CN114044771B - Compound with 5-hydroxyfuran-2 (5H) -ketone skeleton and preparation method thereof - Google Patents

Abstract

The invention provides a compound with a 5-hydroxyfuran-2(5H)-one skeleton and a preparation method thereof, belonging to the technical field of organic synthesis. The present invention uses rhodium to catalyze C-H olefination/directing group migration/lactonization/C-H hydroxylation series reactions to prepare a series of compounds with 5-hydroxyfuran-2(5H)-ketone skeletons, and the reaction conditions are: With indole compound I and 4-hydroxy-2-alkynoate compound II as substrate, [Cp*RhCl ₂ ] ₂ as catalyst, sodium acetate as additive, acetone as solvent, react under air atmosphere to obtain -Hydroxyfuran-2(5H)-one skeleton of the target compound IV. The synthesis method provided by the invention has the advantages of wide substrate application range, high regioselectivity and stereoselectivity, good yield, good functional group tolerance, economical reaction steps, high bond-forming efficiency, mild reaction conditions, and the like. The reaction equation involved in the synthetic reaction of the present invention is as follows:

Description

Compound having 5-hydroxyfuran-2(5H)-one skeleton and preparation method thereof

Technical Field

The invention belongs to the technical field of organic synthesis, and specifically relates to a compound having a 5-hydroxyfuran-2(5H)-one skeleton and a preparation method thereof.

Background Art

Studies have shown that many drugs and active natural product molecules have a furan-2(5H)-one skeleton. As shown below, rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor used to treat osteoarthritis and rheumatoid arthritis, and is also used to relieve acute pain and treat primary dysmenorrhea. The natural product Sorgolactone has seed germination promoting activity, the natural product Lambertellol A has antibacterial activity, and the natural product Kallolide A has anti-inflammatory activity. It can be seen that compounds with a furan-2(5H)-one structure have potential pharmacological application value. Therefore, developing an efficient preparation method to synthesize furan-2(5H)-one compounds has important theoretical and application value.

Summary of the invention

The object of the present invention is to provide a compound having a 5-hydroxyfuran-2(5H)-one skeleton and a preparation method thereof. The synthesis method has the advantages of a wide range of substrate applications, high regioselectivity, high stereoselectivity, good yield, good functional group tolerance, economical reaction steps, high bonding efficiency, mild reaction conditions, etc.

One of the purposes of the present invention is to provide a method for preparing a compound having a 5-hydroxyfuran-2(5H)-one skeleton, wherein the compound having a 5-hydroxyfuran-2(5H)-one skeleton has a structural formula as shown in Formula <IV>, and the preparation method comprises the following steps:

The indole compound represented by formula <Ⅰ> and the 4-hydroxy-2-ynoate compound represented by formula <Ⅱ> are used as substrates, [Cp*RhCl ₂ ] ₂ is used as a catalyst, NaOAc is used as an additive, and acetone is used as a solvent, and the reaction is carried out under air atmosphere to obtain a compound represented by formula <Ⅳ>;

The reaction formula involved in the above method is as follows:

Wherein, R ¹ represents a substituent at any position on the benzene ring, which is selected from the following groups: hydrogen, halogen, alkyl, alkoxy, 3-6 membered heterocyclic ring containing one N, O or S atom, cyano, ester group;

^R2 is selected from the following groups: hydrogen, substituted or unsubstituted alkyl;

R ³ is selected from the following groups: substituted or unsubstituted alkyl;

R ⁴ is selected from the following groups: substituted or unsubstituted alkyl, aryl;

R ⁵ is selected from the following groups: alkyl;

The substitution refers to that one or more hydrogen atoms on the group are replaced by any group selected from the following group: phenyl.

Furthermore, the halogen includes F, Cl, Br or I.

Furthermore, the alkyl group includes methyl, ethyl, isopropyl, n-butyl, tert-butyl or n-pentyl; the alkoxy group includes methoxy or ethoxy; the substituted alkyl group includes benzyl; and the aryl group includes phenyl, p-methyl substituted phenyl or p-chloro substituted phenyl.

Furthermore, the 3-6 membered heterocyclic ring containing one N, O or S atom includes the following groups:

Furthermore, the reaction conditions are: reaction temperature is 25° C., and reaction time is 5-24 h.

Furthermore, the molar ratio of compound I to compound II is 1:1.3.

Furthermore, the amount of the catalyst used is 1% to 10% of the molar amount of compound I, preferably 5% (5% is used as an example in the embodiment).

Furthermore, the molar ratio of the additive to compound I is 1:1.

The second object of the present invention is to provide a compound having a 5-hydroxyfuran-2(5H)-one skeleton prepared by the above method. As shown in the examples of the present invention, the present invention provides a series of compounds that have been successfully synthesized and characterized.

The beneficial effects of the present invention are as follows:

The present invention has developed a type of rhodium-catalyzed C–H olefination/directing group migration/lactonization/C–H hydroxylation tandem reaction, and successfully prepared a series of compounds with a 5-hydroxyfuran-2(5H)-one skeleton. The synthetic reaction has the advantages of a wide range of substrate applications, high regioselectivity and stereoselectivity, good yield, good functional group tolerance, economical reaction steps, high bonding efficiency, mild reaction conditions, etc., and the reaction can be scaled up to gram scale, and has good application value.

DETAILED DESCRIPTION

In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is described in detail below in conjunction with the embodiments. It is necessary to point out that the following embodiments are only used to explain and illustrate the present invention and are not used to limit the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the above invention content still belong to the protection scope of the present invention.

Example 1

Optimization of reaction conditions:

Using indole 1aa and 4-hydroxynon-2-ynoic acid methyl ester 2aa as template substrates, the reaction conditions were optimized according to the steps shown in Table 1.

First, with NaOAc as an additive, 1aa and 2aa were reacted in Acetone (acetone) at 25°C in air atmosphere for 5 h under the catalysis of a series of metal catalysts (No. 1-6). The results showed that when [Cp*RhCl ₂ ] ₂ was used as a catalyst, the target C–H olefination/directing group migration/lactonization/C–H hydroxylation tandem reaction product 4aa was obtained with a yield of 77%, accompanied by the formation of a small amount of byproduct 3aa (No. 6).

Then, [Cp*RhCl ₂ ] ₂ and NaOAc were used as catalyst and additive to screen the solvents (No. 7-11). The results showed that acetone was still the best reaction solvent.

Subsequently, various additives (No. 12-14) were investigated in acetone, the best reaction solvent. In comparison, NaOAc was still the most effective additive.

Finally, blank experiments (No. 15 and 16) were performed. The results showed that both [Cp*RhCl ₂ ] ₂ and NaOAc were indispensable, and the [Cp*RhCl ₂ ] ₂ /NaOAc catalytic system was the key to the successful realization of the C–H olefination/directing group migration/lactonization/C–H hydroxylation tandem reaction.

Table 1. Optimization of reaction ^conditionsa

^a Reaction conditions: 1aa (0.25 mmol), 2aa (0.325 mmol), catalyst (5 mol%), additive (0.25 mmol), air (1 standard atmosphere), solvent (4.0 mL), reaction temperature 25 °C, reaction time 5 h; ^b refers to isolated yield. n-Pent is n-pentyl, Acetone is acetone, DCM is dichloromethane, DCE is 1,2-dichloroethane, THF is tetrahydrofuran, EtOH is ethanol, DMF is N,N-dimethylformamide, and trace indicates trace amount.

Example 2

Investigation of the applicable scope of substrate:

Under the above-mentioned optimal reaction conditions (No. 6), as shown in Table 2, the applicable scope of the substrates of the rhodium-catalyzed C–H olefination/directing group migration/lactonization/C–H hydroxylation tandem reaction was investigated, and a series of compounds 4 with a 5-hydroxyfuran-2(5H)-one skeleton were prepared. First, methyl 4-hydroxynon-2-ynoate 2aa was used as the coupling component to investigate the applicable scope of the indole substrate, synthesize compounds 4aa-4be, and calculate their yields. Then, the applicable scope of 4-hydroxy-2-ynoate ester substrates was investigated, compounds 4bf-4bn were synthesized, and their yields were calculated. The results of the investigation are shown in Table 2.

The specific method is as follows: indole 1 (0.25 mmol), [Cp*RhCl ₂ ] ₂ (5 mol%) and NaOAc (0.25 mmol) are added to a 25 mL Schlenk reaction tube in sequence, and then an acetone (4.0 mL) solution containing 4-hydroxy-2-ynoic acid ester 2 (0.325 mmol) is added thereto, and then the reaction tube is sealed with a rubber stopper, and the obtained reaction mixture is stirred at 25°C for reaction, and the specific reaction time is shown in Table 2. After the reaction is completed, the reaction solvent is first removed by concentration under reduced pressure, and the obtained residue is purified by flash chromatography on silica gel to obtain the target product 4.

Table 2. Substrate application range ^{a, b}

^a Reaction conditions: substrate 1 (0.25 mmol), substrate 2 (0.325 mmol), [Cp*RhCl ₂ ] ₂ (5 mol%), NaOAc (0.25 mmol), air (1 standard atmosphere), acetone (4.0 mL), 25° C., 5-24 h; ^b Isolated yield. n-Pent is n-pentyl, Et is ethyl, n-Bu is n-butyl, and Ph is phenyl.

The above results indicate that the rhodium-catalyzed C–H olefination/directing group migration/lactonization/C–H hydroxylation tandem reaction provided by the present invention has the advantages of a wide range of substrate applicability, high regioselectivity and stereoselectivity, good yield, good functional group tolerance, economical reaction steps, high bonding efficiency, mild reaction conditions, etc., and can efficiently synthesize a series of compounds 4 having a 5-hydroxyfuran-2(5H)-one skeleton.

Example 3

Gram-scale amplification reaction experiment:

According to the reaction conditions shown in the following reaction formula, a gram-scale amplification reaction was carried out. In a 100 mL round-bottom flask, indole 1aa (6 mmol), [Cp*RhCl ₂ ] ₂ (5 mol%) and NaOAc (6 mmol) were added in sequence, and then an acetone solution (40.0 mL) containing 4-hydroxynon-2-ynoic acid methyl ester 2aa (7.8 mmol) was added thereto. The resulting reaction mixture was left open to air at 25°C and stirred for 20 hours. After the reaction was completed, the reaction solvent was first removed by concentration under reduced pressure, and the resulting residue was purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1 → petroleum/ethyl acetate: 4/1), and 1.70 g of a yellow amorphous solid was obtained with a yield of 79%, which was the target product 4aa. The results of the amplified reaction experiment proved that the reaction could be scaled up to a gram-scale, further proving the practicality of this type of reaction.

Example 4

Specific characterization of a series of compounds having a 5-hydroxyfuran-2(5H)-one skeleton prepared in Examples 2 and 3 above (Compounds 1 to 46):

The characterization method uses hydrogen spectrum + carbon spectrum + high-resolution mass spectrometry, and the characterization results of the obtained series of compounds are as follows:

Compound 1 (4aa):

5-Hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (69.1 mg, yield 77%), mp (melting point) 166-167°C.

¹ H NMR (500MHz, DMSO-d ₆ ) δ12.47 (s, 1H), 11.65 (s, 1H), 8.26 (s, 1H), 7.73 (d, J = 8.1Hz, 1H), 7.66 (dd, J＝8.4,0.5Hz,1H),7.44(d,J＝0.9Hz,1H),7.35-7.29(m, 1H),7.13-7.07(m,1H),3.77(s,3H),2.20(ddd ,J＝14.1,11.7,4.5Hz,1H),2.05(ddd, J＝14.0,11.6,4.8Hz,1H),1.31-1.23(m,1H),1.20-1.12(m,4H),1.11-1.01(m,1H), 0.75(t,J＝6.9Hz,3H) ; ¹³ C NMR (125MHz, DMSO-d ₆ ) δ167.94,159.26,158.10, 137.97,127.33,126.92,126.31,122.34,120.75,112.90,112.83,112.81,107.29, 63.61,39.52,30.84,22.36,21.81,13.73; HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₁₉ H ₂₃ N ₂ O ₅ 359.1601; Found 359.1600.

Compound 2 (4ab):

4-(4-Fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(4-fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxa mide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (65.6 mg, yield 70%), mp 178-179°C.

¹ H NMR (500MHz, DMSO-d ₆ ) δ 12.58 (s, 1H), 11.71 (s, 1H), 8.33 (s, 1H), 7.54 (d, J = 8.4Hz, 1H), 7.38 (d, J＝1.1Hz,1H),7.34-7.26(m,1H),6.90(dd,J＝10.4,7.8Hz, 1H),3.77(s,3H),2.20(ddd,J＝14.1,11.6,4.5Hz ,1H),2.04(ddd,J=14.0,11.5,4.8 Hz, 1H), 1.33-1.24 (m, 1H), 1.22-1.15 (m, 4H), 1.13-1.04 (m, 1H), 0.76 (t, J = 6.9Hz, 3H); ¹³ C NMR (125MHz, DMSO-d ₆ ) δ 167.56, 158.88, 157.20, 155.98 (d, J _CF = 248.7Hz), 139.99 (d, J _CF = 9.6Hz), 127.14, 126.57 (d, J _CF = 7.6Hz), 116.88 (d, J _CF =22.4Hz),114.52,109.61(d,J _CF =3.5Hz),107.24,107.06,104.72(d,J _CF =17.8 Hz),63.57,39.11,30.76,22.32,21.77,13.68; HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₁₉ H ₂₂ FN ₂ O ₅ 377.1507; Found 377.1506.

Compound 3 (4ac):

4-(4-Chloro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(4-chloro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amid

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (64.8 mg, yield 66%), mp 162-163°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.57 (s, 1H), 11.75 (s, 1H), 8.40 (s, 1H), 7.69 (d, J = 8.3Hz, 1H), 7.35 (s, 1H),7.32-7.27(m,1H),7.20(d,J＝7.5Hz,1H),3.77(s,3H), 2.24-2.14(m,1H),2.07-1.97(m,1H),1.32 -1.25(m,1H),1.20-1.14(m,4H), 1.12-1.03(m,1H),0.75(t,J＝6.8Hz,3H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ167 .54, H RMS(ESI)m/z:[M+H] ⁺ Calcd for C ₁₉ H ₂₂ ClN ₂ O ₅ 393.1212; Found 393.1209.

Compound 4 (4ad):

4-(4-Bromo-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(4-bromo-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (43.5 mg, yield 40%), mp 146-147°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.56 (s, 1H), 11.75 (s, 1H), 8.40 (s, 1H), 7.73 (d, J = 8.3Hz, 1H), 7.36 (d, J＝7.5Hz,1H),7.28(s,1H),7.26-7.22(m,1H),3.78(s,3H), 2.24-2.15(m,1H),2.04-1.98(m,1H),1.31 -1.25(m,1H),1.20-1.13(m,4H), 1.12-1.04(m,1H),0.76(t,J＝6.6Hz,3H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ167 .49, H RMS(ESI)m/z:[M+H] ⁺ Calcd for C ₁₉ H ₂₂ BrN ₂ O ₅ 437.0707; Found 437.0704.

Compound 5 (4ae):

4-(5-Fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(5-fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxa mide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (64.2 mg, yield 68%), mp 181-182°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.46 (s, 1H), 11.70 (s, 1H), 8.32 (s, 1H), 7.72 (dd, J＝9.0, 4.5Hz, 1H), 7.51 ( dd,J＝9.4,2.1Hz,1H),7.40(s,1H),7.23-7.15(m,1H), 3.77(s,3H),2.24-2.15(m,1H),2.08-1.99(m, 1H), 1.30-1.24 (m, 1H), 1.21-1.14 (m, 4H), 1.11-1.02 (m, 1H), 0.76 (t, J = 6.6Hz, 3H); ¹³ C NMR (150MHz, DMSO- d ₆ )δ 167.76,159.05,157.62,157.41(d,J _CF =234.9Hz),134.80,128.36,127.32(d,J _CF = 10.8Hz),115.20(d,J _CF =27.1Hz),114.54(d,J _CF = 9.2Hz), 113.87, 112.24 (d, J _CF = 5.7Hz), 107.30, 105.99 (d, J _CF = 23.3Hz), 63.63, 39.30, 30.86, 22.37, 21.84, 13.75; HRMS (ESI) m/z: [M+H] ⁺ Calcd forC ₁₉ H ₂₂ FN ₂ O ₅ 377.1507; Found 377.1505.

Compound 6 (4af):

4-(5-Chloro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(5-chloro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (69.3 mg, yield 71%), mp 141-142°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.49 (s, 1H), 11.71 (s, 1H), 8.33 (s, 1H), 7.82 (s, 1H), 7.73 (d, J＝8.8Hz, 1H),7.40(s,1H),7.30(dd,J＝8.8,1.4Hz,1H),3.77(s,3H), 2.23-2.13(m,1H),2.07-1.96(m,1H),1.30 -1.25(m,1H),1.19-1.13(m,4H), 1.10-1.03(m,1H),0.75(t,J＝6.3Hz,3H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ167 .66, H RMS(ESI)m/z:[M+H] ⁺ Calcd for C ₁₉ H ₂₂ ClN ₂ O ₅ 393.1212; Found 393.1207.

Compound 7 (4ag):

4-(5-Bromo-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(5-bromo-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (71.6 mg, yield 66%), mp 145-146°C.

¹ H NMR (500MHz, DMSO-d ₆ ) δ12.48 (s, 1H), 11.69 (s, 1H), 8.31 (s, 1H), 7.97 (d, J = 1.7Hz, 1H), 7.68 (d, J＝8.8Hz,1H),7.44-7.36(m,2H),3.77(s,3H),2.24-2.13(m,1H),2.07-1.97(m,1H),1.33-1.24(m,1H) ,1.21-1.13(m,4H),1.11-1.02(m,1H), 0.76(t,J＝6.8Hz,3H); ¹³ C NMR(125MHz,DMSO-d ₆ )δ167.63,158.90,157.38, 136.46,128.91,128.46,127.92,124.26,115.10,114.36,113.15,111.51,107.26,63.59, 39.16,30.80,22.30,21.7 8,13.71; HRMS(ESI)m/z:[M+ H] ⁺ Calcd for C ₁₉ H ₂₂ BrN ₂ O ₅ 437.0707; Found 437.0709.

Compound eight (4ah):

5-Hydroxy-4-(5-iodo-1H-indol-2-yl)-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-4-(5-iodo-1H-indol-2-yl)-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxa mide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (79.5 mg, yield 66%), mp 135-136°C.

¹ H NMR (500MHz, DMSO-d ₆ ) δ12.45 (s, 1H), 11.67 (s, 1H), 8.28 (s, 1H), 8.14 (s, 1H), 7.57-7.49 (m, 2H), 7.35(d,J＝1.6Hz,1H),3.75(s,3H),2.22-2.10(m,1H), 2.06-1.93(m,1H),1.29-1.21(m,1H),1.19-1.10( m,4H),1.09-1.00(m,1H),0.74(t,J =6.7Hz,3H); ¹³ CNMR(125MHz,DMSO-d ₆ )δ167.66,158.93,157.40,136.76, 133.78,130.61,129.85,127.45,115.36,114.22,111.22,107.26,84.67,63.59,39.18, 30.80,22.30,21.77 ,13.72; HRMS(ESI)m/z:[M+ H] ⁺ Calcd for C ₁₉ H ₂₂ IN ₂ O ₅ 485.0568; Found 485.0567.

Compound 9 (4ai):

4-(6-Fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(6-fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxa mide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (67.1 mg, yield 71%), mp 150-151 °C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.53 (s, 1H), 11.67 (s, 1H), 8.28 (s, 1H), 7.78 (dd, J＝8.7, 5.6Hz, 1H), 7.55 ( d,J＝9.9Hz,1H),7.47(s,1H),7.02-6.96(m,1H),3.77(s,3H),2.24-2.14(m,1H),2.08-1.99(m,1H) ,1.30-1.23(m,1H),1.20-1.13(m,4H), 1.10-1.03(m,1H),0.76(t,J＝6.6Hz,3H); ¹³ C NMR(150MHz,DMSO-d ₆ )δ167.88, 161.48(d,J _CF =241.2Hz),159.20,157.74,138.18(d,J _CF =13.6Hz),127.72(d,J _CF =3.2Hz),124.34,124.13(d,J _CF =10.4Hz),113.20,112.72,110.38(d,J _CF =25.7 Hz),107.23,98.62(d,J _CF =26.4Hz),63.61,39.48,30.83,22.36,21.81,13.73; HRMS(ESI)m /z:[M+H] ⁺ Calcd forC ₁₉ H ₂₂ FN ₂ O ₅ 377.1507; Found 377.1506.

Compound ten (4aj):

4-(6-Chloro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(6-chloro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (72.9 mg, yield 74%), mp 183-184°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.44 (s, 1H), 11.69 (s, 1H), 8.31 (s, 1H), 7.84 (s, 1H), 7.76 (d, J = 8.6Hz, 1H),7.45(s,1H),7.12(dd,J＝8.6,1.6Hz,1H),3.77(s,3H), 2.22-2.15(m,1H),2.06-1.98(m,1H),1.30 -1.24(m,1H),1.20-1.13(m,4H), 1.11-1.04(m,1H),0.76(t,J＝6.6Hz,3H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ167 .71, 158.99,157.47,138.16,130.69,127.78,125.99,123.77,121.36,113.79,112.63, 107.26,63.60,39.26,30.82,22.34,21.80,13.73; HRMS(ESI)m/ z:[M+H] ⁺ Calcd for C ₁₉ H ₂₂ ClN ₂ O ₅ 393.1212; Found 393.1212.

Compound 11 (4ak):

4-(6-Bromo-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(6-bromo-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (81.5 mg, yield 75%), mp 191-192°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.41 (s, 1H), 11.69 (s, 1H), 8.33 (s, 1H), 7.98 (s, 1H), 7.70 (d, J＝8.6Hz, 1H),7.43(s,1H),7.23(d,J＝8.5Hz,1H),3.77(s,3H), 2.22-2.14(m,1H),2.07-1.98(m,1H),1.28-1.24 (m,1H),1.19-1.13(m,4H), 1.10-1.03(m,1H),0.75(t,J=6.4Hz,3H); ¹³ C NMR (150MHz, DMSO-d ₆ ) δ167.76 , H RMS(ESI)m/z:[M+H] ⁺ Calcd for C ₁₉ H ₂₂ BrN ₂ O ₅ 437.0707; Found 437.0706.

Compound twelve (4al):

4-(7-Fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(7-fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxa mide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (61.8 mg, yield 66%), mp 188-189°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.94 (s, 1H), 11.20 (s, 1H), 7.53 (s, 1H), 7.37 (d, J = 7.5Hz, 1H), 6.97-6.85 (m, 2H),5.36(s,1H),3.89(s,3H),2.40-2.29(m,1H), 2.10-2.00(m,1H),1.36-1.28(m,1H),1.23-1.14(m, 4H),1.13-1.05(m,1H),0.79(t,J =6.6Hz,3H); ¹³ CNMR(150MHz, CDCl ₃ )δ169.64,160.62,160.12,149.59(d,J _CF =248.8Hz),130.98(d,J _CF =4.4Hz),128.12(d,J _CF =14.1Hz),127.40,121.37(d,J _CF =5.4Hz),118.42(d,J _CF =4.0Hz ),115.67,111.45(d,J _CF =15.6Hz),110.05, 108.04,64.85,41.00,31.46,22.77,22.44,13.99; HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₁₉ H ₂₂ FN ₂ O ₅ 377.1507; Found 377.1507.

Compound 13 (4am):

5-Hydroxy-N-methoxy-4-(4-methyl-1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-4-(4-methyl-1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (72.1 mg, yield 77%), mp 184-185°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.82 (s, 1H), 11.12 (s, 1H), 7.48 (s, 1H), 7.24-7.16 (m, 2H), 6.84 (d, J = 6.0Hz, 1H),5.22(s,1H),3.86(s,3H),2.51(s,3H),2.37-2.28(m, 1H),2.10-2.03(m,1H),1.34-1.27(m,1H) ,1.22-1.14(m,4H),1.12-1.05(m,1H), 0.79(t,J＝6.8Hz,3H); ¹³ C NMR (150MHz, CDCl ₃ )δ169.87,161.06,159.95, 139.22,132.74,128.49,128.35,126.40,121.22,114.47,110.38,108.51,107.87, 64.76,41.37,31.48,22.82,22.4 6,18.89,14.00; HRMS(ESI)m/z:[ M+H] ⁺ Calcd for C ₂₀ H ₂₅ N ₂ O ₅ 373.1758; Found373.1757.

Compound 14 (4an):

5-Hydroxy-N-methoxy-4-(4-methoxy-1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-4-(4-methoxy-1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carb oxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give an orange amorphous solid (87.1 mg, yield 90%), mp 147-148°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.90 (s, 1H), 11.17 (s, 1H), 7.53 (s, 1H), 7.25-7.19 (m, 1H), 6.97 (d, J = 8.3Hz, 1H),6.36(d,J＝7.7Hz,1H),4.94(s,1H),3.92(s,3H),3.88(s,3H),2.34-2.28(m,1H),2.08-2.00(m ,1H),1.33-1.29(m,1H),1.22-1.14(m,4H), 1.13-1.06(m,1H),0.79(t,J=6.8Hz,3H); ¹³ C NMR (150MHz, CDCl ₃ )δ170.04, 160.86,159.65,154.37,140.47,129.15,126.03,120.21,113.29,108.47,107.79, 105.94,99.57,64.78,55.48,41.27,31.49,22.87 ,22.50,14.02; HRMS(ESI)m/z :[M +H] ⁺ Calcd forC ₂₀ H ₂₅ N ₂ O ₆ 389.1707; Found 389.1704.

Compound 15 (4ao):

5-Hydroxy-N-methoxy-4-(5-methyl-1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-4-(5-methyl-1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (65.6 mg, yield 70%), mp 155-156°C.

¹ H NMR (500MHz, DMSO-d ₆ ) δ 12.44 (s, 1H), 11.63 (s, 1H), 8.23 (s, 1H), 7.56 (d, J = 8.5Hz, 1H), 7.50 (s, 1H),7.35(d,J＝0.7Hz,1H),7.17(dd,J＝8.5,1.2Hz,1H), 3.77(s,3H),2.38(s,3H),2.20(ddd,J＝14.0 ,11.7,4.5Hz,1H),2.04(ddd,J=14.0, 11.5,4.8Hz,1H),1.31-1.23(m,1H),1.21-1.13(m,4H),1.11-1.01(m,1H),0.76(t,J =6.9Hz,3H); ¹³ CNMR( 125MHz, DMSO-d ₆ )δ168.02,159.36,158.25,136.57, 129.55,128.50,127.63,126.92,121.25,112.61,112.35,112.17,107.23,63.58,39.59, 30.80,22.32,21.77,21.07,13.70; HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₂₀ H ₂₅ N ₂ O ₅ 373.1758; Found 373.1756.

Compound 16 (4ap):

5-Hydroxy-N-methoxy-4-(5-methoxy-1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-4-(5-methoxy-1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carb oxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow viscous oil (69.6 mg, yield 72%).

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.47 (s, 1H), 11.63 (s, 1H), 8.26 (s, 1H), 7.59 (d, J = 9.0Hz, 1H), 7.35 (s, 1H),7.18(s,1H),6.99(dd,J＝9.0,2.2Hz,1H),3.77(s,3H), 3.77(s,3H),2.24-2.16(m,1H),2.08-2.01 (m,1H),1.28-1.23(m,1H),1.20-1.13(m,4H),1.10-1.02(m,1H),0.76(t,J=6.4Hz,3H); ¹³ C NMR (150MHz ,DMSO-d ₆ )δ 168.08,159.41,158.18,154.25,133.72,127.78,127.17,118.60,113.99,112.35, 111.87,107.23,101.51,63.61,55.25,39.63,30.86,22.3 8,21.83,13.76; HRMS(ESI) m/z: [M+H] ⁺ Calcd forC ₂₀ H ₂₅ N ₂ O ₆ 389.1707; Found 389.1706.

Compound 17 (4aq):

4-(5-Ethoxy-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(5-ethoxy-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give an orange amorphous solid (69.5 mg, yield 69%), mp 151-152°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.83 (s, 1H), 11.16 (s, 1H), 7.34 (s, 1H), 7.23 (d, J＝9.0Hz, 1H), 6.97 (dd, J＝ 9.0,2.3Hz,1H),6.85(d,J＝1.7Hz,1H),5.07(s,1H), 4.01(q,J＝6.9Hz,2H),3.86(s,3H),2.36-2.28( m,1H),2.09-2.00(m,1H),1.44(t,J =6.9Hz,3H),1.36-1.29(m,1H),1.23-1.16(m,4H),1.14-1.08(m, 1H),0.79(t,J＝ 6.9Hz, 3H); ¹³ C NMR (150MHz, CDCl ₃ ) δ169.96,161.05,159.93,154.18,135.20, 128.33,127.14,121.32,114.78,113.85,108.12,107.80,102.24,64. 79,63.95,41.21, 31.51,22.81 ,22.47,15.01,14.02; HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₂₁ H ₂₇ N ₂ O ₆ 403.1864; Found 403.1861.

Compound 18 (4ar):

5-Hydroxy-N-methoxy-4-(6-methyl-1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-4-(6-methyl-1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (70.0 mg, yield 75%), mp 169-170°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.64(s,1H),11.17(s,1H),7.49-7.43(m,2H),7.04(s,1H),6.88(dd,J＝8.3,0.9 Hz,1H),5.28(s,1H),3.85(s,3H),2.41(s,3H),2.35-2.27 (m,1H),2.08-2.01(m,1H),1.32-1.28(m, 1H), 1.21-1.14 (m, 4H), 1.12-1.06 (m, 1H), 0.78 (t, J = 7.0Hz, 3H); ¹³ C NMR (150MHz, CDCl ₃ )δ170.01,161.12,159.91, 139.86,138.74,126.58,126.09,123.87,122.34,116.04,112.26,107.92,107.85, 64.73,41.31,31.49,22.79,22.4 7,22.45,14.01; HRMS(ESI)m/z:[ M+H] ⁺ Calcd for C ₂₀ H ₂₅ N ₂ O ₅ 373.1758; Found373.1754.

Compound 19 (4as):

5-Hydroxy-N-methoxy-4-(6-methoxy-1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-4-(6-methoxy-1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carb oxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (68.5 mg, yield 71%), mp 135-136°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.72 (s, 1H), 11.20 (s, 1H), 7.48-7.40 (m, 2H), 6.70 (dd, J = 8.9, 2.1Hz, 1H), 6.57 ( d,J＝1.5Hz,1H),5.33(s,1H),3.85(s,3H),3.81(s,3H),2.31(ddd,J＝14.1,12.1,4.4Hz,1H),2.03(ddd ,J＝14.0,12.1,4.4Hz,1H), 1.35-1.30(m,1H),1.22-1.15(m,4H),1.14-1.06(m,1H),0.79(t,J＝6.9Hz,3H ); ¹³ C NMR (150MHz, CDCl ₃ ) δ170.13,161.48,160.99,159.22,140.98,126.37,123.69, 123.04,116.71,114.78,107.65,106.41,93.12,64.72,55.53,41 .46,31.52,22.80, 22.46,14.02; HRMS (ESI)m/z:[M+H] ⁺ Calcd for C ₂₀ H ₂₅ N ₂ O ₆ 389.1707; Found 389.1703.

Compound 20 (4at):

5-Hydroxy-N-methoxy-4-(7-methyl-1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-4-(7-methyl-1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (23.4 mg, yield 25%), mp 168-169°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.91(s,1H),11.11(s,1H),7.50(d,J＝1.8Hz,1H), 7.44(d,J＝8.1Hz,1H),7.07 (d,J＝6.9Hz,1H),7.00-6.95(m,1H),5.30(s,1H), 3.86(s,3H),2.50(s,3H),2.39-2.30(m,1H), ¹³ C NMR(150MHz, CDCl _3. 47,16.81,14.03; HRMS(ESI)m/z: [M+H] ⁺ Calcdfor C ₂₀ H ₂₅ N ₂ O ₅ 373.1758; Found 373.1755.

Compound 21 (4au):

5-hydroxy-N-methoxy-4-(7-methoxy-1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carb oxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (65.2 mg, yield 67%), mp 183-184°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.95 (s, 1H), 11.06 (s, 1H), 7.44 (d, J = 1.5Hz, 1H), 7.17 (d, J = 8.2Hz, 1H), 6.99 -6.92(m,1H),6.64(d,J＝7.5Hz,1H),5.06(s,1H), 3.97(s,3H),3.85(s,3H),2.36-2.28(m,1H), ¹³ C NMR(150MHz, CDCl _3. 79,22.45,14.00; HRMS(ESI)m/z: [M+H] ⁺ Calcdfor C ₂₀ H ₂₅ N ₂ O ₆ 389.1707; Found 389.1706.

Compound 22 (4av):

4-(5-(Furan-2-yl)-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(5-(furan-2-yl)-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-ca rboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give an orange amorphous solid (49.0 mg, yield 46%), mp 153-154°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.84 (s, 1H), 11.22 (s, 1H), 7.84 (s, 1H), 7.52 (dd, J = 8.7, 1.4Hz, 1H), 7.48 (s, 1H),7.45(d,J＝1.4Hz,1H),7.26-7.24(m,1H),6.53(d,J＝3.3Hz,1H),6.46(dd,J＝3.2,1.7Hz,1H), 5.05(s,1H),3.89(s,3H),2.39-2.31(m, 1H),2.10-2.03(m,1H),1.40-1.31(m,1H),1.24-1.17(m,4H),1.17-1.10(m,1H), 0.79(t,J＝6.9Hz,3H) ; ¹³ C NMR (150MHz, CDCl ₃ ) δ169.79,160.92,159.90, 154.43,141.83,138.56,128.00,127.49,125.16,124.74,117.13,115.83,113.13, 111.80,107.91,104.35,64.81,41.12,31.48,22.79,22.44,13.99; HRMS(ESI)m/z: [MH] ^- Calcd for C ₂₃ H ₂₃ N ₂ O ₆ 423.1562; Found 423.1564.

Compound 23 (4aw):

5-Hydroxy-N-methoxy-2-carbonyl-5-pentyl-4-(5-(thiophen-2-yl)-1H-indol-2-yl)-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-2-oxo-5-pentyl-4-(5-(thiophen-2-yl)-1H-indol-2-yl)-2,5-dihydrofuran-3 -carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give an orange amorphous solid (77.7 mg, yield 71%), mp 134-135°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.85(s,1H),11.23(s,1H),7.79(s,1H),7.53-7.46(m,2H),7.26-7.24(m,1H), 7.24(s,1H),7.20-7.17(m,1H),7.05(dd,J＝5.0,3.6Hz, 1H),5.04(s,1H),3.89(s,3H),2.39-2.32(m, 1H),2.12-2.04(m,1H),1.39-1.32(m,1H),1.24-1.16(m,4H),1.16-1.09(m,1H),0.80(t,J＝7.0Hz,3H) ; ^13C NMR (150 MHz, CDCl ₃ ) δ169.77,160.88,159.94,144.95,138.63,128.21,128.15,127.61, 127.07,124.32,122.77,119.20,115.69,113.21,107.93,64 .83,41.14,31.49,22.81, 22.46,14.01; HRMS(ESI)m/z:[MH] ^- Calcd for C ₂₃ H ₂₃ N ₂ O ₅ S 439.1333; Found 439.1336.

Compound twenty-four (4ax):

4-(5-Cyano-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(5-cyano-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxa mide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 4/1→petroleum/ethyl acetate: 2/1) to give a yellow amorphous solid (63.3 mg, yield 66%), mp 204-205°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.62 (s, 1H), 11.75 (s, 1H), 8.38 (s, 1H), 8.34 (s, 1H), 7.88 (d, J＝8.6Hz, 1H),7.62(dd,J＝8.7,1.3Hz,1H),7.51(s,1H),3.77(s,3H), 2.23-2.13(m,1H),2.05-1.97(m,1H),1.31 -1.27(m,1H),1.19-1.14(m,4H), 1.11-1.04(m,1H),0.76(t,J＝6.2Hz,3H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ167 .36, 158.60,156.70,139.06,128.89,128.42,127.42,126.74,120.04,115.77,114.49, 112.35,107.28,102.88,63.60,38.88,30.81,22.31,21.79, 13.73; HRMS(ESI)m/z: [M+H ] ⁺ Calcd for C ₂₀ H ₂₂ N ₃ O ₅ 384.1554; Found384.1552.

Compound 25 (4ay):

Methyl 2-(2-hydroxy-4-(methoxycarbamoyl)-5-carbonyl-2-pentyl-2,5-dihydrofuran-3-yl)-1H-indole-5-carboxylate

methyl2-(2-hydroxy-4-(methoxycarbamoyl)-5-oxo-2-pentyl-2,5-dihydrofuran-3-yl)-1H-indole -5-carboxylate

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (75.1 mg, yield 72%), mp 141-142°C.

¹ H NMR (600MHz, CDCl ₃ ) δ13.01 (s, 1H), 11.28 (s, 1H), 8.14 (s, 1H), 7.80 (dd, J = 8.8, 1.2Hz, 1H), 7.47 (s, 1H),7.25(d,J＝8.2Hz,1H),5.68(s,1H),3.91(s,3H), 3.88(s,3H),2.35(ddd,J＝14.2,12.0,4.4Hz,1H ),2.04(ddd,J＝14.0,12.1,4.4Hz, 1H),1.41-1.33(m,1H),1.24-1.16(m,4H),1.15-1.08(m,1H),0.79(t,J =6.9Hz, 3H); ¹³ C NMR (150MHz, CDCl ₃ ) δ169.67,168.21,160.53,160.02,140.60,128.28, 127.80,127.01,126.24,122.62,116.49,112.37,110.37,108.08,6 4.85,52.41,40.87, 31.47,22.77, 22.44,13.99; HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₂₁ H ₂₅ N ₂ O ₇ 417.1656; Found 417.1650.

Compound 26 (4az):

5-Hydroxy-N-methoxy-4-(3-methyl-1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-4-(3-methyl-1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 4/1→petroleum/ethyl acetate: 2/1) to give a yellow amorphous solid (15.5 mg, yield 17%), mp 137-138°C.

¹ H NMR (600MHz, CDCl ₃ ) δ10.80 (s, 1H), 10.56 (s, 1H), 7.57 (d, J = 8.1Hz, 1H), 7.30-7.26 (m, 1H), 7.19 (d, J＝8.3Hz,1H),7.13-7.06(m,1H),6.33(s,1H),3.86(s,3H),2.36(s,3H),1.98(ddd,J＝15.7,11.6,4.5Hz ,1H),1.65(ddd,J＝14.0,11.9,4.0 Hz,1H),1.31-1.27(m,1H),1.16-1.02(m,5H),0.74(t,J＝7.1Hz,3H); ^13C NMR (150MHz, CDCl ₃ )δ169.85,161.09,160.57,138.24,128.87,126.95,124.04,123.92, 120.84,120.38,112.14,111.76,107.80,64.92,37.48,31.34,2 2.39,22.36,13.89, 12.36; HRMS(ESI) m/z:[M+H] ⁺ Calcd for C ₂₀ H ₂₅ N ₂ O ₅ 373.1758; Found 373.1761.

Compound 27 (4ba):

4-(3-Benzyl-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

4-(3-benzyl-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 4/1→petroleum/ethyl acetate 2/1) to give a yellow amorphous solid (32.9 mg, yield 29%), mp 115-116 °C.

¹ H NMR (600MHz, CDCl ₃ ) δ10.77 (s, 1H), 10.61 (s, 1H), 7.31 (d, J = 8.2Hz, 1H), 7.25-7.21 (m, 2H), 7.19-7.15 ( m,2H),7.14-7.10(m,1H),7.02-6.94(m,3H),6.17(s, 1H),4.38(d,J＝16.8Hz,1H),4.09(d,J＝16.8Hz ,1H),3.86(s,3H),1.91-1.82(m, 1H),1.55-1.48(m,1H),1.23-1.18(m,1H),1.09-1.03(m,2H),1.01-0.92(m,3H), 0.73(t,J＝7.3Hz,3H) ; ¹³ C NMR (150MHz, CDCl ₃ ) δ169.59,161.28,160.46, 140.44,138.32,128.56,128.45,128.41,126.70,126.15,125.28,124.30,121.70, 120.61,112.84,112.16,107.88,64.96,37.54,32.54,31.37,22.39,22.32,14.00; HRMS(ESI)m/z:[M+H] ⁺ Calcd forC ₂₆ H ₂₉ N ₂ O ₅ 449.2071; Found 449.2 069.

Compound 28 (4bb):

N-ethoxy-5-hydroxy-4-(1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

N-ethoxy-5-hydroxy-4-(1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (72.7 mg, yield 78%), mp 152-153 °C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.89(s,1H),11.07(s,1H),7.60(d,J＝8.1Hz,1H), 7.49(s,1H),7.36(d,J＝ 8.3Hz,1H),7.32-7.28(m,1H),7.11-7.05(m,1H),5.05(s,1H),4.12-3.98(m,2H),2.38-2.29(m,1H),2.11 ¹³ C NMR (150MHz, CDCl ₃ ) δ169.91,160.86,159.93,139.15,127.90,127.87,126.93,122.81,121.38, 115.68,112.94,109.26,107.88,72.84,41.19,31.48 ,22.80,22.45,14.01,13.56; HRMS(ESI )m/z:[M+H] ⁺ Calcdfor C ₂₀ H ₂₅ N ₂ O ₅ 373.1758; Found 373.1759.

Compound 29 (4bc):

5-Hydroxy-4-(1H-indol-2-yl)-N-isopropoxy-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-4-(1H-indol-2-yl)-N-isopropoxy-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxamide The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1 → petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (74.0 mg, yield 77%), mp 134-135°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.93(s,1H),10.98(s,1H),7.59(d,J＝8.1Hz,1H), 7.48(s,1H),7.37(d,J＝ 8.4Hz,1H),7.33-7.27(m,1H),7.11-7.04(m,1H),4.97(s, 1H),4.26-4.18(m,1H),2.33(ddd,J＝16.1,11.8, 4.5Hz,1H),2.05(ddd,J＝13.9, 12.1,4.2Hz,1H),1.35-1.28(m,7H),1.23-1.11(m,5H),0.79(t,J＝6.9Hz,3H ); ¹³ C NMR (150MHz, CDCl ₃ ) δ169.97,160.90,159.76,139.13,127.90,127.77,126.99, 122.79,121.32,115.58,112.97,109.44,107.84,79.06,41.18,3 1.49,22.80,22.46, 20.67,20.62,14.01 ;HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₂₁ H ₂₇ N ₂ O ₅ 387.1914; Found 387.1913.

Compound 30 (4bd):

N-(tert-Butyloxy)-5-hydroxy-4-(1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

N-(tert-butoxy)-5-hydroxy-4-(1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (50.4 mg, yield 50%), mp 139-140°C.

¹ H NMR (600MHz, CDCl ₃ ) δ13.07(s,1H),10.82(s,1H),7.62(d,J＝8.2Hz,1H), 7.49(s,1H),7.42(d,J＝ 8.4Hz,1H),7.35-7.29(m,1H),7.12-7.06(m,1H),4.90(s,1H),2.39-2.30(m,1H),2.11-2.03(m,1H),1.40 -1.31 (m, 10H), 1.23-1.11 (m, 5H), 0.80 (t, J = 6.3Hz, 3H); ¹³ C NMR (150MHz, CDCl ₃ ) δ170.17, 161.12, 159.60, 139.14,127.92,127.67,127.07,122.77,121.27,115.47,113.06,109.69,107.82, 83.55,41.17,31.49,26.36,22.82,22.47,14.01; HRMS(ESI)m/z :[M+H] ⁺ Calcd for C ₂₂ H ₂₉ N ₂ O ₅ 401.2071; Found 401.2069.

Compound 31 (4be):

N-(Benzyloxy)-5-hydroxy-4-(1H-indol-2-yl)-2-carbonyl-5-pentyl-2,5-dihydrofuran-3-carboxamide

N-(benzyloxy)-5-hydroxy-4-(1H-indol-2-yl)-2-oxo-5-pentyl-2,5-dihydrofuran-3-carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (77.8 mg, yield 72%), mp 129-130°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.88 (s, 1H), 11.05 (s, 1H), 7.61 (d, J = 8.1Hz, 1H), 7.50 (s, 1H), 7.46-7.34 (m, 6H),7.34-7.29(m,1H),7.12-7.07(m,1H),5.04-4.92(m, 2H),2.32(ddd,J＝14.1,11.9,4.4Hz,1H),2.05(ddd, J＝13.9,12.0,4.4Hz,1H), 1.35-1.29 (m, 1H), 1.23-1.14 (m, 4H), 1.14-1.07 (m, 1H), 0.80 (t, J = 6.9Hz, 3H); ¹³ C NMR (150MHz, CDCl ₃ ) δ 169. 71,160.78,159.88,139.18,134.53,129.26,129.16, 128.85,127.92,126.92,122.84,121.43,115.69,112.99,109.28,107.84,78.84,41.19, 31.47,22.80,22.47,14.00; HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₂₅ H ₂₇ N ₂ O ₅ 435.1914; Found 435.1911.

Compound 32 (4bf):

5-Ethyl-5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-carbonyl-2,5-dihydrofuran-3-carboxamide

5-ethyl-5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-oxo-2,5-dihydrofuran-3-carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (54.7 mg, yield 69%), mp 175-176°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.48 (s, 1H), 11.69 (s, 1H), 8.30 (s, 1H), 7.74 (d, J = 8.1Hz, 1H), 7.67 (d, J＝8.4Hz,1H),7.44(s,1H),7.35-7.31(m,1H),7.14-7.09(m,1H),3.78(s,3H),2.30-2.20(m,1H),2.14 -2.05(m,1H),0.76(t,J＝7.4Hz,3H); ¹³ C NMR(150MHz,DMSO-d ₆ )δ167.97,159.25,157.80,137.97,127.33,126.87, 126.32,122.31,120.77,113.05,112.90,112.85,107.68,63.61,32.78,7.45; HRMS (ESI)m/z:[M +H] ⁺ Calcd forC ₁₆ H ₁₇ N ₂ O ₅ 317.1132; Found 317.1133.

Compound 33 (4bg):

5-Butyl-5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-carbonyl-2,5-dihydrofuran-3-carboxamide

5-butyl-5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-oxo-2,5-dihydrofuran-3-carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (52.8 mg, yield 61%), mp 166-167°C.

¹ H NMR (600MHz, CDCl ₃ ) δ12.85(s,1H),11.11(s,1H),7.61(d,J＝8.1Hz,1H), 7.51(s,1H),7.36(d,J＝ 8.4Hz,1H),7.32-7.28(m,1H),7.10-7.05(m,1H),5.31(s,1H),3.84(s,3H),2.39-2.28(m,1H),2.12-2.02 (m,1H),1.32-1.21(m,3H),1.13-1.03 (m,1H),0.79(t,J＝7.2Hz,3H); ¹³ C NMR (150MHz, CDCl ₃ )δ169.89,160.87, 160.09,139.16,127.96,127.88,126.88,122.83,121.44,115.79,112.91,109.06, 107.98,64.75,40.97,25.16,22.45,13.8 7; HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₁₈ H ₂₁ N ₂ O ₅ 345.1445; Found 345.1443.

Compound thirty-four (4bh):

5-Benzyl-5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-carbonyl-2,5-dihydrofuran-3-carboxamide

5-benzyl-5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-oxo-2,5-dihydrofuran-3-carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow viscous oil (33.8 mg, yield 36%).

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.62 (s, 1H), 11.44 (s, 1H), 8.53 (s, 1H), 7.81 (d, J = 8.1Hz, 1H), 7.70 (d, J＝8.4Hz,1H),7.67(s,1H),7.39-7.34(m,1H),7.20-7.13(m,4H),6.96-6.90(m,2H),3.68(s,3H),3.54 (d, J＝13.7Hz, 1H), 3.45 (d, J＝13.8Hz, 1H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ167.62,158.94,158.05,137.99,133.77, 130.13,127.96,127.50,127.29,127.05,126.52,122.52,120.85,113.63,112.98, 112.71,106.67, 63.53,45.73; HRMS(ESI)m/z:[M+ H] ⁺ Calcd for C ₂₁ H ₁₉ N ₂ O ₅ 379.1288; Found 379.1290.

Compound thirty-five (4bi):

5-Hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-carbonyl-5-phenyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-oxo-5-phenyl-2,5-dihydrofuran-3-carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (59.8 mg, yield 66%), mp 214-215°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.41 (s, 1H), 11.80 (s, 1H), 9.08 (s, 1H), 7.65-7.60 (m, 3H), 7.58 (d, J = 8.1 Hz,1H),7.43-7.39(m,2H),7.39-7.35(m,1H),7.29-7.25(m,1H),7.05-7.01(m,1H),6.99(s,1H),3.83( s,3H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ 168.28,159.25,157.84,138.75,137.76,129.28,128.62,127.06,126.90,126.35, 125.33,122.18,120.75,113.60,112.99,112.87,105.45,63 .69; HRMS(ESI)m/z:[M +H] ⁺ Calcd forC ₂₀ H ₁₇ N ₂ O ₅ 365.1132; Found 365.1133.

Compound thirty-six (4bj):

4-(4-Fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-carbonyl-5-phenyl-2,5-dihydrofuran-3-carboxamide

4-(4-fluoro-1H-indol-2-yl)-5-hydroxy-N-methoxy-2-oxo-5-phenyl-2,5-dihydrofuran-3-carbox amide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 4/1→petroleum/ethyl acetate: 2/1) to give a yellow amorphous solid (64.6 mg, yield 68%), mp 236-237°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.54 (s, 1H), 11.85 (s, 1H), 9.14 (s, 1H), 7.63 (d, J = 7.7Hz, 2H), 7.50 (d, J＝8.4Hz,1H),7.44-7.36(m,3H),7.27-7.21(m,1H),6.93(s, 1H),6.82(dd,J＝10.3,7.9Hz,1H),3.83(s ,3H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ 167.96,158.89,157.00,155.78(d,J _CF ＝248.7Hz),139.76(d,J＝9.6Hz),138.34, 129.41,128.68,127.14,126.65(d,J _CF ＝7.5Hz),125.35,116.66(d,J _CF ＝22.2Hz), 114.57,109.62 (d,J _CF =3.6Hz),107.79,105.40,104.70(d,J _CF =18.0Hz),63.67; HRMS(ESI)m/z:[M+H] ⁺ Calcdfor C ₂₀ H ₁₆ FN ₂ O ₅ 383.1038; Found 383.1037.

Compound 37 (4bk):

5-Hydroxy-N-methoxy-4-(4-methyl-1H-indol-2-yl)-2-carbonyl-5-phenyl-2,5-dihydrofuran-3-carboxamide

5-hydroxy-N-methoxy-4-(4-methyl-1H-indol-2-yl)-2-oxo-5-phenyl-2,5-dihydrofuran-3-carbo xamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow viscous oil (77.2 mg, yield 82%).

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.40 (s, 1H), 11.79 (s, 1H), 9.09 (s, 1H), 7.63 (d, J = 7.6Hz, 2H), 7.45-7.39 ( m,3H),7.39-7.35(m,1H),7.19-7.14(m,1H),7.00(s,1H), 6.82(d,J＝6.9Hz,1H),3.83(s,3H),2.34 (s,3H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ 168.36,159.31,157.84,138.79,137.66,131.05,129.25,128.56,127.43,126.58, 126.40,125.30,120.51,112.63,111.91,110.45,105.40,63 .65,18.19; HRMS(ESI) m/z:[M+H ] ⁺ Calcd forC ₂₁ H ₁₉ N ₂ O ₅ 379.1288; Found 379.1290.

Compound thirty-eight (4bl):

Methyl 2-(2-hydroxy-4-(methoxycarbamoyl)-5-carbonyl-2-phenyl-2,5-dihydrofuran-3-yl)-1H-indole-5-carboxylate

methyl2-(2-hydroxy-4-(methoxycarbamoyl)-5-oxo-2-phenyl-2,5-dihydrofuran-3-yl)-1H-indol e-5-carboxylate

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 4/1→petroleum/ethyl acetate: 2/1) to give a yellow amorphous solid (53.7 mg, yield 51%), mp 234-235°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.49 (s, 1H), 11.86 (s, 1H), 9.15 (s, 1H), 8.31 (s, 1H), 7.82 (d, J = 8.4Hz, 1H),7.73(d,J＝8.7Hz,1H),7.63(d,J＝7.4Hz,2H), 7.44-7.33(m,3H),7.18(s,1H),3.83(s,3H), 3.82 (s, 3H); ¹³ C NMR (150MHz, DMSO-d ₆ ) δ167.99,166.61,158.84,157.05,139.77,138.29,129.34,128.62,128.39, _Found ^423.1185 _{​ ​ ​} .

Compound 39 (4bm):

5-Hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-carbonyl-5-(p-benzyl)-2,5-dihydrofuran-3-carboxamide

5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-oxo-5-(p-tolyl)-2,5-dihydrofuran-3-carboxamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (66.5 mg, yield 70%), mp 242-243°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.40 (s, 1H), 11.78 (s, 1H), 9.00 (s, 1H), 7.62 (d, J = 8.4Hz, 1H), 7.58 (d, J＝8.1Hz,1H),7.49(d,J＝8.2Hz,2H),7.29-7.25(m,1H), 7.20(d,J＝8.2Hz,2H),7.05-7.01(m,1H), 6.99(s,1H),3.82(s,3H),2.27(s,3H); ¹³ C NMR(150MHz,DMSO-d ₆ )δ168.79,159.75,158.41,139.18,138.18,136.35, 129.59,127.50,127.39,126.76,125.73,122.62,121.18,114.04,113.31,106.03, 64.12,21.16; HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₂₁ H ₁₉ N ₂ O ₅ 379. 1288; Found 379.1286.

Compound 40 (4bn):

5-(4-Chlorophenyl)-5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-carbonyl-2,5-dihydrofuran-3-carboxamide

5-(4-chlorophenyl)-5-hydroxy-4-(1H-indol-2-yl)-N-methoxy-2-oxo-2,5-dihydrofuran-3-carbo xamide

The reaction mixture was directly purified by flash chromatography on silica gel (petroleum/ethyl acetate: 8/1→petroleum/ethyl acetate: 4/1) to give a yellow amorphous solid (59.9 mg, yield 60%), mp 248-249°C.

¹ H NMR (600MHz, DMSO-d ₆ ) δ12.40 (s, 1H), 11.79 (s, 1H), 9.19 (s, 1H), 7.67-7.62 (m, 3H), 7.59 (d, J = 8.1 Hz,1H),7.47(d,J=8.7Hz,2H),7.31-7.25(m,1H), 7.07-7.00(m,1H),6.97(s,1H),3.83(s,3H); ¹³ C NMR (150MHz, DMSO-d ₆ )δ 168.11,159.17,157.34,137.85,137.83,134.05,128.71,127.46,127.11,126.75, 126.45,122.24,120.82,113.59,113.17,112.91,104.89,63.71; HRMS(ESI)m/z:[M +H] ⁺ Calcd forC ₂₀ H ₁₆ ClN ₂ O ₅ 399.0742; Found 399.0745.

Claims (9)

1. A method for preparing a compound having a 5-hydroxyfuran-2(5H)-one skeleton, characterized in that the compound having a 5-hydroxyfuran-2(5H)-one skeleton has a structural formula as shown in Formula <Ⅳ>, and the preparation method comprises the following steps: The indole compound represented by formula <Ⅰ> and the 4-hydroxy-2-ynoate compound represented by formula <Ⅱ> are used as substrates, [Cp*RhCl ₂ ] ₂ is used as a catalyst, sodium acetate is used as an additive, and acetone is used as a solvent, and the reaction is carried out under air atmosphere to obtain the compound represented by formula <Ⅳ>;

Wherein, R ¹ represents a substituent at any position on the benzene ring, which is selected from the following groups: hydrogen, halogen, alkyl, alkoxy, 3-6 membered heterocyclic ring containing one N, O or S atom, cyano, ester group; ^R2 is selected from the following groups: hydrogen, substituted or unsubstituted alkyl; R ³ is selected from the following groups: substituted or unsubstituted alkyl; R ⁴ is selected from the following groups: substituted or unsubstituted alkyl, aryl; R ⁵ is selected from the following groups: alkyl; The substitution refers to that one or more hydrogen atoms on the group are replaced by any group selected from the following group: phenyl. 2. The preparation method according to claim 1, characterized in that the halogen is F, Cl, Br or I. 3. The preparation method according to claim 1 is characterized in that the alkyl group is methyl, ethyl, isopropyl, n-butyl, tert-butyl or n-pentyl; the alkoxy group is methoxy or ethoxy; the substituted alkyl group is benzyl; and the aryl group is phenyl, p-methyl substituted phenyl or p-chloro substituted phenyl. 4. The preparation method according to claim 1, characterized in that the 3-6 membered heterocyclic ring containing one N, O or S atom is the following group:

5. The preparation method according to claim 1, characterized in that the reaction conditions are: reaction temperature is 25°C, and reaction time is 5-24h. 6. The preparation method according to claim 1, characterized in that the molar ratio of compound I to compound II is 1:1.3. 7. The preparation method according to claim 1, characterized in that the amount of the catalyst used is 1% to 10% of the molar amount of compound I. 8. The preparation method according to claim 7, characterized in that the amount of the catalyst is 5% of the molar amount of compound I. 9. The preparation method according to claim 1, characterized in that the molar ratio of the additive to compound I is 1:1.