CN113563328A - Preparation method of 1, 3-disubstituted-2-fluoro indolizine derivative - Google Patents
Preparation method of 1, 3-disubstituted-2-fluoro indolizine derivative Download PDFInfo
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Abstract
The invention discloses a preparation method for synthesizing a 1, 3-disubstituted 2-fluoro indolizine derivative by a one-pot method, which comprises the following steps: dissolving the 2, 2-difluorovinylbenzene derivative, a nitrogen-containing heterocyclic compound and a salt formed by ethyl bromoacetate in an organic solvent, opening the solvent, and performing cyclization and oxidation under the action of alkali and under the condition of heating to obtain the corresponding 2-fluoro indolizine derivative. The operation process is simple, the complicated operation of no water and no oxygen is avoided, and meanwhile, the use of a noble metal catalyst is avoided, so that the method is convenient for industrial application; the method can be easily expanded to hectogram level, and is suitable for industrial mass production.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a 1, 3-disubstituted-2-fluoro indolizine derivative.
Background
It is well known that the introduction of fluorine atoms into organic molecules can significantly affect their physical, chemical and biological properties. In particular, the introduction of fluorine-containing groups (F, CF3, HCF2,) at specific positions on heterocyclic organic molecules is of particular interest, and methods have been developed, but few relate to indolizine derivatives. Indolizine is a specific structural skeleton found in many natural alkaloids, pesticides and pharmaceutically active molecules. Many substituted indolizines possess a broad spectrum of biological activities such as antitubercular, antibacterial, antitumor, anti-inflammatory and antioxidant activities.
Professor Tabolin developed a route to 1-fluoro indolizine derivatives using oxidative [3+2] cyclization of nitrofluoroolefins and pyridine ylides and required an excess of copper (ii) as the oxidant (scheme 1a, v.a. motornov, a.a. Tabolin, y.v. nelumbina, v.g. nenajdenko, s.l. ioffe, Organic & Biomolecular Chemistry 2019,17, 1442). In 2003, professor chenqingyun and professor wanshawu respectively report a method for synthesizing 2-fluoroindolizine by the [3+2] cycloaddition reaction of fluoroolefin (CF2 ═ CFX, X ═ Cl, Br, CF3, OTs) with pyridine ylide (scheme 1b, k.wu, q. -y.chen, Synthesis 2003,1, 35; k.wu, q. -y.chen j.fluorine chem.2003,122, 171; x.fang, y. -m.wu, j.deng, s. -w.wang, Tetrahedron 2004,60, 5487). The C1 position of the obtained 2-fluoro indolizine is hydrogen, and can be converted into 1, 3-disubstituted-2-fluoro indolizine through halogenation and palladium-catalyzed cross-coupling reaction.
Disclosure of Invention
The invention provides a method for synthesizing a 1, 3-disubstituted 2-fluoro indolizine derivative by a one-pot method, the preparation method has simple steps, and the raw materials are 2, 2-difluorovinylbenzene derivative, salt formed by a nitrogen-containing heterocyclic compound and ethyl bromoacetate, and are simple and easy to obtain. The operation process is simple, the complicated operation of no water and no oxygen is avoided, and meanwhile, the use of a noble metal catalyst is avoided, so that the method is convenient for industrial application; the method can be easily expanded to hectogram level, and is suitable for industrial mass production.
The structure of the 2, 2-difluorovinylbenzene derivative is shown as a formula (I) or (II):
the salt structure formed by the nitrogen-containing heterocyclic compound and bromide is shown as the formula (III):
the structure of the 1, 3-disubstituted-2-fluoro indolizine derivative is shown as a formula (IV):
the reaction formula is as follows:
in the general formulae (I), (II), (III), (IV) and (V):
R1is H, C1～C6Alkyl, substituted or unsubstituted phenyl, thienyl or furyl, or R1Form a fused aromatic ring with a benzene ring;
R2is alkoxycarbonyl, carbonyl, nitrile or sulfonic group;
R3is H, C1～C6Alkyl, halogen, alkoxycarbonyl, substituted or unsubstituted phenyl, benzyl, pyridyl, thienyl or furyl;
R4and R5Independently selected from H, C1～C6Alkyl, substituted or unsubstituted phenyl or benzyl;
the substituent on the phenyl is C1～C6Alkyl radical, C1～C6Alkoxy or halogen.
The reaction goes through a [3+2] cycloaddition reaction of pyridine ylide (other heterocyclic ylide) and 2, 2-difluorovinylbenzene derivative and a subsequent oxidation reaction process. Under the action of oxygen in the air, non-aromatic compounds generated in the reaction process are immediately oxidized into corresponding 1, 3-disubstituted-2-fluoro indolizine derivatives. The reaction is carried out under basic conditions.
In the present invention, the optional post-processing procedure includes: filtering, mixing the sample with silica gel, and finally purifying by column chromatography to obtain the corresponding 1, 3-disubstituted-2-fluoro indolizine derivative, wherein the purification by column chromatography is a technical means commonly used in the field.
Preferably, R1Is C1～C6Alkyl, optionally substituted phenyl, thienyl or furyl.
Preferably, R2Is ester group, carbonyl group, nitrile group or sulfonic group.
Preferably, R3Is ethyl, propyl, butyl, isopropyl, phenyl, benzyl, pyridyl, thienyl or furyl.
Preferably, R4Is ethyl, propyl, butyl, isopropyl, phenyl or benzyl.
Preferably, R5Is ethyl, propyl, butyl, isopropyl, phenyl or benzyl.
The phenyl group may have various substituents such as methyl, methoxy, F, Cl, Br, etc.
Preferably, the 2, 2-difluorovinylbenzene derivative: salts of nitrogen-containing heterocyclic compounds with bromides: base 1.0:1.2-4.0: 1.2-4.0; as further preference, the 2, 2-difluorovinylbenzene derivative: salts of nitrogen-containing heterocyclic compounds with bromides: base 1.0:1.5: 2.0.
Preferably, the reaction time is 4-24 hours, and the yield of the reaction is affected when the reaction time is too long or too short.
In the present invention, the organic solvent capable of sufficiently dissolving the raw material can cause the reaction, but the difference in reaction efficiency is large, and the aprotic solvent is preferably an aprotic solvent which can effectively promote the reaction; preferably, the organic solvent is acetonitrile, DMF, DCM or dioxane; further preferably, the organic solvent is a mixed solvent of DMF and dioxane, and in this case, various raw materials can be converted into products with high conversion rate.
The amount of the organic solvent can be used for better dissolving the raw materials, and the amount of the organic solvent used for 1mmol of the 2, 2-difluorovinylbenzene derivative is about 3-5 mL.
Preferably, the base comprises the organic base Et3N, DBU, DBN, DMAP, pyridine, N-methylmorpholine and the inorganic bases sodium carbonate, potassium carbonate, sodium bicarbonate, potassium phosphate, cesium fluoride, cesium carbonate and the like. As a further preference, the base is potassium carbonate, with which the 2, 2-difluorovinylbenzene derivative can be converted in high yield into the corresponding 1, 3-disubstituted-2-fluoroindolizine derivative.
As a further preference, the 1, 3-disubstituted-2-fluoro indolizine derivative is one of the compounds shown in formula (I-1) and formula (I-6):
in the preparation method, the 2, 2-difluorovinylbenzene derivative can be conveniently synthesized by corresponding commercial aldehyde and sodium difluorochloroacetate, and the salt formed by the nitrogen heterocyclic compound and the bromide can be directly synthesized by the heterocyclic compound and the bromide. The equation is as follows:
compared with the prior art, the invention has the beneficial effects that: the reaction is operated in one pot, no water or oxygen is needed for the reaction, the preparation method has no precious transition catalysis, and thus, the phenomenon that residual transition metal influences the biological activity of the obtained 1, 3-disubstituted-2-fluoro indolizine derivative is avoided; the reaction raw materials are cheap and easy to obtain, the designability of the reaction substrate is strong, the compatibility of the substrate functional group is good, various different substituted 1, 3-disubstituted-2-fluoro indolizine derivatives can be designed and synthesized according to actual needs, and the practicability is strong.
Detailed Description
The invention is further described with reference to specific examples.
Example 1
Pyridinium salt 1.2(0.8mmol), 4-chloro-1- (2, 2-difluorovinyl) -2-fluorobenzene 1.1(0.4mmol) and K2CO3(0.8mmol) was dissolved in a mixed solvent of DMF and dioxane (2mL, v/v ═ 1/1). Stirring for 12h at 60 ℃ in air atmosphere, and adding 10 ml of water into the reaction system to quench the reaction after the reaction is finished. After DCM extraction (3X 20mL), the organic layers were combined and dried over anhydrous sodium sulfate, the organic solvent was removed under reduced pressure and the corresponding ethyl 1- (3-chloro-2-fluorophenyl) -2-fluoroazindol-3-carboxylate (94mg, 70%) was isolated on silica gel as a white solid with a melting point of 112-.1H NMR(400MHz,CDCl3)δ9.48(d,J＝7.1Hz,1H),7.40(q,J＝8.0,7.6Hz,3H),7.20–7.14(m,2H),6.91(td,J＝7.0,1.2Hz,1H),4.43(q,J＝7.1Hz,2H),1.42(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ160.8(d,J＝4.2Hz),155.6(d,J＝250.6Hz),155.5(d,J＝264.9Hz),132.5(d,J＝5.7Hz),130.1(q,J＝1.3Hz),129.7,127.6,124.7(d,J＝4.6Hz),124.2,122.2(d,J＝18.3Hz),120.0(dd,J＝15.9,2.5Hz),117.3(t,J＝4.2Hz),113.5(d,J＝2.9Hz),101.5(d,J＝21.1Hz),95.5(d,J＝12.2Hz),60.3,14.6.19F NMR(376MHz,CDCl3)δ-139.71.HRMS(ESI-TOF):m/z calculated for C17H13ClF2NO2 +[M+H]+:336.0597,found:336.0612.
Example 2
Pyridinium salt 1.2(0.8mmol), 4-bromo-2- (2, 2-difluorovinyl) thiophene 2.1(0.4mmol) and K2CO3(0.8mmol) was dissolved in a mixed solvent of DMF and dioxane (2mL, v/v ═ 1/1). Stirring for 12h at 60 ℃ in air atmosphere, and after the reaction is finished, feeding the mixture into a reaction systemThe reaction was quenched with 10 ml of water. After extraction with DCM (3X 20mL), the organic layers were combined and dried over anhydrous sodium sulfate, the organic solvent was removed under reduced pressure and the corresponding ethyl 1- (4-bromothien-2-yl) -2-fluoroazindol-3-carboxylate (100mg, 68%) was isolated on silica gel. White solid, melting point: 80-81 ℃.1H NMR(400MHz,CDCl3)δ9.41(d,J＝7.1Hz,1H),7.74(d,J＝9.0Hz,1H),7.17(q,J＝5.6,5.1Hz,4H),6.87(t,J＝6.9Hz,1H),4.42(q,J＝7.1Hz,2H),1.42(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ160.5(d,J＝4.1Hz),154.8(d,J＝264.8Hz),133.4(d,J＝4.0Hz),131.5(d,J＝5.1Hz),127.6,127.0(d,J＝3.6Hz),124.6,120.7(d,J＝1.5Hz),117.1(d,J＝5.0Hz),113.6(d,J＝2.8Hz),110.4,101.4(d,J＝20.4Hz),95.3(d,J＝11.0Hz),60.4,14.6.19F NMR(376MHz,CDCl3)δ-139.71.HRMS(ESI-TOF):m/z calculated for C15H12BrFNO2S+[M+H]+:367.9751,found:367.9762.
Example 3
Pyridinium salt 3.2(0.8mmol), methyl 4- (2, 2-difluorovinyl) benzoate 3.1(0.4mmol) and K2CO3(0.8mmol) was dissolved in a mixed solvent of DMF and dioxane (2mL, v/v. 1/1). Stirring for 12h at 60 ℃ in air atmosphere, and adding 10 ml of water into the reaction system to quench the reaction after the reaction is finished. DCM extraction (3X 20mL) after the organic layer and anhydrous sodium sulfate drying, decompression spin off organic solvent silica gel column separation corresponding 2-fluoro-1- (4- (methoxy carbonyl) phenyl) -6-methyl pyrrolo [2, 1-a-]Isoquinoline-3-carboxylic acid ethyl ester (86mg, 53%). White solid, melting point: 160 ℃ and 161 ℃.1H NMR(400MHz,CDCl3)δ9.12(s,1H),8.17(d,J＝8.0Hz,2H),7.77(dd,J＝16.7,8.2Hz,2H),7.58(d,J＝7.9Hz,2H),7.48(t,J＝7.6Hz,1H),7.24(t,J＝7.74Hz,1H),4.42(q,J＝7.1Hz,2H),3.98(s,3H),2.49(s,3H),1.42(t,J＝7.0Hz,3H).13C NMR(101MHz,CDCl3)δ167.0,160.8(d,J＝7.1Hz),154.8(d,J＝260.7Hz)137.00(d,J＝1.1Hz),131.0,130.2,129.8,129.6,127.9,127.6(d,J＝4.1Hz),127.0,124.5(d,J＝3.7Hz),124.1,124.0,122.4,119.1(d,J＝2.6Hz),105.4(d,J＝13.0Hz),102.0(d,J＝19.7Hz),60.4,52.3,16.7,14.6.19F NMR(376MHz,CDCl3)δ-145.68.HRMS(ESI-TOF):m/z calculated for C24H21FNO4 +[M+H]+:406.1449,found:406.1457.
Example 4
Pyridinium salt 4.2(0.8mmol), (E) - (4, 4-difluorobutane-1, 3-dien-1-yl) benzene 4.1(0.4mmol) and K2CO3(0.8mmol) was dissolved in a mixed solvent of DMF and dioxane (2mL, v/v. 1/1). Stirring for 12h at 60 ℃ in air atmosphere, and adding 10 ml of water into the reaction system to quench the reaction after the reaction is finished. After DCM extraction (3X 20mL), the organic layers were combined and dried over anhydrous sodium sulfate, the organic solvent was removed under reduced pressure and the corresponding (E) -2-fluoro-1-styryl-3-nitrilotriindolizine (57mg, 55%) was isolated from the silica gel column. White solid, melting point: 124 ℃ and 125 ℃.1H NMR(400MHz,CDCl3)δ8.10(d,J＝6.9Hz,1H),7.66(d,J＝9.0Hz,1H),7.49(d,J＝7.6Hz,2H),7.36(t,J＝7.6Hz,2H),7.28(s,1H),7.17(t,J＝7.5Hz,1H),7.06(q,J＝16.5Hz,2H),6.89(t,J＝6.9Hz,1H).13C NMR(101MHz,CDCl3)δ156.7(d,J＝265.8Hz),137.6,132.0(d,J＝6.1Hz),129.4(d,J＝6.2Hz),128.8,127.6,126.1,125.7,124.0,117.8(d,J＝5.0Hz),114.7(d,J＝3.3Hz),114.0(d,J＝2.7Hz),110.9(d,J＝3.8Hz),99.7(d,J＝8.2Hz).19F NMR(376MHz,CDCl3)δ-143.54.HRMS(ESI-TOF):m/z calculated for C17H12FN2 +[M+H]+:263.0979,found:263.0997.
Example 5
Pyridinium salt 1.2(0.8mmol), (E) - (4, 4-difluoro-2-methylbutane-13-dien-1-yl) benzene 5.1(0.4mmol) and K2CO3(0.8mmol) was dissolved in a mixed solvent of DMF and dioxane (2mL, v/v. 1/1). Stirring for 12h at 60 ℃ in air atmosphere, and adding 10 ml of water into the reaction system to quench the reaction after the reaction is finished. After extraction with DCM (3X 20mL), the organic layers were combined and dried over anhydrous sodium sulfate, the organic solvent was removed under reduced pressure and the corresponding ethyl (E) -2-fluoro-1- (1-phenylpropyl-1-en-2-yl) indolizine-3-carboxylate 5.3(72mg, 56%) was isolated on silica gel. White solid, melting point: 46-47 ℃.1H NMR(400MHz,CDCl3)δ9.41(d,J＝7.1Hz,1H),7.67(d,J＝9.0Hz,1H),7.40-7.24(m,4H),7.25-7.21(m,1H),7.07(d,J＝7.1Hz,1H),6.80(td,J＝7.0,1.0Hz,1H),6.70(s,1H),4.41(q,J＝7.1Hz,2H),2.34(s,3H),1.42(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ160.8(d,J＝4.0Hz),155.3(d,J＝263.6Hz),137.8,132.3(d,J＝6.7Hz),129.9(d,J＝1.4Hz),129.1,128.3,128.1(d,J＝3.0Hz),127.4,126.6,123.4,117.7(d,J＝5.4Hz),112.9(d,J＝3.0Hz),105.6(d,J＝10.4Hz),100.9(d,J＝21.7Hz),60.1,18.9(d,J＝3.0Hz),14.7.19F NMR(376MHz,CDCl3)δ-139.70.HRMS(ESI-TOF):m/z calculated for C20H19FNO2 +[M+H]+:324.1394,found:324.1414。
Example 6
Pyridinium salt 1.2(0.8mmol), (3S, 8R, 9S, 10S, 13S, 14S) -10, 13-dimethyl-17-oxohexadecahydro-1H-cyclopenta [ a ]]Phenanthren-3-yl 4- (2, 2-difluorovinyl) benzoate 6.1(0.4mmol) and K2CO3(0.8mmol) was dissolved in a mixed solvent of DMF and dioxane (2mL, v/v. 1/1). Stirring for 12h at 60 ℃ in air atmosphere, and adding 10 ml of water into the reaction system to quench the reaction after the reaction is finished. DCM extraction (3X 20mL) after the organic layer and dried with anhydrous sodium sulfate, decompression spin off the organic solvent silica gel column separation corresponding 1- (4- ((((3S, 8R, 9S, 10S, 13S, 14S) -10, 13-two methyl-17-oxo hexadecahydro-1H-cyclopentyl [ a)]Phenanthren-3-yl) oxy) carbonyl) phenyl) -2-Fluoroindolizine-3-carboxylate 6.3(151mg, 63%). White solid, melting point: 218 ℃ and 219 ℃.1H NMR(400MHz,CDCl3)δ9.47(d,J＝7.1Hz,1H),8.12(d,J＝8.2Hz,2H),7.71(d,J＝8.9Hz,1H),7.64(d,J＝8.1Hz,2H),7.18((d,J＝7.4Hz,1H),6.90(t,J＝7.0Hz,1H),4.96(tt,J＝10.8,4.7Hz,1H),4.43(q,J＝7.1Hz,2H),2.43(dd,J＝19.2,8.8Hz,1H),2.11-2.02(m,1H),1.99-1.90(m,2H),1.80(d,J＝11.5Hz,4H),1.68(t,J＝10.4Hz,3H),1.53(dt,J＝20.9,10.5Hz,3H),1.42(t,J＝7.1Hz,3H),1.36(d,J＝11.0Hz,2H),1.31-1.25(m,3H),1.12(td,J＝13.3,3.2Hz,1H),1.02(td,J＝12.9,12.0,5.1Hz,1H),0.88(d,J＝17.0Hz,6H),0.75(t,J＝11.2Hz,1H).13C NMR(101MHz,CDCl3)δ221.3,166.0,160.8(d,J＝4.1Hz),155.3(d,J＝264.4Hz),135.6(d,J＝2.8Hz),132.3(d,J＝1.9Hz),130.2,128.9,128.3(d,J＝1.9Hz),127.8,124.5,116.9(d,J＝5.3Hz),113.6(d,J＝2.8Hz),101.6(d,J＝9.4Hz),101.4,74.3,60.3,54.5,51.5,47.9,44.9,36.9,36.0,35.9,35.2,34.2,31.7,31.0,28.5,27.7,21.9,20.6,14.7,14.0,12.4.19F NMR(376MHz,CDCl3)δ-142.87.HRMS(ESI-TOF):m/z calculated for C37H43FNO5[M+H]+:600.3120,found:600.3128。
Claims (10)
1. A method for synthesizing a 1, 3-disubstituted-2-fluoro indolizine derivative by a one-pot method is characterized by comprising the following steps: dissolving a 2, 2-difluorovinylbenzene derivative, a nitrogen-containing heterocyclic compound and a salt formed by a halogenated compound in an organic solvent, opening the solvent, and performing cyclization and oxidation under the action of alkali and heating to obtain the 1, 3-disubstituted-2-fluoro indolizine derivative;
the structure of the 2, 2-difluorovinylbenzene derivative is shown as a formula (I) or (II):
the structure of the salt formed by the nitrogen-containing heterocyclic compound and the halogenated compound is shown as the formula (III):
the structure of the 1, 3-disubstituted-2-fluoro indolizine derivative is shown as a formula (IV) or (V):
in the general formulae (I), (II), (III), (IV) and (V):
R1is H, C1～C6Alkyl, substituted or unsubstituted phenyl, thienyl or furyl, or R1Form a fused aromatic ring with a benzene ring;
R2is alkoxycarbonyl, carbonyl, nitrile or sulfonic group;
R3is H, C1～C6Alkyl, halogen, alkoxycarbonyl, substituted or unsubstituted phenyl, benzyl, pyridyl, thienyl or furyl;
R4and R5Independently selected from H, C1～C6Alkyl, substituted or unsubstituted phenyl or benzyl;
the substituent on the phenyl is C1～C6Alkyl radical, C1～C6Alkoxy or halogen;
x is fluorine ion, chlorine ion, bromine ion or iodine ion.
2. The one-pot process for the synthesis of 1, 3-disubstituted-2-fluoroindolizine derivatives according to claim 1, wherein R is1Is ethyl, propyl, butyl, isopropyl, substituted or unsubstituted phenyl, thienyl or furyl, or R1Form a fused aromatic ring with a benzene ring;
the substituent on the phenyl is methyl, methoxy, F, Cl or Br.
3. The one-pot synthesis of 1, 3-disubstituted-2-fluoro indolizine derivatives according to claim 1Characterized in that R is2Is ethoxycarbonyl, carbonyl, nitrile group or sulfonic group.
4. The one-pot process for the synthesis of 1, 3-disubstituted-2-fluoroindolizine derivatives according to claim 1, wherein R is3Is ethyl, propyl, butyl, isopropyl, substituted or unsubstituted phenyl, benzyl, pyridyl, thienyl or furyl;
the substituent on the phenyl is methyl, methoxy, F, Cl or Br.
5. The one-pot process for the synthesis of 1, 3-disubstituted-2-fluoroindolizine derivatives according to claim 1, wherein R is4Is ethyl, propyl, butyl, isopropyl, substituted or unsubstituted phenyl or benzyl;
the substituent on the phenyl is methyl, methoxy, F, Cl or Br.
6. The one-pot process for the synthesis of 1, 3-disubstituted-2-fluoroindolizine derivatives according to claim 1, wherein R is5Is ethyl, propyl, butyl, isopropyl, substituted or unsubstituted phenyl or benzyl;
the substituent on the phenyl is methyl, methoxy, F, Cl or Br.
7. The one-pot method for synthesizing the 1, 3-disubstituted-2-fluoro indolizine derivative according to claim 1, wherein the base is an organic base or an inorganic base;
the organic base is Et3N, DBU, DBN, DMAP, pyridine or N-methylmorpholine;
the inorganic base is sodium carbonate, potassium carbonate, sodium bicarbonate, potassium phosphate, cesium fluoride or cesium carbonate.
8. The method for synthesizing the 1, 3-disubstituted-2-fluoro indolizine derivative according to claim 1, wherein the reaction temperature is 50-70 ℃ and the reaction time is 4-24 hours.
9. The method for synthesizing 1, 3-disubstituted-2-fluoro indolizine derivative according to claim 1, wherein the organic solvent is one or a mixture of methanol, ethanol, dichloromethane, chloroform, 1, 2-dichloroethane, toluene, DMF, DMSO, THF, dioxane and acetonitrile.
10. The method for synthesizing the 1, 3-disubstituted-2-fluoro indolizine derivative according to claim 1, wherein the 1, 3-disubstituted-2-fluoro indolizine derivative is one of the compounds represented by the formulas (I-1) to (I-6):
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US11530217B1 (en) | 2022-06-29 | 2022-12-20 | King Faisal University | Antitubercular compounds |
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Non-Patent Citations (3)
| Title |
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| THIBAUT MARTINEZ 等: "Straightforward Access to 2‑Iodoindolizines via Iodine-Mediated Cyclization of 2‑Pyridylallenes", 《ORGANIC PROCESS RESEARCH&DEVELOPMENT》 * |
| VLADIMIR A. MOTORNOV 等: "Copper-mediated oxidative [3+2]-annulation of nitroalkenes and pyridinium ylides: general access to functionalized indolizines and efficient synthesis of 1-fluoroindolizines", 《ORGANIC&BIOMOLECULAR CHEMISTRY》 * |
| XIANG FANG 等: "Synthesis of monofluorinated indolizines and their derivatives by the 1,3-dipolar reaction of N-ylides with fluorinated vinyl tosylates", 《TETRAHEDRON》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US11530217B1 (en) | 2022-06-29 | 2022-12-20 | King Faisal University | Antitubercular compounds |
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