CN112574041A - Synthesis method of chiral beta-hydroxy 1, 3-dicarbonyl compound - Google Patents
Synthesis method of chiral beta-hydroxy 1, 3-dicarbonyl compound Download PDFInfo
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Abstract
The invention discloses a method for synthesizing chiral beta-hydroxy-1, 3-dicarbonyl compounds with important synthons by catalyzing common carbonyl compounds and 1, 3-acetone dicarboxylic acid monoester compounds to directly perform decarboxylation addition reaction by using transition metal salts and chiral ligands.
Description
Technical Field
The invention relates to the field of organic chemistry, in particular to a synthetic method of a 3-carbonyl 5-hydroxy ester compound and a decarboxylation addition synthetic method thereof.
Background
The main skeleton of the chiral beta-hydroxy 1, 3-dicarbonyl compound is a structure formed by the participation of end-position methyl of the 1, 3-dicarbonyl compound in bonding, and high-activity methylene does not directly participate in reaction and plays an important role in subsequent modification and derivation. And the skeleton is widely present in a plurality of natural products and drug molecules, such as natural products Diospongin A, Z/E- (+) -Cryptofolione, (R) - (+) -goniothalamin, psymberin, (+) - (6R,2S) -cryptocaryalactone, and the like. Is an important synthon and intermediate in organic synthesis and drug development engineering. Therefore, the development of a simple and efficient synthesis strategy for chiral beta-hydroxy 1, 3-dicarbonyl compounds is of great significance.
Regarding the terminal position of 1, 3-dicarbonyl compounds, the realization of high-selectivity direct functionalization under mild conditions is always an urgent problem to be solved in synthetic application, and has great difficulty and great challenge. From the prior literature reports, the early main strategy is to directly utilize 1, 3-dicarbonyl compounds such as acetylacetone and the like to realize the simultaneous activation of terminal and middle methylene under the action of a superbase alkyl metal reagent to obtain a beta hydroxy-1, 3-dicarbonyl compound product with terminal methyl participating in bonding. Under mild conditions, only products with methylene groups participating in the reaction are obtained (adv. Synth. Catal.,2005,347, 816-824; Tetrahedron,2011,67, 4960-4966). Until 2012, the applicant realized that under mild conditions and tertiary amine catalysis, terminal methyl groups of common 1, 3-dicarbonyl compounds directly participate in the reaction to obtain beta-hydroxy-1, 3-dicarbonyl compounds (chem. eur., j.2012,18, 11899-11903; org. lett.2020,22,1, 6-10). The method has good promotion effect on realizing the functionalization of the 1, 3-dicarbonyl compounds for synthesis. However, the research has the obvious defect of limited substrate range at that time, only has good applicability to a special substrate isatin with high activity, and basically does not react with common carbonyl compounds. On the basis, a new substrate structure is designed and developed, a proper catalytic system is explored, and the synthesis of chiral beta-hydroxy-1, 3-dicarbonyl compounds based on common carbonyl compounds such as aldehyde substrates is particularly important. In addition, the existing reports have a plurality of limitations, so that the development and design of a new synthesis way, the construction of a chiral beta-hydroxy-1, 3-dicarbonyl compound under mild conditions and the high-yield synthesis of the chiral beta-hydroxy-1, 3-dicarbonyl compound have important promotion effects on the development and design of drug molecules and the research of basic methodology.
Disclosure of Invention
The invention aims to solve the technical problem of providing a chiral beta-hydroxy-1, 3-dicarbonyl compound and a preparation method thereof.
The first object of the invention is to provide a chiral beta hydroxy-1, 3-dicarbonyl compound, the structural formula of which is shown in formula 3:
in the formula, R1Selected from hydrogen, substituted or unsubstituted C6-C20Aryl, substituted or unsubstituted C2-C20Heterocyclic aryl, substituted or unsubstituted C1-C20An aliphatic group;
R2selected from hydrogen, C1-C20Ester group, substituted or unsubstituted C1-C20Alkyl radical, C1-C20An amide group;
R3is selected from C1-C20Alkyl radical, C6-C20aryl-C1-C20An alkyl group;
wherein R is1,R2Not hydrogen at the same time;
and wherein the substituents in any of said "substituted or unsubstituted" are halogen, C1-C6Alkyl radical, C1-C6Acyl radical, C1-C6Alkoxycarbonyl, -NO2、-CN、C1-C6A haloalkyl group.
Preferably, R1Is selected from substituted or unsubstituted phenyl, wherein the substituent in the substituted or unsubstituted is selected from C1-C6Acyl radical, C1-C6Alkoxycarbonyl, -NO2、-CN、C1-C6A haloalkyl group;
R2selected from hydrogen;
R3selected from methyl, ethyl, isopropyl, tert-butyl, n-pentyl and benzyl.
Most preferably, R1Is 4-nitrophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-cyanophenyl, 2, 4-dinitrophenyl; r2Is hydrogen; r3Selected from methyl, ethyl, isopropyl, tert-butyl, n-butylPentyl and benzyl.
As a second invention object, the invention provides a method for synthesizing chiral beta-hydroxy-1, 3-dicarbonyl compounds, which has the advantages of simple operation, reasonable process, low toxicity, mild reaction conditions, high reaction yield and good product quality, and comprises the following steps:
the preparation method comprises the following steps of taking a carbonyl compound shown as a formula 1 and a 1, 3-acetone dicarboxylic acid monoester compound shown as a formula 2 as raw materials, taking a transition metal salt and a chiral ligand as catalysts in an organic solvent A, stirring and reacting at a certain temperature, and after the reaction is finished, separating and purifying to obtain a chiral beta hydroxy-1, 3-dicarbonyl compound shown as a formula 3; the reaction formula is as follows:
in the above reaction formula, R1,R2,R3Having a structure as defined herein in any of the preceding paragraphs.
According to the aforementioned synthesis method of the present invention, the metal species of the transition metal salt in the catalyst system is selected from one or a combination of any of the following: ruthenium, rhodium, palladium, silver, copper, aluminum, nickel, zinc. Preferably one of the following: aluminum, nickel and zinc. Most preferably zinc.
The transition metal salt is selected from the group consisting of halogen salts, sulfates, carbonates, triflates, acetates, bicarbonates, bisulfates, and the like of the above-mentioned various metal ions. Preferably an acetate salt.
Preferably, therefore, in the present invention, the transition metal salt is Zn (OAc)2And their various hydrates, most preferably Zn (OAc)2·2H2O。
According to the aforementioned synthesis method of the present invention, the chiral ligand in the catalyst system is selected from one of the following:
most preferably, the chiral ligand in the catalyst system is selected from the aforementioned L8.
The organic solvent A used in the present invention is an organic solvent which does not react with the reactants and the product. The mass amount of the organic solvent A is 1 to 100 times, preferably 10 to 50 times of the mass amount of the carbonyl compound of the formula 1 and the 1, 3-acetonic acid monoester compound of the formula 2. The organic solvent A is selected from one or a combination of any of the following: dichloromethane, ethyl acetate, tetrahydrofuran, acetonitrile, toluene, methanol, chloroform. Preferably one of the following: tetrahydrofuran, acetonitrile. Tetrahydrofuran is most preferred.
The synthesis method according to the invention is preferably carried out by using an auxiliary agent. In the presence of a certain amount of auxiliary agent, the enantioselectivity of the target product can be obviously improved. Preferably, the adjuvant is selected from triethylamine, diisopropylethylamine or quinine, most preferably the adjuvant is triethylamine. In the invention, the molar ratio of the auxiliary agent to the carbonyl compound of formula 1 is 1: 0.2-1, preferably 1:1.
According to the synthesis method of the invention, the feeding molar ratio of the carbonyl compound of formula 1 to the 1, 3-acetonic acid monoester compound of formula 2 is 1: 1-2, preferably 1: 1.2 to 1.5, most preferably 1: 1.2.
the molar ratio of the transition metal salt to the chiral ligand is 1: 1-1: 5, and preferably 1: 1-1: 2. The molar ratio of the transition metal salt to the carbonyl compound of the formula 1 is 1 to 20 percent, preferably 10 to 20 percent.
In the present invention, the reaction temperature of the stirring reaction at the certain temperature is-80 ℃ to 60 ℃, preferably-80 ℃ to 30 ℃, and most preferably-80 ℃ to-40 ℃, and the reaction time is generally 3 to 72 hours, preferably 6 to 48 hours, and most preferably 12 to 24 hours. In the invention, the reaction at low temperature obviously improves the para-selectivity of the target product.
The separation and purification of the invention adopts a column chromatography separation and purification method. And (3) after the reaction is finished, evaporating the solvent from the obtained reaction solution, and carrying out column chromatography separation, purification and concentration to obtain the target product chiral beta-hydroxy-1, 3-dicarbonyl compound. Further, the leacheate is a mixture of petroleum ether and ethyl acetate, and the ratio of the petroleum ether to the ethyl acetate is 10: 1-2: 1, preferably 6: 1-3: 1.
the invention firstly utilizes transition metal salt and chiral ligand to catalyze common carbonyl compounds and 1, 3-acetone dicarboxylic acid monoester compounds to directly carry out decarboxylation addition reaction to synthesize chiral beta-hydroxy-1, 3-dicarbonyl compounds with important synthons. The beneficial effects are mainly as follows: 1, the operation is simple; 2, the cost is low; 3, the reaction yield is high; 4, high stereoselectivity. Therefore, the invention has higher basic research value and social and economic benefits.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described below with reference to specific embodiments. It should be understood that the preparation method of the embodiment of the present invention is only used for illustrating the present invention and not for limiting the present invention, the protection scope of the present invention is not limited thereto, and the simple modification of the preparation method of the present invention under the concept of the present invention falls within the protection scope of the present invention.
Examples 1-8 Effect of chiral ligand species
The p-nitrobenzaldehyde shown in the formula 1u and the compound shown in the formula 2a are used as raw materials, the influence of different chiral ligand types on the yield and the enantioselectivity of target products is discussed, and the results are shown in the table 1.
The chiral ligand species are shown below:
table 1:
areaction conditions are as follows: 1a (0.2mmol),2a (0.24mmol), 20 mol% catalyst (metal: ligand molar ratio ═ 1:1.1), THF (1mL), at-40 ℃ for 12 h;bthe yield of the separation;cchiral HPLC determines the ee value of the product.
Taking example 8 as an example, a typical experimental run is as follows:
to a Schlenk closed-loop reactor equipped with a magnetic stirrer were sequentially added p-nitrobenzaldehyde (0.2mmol) represented by formula 1a, a compound (0.24mmol) of formula 2a, Zn (OAc)2·2H2Replacing the atmosphere in a reactor with nitrogen gas by using O (20mol percent, namely 0.04mmol), chiral ligand L8(0.044mmol) and THF (1mL), then placing the reactor at-40 ℃ for stirring and reacting for 12h, evaporating a solvent after the reaction is finished, and carrying out column chromatography separation, purification and concentration to obtain the target product chiral beta-hydroxy-1, 3-dicarbonyl compound, wherein a eluent separated by the column chromatography is a mixture of petroleum ether and ethyl acetate, and the ratio of the petroleum ether to the ethyl acetate is 6: 1-3: 1. yield 55%, e.e.24%;1H NMR(500MHz,Chloroform-d)δ8.19(d,J＝8.8Hz,2H),7.56(d,J＝8.7Hz,2H),5.31(dd,J＝7.9,4.4Hz,1H),3.74(s,4H),3.54(s,3H),3.05–2.92(m,2H).13C NMR(126MHz,Chloroform-d)δ202.16,167.22,149.86,147.38,126.48,123.75,68.81,52.56,51.22,49.44。
examples 9-21 Effect of reaction auxiliary Agents
Using p-nitrobenzaldehyde shown in a formula 1a and a compound shown in a formula 2a as raw materials, and reacting the raw materials in Zn (OAc)2·2H2The influence of different auxiliary agents on the yield and the enantioselectivity of the target product is discussed under the catalytic system of O and chiral ligand L8, and the results are shown in Table 2.
Table 2:
areaction conditions are as follows: 1a (0.2mmol),2a (0.24mmol), 20 mol% catalyst (metal: ligand molar ratio ═ 1:2 or 1:1.1), adjuvant (1eq.), THF (1mL), at-40 ℃ for 12 h;bthe yield of the separation;cchiral HPLC determines the ee value of the product.
Taking example 21 as an example, a typical experimental run is as follows:
to a Schlenk closed-loop reactor equipped with a magnetic stirrer were sequentially added p-nitrobenzaldehyde (0.2mmol) represented by formula 1a, a compound (0.24mmol) of formula 2a, Zn (OAc)2·2H2Replacing the atmosphere in the reactor by nitrogen, placing the reactor at-40 ℃ for stirring and reacting for 12 hours, evaporating the solvent after the reaction is finished, and carrying out column chromatography separation and purification and concentration to obtain the target product chiral beta-hydroxy-1, 3-dicarbonyl compound, wherein the eluent separated by the column chromatography is a mixture of petroleum ether and ethyl acetate, and the ratio of the petroleum ether to the ethyl acetate is 6: 1-3: 1. yield 53%, e.e.73%.
Examples 21-28 Effect of catalyst amount, reaction temperature and time
Using p-nitrobenzaldehyde shown in a formula 1a and a compound shown in a formula 2a as raw materials, and reacting the raw materials in Zn (OAc)2·2H2The influence of different catalyst dosages, reaction temperatures and times on the yield of the target product and the enantioselectivity is discussed under the catalysis system of O and chiral ligand L8, and the results are shown in Table 3.
Table 3:
areaction conditions are as follows: 1a (0.2mmol),2a (0.24mmol), the amounts of catalyst indicated (metal: ligand molar ratio ═ 1:1.1), adjuvant (1eq.), THF (1mL), and the reactions were carried out at the indicated temperatures for the stated times；bThe yield of the separation;cchiral HPLC determines the ee value of the product.
Taking example 27 as an example, a typical test run is as follows:
to a Schlenk closed-loop reactor equipped with a magnetic stirrer were sequentially added p-nitrobenzaldehyde (0.2mmol) represented by formula 1a, a compound (0.24mmol) of formula 2a, Zn (OAc)2·2H2Replacing the atmosphere in the reactor by nitrogen, placing the reactor at-80 ℃ for stirring and reacting for 24 hours, evaporating the solvent after the reaction is finished, and carrying out column chromatography separation and purification and concentration to obtain the target product chiral beta-hydroxy-1, 3-dicarbonyl compound, wherein the eluent separated by the column chromatography is a mixture of petroleum ether and ethyl acetate, and the ratio of the petroleum ether to the ethyl acetate is 6: 1-3: 1, yield 49%, e.e.95%.
Examples 28-36 reaction substrate extension test
Following the procedure of example 27, a series of chiral β -hydroxy-1, 3-dicarbonyl compounds were prepared, replacing only the starting materials, with the following results:
the structural characterization data for the products prepared by the methods of examples 28-36 are as follows:
compound 3b:1H NMR(400MHz,Chloroform-d)δ8.21(d,J＝8.8Hz,2H),7.56(d,J＝8.6Hz,2H),5.32(t,J＝6.2Hz,1H),4.21(q,J＝7.2Hz,2H),3.51(s,2H),3.46(s,1H),2.98(d,J＝6.1Hz,2H),1.29(t,J＝7.1Hz,3H).13C NMR(126MHz,Chloroform-d)δ202.35,166.81,149.91,147.39,126.48,123.75,68.83,61.70,51.21,49.70,14.04。
compound 3c:1H NMR(400MHz,Chloroform-d)δ8.21(d,J＝8.7Hz,2H),7.56(d,J＝8.7Hz,2H),5.32(t,J＝6.2Hz,1H),5.12–4.98(m,1H),3.52(d,J＝3.8Hz,1H),3.48(s,2H),3.03–2.88(m,2H),1.26(d,J＝6.3Hz,6H).13C NMR(126MHz,Chloroform-d)δ202.82,166.62,150.16,147.72,126.80,126.76,124.11,124.07,69.82,69.14,51.50,50.31,22.00,21.96。
compound 3d:1H NMR(500MHz,Chloroform-d)δ7.63(d,J＝8.3Hz,2H),7.49(d,J＝8.3Hz,2H),5.24(dd,J＝8.7,3.6Hz,1H),3.72(s,3H),3.69(s,1H),3.53(s,2H),3.04–2.87(m,2H).13C NMR(126MHz,Chloroform-d)δ202.02,167.27,148.15,132.32,126.40,118.64,111.31,68.93,52.46,51.24,49.47。
compound 3e:1H NMR(500MHz,Chloroform-d)δ8.21(d,J＝8.2Hz,2H),7.56(d,J＝8.2Hz,2H),5.31(t,J＝6.1Hz,1H),3.58(s,1H),3.43(s,2H),2.97(d,J＝6.1Hz,2H),1.48(d,J＝8.3Hz,9H).13C NMR(126MHz,Chloroform-d)δ202.93,165.99,149.90,147.41,126.46,123.76,82.66,68.86,51.19,50.96,27.95。
compound 3f:1H NMR(400MHz,Chloroform-d)δ8.18(d,J＝8.8Hz,2H),7.48(d,2H),7.42-7.31(m,6H),5.27(t,J＝6.1Hz,1H),5.18(s,2H),3.56(s,2H),3.43(s,1H),2.93(d,J＝6.1Hz,2H).13C NMR(126MHz,Chloroform-d)δ202.13,166.47,149.59,147.45,134.99,128.71,128.69,128.51,126.43,123.78,68.82,67.47,51.15,49.70。
compound 3g:1H NMR(400MHz,Chloroform-d)δ8.21(d,J＝8.8Hz,2H),7.55(d,J＝8.7Hz,2H),5.32(t,J＝6.2Hz,1H),4.14(t,J＝6.8Hz,2H),3.52(s,2H),3.51–3.43(m,1H),2.98(d,J＝6.1Hz,2H),1.64(p,J＝7.0Hz,2H),1.38–1.27(m,4H),0.93–0.86(m,3H).13C NMR(126MHz,Chloroform-d)δ202.41,166.84,149.78,147.43,126.46,123.78,68.84,65.90,51.21,49.70,28.12,27.92,22.22,13.88。
compound 3h:1H NMR(500MHz,Chloroform-d)δ7.96(dd,J＝8.3,1.3Hz,1H),7.89(dd,J＝7.9,1.4Hz,1H),7.70–7.64(m,1H),7.48–7.42(m,1H),5.76–5.67(m,1H),3.75(s,3H),3.67(d,J＝3.5Hz,1H),3.56(d,J＝1.5Hz,2H),3.19(dd,J＝17.5,2.2Hz,1H),2.89(dd,J＝17.6,9.3Hz,1H).13C NMR(126MHz,Chloroform-d)δ202.15,167.21,147.15,138.26,133.80,128.39,128.19,124.44,65.46,52.48,50.81,49.25。
compound 3 i:1H NMR(500MHz,Chloroform-d)δ8.25(t,J＝1.9Hz,1H),8.13(dd,J＝8.2,2.3Hz,1H),7.72(d,J＝7.6Hz,1H),7.53(t,J＝7.9Hz,1H),5.31(dt,J＝7.8,3.5Hz,1H),3.74(s,3H),3.60(d,J＝3.5Hz,1H),3.55(s,2H),3.07–2.95(m,2H).13C NMR(126MHz,Chloroform-d)δ202.17,167.22,148.42,144.80,131.84,129.52,122.63,120.72,68.70,52.52,51.23,49.45。
compound 3j:1H NMR(500MHz,Chloroform-d)δ8.85(d,J＝2.4Hz,1H),8.51(dd,J＝8.8,2.4Hz,1H),8.20(d,J＝8.6Hz,1H),5.83(d,J＝9.2Hz,1H),3.76(d,J＝12.7Hz,4H),3.56(s,2H),3.24(dd,J＝17.9,2.3Hz,1H),2.89(dd,J＝17.9,9.2Hz,1H).13C NMR(126MHz,Chloroform-d)δ201.72,167.00,147.20,146.97,144.73,130.26,127.74,120.09,65.47,52.65,50.31,49.18。
Claims (10)
1. a chiral beta-hydroxy-1, 3-dicarbonyl compound has a structural formula shown as formula 3:
in the formula, R1Selected from hydrogen, substituted or unsubstituted C6-C20Aryl, substituted or unsubstituted C2-C20Heterocyclic aryl, substituted or unsubstituted C1-C20An aliphatic group;
R2selected from hydrogen, C1-C20Ester group, substituted or unsubstituted C1-C20Alkyl radical, C1-C20An amide group;
R3is selected from C1-C20Alkyl radical, C6-C20aryl-C1-C20An alkyl group;
wherein R is1,R2Not hydrogen at the same time;
and wherein the substituents in said "substituted or unsubstituted" are halogen, C1-C6Alkyl radical, C1-C6Acyl radical, C1-C6Alkoxycarbonyl, -NO2、-CN、C1-C6A haloalkyl group.
2. The chiral beta hydroxy-1, 3-dicarbonyl compound of claim 1, wherein R is1Is selected from substituted or unsubstituted phenyl, wherein the substituent in the substituted or unsubstituted is selected from C1-C6Acyl radical, C1-C6Alkoxycarbonyl, -NO2、-CN、C1-C6A haloalkyl group;
R2selected from hydrogen;
R3selected from methyl, ethyl, isopropyl, tert-butyl, n-pentyl and benzyl.
3. Chiral beta hydroxy-1, 3-dicarbonyl compounds as claimed in claim 2, characterized in that R1Is 4-nitrophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-cyanophenyl, 2, 4-dinitrophenyl; r2Is hydrogen; r3Selected from methyl, ethyl, isopropyl, tert-butyl, n-pentyl and benzyl.
4. A process for the preparation of chiral β -hydroxy-1, 3-dicarbonyl compounds as claimed in any one of claims 1 to 3, characterized in that:
taking a carbonyl compound shown in a formula 1 and a chiral ligand shown in a formula 2 as raw materials, stirring and reacting in an organic solvent A at a certain temperature by taking a transition metal salt and the chiral ligand as catalysts, and separating and purifying after the reaction to obtain a chiral beta-hydroxy-1, 3-dicarbonyl compound shown in a formula 3; the reaction formula is as follows:
in the above reaction formula, R1,R2,R3Having the formula (I) as defined in any one of claims 1 to 3;
wherein the transition metal salt is a halogen salt, a sulfate, a carbonate, a triflate, an acetate, a bicarbonate or a bisulfate; the metal species is selected from one or any combination of the following: ruthenium, rhodium, palladium, silver, copper, aluminum, nickel, zinc;
the chiral ligand is selected from one of the following:
5. the method of claim 4, wherein the transition metal salt is Zn (OAc)2And their various known hydrates, most preferably Zn (OAc)2·2H2O。
6. The method according to claim 4, wherein the amount of the organic solvent A is 1 to 100 times, preferably 10 to 50 times, the mass of the carbonyl compound of formula 1 and the 1, 3-acetonedicarboxylic acid monoester compound of formula 2; the organic solvent A is selected from one or a combination of any of the following: dichloromethane, ethyl acetate, tetrahydrofuran, acetonitrile, toluene, methanol, chloroform, and most preferably tetrahydrofuran.
7. The process according to claim 4, characterized in that it preferably uses a co-agent selected from triethylamine, diisopropylethylamine or quinine; most preferably, the auxiliary agent is triethylamine; the molar ratio of the auxiliary agent to the carbonyl compound shown in the formula 1 is 1: 0.2-1, and preferably 1:1.
8. The method according to claim 4, wherein the feeding molar ratio of the carbonyl compound of formula 1 to the 1, 3-acetone dicarboxylic acid monoester compound of formula 2 is 1: 1-2, preferably 1: 1.2 to 1.5, most preferably 1: 1.2.
9. the method according to claim 4, wherein the molar ratio of the transition metal salt to the chiral ligand is 1:1 to 1:5, preferably 1:1 to 1: 2; the molar ratio of the transition metal salt to the carbonyl compound of the formula 1 is 1 to 20 percent, preferably 10 to 20 percent.
10. The method according to claim 4, wherein the reaction temperature of the stirring reaction at the certain temperature is-80 ℃ to 60 ℃, preferably-80 ℃ to 30 ℃, and most preferably-80 ℃ to-40 ℃, and the reaction time is 3 to 72 hours, preferably 6 to 48 hours, and most preferably 12 to 24 hours.
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| CN101431996A (en) * | 2006-03-22 | 2009-05-13 | 加利福尼亚大学董事会 | Inhibitors of protein prenyltransferases |
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| MASAHIRO MINENO等: "Double Reformatsky Reaction: Divergent Synthesis of δ‑Hydroxy-β-ketoesters", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
| REGISTRY: "2514966-72-2等", 《STN》 * |
| ROSARIA VILLANO等: "Synthesis of multifunctionalized building blocks via vinylogous addition of Chan’s diene to carbonyl and carbonyl-related electrophiles, mediated by molecular iodine", 《TETRAHEDRON》 * |
| VILLANO ROSARIA等: "Solvent-free asymmetric vinylogous aldol reaction of Chan"s diene with aromatic aldehydes catalyzed by hydrogen bonding", 《TETRAHEDRON》 * |
| ZHU XUE-FENG等: "Phosphine-catalyzed synthesis of 1,3-dioxan-4-ylidenes", 《ORGANIC LETTERS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113856764A (en) * | 2021-10-29 | 2021-12-31 | 华中科技大学 | Transition metal catalyst and preparation method and application thereof |
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| CN112574041B (en) | 2022-10-28 |
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