Polysubstituted pyrrole compounds and methods for their synthesis

Abstract

This invention discloses a polysubstituted pyrrole compound and its synthetic method. The method includes mixing a 1,3-dicarbonyl ketone imine and an alkenyl fluoroborate potassium with a solvent under an inert gas atmosphere, and carrying out an addition reaction in the presence of a rhodium catalyst, a molecular sieve, and a proton source. After the addition reaction is complete, a Lewis acid is added and the solvent is replenished. The reaction is continued at room temperature with stirring to prepare the pyrrole compound. The 1,3-dicarbonyl ketone imine is of formula 1, the alkenyl fluoroborate potassium is of formula 2, and the obtained polysubstituted pyrrole compound is of formula 4: wherein R... 1 -R 4 Each group is independently selected from H, saturated or unsaturated alkyl, aryl or heterocyclic aryl, or ester group, and R 1 -R 4 At least two of the groups are not simultaneously H, and Ar is either substituted or unsubstituted aryl groups. This method has the advantage of being simple to operate.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of pharmaceutical chemistry, and in particular, the present application relates to polysubstituted pyrrole compounds and a method for preparing the same. BACKGROUND

[0002] Pyrroles are one of the most common simple heterocycles, as they are widely present in a large number of natural and non-natural compounds, and have important values in pharmacology and material science. The most famous natural pyrroles are heme derivatives and chlorophyll, and pyrrole structural fragments are also particularly common in marine-derived natural products. Among them, Lamellarins are compounds isolated from marine invertebrates, and have anti-tumor and anti-HIV activities. Most of these alkaloids are usually derived from a unique tetraloop structure containing a pyrrole fragment, and some alkaloids (such as Lamellarins R) are pyrrole derivatives. Sunitinib (Sutent) is a new type of multi-targeted oral drug for treating tumors, which is used for treating gastrointestinal stromal tumors and metastatic renal cell carcinoma that do not respond to standard therapy or cannot tolerate:

[0003]

[0004] In addition, Atorvastatin (HMG-CoA reductase inhibitor) is widely used as a cholesterol-lowering drug, and is the active ingredient of a best-selling drug that has been commercialized, and its structural formula is as follows:

[0005]

[0006] The above important pharmaceutical active compounds and important structures of research pharmaceutical active compounds can be obtained by substitution reaction through pyrrole polysubstitutes with ester group substituents at position 2, therefore, the synthesis and application of polysubstituted pyrrole compounds, especially compounds with ester group substituents at position 2 C, are increasingly valued by people. However, the above polysubstituted pyrrole compounds generally have the disadvantages of complex synthesis method and difficult to obtain raw materials. Therefore, the current polysubstituted pyrrole compounds and the method for preparing the same still need to be improved. SUMMARY

[0007] In order to solve the above problems, the purpose of the present application is to provide a method for preparing polysubstituted pyrrole compounds. The method can simply prepare polysubstituted pyrrole compounds with ester groups at position 2 of the pyrrole ring, and the compounds can be widely used in drug synthesis and related analysis, and in particular, Sunitinib can be simply prepared by adjusting the type of substituent group.

[0008] In one aspect of the present invention, a method for synthesizing a polysubstituted pyrrole compound is provided, characterized in that: under the protection of an inert gas, a 1,3-dicarbonyl ketone imine and an alkenyl fluoroborate potassium are mixed with a solvent, and an addition reaction is carried out under the conditions of a rhodium catalyst, a molecular sieve, and a proton source. After the addition reaction is completed, a Lewis acid is added and the solvent is replenished, and the reaction is continued with stirring at room temperature to prepare the above-mentioned polysubstituted pyrrole compound, wherein the 1,3-dicarbonyl ketone imine is of formula 1, the alkenyl fluoroborate potassium is of formula 2, and the obtained polysubstituted pyrrole compound is of formula 4.

[0009]

[0010] Among them, R 1 -R 4 Each group is independently selected from H, saturated or unsaturated alkyl, aryl or heterocyclic aryl, or ester group, and R 1 -R 4 At least two of them are not simultaneously H.

[0011] In Equation 4, R 2 The carbon atom connected in the OC (=O) structure is at position 2 of the pyrrole ring.

[0012] In one embodiment of this application, Ar is aryl, and R is... 1 It is a C1-C10 alkyl group, R 2 It is methyl, ethyl, allyl, tert-butyl, or benzyl, R 3 It is a C1-C12 alkyl, substituted or unsubstituted aryl, heterocyclic aryl, or ester group, wherein the substituent of the substituted aryl group is selected from at least one of C1-C3 alkyl, C1-C3 alkoxy, and halogen, R 4 It is H, methyl, phenyl, or related to R 3 Forming a ring.

[0013] In one embodiment of this application, R 3 R 4 Together with the two carbon atoms on the pyrrole ring, they form a cycloalkyl group.

[0014] In one embodiment of this application, the organic solvent is selected from one or more of 1,4-dioxane, toluene, N,N-dimethylformamide, dichloromethane, and 1,2-dichloroethane.

[0015] In one embodiment of this application, the rhodium catalyst is selected from one or more of the following: dimeric hydroxy(1,5-cyclooctadiene) rhodium, di(ethylene) rhodium chloride dimer, di(1,5-cyclooctadiene) tetrafluoroborate rhodium, and (1,5-cyclooctadiene) rhodium chloride dimer.

[0016] In an embodiment of the present application, the Lewis acid comprises at least one of zinc bromide, zinc chloride, copper triflate.

[0017] In an embodiment of the present application, the molar ratio of 1,3-dicarbonyl ketimine, potassium enylate, rhodium metal catalyst and Lewis acid in the reactants is (0.6-1.2):(1.5-2.5):(0.01-0.05):(3-8).

[0018] In an embodiment of the present application, the proton source is selected from at least one of water, methanol, ethanol, isopropanol, tert-butanol.

[0019] In an embodiment of the present application, the polysubstituted pyrrole compound comprises at least one selected from the group consisting of:

[0020]

[0021] In an embodiment of the present application, the method further comprises separating the reactants using column chromatography.

[0022] In another aspect of the present application, a polysubstituted pyrrole compound is provided. The polysubstituted pyrrole compound is obtained using the method described above. BRIEF DESCRIPTION OF DRAWINGS

[0023] The above and / or additional aspects and advantages of the present application will become apparent and be readily understood from the following description, taken in conjunction with the accompanying drawings, in which:

[0024] Figure 1 HNMR spectrum of 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylic acid ethyl ester (structure 4a) synthesized for example 1. 1 HNMR spectrum of 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylic acid ethyl ester (structure 4a) synthesized for example 1.

[0025] Figure 2 HNMR spectrum of 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylic acid ethyl ester (structure 4a) synthesized for example 1. 13 HNMR spectrum of 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylic acid ethyl ester (structure 4a) synthesized for example 1.

[0026] Figure 3 HNMR spectrum of 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylic acid ethyl ester (structure 4a) synthesized for example 1. 1 HNMR spectrum of 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylic acid ethyl ester (structure 4a) synthesized for example 1.

[0027] Figure 4 HNMR spectrum of 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylic acid ethyl ester (structure 4a) synthesized for example 1. 13 HNMR spectrum of 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylic acid ethyl ester (structure 4a) synthesized for example 1.

[0028] Figure 5HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 1 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0029] Figure 6 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 13 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0030] Figure 7 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 1 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0031] Figure 8 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 13 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0032] Figure 9 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 1 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0033] Figure 10 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 13 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0034] Figure 11 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 1 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0035] Figure 12 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 13 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0036] Figure 13 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 1 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0037] Figure 14 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3 13 HNMR spectrum of 3-methyl-1,4-diphenyl-1 H-pyrrole-2-carboxylic acid tert-butyl ester (structure 4c) synthesized for example 3

[0038] Figure 15 Ethyl 4-(3-chlorophenyl)-3-methyl-1-phenyl-1H-pyrrole-2-carboxylate (structural formula 4h) synthesized in Example 8 1 HNMR spectrum;

[0039] Figure 16 Ethyl 4-(3-chlorophenyl)-3-methyl-1-phenyl-1H-pyrrole-2-carboxylate (structural formula 4h) synthesized in Example 8 13 C NMR spectrum;

[0040] Figure 17 Ethyl 4-(2-chlorophenyl)-3-methyl-1-phenyl-1H-pyrrole-2-carboxylate (structural formula 4i) synthesized in Example 9 1 H NMR spectrum;

[0041] Figure 18 Ethyl 4-(2-chlorophenyl)-3-methyl-1-phenyl-1H-pyrrole-2-carboxylate (structural formula 4i) synthesized in Example 9 13 C NMR spectrum;

[0042] Figure 19 Ethyl 4-(3,5-difluorophenyl)-3-methyl-1-phenyl-1H-pyrrole-2-carboxylate (structural formula 4j) synthesized in Example 10 1 H NMR spectrum;

[0043] Figure 20 Ethyl 4-(3,5-difluorophenyl)-3-methyl-1-phenyl-1H-pyrrole-2-carboxylate (structural formula 4j) synthesized in Example 10 13 C10 NMR spectrum.

[0044] Figure 21 Ethyl 3-methyl-1-phenyl-4-(thiophen-2-yl)-1H-pyrrole-2-carboxylate (structural formula 4k) synthesized in Example 11 1 HNMR spectrum;

[0045] Figure 22 Ethyl 3-methyl-1-phenyl-4-(thiophen-2-yl)-1H-pyrrole-2-carboxylate (structural formula 4k) synthesized in Example 11 13 C10 NMR spectrum.

[0046] Figure 23 Ethyl 3-methyl-1-phenyl-4,5,6,7-tetrahydro-1H-indole-2-carboxylate (structural formula 4l) synthesized in Example 12 1 HNMR spectrum;

[0047] Figure 24 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12 13 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12

[0048] Figure 25 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12 1 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12

[0049] Figure 26 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12 13 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12

[0050] Figure 27 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12 1 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12

[0051] Figure 28 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12 13 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12

[0052] Figure 29 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12 1 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12

[0053] Figure 30 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12 13 HNMR spectrum of 3-methyl-l-phenyl-4,5,6,7-tetrahydro-lH-indole-2-carboxylic acid ethyl ester (Formula 4I) synthesized for Example 12 DETAILED DESCRIPTION

[0054] In the following, only certain exemplary embodiments are described in brief. As the person skilled in the art can recognize, the described embodiments can be modified in various different ways without departing from the spirit or the scope of the present application, and different embodiments can be combined arbitrarily without conflict. Therefore, the following description is to be considered as being essentially exemplary rather than limiting.

[0055] In one aspect of the present application, a method for synthesizing a polysubstituted pyrrole compound is provided. The method comprises mixing 1,3-dicarbonyl ketimine, enoic potassium fluoroborate and a solvent under the protection of inert gas, and then adding Lewis acid to the mixture after the addition reaction catalyzed by rhodium metal catalyst, in the presence of molecular sieve and proton source. The reaction is continued at room temperature to obtain the polysubstituted pyrrole compound. The 1,3-dicarbonyl ketimine is shown in the following formula 1, and the enoic potassium fluoroborate is shown in the following formula 2:

[0056]

[0057] The polysubstituted pyrrole compound obtained is shown in the following formula 4:

[0058]

[0059] wherein R 1 -R 4 are independently selected from H, saturated or unsaturated alkyl, aryl or heterocyclic aryl, or ester group, and R 1 -R 4 are not simultaneously H.

[0060] The above method uses 1,3-dicarbonyl ketimine and commercially available enoic potassium fluoroborate as raw materials, and the addition reaction is carried out under the condition of rhodium metal catalyst. The polysubstituted pyrrole compound can be obtained by one-pot reaction after adding Lewis acid. The reaction condition is mild, and no special reaction container and environment are required. The method has the advantages of simple operation and simple raw materials. Further, the polysubstituted pyrrole compound prepared by the method can be widely used in drug synthesis and related analysis, and in particular, it can be used to simply prepare sunitinib by adjusting the type of substituent group.

[0061] For example, the reaction in the method can be carried out as follows: using dimeric hydroxyl (1,5-cyclooctadiene) rhodium as catalyst, and heating the reaction under the condition of molecular sieve and methanol as proton source, to obtain the intermediate product shown in the following formula 3. Then, zinc bromide or other Lewis acid is added to the system, and the final product polysubstituted pyrrole compound can be obtained by stirring the reaction at room temperature.

[0062]

[0063] In one embodiment of the present application, Ar in the 1,3-dicarbonyl ketimine can be aryl, for example, specifically phenyl or substituted phenyl. R 1 is C1-C10 alkyl or aryl, for example, can be aryl, or C1-C4 alkyl, R 2 is methyl, ethyl, allyl, tert-butyl or benzyl, R 3It is a C1-C12 alkyl, substituted or unsubstituted aryl, heterocyclic aryl, or ester group, wherein the substituent of the substituted aryl group is selected from at least one of C1-C3 alkyl, C1-C3 alkoxy, and halogen, R 4 It is H, methyl, phenyl, or related to R 3 Formation of a ring. When R 1 -R 4 When the Ar substituent is selected from the above range, the reaction system exhibits high reactivity and selectivity, and the yield of polysubstituted pyrrole compounds is also high. Especially R... 2 When the above-mentioned groups are used, 1,3-dicarbonyl ketone imines can be composed of more readily available compounds, which is beneficial for further reducing production costs.

[0064] In the embodiments of this application, stirring reaction at room temperature and continued stirring reaction at room temperature refer to the reaction being carried out without additional cooling or heating of the reaction system. Room temperature is the ambient temperature of the reaction system, and the specific temperature range of room temperature is not particularly limited, for example, it can be 10℃-30℃.

[0065] In one embodiment of this application, R 3 R 4 Together with the two carbon atoms on the pyrrole ring, they form a cycloalkyl group.

[0066] In one embodiment of this application, the organic solvent is not particularly limited, and may be selected from one or more of 1,4-dioxane, toluene, N,N-dimethylformamide, dichloromethane, and 1,2-dichloroethane, specifically, dichloromethane.

[0067] In one embodiment of this application, the rhodium catalyst is selected from one or more of the following: dimeric hydroxy(1,5-cyclooctadiene)rhodium, di(ethylene)chlororhodium dimer, di(1,5-cyclooctadiene)tetrafluoroborate rhodium, and (1,5-cyclooctadiene)chlororhodium dimer; and the Lewis acid includes at least one of zinc bromide, zinc chloride, and copper trifluoromethanesulfonate. Selecting the above catalyst and Lewis acid can further improve the conversion rate of the reaction.

[0068] In one embodiment of this application, the molar ratio of 1,3-dicarbonyl ketone imine, potassium alkenyl fluoroborate, rhodium catalyst, and Lewis acid in the reactants is (0.6-1.2):(1.5-2.5):(0.01-0.05):(3-8). Specifically, the molar ratio of 1,3-dicarbonyl ketone imine, potassium alkenyl fluoroborate, rhodium catalyst, and Lewis acid can be (0.9-1):(1.8-2.2):(0.02-0.03):(4-6), and in some preferred examples, it can be 1:2:0.025:5.

[0069] In one embodiment of this application, the proton source is selected from at least one of water, methanol, ethanol, isopropanol, and tert-butanol.

[0070] In one embodiment of this application, the polysubstituted pyrrole compound comprises at least one selected from the following:

[0071]

[0072]

[0073] In one embodiment of this application, the method further includes separating and purifying the product. For example, column chromatography can be used to separate the reactants.

[0074] In another aspect of this application, a polysubstituted pyrrole compound is proposed. This polysubstituted pyrrole compound is obtained using the method described above.

[0075] The embodiments of the present invention are described in detail below. These embodiments are exemplary and are only used to explain the present invention, and should not be construed as limiting the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the art or according to the product instructions. Reagents or instruments used, unless otherwise specified, are all commercially available conventional products.

[0076] Example 1: Synthesis of ethyl 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylate (structural formula 4a):

[0077]

[0078] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (88 mg, 0.4 mmol), potassium alkenyl fluoroborate (168 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane (DCM) were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (99.1 mg, 81% yield).

[0079] refer toFigure 1 as well as Figure 2 The results of the product structure confirmation are as follows: 1 H NMR (400MHz, Chloroform-d) δ7.41(q,J=6.6,5.0Hz,7H),7.31(t,J=5.4Hz,3H),6.96(s,1H),4.14(q,J=7.1Hz,2H),2.48(s,3H),1.10(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ161.45,141.38,134.80,128.62,128.57,128.47,128.00,127.4 6,126.73,126.42,126.39,126.09,121.69,59.77,14.03,12.11.HRMS(ESI)m / z.calcd for[M+Na]+C20H19NO2Na:328.1313; found:328.1313.

[0080] Example 2: Methyl 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylate (Structural Formula 4b):

[0081]

[0082] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (82 mg, 0.4 mmol), potassium alkenyl fluoroborate (168 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (97.5 mg, 84% yield).

[0083] refer to Figure 3 as well as Figure 4 The structural confirmation results are as follows: 1H NMR (400MHz, Chloroform-d) δ7.52–7.37(m,7H),7.34(d,J=7.2Hz,3H),6.99(s,1H),3.72(s,3H),2.51(s,3H). 13 C NMR (101MHz, CDCl3) δ161.96,141.24,134.77,128.67,128.65,128.51,128.07,12 7.54,127.05,126.51,126.46,126.02,121.46,50.92,12.22.HRMS(ESI)m / z.calcd for[M+Na]+C19H17NO2Na:314.1157; found:314.1157.

[0084] Example 3: tert-butyl 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylate (structural formula 4c):

[0085]

[0086] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (98.8 mg, 0.4 mmol), potassium alkenyl fluoroborate (168 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (104.1 mg, 79% yield).

[0087] refer to Figure 5 as well as Figure 6 The structural confirmation results are as follows: 1 H NMR (400MHz, Chloroform-d) δ7.50–7.36(m,7H),7.36–7.28(m,3H),6.93(s,1H),2.50(s,3H),1.32(s,9H). 13C NMR (101MHz, CDCl3) δ160.68,141.75,134.95,128.65,128.60,128.47,127.59,127.2 9,126.42,126.33,126.01,125.92,122.99,80.52,28.05,11.99.HRMS(ESI)m / z.calcd for[M+Na]+C22H23NO2Na:356.1626; found:356.1626.

[0088] Example 4: Allyl 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylic acid (structural formula 4d):

[0089]

[0090] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (92.4 mg, 0.4 mmol), potassium alkenyl fluoroborate (168 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (72.1 mg, 57% yield).

[0091] refer to Figure 7 as well as Figure 8 The structural confirmation results are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.48–7.35(m,7H),7.31(t,J=5.8Hz,3H),6.98(s,1H),5.7 8(ddt,J=16.3,10.8,5.6Hz,1H),5.21–5.07(m,2H),4.61(d,J=5.4Hz,2H),2.50(s,3H). 13C NMR (101MHz, CDCl3) δ161.08,141.29,134.73,132.27,129.42,128.64,128.47,128.35,12 7.52,127.08,126.53,126.43,126.06,117.69,114.24,64.58,12.22.HRMS(ESI)m / z.calcd for[M+Na]+C21H19NO2Na:340.1313; found:340.1313.

[0092] Example 5: Benzyl 3-methyl-1,4-diphenyl-1H-pyrrole-2-carboxylate (structural formula 4e):

[0093]

[0094] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (112.4 mg, 0.4 mmol), potassium alkenyl fluoroborate (168 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (119.2 mg, 81% yield).

[0095] refer to Figure 9 as well as Figure 10 The structural confirmation results are as follows: 1 H NMR (400MHz, Chloroform-d) δ7.48–7.36(m,7H),7.35–7.26(m,5H),7.22–7.12(m,2H),6.99(s,1H),5.19(s,2H),2.54(s,3H). 13CNMR (101MHz, CDCl3) δ161.21,141.32,136.03,134.72,128.72,128.67,128.64,128.52,128.38,12 8.13,127.94,127.55,127.17,126.59,126.49,126.09,121.39,65.75,12.32.HRMS(ESI)m / z.calcd for[M+Na]+C25H21NO2Na:390.1470; found:390.1470.

[0096] Example 6: Ethyl 3-methyl-4-phenyl-1-(p-tolyl)-1H-pyrrole-2-carboxylate (Structural Formula 4f)

[0097]

[0098] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (118.1 mg, 0.4 mmol), potassium alkenyl fluoroborate (168 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ (1f) were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (108.6 mg, 85% yield).

[0099] refer to Figure 11 as well as Figure 12 The structural confirmation results are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.48–7.37(m,4H),7.31(dt,J=5.9,3.0Hz,1H),7.27–7.17(m ,4H),6.97(s,1H),4.20(q,J=7.1Hz,2H),2.52(s,3H),2.44(s,3H),1.18(t,J=7.1Hz,3H). 13C NMR (101MHz, CDCl3) δ161.53,138.88,137.33,134.92,129.19,128.67,128.49,127.67,1 26.89,126.37,126.27,125.92,121.71,59.78,21.17,14.17,12.22.HRMS(ESI)m / z.calcd for[M+Na]+C21H21NO2Na:342.1470; found:342.1470.

[0100] Example 7: Ethyl 3-methyl-1-phenyl-4-(p-tolyl)-1H-pyrrole-2-carboxylate (structural formula 4g)

[0101]

[0102] Under argon protection, the following substances were added sequentially to the reactor: [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (87.6 mg, 0.4 mmol), potassium alkenyl fluoroborate (179.2 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), structural formula 1a, and potassium alkenyl fluoroborate (2 g), respectively. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (104.6 mg, 82% yield).

[0103] refer to Figure 13 as well as Figure 14 The structural confirmation results are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.41(dt,J=13.6,6.7Hz,3H),7.32(d,J=7.7Hz,4H),7.23(d,J=7 .8Hz,2H),6.95(s,1H),4.15(q,J=7.1Hz,2H),2.49(s,3H),2.40(s,3H),1.12(t,J=7.1Hz,3H). 13C NMR (101MHz, CDCl3) δ161.49,141.44,136.06,131.82,129.21,128.57,128.53,128.05,1 27.42,126.66,126.37,126.11,121.59,59.75,21.18,14.05,12.14.HRMS(ESI)m / z.calcd for[M+Na]+C21H21NO2Na:342.1470; found:342.1470.

[0104] Example 8: Ethyl 4-(3-chlorophenyl)-3-methyl-1-phenyl-1H-pyrrole-2-carboxylate (structural formula 4h)

[0105]

[0106] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (87.6 mg, 0.4 mmol), potassium alkenyl fluoroborate (195.6 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (111.5 mg, 82% yield).

[0107] refer to Figure 15 as well as Figure 16 The structural confirmation results are as follows: 1 H NMR (400MHz, Chloroform-d) δ7.50–7.36(m,4H),7.36–7.21(m,5H),6.96(s,1H),4.16(q,J=7.1Hz,2H),2.49(s,3H),1.11(t,J=7.1Hz,3H). 13C NMR (101MHz, CDCl3) δ161.33,141.22,136.71,134.30,129.71,128.64,128.51,127.81,127.6 3,126.76,126.69,126.43,126.08,125.10,121.96,59.87,14.04,12.08.HRMS(ESI)m / z.calcd for[M+Na]+C20H18ClNO2Na:362.0924; found:362.0924.

[0108] Example 9: Ethyl 4-(2-chlorophenyl)-3-methyl-1-phenyl-1H-pyrrole-2-carboxylate (Structural Formula 4i)

[0109]

[0110] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (87.6 mg, 0.4 mmol), potassium alkenyl fluoroborate (195.6 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (108.7 mg, 80% yield).

[0111] refer to Figure 17 as well as Figure 18 The structural confirmation results are as follows: 1 H NMR (400MHz, Chloroform-d) δ7.57–7.23(m,9H),6.96(s,1H),4.17(q,J=7.1Hz,2H),2.33(s,3H),1.14(t,J=7.1Hz,3H). 13CNMR (101MHz, CDCl3) δ161.41,141.26,134.28,133.55,132.43,129.72,129.49,128.55,128.3 9,127.82,127.50,126.49,126.18,123.47,120.94,59.77,14.10,12.26.HRMS(ESI)m / z.calcd for[M+Na]+C20H18ClNO2Na:362.0924; found:362.0924.

[0112] Example 10: Ethyl 4-(3,5-difluorophenyl)-3-methyl-1-phenyl-1H-pyrrole-2-carboxylate (Structural Formula 4j)

[0113]

[0114] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (87.6 mg, 0.4 mmol), potassium alkenyl fluoroborate (196.8 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (103.8 mg, 76% yield).

[0115] refer to Figure 19 as well as Figure 20 The structural confirmation results are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.50–7.35(m,3H),7.30(d,J=6.8Hz,2H),6.97(s,1H),6.93(d,J =6.3Hz,2H),6.73(t,J=9.0Hz,1H),4.14(q,J=7.1Hz,2H),2.49(s,3H),1.10(t,J=7.1Hz,3H). 13C NMR (101MHz, CDCl3) δ163.07 (dd, J = 247.4, 13.4Hz), 161.21, 141.07, 138.15 (t, J = 10.3Hz), 128.66, 127.75, 127. 55,126.72,126.05,124.39(t,J=2.6Hz),122.22,112.05–109.10(m),101.62(t,J=25.4Hz),59.94,13.98,12.01. 19 F NMR(376MHz, CDCl3)δ-110.33.HRMS(ESI)m / z.calcd for[M+Na]+C20H17F2NO2Na:364.1125; found:364.1125.

[0116] Example 11: Ethyl 3-methyl-1-phenyl-4-(thiophen-2-yl)-1H-pyrrole-2-carboxylate (structural formula 4k)

[0117]

[0118] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (87.6 mg, 0.4 mmol), potassium alkenyl fluoroborate (172.9 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (94.7 mg, 76% yield).

[0119] refer to Figure 21 as well as Figure 22 The structural confirmation results are as follows: 1H NMR(400MHz,Chloroform-d)δ7.40(dd,J=10.8,7.2Hz,3H),7.29(d,J=6.8Hz,2H),7.24(d,J=5.1Hz ,1H),7.08(t,J=5.0Hz,2H),7.03(s,1H),4.13(q,J=7.1Hz,2H),2.55(s,3H),1.09(t,J=7.1Hz,3H). 13 CNMR (101MHz, CDCl3) δ161.27,141.17,136.55,128.60,127.98,127.62,127.45,126.7 4,126.11,124.34,123.68,121.92,119.37,59.84,13.98,12.08.HRMS(ESI)m / z.calcd for[M+Na]+C18H17NO2SNa:334.0878; found:334.0878.

[0120] Example 12: Ethyl 3-methyl-1-phenyl-4,5,6,7-tetrahydro-1H-indole-2-carboxylate (Structural Formula 4l)

[0121]

[0122] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (87.6 mg, 0.4 mmol), potassium alkenyl fluoroborate (150.4 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (71.4 mg, 63% yield).

[0123] refer to Figure 23 as well as Figure 24 The structural confirmation results are as follows: 1H NMR(400MHz,Chloroform-d)δ7.37(dd,J=12.2,7.3Hz,3H),7.17(d,J=6.8Hz,2H),4.05(q,J=7.1Hz,2H) ,2.47(t,J=5.8Hz,2H),2.31(s,3H),2.24(t,J=5.8Hz,2H),1.75(q,J=7.8Hz,4H),1.04(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ161.55,140.10,136.04,128.45,127.93,127.64,127.35,119.76,118.94,59.06,23.26, 23.03,22.93,21.21,14.05,10.97.HRMS(ESI)m / z.calcdfor[M+Na]+C18H21NO2Na:306.1470; found:306.1470.

[0124] Example 13: Ethyl 3,5-dimethyl-1-phenyl-1H-pyrrole-2-carboxylate (structural formula 4m)

[0125]

[0126] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (87.6 mg, 0.4 mmol), potassium alkenyl fluoroborate (118.4 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (49.6 mg, 51% yield).

[0127] refer to Figure 25 as well as Figure 26 The structural confirmation results are as follows: 1H NMR (400MHz, Chloroform-d) δ7.41 (q, J=7.9, 7.2Hz, 3H), 7.17 (d, J=6.2Hz, 2H), 5. 92(s,1H),4.04(q,J=7.1Hz,2H),2.38(s,3H),1.97(s,3H),1.05(t,J=7.1Hz,3H). 13 C NMR(101MHz, CDCl3)δ161.29,140.32,136.04,130.26,128.58,127.87,127.73,120.70,111.11,59.13,14.03,13.80,12.83.HRMS(ESI)m / z.calcd for[M+Na]+C15H17NO2Na:266.1157; found:266.1157.

[0128] Example 14: Diethyl 3,5-dimethyl-1-phenyl-1H-pyrrole-2,4-dicarboxylate (structural formula 4n)

[0129]

[0130] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (87.6 mg, 0.4 mmol), potassium alkenyl fluoroborate (176 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (68.1 mg, 54% yield).

[0131] refer to Figure 27 as well as Figure 28 The structural confirmation results are as follows: 1H NMR(400MHz,Chloroform-d)δ7.44(dd,J=5.3,1.8Hz,3H),7.21–6.94(m,2H),4.32(q,J=7.1Hz,2 H), 4.02 (q, J = 7.1Hz, 2H), 2.62 (s, 3H), 2.23 (s, 3H), 1.37 (t, J = 7.1Hz, 3H), 0.99 (t, J = 7.1Hz, 3H). 13 C NMR (101MHz, CDCl3) δ165.62,161.11,141.69,139.43,131.58,128.83,128.33,1 27.77,121.78,113.34,59.67,14.46,13.82,12.98,12.39.HRMS(ESI)m / z.calcd for[M+Na]+C18H21NO4Na:338.1368; found:338.1368.

[0132] Example 15: Ethyl 1-(2-methoxyphenyl)-3-neopentyl-4,5,6,7-tetrahydro-1H-indole-2-carboxylate (Structural Formula 4o)

[0133]

[0134] Under argon protection, [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), 1,3-dicarbonyl ketone imine (122.1 mg, 0.4 mmol), potassium alkenyl fluoroborate (150.4 mg, 0.8 mmol), and 200 mg of [Rh(COD)OH]₂ (4.6 mg, 0.01 mmol), structural formula 1O, were added sequentially to the reactor. Molecular sieve (MS) was used, and 3 equivalents of methanol and 2 mL of 1,4-dioxane were added. The bottle was sealed with the cap, and the heating plate temperature was adjusted to 80°C. After 2 hours, heating was stopped, and the mixture was cooled to room temperature. Zinc bromide (450 mg, 2 mmol) and 2 mL of dichloromethane were added, and the reaction was continued with stirring at room temperature for 12 hours. 10 mL of water was added, followed by extraction three times with EA (10 mL). The extracted organic phase was dried, concentrated, and subjected to column chromatography under the following conditions: the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate at a ratio of 10:1, yielding a colorless oil (79.8 mg, 54% yield).

[0135] refer to Figure 29 as well as Figure 30 The structural confirmation results are as follows: 1H NMR(400MHz,Chloroform-d)δ7.33(t,J=7.8Hz,1H),7.13(d,J=6.2Hz,1H),6.98(t,J=7.1Hz,2H),4.00(q,J=6.4,5.8Hz ,2H),3.74(s,3H),2.93–2.63(m,2H),2.49(s,2H),2.37–2.11(m,2H),1.73(m,4H),1.03(t,J=7.1Hz,3H),0.97(s,9H). 13 C NMR (101MHz, CDCl3) δ161.77,155.36,135.35,129.56,129.34,129.08,128.70,121.09,120.29,119.5 5,111.86,58.81,55.82,37.92,33.80,29.95,23.73,23.02,22.83,22.61,13.96.HRMS(ESI)m / z.calcd for[M+Na]+C23H31NO3Na:392.2202; found:392.2202.

[0136] The foregoing application provides many different implementations or examples for carrying out different structures of this application. To simplify this application, the components and arrangements of specific examples are described above. Of course, these are merely examples and are not intended to limit this application. Furthermore, reference numerals and / or reference letters may be repeated in different examples; such repetition is for simplification and clarity and does not in itself indicate a relationship between the various implementations and / or arrangements discussed.

[0137] The above are merely specific embodiments of this application, but the scope of protection of this application is not limited thereto. Any person skilled in the art can easily conceive of various variations or substitutions within the technical scope disclosed in this application, and these should all be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.

Claims

1. A method of synthesizing a polysubstituted pyrrole compound, characterized by: under the protection of inert gas, 1,3-dicarbonyl ketimine and alkenyl potassium fluoroborate and solvent are mixed, and addition reaction is carried out under the catalysis of metal rhodium catalyst, the presence of molecular sieve and proton source, after the addition reaction is completed, a Lewis acid is added and the solvent is supplemented, and the reaction is continuously stirred at room temperature to obtain the polysubstituted pyrrole compound, The polysubstituted pyrrole compound obtained includes at least one of the following: 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4g, 4h, 4i, 4j, 4k, 4l, 4m, 4n, 4o, The metal rhodium catalyst is selected from one or more of dimeric hydroxy(1,5-cyclooctadiene)rhodium, bis(ethylene)chloro rhodium dimer, bis(1,5-cyclooctadiene)rhodium tetrafluoroborate, and (1,5-cyclooctadiene)chloro rhodium dimer. The proton source is selected from at least one of water, methanol, ethanol, isopropanol, and tert-butanol.

2. The method of claim 1, wherein, The organic solvent is selected from one or more of 1,4-dioxane, toluene, N,N-dimethylformamide, dichloromethane, and 1,2-dichloroethane.

3. The method of claim 1, wherein, The metal rhodium catalyst is selected from one or more of dimeric hydroxy(1,5-cyclooctadiene)rhodium, bis(ethylene)chloro rhodium dimer, bis(1,5-cyclooctadiene)rhodium tetrafluoroborate, and (1,5-cyclooctadiene)chloro rhodium dimer. And / or, the Lewis acid includes at least one of zinc bromide, zinc chloride, and copper triflate.

4. The method of claim 1, wherein, Further comprising: The reactants are separated and treated by column chromatography.

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