference to specific examples, which are not intended to limit the invention in any way. Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present invention are those conventional in the art and can be purchased directly or synthesized by known literature methods.
Example 1
The embodiment provides a preparation method of RXR agonist, which comprises the following specific steps:
first, a compound shown in a formula A, a compound shown in a formula B and a compound shown in a formula D are prepared:
(1) Preparing a compound represented by formula a: a dried flask was taken, and a compound of formula A1 (500 mg,4.1mmol,1.0 eq) and dried tetrahydrofuran (20 ml) were added and cooled to 0 ℃. Acetylylmagnesium bromide (0.5 mol/L in THF,12.2mL,6.1mmol,1.5 eq) was added and the mixture was slowly warmed to room temperature. After the reaction, cooling to 0 ℃ again, adding ammonium chloride solution for quenching. The organic phase was extracted with ethyl acetate, dried over sodium sulfate and the solvent was removed under reduced pressure. The residue was dissolved in methylene chloride (20 ml), cooled to 0℃and pyridine (1.0 mL,12.2mmol,3.0 eq) was added, followed by dropwise addition of methyl chloroformate (573.4 mg,6.1mmol,1.5 eq). After completion of the dropwise addition, 4-dimethylaminopyridine (50 mg,0.41mmol,0.1 eq) was added, and the reaction was warmed to room temperature and kept for 1 hour. 2N hydrochloric acid was added, the organic phase was extracted with dichloromethane, dried over sodium sulfate, and after removal of the solvent under reduced pressure, column chromatography was performed (petroleum ether/ethyl acetate=20/1) to give the compound represented by formula a (676.6 mg, 80%).
1 H NMR(500MHz,CDCl 3 )δ5.18(td,J＝6.5,2.2Hz,1H),3.77(s,3H),3.51(t,J＝6.6Hz,2H),2.51(d,J＝2.2Hz,1H),1.86–1.76(m,4H),1.65–1.54(m,2H). 13 CNMR(126MHz,CDCl 3 )δ154.9,80.2,74.8,67.5,55.0,44.5,33.8,31.9,22.2.IR(KBr,cm -1 )3292,2957,1752,1443,1266,958,790,650.HRMS(ESI)calcd for C 9 H 14 ClO 3 + [M+H] + :205.0626,found:205.0634.
(2) Preparing a compound represented by formula B: a dry 100mL flask with stirrer was taken and magnesium turnings (360 mg,2.0 eq) were added. After nitrogen substitution, 20mL of dry tetrahydrofuran and the compound represented by formula B1 (2.0 g) were added. Stirring for 3 hours at room temperature to prepare the format reagent. A further 100mL dry flask with stirrer was taken, after which trimethoxyboron (1.2 g,1.5 eq) and 10mL diethyl ether were added after nitrogen substitution and cooled to 0deg.C. The prepared grignard reagent was then added dropwise to the flask using a syringe and stirring was continued for 1 hour until the reaction was complete. After addition of dilute hydrochloric acid, extraction with diethyl ether was performed 3 times, drying was performed, and the solvent was removed under reduced pressure, followed by column chromatography to give the compound represented by formula B2 (1.3 g, 75%). A50 mL dry Schlemk tube with stirring was taken, 2-bromopropene (1.3 g,2.0 eq), palladium acetate (125 mg, 10%), triphenylphosphine (254 mg, 20%) and potassium phosphate (3.56 g,3.0 eq) were added and nitrogen was replaced. Then, the compound of formula B2 (1.3 g) and 15mL of dried toluene were added. Heat to 90 ℃ and stir for 5 hours. After the reaction was completed, cooled to room temperature, transferred to a separating funnel, added with water and extracted 3 times with ethyl acetate, dried, and separated by column chromatography (eluent: petroleum ether) after removing the solvent under reduced pressure to give the compound of formula B (1.1 g, 86%).
(3) Preparing a compound represented by formula D: ethyl glyoxylate (D1 compound, 1.0 g) and 2- (triphenylphosphine) propanal (4.6 g,1.5 eq.) were taken in a 100mL flask with stirring and 50mL of dry dichloromethane was added. Triethylamine (2.7 ml,2.0 eq) was added dropwise after cooling to 0 ℃. After the addition was completed, the reaction was slowly warmed to room temperature and stirring was continued for 3 hours until the reaction was complete. The solvent was removed under reduced pressure and column chromatography (eluent: petroleum ether/ethyl acetate=10/1) was carried out to give the compound represented by D2 (1.1 g, 79%). Bromomethyltriphenylphosphine (4.1 g,1.5 eq) was weighed into a 50mL flask with stirring, after nitrogen substitution 20mL of dry tetrahydrofuran was added and cooled to 0 ℃. N-butyllithium solution (4.6 mL,1.5eq, 2.5M) was then added dropwise and stirring continued for 1 hour. Another 100mL dry flask with stirring was taken, and after nitrogen substitution, the compound shown as D2 (1.1 g) was placed therein and 10mL dry tetrahydrofuran was added. After cooling to 0 ℃, the reagents prepared above were added dropwise to the flask with a syringe and the reaction was continued for 2 hours until TLC monitored complete reaction of the starting materials. Saturated ammonium chloride solution was added, followed by extraction with diethyl ether 3 times, drying, and removal of the excess solvent under reduced pressure, followed by column chromatography to give the compound represented by formula D (0.9 g, 83%).
The preparation method of RXR agonist AGN194204 comprises the following steps:
s1, preparing a compound shown in a formula C: a dry, stirred, shellac tube was charged with lithium t-butoxide (78 mg,0.98mmol,1.0 eq), IPrCuCl (4.8 mg,0.98% mmol,1% eq) and triphenylsilane (29 mg,1.12mmol,1.2 eq), and after three nitrogen substitutions ethylene glycol dimethyl ether (10 ml) was added and stirred at room temperature for 5 minutes. A solution (1 ml) of the compound represented by formula A (200 mg,0.98mmol,1.0 eq) in ethylene glycol dimethyl ether was added thereto, and stirring was continued for 5 minutes. The compound of formula B (349mg, 1.5mmol,1.5 eq) was added and incubated at 40℃for 12 hours. Saturated ammonium chloride solution was added, followed by extraction with ethyl acetate (3X 10 mL), saturated brine of the organic phase, drying over sodium sulfate, and removal of excess solvent under reduced pressure, followed by column chromatography (eluent: petroleum ether) to give the compound of formula C (208 mg, 59%).
S2, preparing a compound shown in a formula E: a dry, stirred, schlemk tube was charged with the compound of formula C (100 mg,0.28mmol,1.0 eq.) and replaced three times with nitrogen with dichloromethane (10 ml), the compound of formula D (118 mg,0.84mmol,3.0 eq.) and Hoveyda-Grubbs II catalyst (17 mg,0.028mmol,0.1 eq.). The reaction was heated to reflux for 24 hours. After TLC monitored complete reaction of starting materials, cool to room temperature. The excess solvent was removed under reduced pressure and separated by column chromatography (eluent petroleum ether/ethyl acetate=20/1) to give the compound of formula E (81 mg, 76%).
S3, preparing AGN 194204: a dry stirred flask was charged with the compound of formula E (60 mg,0.16mmol,1.0 eq), tetrahydrofuran (2 mL), methanol (2 mL), aqueous sodium hydroxide (0.4 mL,2N,5.0 eq) and stirred at 40℃for 3 hours until the reaction was complete. After cooling to room temperature, hydrochloric acid (1 ml,2 n) was added to adjust ph=6. Subsequently extracted with ethyl acetate (3×10 mL), the organic phase was saturated brine, dried over sodium sulfate, and the excess solvent was removed under reduced pressure, and column chromatographed (petroleum ether/ethyl acetate=3/1) to give AGN194204 (46 mg, 81%).
1 H NMR(500MHz,CDCl 3 )δ7.21(d,J＝8.1Hz,1H),7.12(d,J＝2.0Hz,1H),7.02(dd,J＝8.1,2.0Hz,1H),6.20(d,J＝15.5Hz,1H),5.64(s,1H),5.26(dd,J＝15.5,10.0Hz,1H),1.97(d,J＝1.1Hz,3H),1.72(ddd,J＝10.1,8.2,5.1Hz,1H),1.66(d,J＝1.6Hz,4H),1.42(s,3H),1.26(s,9H),1.20(s,3H),1.19–1.16(m,1H),1.14(t,J＝5.0Hz,1H). 13 C NMR(126MHz,CDCl 3 )δ172.5,155.2,144.6,142.9,141.5,139.6,131.3,127.6,126.5,126.3,115.3,35.2,35.1,34.2,34.0,32.0,31.9,31.8,30.7,29.8,28.7,22.2,13.7.IR(KBr,cm -1 )2959,2919,1664,1600,1442,1240,1075,959,819,440.HRMS(ESI)calcd for C 24 H 32 NaO 2 + [M+Na] + :375.2295,found:375.2299.
Examples 2 to 9
Examples 2-9 provide a series of RXR agonists, prepared in the same manner as example 1, except that different aza-carbene copper catalysts and different levels of aza-carbene copper catalysts were used, see in particular table 1, and the yields were expressed as the yields of the compounds of formula C of step S1.
Table 1 examples 2 to 9
| Examples | Catalyst | Yield/%of the Compound of formula C |
| 2 | SIPrCuCl(0.1％) | 50 |
| 3 | IMesCuCl(0.1％) | 34 |
| 4 | SIMesCuCl(0.1％) | 29 |
| 5 | IPrCuCl(10％) | 60 |
| 6 | IPrCuCl(2％) | 59 |
| 7 | IPrCuCl(1％) | 59 |
| 8 | IPrCuCl(0.5％) | 57 |
| 9 | IPrCuCl(0.01％) | 20 |
From examples 1 to 9, the yield was 20% even when the content of the Azacarbene copper catalyst was 0.01% eq, and the yield was better when IPrCuCl was used as the Azacarbene copper catalyst.
Examples 10 to 16
Examples 10 to 16 provide a series of RXR agonists, prepared in the same manner as example 1, except that they were prepared using different silicon reagents providing hydrogen sources and different levels of silicon reagents, as shown in table 2, using the compound yield of formula C of step S1.
Table 2 examples 10 to 16
From examples 10 to 14, phenylsilane, triphenylsilane, polymethylhydrosiloxane, tetramethyldisilazane, trimethoxysilane, triethylsilane were all able to prepare the compounds of formula C.
Examples 17 to 19
Examples 17 to 19 provide a series of RXR agonists, prepared in the same manner as in example 1, except that compounds of formula A of different R groups were used, see in particular Table 3, and the yields were expressed as the yields of compounds of formula C of step S1.
Table 3 examples 17 to 19
Examples 20 to 22
Examples 20-22 provide a series of RXR agonists, prepared in the same manner as example 1, except that the bases in steps S1 or S3 are different, as shown in Table 4.
Table 4 examples 20 to 22
Examples 23 to 32
Examples 23 to 32 provide a series of RXR agonists, prepared in the same manner as example 1, except that step S1 was performed using different reaction solvents, temperatures and times, see specifically table 5, and the yields were expressed as the yields of the compounds of formula C in step S1.
Table 5 examples 23 to 32
From examples 1 and 23 to 24, it was found that the yield was good at a temperature of 25 to 60 ℃.
From examples 1 and 25 to 26, the reaction time was found to be in good yields when it was in the range of 6 to 24 hours.
From examples 1 and 27-32, RXR agonists can be prepared using different solvents.
It is to be understood that the above examples of the present invention are provided by way of illustration only and not by way of limitation of the embodiments of the present invention. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. Any modification, equivalent replacement, improvement, etc. which come within the spirit and principles of the invention are desired to be protected by the following claims.
Claims (7)
1. A method of preparing a RXR agonist comprising the steps of:
s1, reacting a compound shown in a formula A with a compound shown in a formula B under the conditions of an aza-carbene copper catalyst, a silicon reagent for providing a hydrogen source, a solvent and an organic base to generate a compound shown in a formula C;
s2, reacting a compound shown in a formula C with a compound shown in a formula D under the condition of a Holland-Gellan II catalyst to generate a compound shown in a formula E;
s3, removing ethyl from the compound shown in the formula E to generate RXR agonist;
wherein R is methyl formate, acetyl, tosyl or trifluoromethanesulfonyl;
s1, selecting an aza-carbene copper catalyst from IPrCuCl, SIPrCuCl, IMesCuCl or SIMesCuCl; the silicon reagent for providing the hydrogen source is selected from one of phenylsilane, triphenylsilane, polymethylhydrosiloxane, tetramethyldisilazane, trimethoxysilane and triethylsilane; the organic base is selected from lithium tert-butoxide, potassium tert-butoxide or sodium tert-butoxide.
2. The method for preparing RXR agonist according to claim 1, wherein the aza-carbene copper catalyst of step s1 is IPrCuCl.
3. The method for preparing RXR agonist according to claim 1, wherein the reaction temperature of step s1 is 25 to 60 ℃.
4. The method for preparing the RXR agonist according to claim 1, wherein the solvent in the step S1 is one or more of ethylene glycol dimethyl ether, tetrahydrofuran, toluene, methylene dichloride, dichloroethane, acetonitrile and 1, 4-dioxane.
5. The method for preparing the RXR agonist according to claim 1, wherein in S3, the compound shown in the formula E is subjected to ethyl removal under the action of inorganic base.
6. The method of preparing RXR agonists according to claim 5, wherein the inorganic base is potassium hydroxide and/or sodium hydroxide.
7. The method for preparing RXR agonist according to claim 1, wherein the compound of formula a is prepared by the following reaction:
the protecting reagent is one of methyl chloroformate, p-toluenesulfonyl chloride, acetic anhydride or trifluoromethanesulfonic anhydride.
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|---|---|---|---|---|
| CN1176150A (en) * | 1996-09-10 | 1998-03-18 | 大连金菊化工厂 | Catalyst for the reaction of cyclopropane to tetramethyl ethylene |
| AU2007264114A1 (en) * | 2006-06-28 | 2008-01-03 | Sanofi-Aventis | New CXCR2 inhibitors |
| CN103772297A (en) * | 2014-01-26 | 2014-05-07 | 上海工程技术大学 | Chiral hexahydroxy n-heterocyclic carbine precursor compound as well as preparation method and application thereof |
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| DE102011012334A1 (en) * | 2011-02-24 | 2012-09-13 | Studiengesellschaft Kohle Mbh | Cyclopropenyl-ylidene stabilized phosphenium cations |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1176150A (en) * | 1996-09-10 | 1998-03-18 | 大连金菊化工厂 | Catalyst for the reaction of cyclopropane to tetramethyl ethylene |
| AU2007264114A1 (en) * | 2006-06-28 | 2008-01-03 | Sanofi-Aventis | New CXCR2 inhibitors |
| CN103772297A (en) * | 2014-01-26 | 2014-05-07 | 上海工程技术大学 | Chiral hexahydroxy n-heterocyclic carbine precursor compound as well as preparation method and application thereof |
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| Title |
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| "A new ruthenium-catalyzed cyclopropanation of alkenes using propargylic acetates as a precursor of vinylcarbenoids";Koji Miki 等;《Tetrahedron Letters》;第44卷(第10期);第2019-2022页 * |
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