CN112047951A - Chiral spiro [ pyrrole-2, 2' -furan ] compound and preparation method thereof - Google Patents
Chiral spiro [ pyrrole-2, 2' -furan ] compound and preparation method thereof Download PDFInfo
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Abstract
Chiral spiro [ pyrrole-2, 2' -furan]A compound and a preparation method thereof, belonging to spiro [ pyrrole-2, 2' -furan]The technical field of compound preparation. The chiral spiro [ pyrrole-2, 2' -furan]The structural formula of the compound is shown as the following, R1And R2Which may be the same or different, are hydrogen, fluoro, chloro, bromo, methyl, methoxy, cyano, and the like; r3Fluorine, chlorine, bromine, methyl, nitro, carboxylic ester or trifluoromethyl, etc. Dissolving 3-hydroxy-3 indolyl oxindole and its derivative in organic solvent, adding chiral phosphoryl imine acid catalyst while stirring, and adding
Molecular sieve, 1-styryl-2-naphthol and derivatives thereof, reacting completely, distilling off solvent under reduced pressure, and purifying by flash column chromatography to obtain chiral spiro [ pyrrole-2, 2' -furan]A compound is provided. The method has the advantages of mild reaction conditions, less catalyst consumption, high yield up to 93 percent and antipodal yieldThe selectivity can reach 99%, and the reaction time is short.
Description
Technical Field
The invention belongs to the technical field of preparation of spiro [ pyrrole-2, 2 '-furan ] compounds, and particularly relates to a chiral spiro [ pyrrole-2, 2' -furan ] compound and a preparation method thereof.
Background
In modern organic chemistry, spiro [ pyrrole-furans]The skeleton structure derives a series of compounds with biological activity. In recent years, the preparation of spiro [ pyrrole-furans ] with chirality]Structural compounds are beginning to receive attention. Such as 5-Chloro-Armeniasprol A[1]The structure of (A) comprises a chiral spiro [ pyrrole, furan]The structure has strong antibacterial activity, such as activity against staphylococcus aureus, enterococcus and streptococcus pneumoniae. Lycoplanine A[2]Comprising chiral spiro [ pyrrole-2, 2' -furans]Has unique calcium channel inhibiting activity. Elmenol G[2]Has inhibitory effect on induced withering caused by tumor cells. Natural product Strobilantoside A[3]The medicine has the main components of south isatis root, and has excellent treating effect on viral hepatitis, influenza, cold, pneumonia, inflammation, herpes, erysipelas and venomous snake bite. From this, spiro [ pyrrole-2, 2' -furan ] can be seen]The compound is a very important structure. However, the current catalytic synthesis of spiro [ pyrrole-2, 2' -furans]The reports of the compound are few. The invention provides a method for continuous [3+2] catalysis by asymmetry]/[4+1]Synthesis of chiral spiro [ pyrrole-2, 2' -furan by cycloaddition reaction]Novel process for intermediates, further applicable to spiro [ pyrrole-furans]Synthesis of biologically active molecules.
Reference documents:
[1]Couturier C,Bauer A,Rey A,et al.Armeniaspiroles,a new class of antibacterials:antibacterial activities and total synthesis of 5-chloro-Armeniaspirole A[J],Bioorg.Med.Chem.Lett.2012,22:6292-6296；
[2]Sengoku T,Nagai Y,Inuzuka T,et al.New Synthetic Methodology Toward Azaspiro-γ-Lactones by Oxidative C–H Spirocyclization[J],Synlett 2019,30:199–202；
[3]Gu W,Zhang Y,Hao X,et al,Indole Alkaloid Glycosides from the Aerial Parts of Strobilanthes cusia[J],J.Nat.Prod.2014,77:2590-2594。
disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a chiral spiro [ pyrrole-2, 2' -furan ] compound with reasonable process design, convenient operation and high yield and a preparation method thereof.
The structural formula of the chiral spiro [ pyrrole-2, 2' -furan ] compound is shown as follows:
in the formula: r1And R2Which may be the same or different, are hydrogen, fluoro, chloro, bromo, methyl, methoxy, cyano, and the like; r3Fluorine, chlorine, bromine, methyl, nitro, carboxylic ester or trifluoromethyl, etc.
The preparation method of the chiral spiro [ pyrrole-2, 2' -furan ] compound is characterized by comprising the following steps:
dissolving 3-hydroxy-3-indolyl oxindole and its derivative in organic solvent in the molar amount of 1-styryl-2-naphthol and 1-1.5 times that of the derivative to prepare 0.1-5M solution, adding chiral phosphoryl imine acid catalyst while stirring and adding
Reacting a molecular sieve (the mass amount of which is 1-5 times of that of 3-hydroxy-3 indolyl oxindole and derivatives thereof) and 1-styryl-2-naphthol and derivatives thereof, decompressing and evaporating a solvent after the reaction is completed, and purifying a product through fast column chromatography to obtain the chiral spiro [ pyrrole-2, 2 '-furan: (the invention) chiral spiro [ pyrrole-2, 2' -furan]A compound is provided.
The structural formula of the 3-hydroxy-3-indolyl oxindole and the derivative thereof is shown as follows,
R1and R2Which may be the same or different, are hydrogen, fluoro, chloro, bromo, methyl, methoxy, cyano, and the like;
the structural formula of the 1-styryl-2-naphthol and the derivative thereof is shown as follows,
R3fluorine, chlorine, bromine, methyl, nitro, carboxylic ester, trifluoromethyl and the like.
The reaction formula is as follows:
preferably, in the above preparation method, the chiral phosphinimide acid catalyst has the following structural formula:
respectively, 3' substituted H8BINOL-derived phosphinimide acid catalysts and 3,3 '-substituted BINOL-derived phosphinimide acid catalysts, wherein the 3, 3' -substituted R group can be 1-naphthyl, 2-naphthyl, 3, 5-bis (trifluoromethyl) phenyl, etc.
In the prior art, chiral phosphoric acid is catalyzed by screening the types of catalysts to only obtain a product with low enantioselectivity, and the product lacks strong chiral control capability. In the related documents, other types of catalysts also have poor chiral control effect on the reaction, so the catalyst used in the invention is a chiral phosphinimide catalyst, wherein the yield and enantioselectivity of the product obtained by catalyzing the 3,3 ' -substituted BINOL-derived phosphinimide acid are the highest, for example, the 3,3 ' -substituted 2-naphthyl BINOL-derived phosphinimide acid is used as the catalyst, and the ee value of the obtained spiro [ pyrrole-2, 2 ' -furan ] compound is 99%.
Preferably, in the preparation method, the molar amount of the chiral phosphinimide acid catalyst is 0.1-10% of 3-hydroxy-3 indolyl oxide and derivatives thereof; more preferably, the molar amount of the chiral phosphoryl imine acid is 1-5% of 3-hydroxy-3 indolyl oxide and derivatives thereof.
Through the screening of the reaction temperature, the reaction is carried out smoothly at 0-40 ℃, the yield higher than 80% and the ee value higher than 90% are obtained, and the enantioselectivity of the obtained product is obviously reduced to 63% at 40-80 ℃. Preferably, in the preparation method, the reaction temperature is 0-40 ℃, and the reaction time is 12-72 hours; more preferably, the reaction temperature is 2-30 ℃ and the reaction time is 24-48 hours.
Preferably, in the above preparation method, the organic solvent is dichloromethane, ethyl acetate, petroleum ether, toluene, chloroform, 1, 2-dichloroethane, or the like.
The invention has the beneficial effects that:
1. the invention determines the preparation method of the first example of chiral spiro [ pyrrole-2, 2' -furan ] compound through a large number of experimental screens, and 3-hydroxy-3-indolyl oxindole and derivatives thereof and 1-styryl-2-naphthol and derivatives thereof are subjected to asymmetric [3+2]/[4+1] continuous cycloaddition reaction under the catalysis of chiral phosphorus imido acid, and can be carried out in a conventional reaction vessel. The method has the advantages that the reaction temperature is only 0-40 ℃, the dosage of the catalyst is only 0.1-10% of the molar dosage of the substituted 3-hydroxy-3-indolyl oxoindole, the yield is up to more than 90%, the enantioselectivity can reach 99% at the highest, the reaction time is short, and the method is a method for efficiently synthesizing the chiral spiro [ pyrrole-2, 2' -furan ] compound.
2. The whole process is reasonable in design, simple in process operation and high in efficiency, particularly the optimal reaction conditions including the type and the amount of the catalyst, the reaction temperature, the reaction time, the molecular sieve and the like are screened, so that the reaction yield can be obviously improved, the side reaction is reduced, the production cost is greatly reduced, and the method has a good application prospect.
3. The synthesis method described in the present invention can be further used for the synthesis of pharmaceutically active spiro [ pyrrole-2, 2' -furan ] drug molecules described in the background art.
Detailed Description
In the following examples, the present invention is illustrated by way of examples. The specific material ratios, process conditions and results described in the examples are illustrative of the invention and should not, nor should they limit the invention as detailed in the claims.
Example 1: preparation of spiro [ pyrrole-2, 2' -furan ] racemate
3-hydroxy-3-indolyloxndole (11.2g, 0.04mol) and 1-styryl-2-naphthol (9.86g, 0.04mol) were dissolved in 0.5L of chloroform, and p-toluenesulfonic acid (0.34g, 2mmol) and ethyl acetate were added with stirring
Molecular sieve (15g), reacted at 30 ℃ for 24 hours, after completion of the reaction, the solvent was evaporated under reduced pressure and the product was purified by flash column chromatography to give a white solid (18.0g, 89% yield;1H NMR(400MHz,CDCl3)7.73(t,J＝8.0Hz,2H),7.45(d,J＝7.0Hz,1H),7.24–7.04(m,10H),6.93(t,J＝7.1Hz,1H),6.76–6.66(m,2H),6.58(d,J＝7.2Hz,2H),6.45(d,J＝6.8Hz,1H),5.33(s,1H),5.27(d,J＝11.1Hz,1H),4.43(s,1H),3.68(d,J＝11.0Hz,1H),2.73(s,3H).13C NMR(101MHz,CDCl3)175.1,155.3,149.6,143.9,136.1,130.6,129.9,129.4,129.1,129.0,128.4,128.4,128.2,127.6,126.2,125.1,123.9,122.9,122.7,122.5,122.1,121.0,118.9,115.3,112.3,109.1,107.7,66.7,64.9,63.4,56.5,25.5.HRMS(ESI):calcd for C35H26N2O2[M+H]+,507.2067；found,507.2065.
example 2: preparation of chiral spiro [ pyrrole-2, 2' -furan ].
Dissolving 3-hydroxy-3-indoxyl oxindole (33.6g, 0.12mol) and 1-styryl-2-naphthol (24.6g, 0.1mol) in 2L of chloroform, and adding a 3, 3' -1-naphthyl substituted BINOL skeleton-derived phosphoryl imidic acid catalyst (2g, 1.69mmol) and
molecular sieve (70g), reacting at 30 deg.C for 24 hr, distilling off solvent under reduced pressure after reaction is complete, and purifying by flash column chromatography to obtain white solid (46.6g, 92% yield, 99% ee, [ alpha ], [ beta ] -cyclodextrin]D 20＝+298.7(c＝1.0,CHCl3)；1H NMR(400MHz,CDCl3)7.73(t,J＝8.0Hz,2H),7.45(d,J＝7.0Hz,1H),7.24–7.04(m,10H),6.93(t,J＝7.1Hz,1H),6.76–6.66(m,2H),6.58(d,J＝7.2Hz,2H),6.45(d,J＝6.8Hz,1H),5.33(s,1H),5.27(d,J＝11.1Hz,1H),4.43(s,1H),3.68(d,J＝11.0Hz,1H),2.73(s,3H).13C NMR(101MHz,CDCl3)175.1,155.3,149.6,143.9,136.1,130.6,129.9,129.4,129.1,129.0,128.4,128.4,128.2,127.6,126.2,125.1,123.9,122.9,122.7,122.5,122.1,121.0,118.9,115.3,112.3,109.1,107.7,66.7,64.9,63.4,56.5,25.5.HPLC analysis:Daicel Chiralcel AD-H column,n-hexane/i-PrOH＝70/30,flow rate＝1.0mL/min,λ＝254nm,retention time:tmajor＝20.251min,tminor＝9.036min.HRMS(ESI):calcd for C35H26N2O2[M+H]+,507.2067；found,507.2065.
Example 3: preparation of chiral spiro [ pyrrole-2, 2' -furan ]
3-hydroxy-3- (5-methylindole) oxoindole (8.76g, 36mmol) and 1-styryl-2-naphthol (7.38g, 30mmol) were dissolved in 200mL of toluene, and the mixture was stirredAdding a 3, 3' -1-naphthyl substituted H8-BINOL skeleton-derived phosphinimido acid catalyst (2g, 1.69mmol) and
molecular sieve (20 g), at 30 deg.C for 48 hr, after reaction completely, the solvent was evaporated under reduced pressure, and the product was purified by flash column chromatography to give a white solid (14.1g, 90% yield, 95% ee, [ alpha ], [ beta ] -cyclodextrin]D 20＝+276.2(c＝1.0,CHCl3)；1H NMR(400MHz,CDCl3)7.73(t,J＝8.8Hz,2H),7.45(d,J＝7.2Hz,1H),7.25–7.07(m,9H),6.92(t,J＝7.1Hz,2H),6.71–6.63(m,2H),6.58(d,J＝7.7Hz,1H),6.27(s,1H),5.24(d,J＝11.2Hz,1H),5.19(s,1H),4.40(s,1H),3.66(d,J＝11.2Hz,1H),2.73(s,3H),2.11(s,3H).13C NMR(101MHz,CDCl3)175.1,155.3,147.4,143.9,136.1,130.6,129.9,129.5,129.4,129.1,128.9,128.4,128.4,128.3,128.2,127.6,126.2,125.5,123.9,123.5,122.7,122.5,122.0,121.0,115.8,112.3,109.2,107.7,66.6,65.1,63.4,56.4,25.5,20.7.HPLC analysis:Daicel Chiralcel AD-H column,n-hexane/i-PrOH＝70/30,flow rate＝1.0mL/min,λ＝254nm,retention time:tmajor＝18.243min,tminor＝8.745min.HRMS(ESI):calcd for C36H28N2O2[M+H]+,521.2224；found,521.2230.
Example 4: preparation of chiral spiro [ pyrrole-2, 2' -furan ]
3-hydroxy-3-indolyl-6-chloro-oxindole (15.6g, 50mmol) and 1-styryl-2-naphthol (12.3g, 50mmol) were dissolved in 500mL of dichloromethane, and 3, 3' -position 2-naphthyl substituted BINOL-derived phosphinimide acid catalyst (2.5g, 2.11mmol) and
molecular sieve (35g), reacting at 30 deg.C for 48 hr, vacuum evaporating solvent, and purifying by flash column chromatography to obtain white productSolid (23.8g, 88% yield, 99% ee, [ alpha ]]D 20＝+283.2(c＝1.0,CHCl3)；1H NMR(400MHz,CDCl3)7.73(t,J＝9.2Hz,2H),7.36(t,J＝7.1Hz,1H),7.22–7.05(m,9H),6.92(t,J＝7.2Hz,1H),6.73(d,J＝7.8Hz,1H),6.68–6.56(m,3H),6.47(d,J＝7.3Hz,1H),5.30(s,1H),5.24(d,J＝11.2Hz,1H),4.38(s,1H),3.63(d,J＝11.2Hz,1H),2.70(s,3H).13C NMR(101MHz,CDCl3)175.0,155.2,149.5,145.0,135.8,134.2,130.5,130.0,129.4,129.2,128.9,128.4,128.3,127.8,127.5,126.3,124.7,123.8,123.1,122.8,122.8,122.4,120.8,119.0,115.1,112.3,109.1,108.6166.4,64.8,63.4,56.4,25.6.HPLC analysis:Daicel Chiralcel AD-H column,n-hexane/i-PrOH＝70/30,flow rate＝1.0mL/min,λ＝254nm,retention time:tmajor＝17.028min,tminor＝9.111min.HRMS(ESI):calcd for C35H25ClN2O2[M+H]+,541.1677；found,541.1679.
Example 5: preparation of chiral spiro [ pyrrole-2, 2' -furan ]
3-hydroxy-3-indolyloxndole (55.6g, 0.2mol) and 1- (4-fluoro-styryl) -2-naphthol (52.8g, 0.2mol) were dissolved in 1L of diethyl ether, and H substituted with 3, 3' -2-naphthyl was added with stirring8-BINOL-derivatized phosphinimidate catalyst (3g, 2.54mmol) and
molecular sieves (70g) were reacted at 25 ℃ for 36 hours, after completion of the reaction the solvent was distilled off under reduced pressure and the product was purified by flash column chromatography to give a white solid (90.4g, 86% yield, 98% ee, [ alpha ], (see FIG. ])]D 20＝+344.3(c＝1.0,CHCl3)；1H NMR(400MHz,CDCl3)7.74(d,J＝6.0Hz,2H),7.43(d,J＝6.8Hz,1H),7.24–7.06(m,7H),7.04–6.96(m,1H),6.81(t,J＝7.5Hz,2H),6.71(d,J＝7.6Hz,2H),6.60(t,J＝8.0Hz,2H),6.45(d,J＝6.6Hz,1H),5.35(s,1H),5.22(d,J＝11.0Hz,1H),4.42(s,1H),3.67(d,J＝10.9Hz,1H),2.75(s,3H).13C NMR(101MHz,CDCl3)175.1,162.3(d,J＝245Hz),155.3,149.5,143.8,132.0(d,J＝3Hz),130.5,130.4,130.1,129.5,129.1,128.9,128.6(d,J＝7Hz),126.4,124.9,123.7,122.8(d,J＝6Hz),122.7,122.0,120.8,118.9,115.2,115.0,112.3,109.1,107.9,66.7,64.0,63.3,56.5,25.57.HPLC analysis:Daicel Chiralcel AD-H column,n-hexane/i-PrOH＝80/20,flow rate＝1.0mL/min,λ＝254nm,retention time:tmajor＝19.433min,tminor＝24.662min.HRMS(ESI):calcd for C35H25FN2O2[M+H]+,525.1973；found,525.1970.
Example 6: preparation of chiral spiro [ pyrrole-2, 2' -furan ].
3-hydroxy-3-indolyloxndole (5.56g, 20mmol) and 1- (4-bromo-styryl) -2-naphthol (5.93g, 18mmol) were dissolved in 100mL of ethyl acetate and H substituted with trifluoromethyl at the 3, 3' -position was added with stirring8BINOL-derivatized phosphoramidite catalyst (1.5g, 0.98mmol) and
molecular sieves (7g) were reacted at 30 ℃ for 24 hours, the solvent was distilled off under reduced pressure after completion of the reaction, and the product was purified by flash column chromatography to give a white solid (9.94g, 94% yield 98% ee, [ alpha ], []D 20＝+269.8(c＝1.0,CHCl3)；1H NMR(400MHz,CDCl3)7.74(d,J＝7.9Hz,2H),7.41(d,J＝6.4Hz,1H),7.25–6.97(m,J＝33.2,23.8,7.4Hz,10H),6.76–6.66(m,2H),6.64–6.54(m,2H),6.45(d,J＝6.1Hz,1H),5.37(s,1H),5.22(d,J＝10.7Hz,1H),4.42(s,1H),3.65(d,J＝10.8Hz,1H),2.75(s,3H).13C NMR(101MHz,CDCl3)175.0,155.3,149.5,143.8,135.4,131.4,130.6,130.5,130.2,129.4,129.2,128.7,128.7,128.6,126.6,124.8,123.7,122.9,122.7,122.0,121.7,120.7,118.9,115.2,112.4,109.1,108.0,99.9,66.6,64.0,63.6,56.4,25.6.HPLC analysis:Daicel Chiralcel AD-H column,n-hexane/i-PrOH＝80/20,flow rate＝1.0mL/min,λ＝254nm,retention time:tmajor＝21.043min,tminor＝17.755min.HRMS(ESI):calcd for C35H25BrN2O2[M+H]+,585.1172；found,585.1174.
Example 7: preparation of chiral spiro [ pyrrole-2, 2' -furan ]
3-hydroxy-3- (6-fluoroindole) oxoindole (2.96g, 10mmol) and 1-styryl-2-naphthol (2.46g, 10mmol) were dissolved in 100mL of petroleum ether, and H8-BINOL-derived phosphinimide acid catalyst (0.2g, 0.17mmol) substituted at the 3, 3' -position with 1-naphthyl and
molecular sieves (7g) were used, reacted at 35 ℃ for 24 hours, after completion of the reaction, the solvent was distilled off under reduced pressure, and the product was purified by flash column chromatography to give a white solid (4.77g, 91% yield, 98% ee, [ alpha ], (see FIG. ])]D 20＝+276.3(c＝1.0,CHCl3)；1H NMR(400MHz,CDCl3)7.71(d,J＝8.8Hz,2H),7.43(d,J＝7.3Hz,1H),7.24–7.06(m,9H),6.94(t,J＝7.5Hz,1H),6.68(d,J＝8.4Hz,1H),6.58(d,J＝7.7Hz,1H),6.40–6.33(m,2H),6.29–6.21(m,1H),5.46(s,1H),5.26(d,J＝11.2Hz,1H),4.34(d,J＝11.9Hz,1H),3.66(d,J＝11.2Hz,1H),2.76(s,3H).13C NMR(101MHz,CDCl3)175.1,164.2(d,J＝242Hz),155.2,151.0,150.9,143.8,136.0,130.5,130.0,129.4,128.9,128.8,128.6,128.4,128.2,127.6,126.4,123.9,123.5(d,J＝11Hz),122.8(d,J＝21Hz),122.1,120.9,120.5(d,J＝23Hz),115.8,112.2,107.8,104.9(d,J＝23Hz),96.8(d,J＝27Hz),66.7,64.7,62.5,56.3,25.5.HPLC analysis:Daicel Chiralcel AD-H column,n-hexane/i-PrOH＝70/30,flow rate＝1.0mL/min,λ＝254nm,retention time:tmajor＝30.519min,tminor＝10.231min.HRMS(ESI):calcd for C35H25FN2O2[M+H]+,525.1973；found,525.1980.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be construed as the protection scope of the present invention.
Claims (10)
1. A chiral spiro [ pyrrole-2, 2' -furan ] compound has a structural formula shown as follows:
wherein R is1And R2Identical or different and is hydrogen, fluorine, chlorine, bromine, methyl, methoxy or cyano; r3Is fluorine, chlorine, bromine, methyl, nitro, carboxylic ester or trifluoromethyl.
2. A chiral spiro [ pyrrole-2, 2' -furan as claimed in claim 1]A process for the preparation of a compound, characterized in that: dissolving 3-hydroxy-3-indolyl oxindole and its derivative in organic solvent to prepare 0.1-5M solution, adding chiral phosphoryl imido acid catalyst while stirring and adding
Molecular sieves and 1-styryl-2-naphthol and derivatives thereof; after the reaction is completed, the solvent is evaporated out under reduced pressure, and then the product is purified by flash column chromatography, so that the chiral spiro [ pyrrole-2, 2' -furan is obtained]A compound is provided.
3. A process for the preparation of a chiral spiro [ pyrrole-2, 2' -furan ] compound according to claim 2, characterized in that: the structural formula of the chiral phosphinimide acid catalyst is shown as one of the following formulas,
r is 1-naphthyl, 2-naphthyl, 3, 5-bis (trifluoromethyl) phenyl or phenyl.
4. A process for the preparation of a chiral spiro [ pyrrole-2, 2' -furan ] compound according to claim 2, characterized in that: the structural formula of the 3-hydroxy-3-indolyl oxindole and the derivative thereof is shown as follows,
R1and R2Identical or different and are hydrogen, fluorine, chlorine, bromine, methyl, methoxy or cyano.
5. A process for the preparation of a chiral spiro [ pyrrole-2, 2' -furan ] compound according to claim 2, characterized in that: the structural formula of the 1-styryl-2-naphthol and the derivative thereof is shown as follows,
R3is fluorine, chlorine, bromine, methyl, nitro, carboxylic ester or trifluoromethyl.
6. A chiral spiro [ pyrrole-2, 2' -furan of claim 2]A process for the preparation of a compound, characterized in that: the molar amount of the chiral phosphinimide acid catalyst is 0.1-10% of the molar amount of 3-hydroxy-3-indolyl oxindole and derivatives thereof,
the mass dosage of the molecular sieve is 1-5 times of the dosage of 3-hydroxy-3-indolyl oxide and derivatives thereof, and the molar dosage of the 3-hydroxy-3-indolyl oxide and derivatives thereof is 1-1.5 times of the molar dosage of 1-styryl-2-naphthol and derivatives thereof.
7. The method of claim 6, wherein the chiral spiro [ pyrrole-2, 2' -furan ] compound is prepared by: the molar dosage of the chiral phosphoryl imine acid is 1-5% of the molar dosage of the 3-hydroxy-3-indolyl oxindole and the derivatives thereof.
8. A process for the preparation of a chiral spiro [ pyrrole-2, 2' -furan ] compound according to claim 2, characterized in that: the reaction temperature is 0-40 ℃, and the reaction time is 12-72 hours.
9. The method of claim 8, wherein the chiral spiro [ pyrrole-2, 2' -furan ] compound is prepared by: the reaction temperature is 2-30 ℃, and the reaction time is 24-48 hours.
10. A process for the preparation of a chiral spiro [ pyrrole-2, 2' -furan ] compound according to claim 2, characterized in that: the organic solvent is dichloromethane, ethyl acetate, petroleum ether, toluene, chloroform or 1, 2-dichloroethane.
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