Method for controllably divergently synthesizing functionalized pyrrole skeleton compound

Abstract

The invention provides a method for controllable divergent synthesis of a functionalized pyrrole skeleton compound, and belongs to the technical field of chemical synthesis. The synthesis method comprises the following steps. The synthesis method disclosed by the invention is simple and economic in initial raw materials, adopts a one-pot method, and is simple and mild in conditions. Through continuous research and screening, enamine and alkyne aldehyde can form an intermediate azafulvene quaternary ammonium salt with high reaction activity in situ under the specific catalyst and ligand, the intermediate can be compatible with various nucleophilic reagents, intermolecular and intramolecular nucleophilic reactions can be achieved with the various nucleophilic reagents, and the reaction efficiency is improved. Therefore, various pyrrole skeleton compounds functionalized or polycyclic fused at specific sites are efficiently constructed, and the pyrrole skeleton compounds have excellent chemical selectivity. The pyrrole skeleton compound obtained by the synthesis method is high in purity and good in yield. The synthesis of the pyrrole skeleton compound can be effectively promoted, and the method has a good application prospect. # imgabs0 # or # imgabs1 #

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically relating to a method for the controlled divergent synthesis of functionalized pyrrole skeleton compounds. Background Technology

[0002] The pyrrole skeleton plays a crucial role in nitrogen-rich heterocyclic compounds, exerting significant influence in various fields such as pharmaceutical and natural product synthesis. For example, UBCS039 is a specific activator of SIRT6, PPQ-102 is a potent CFTR inhibitor, Tolmetin is a potent COX inhibitor, and Prodigiosin is a potent inhibitor of the Wnt / β-catenin pathway. The synthesis of compounds containing the pyrrole skeleton has been a focus of attention for many years, and various synthetic methods have been developed. However, these methods typically require multi-step reactions, complex procedures, and limited starting materials. For instance, the literature "Visible-Light-Induced Formal[3+2] Cycloaddition for Pyrrole Synthesis under Metal-Free Conditions" illustrates this point.

[0003] (Doi: 10.1002 / anie.201400602) and the literature "Iron-Catalyzed RadicalCycloaddition of 2H-Azirines and Enamides for the Synthesis of Pyrroles"

[0004] The method disclosed in (Doi:10.1021 / acs.orglett.7b04007) utilizes 2H-acarin and unsaturated alkenes / alkynes to synthesize polysubstituted pyrroles. However, the pyrrole skeletons constructed based on this type of substrate remain limited. For example, the method disclosed in the literature "Pd-Catalyzed Oxidative Coupling of Enamides and Alkynes for Synthesis of Substituted Pyrroles" (Doi:10.1021 / ol403517p) utilizes palladium(II)-catalyzed CH-activated oxidative cyclization of alkenes and alkynes to synthesize substituted pyrroles, but it faces limitations such as complex operation steps and high temperatures. Furthermore, existing synthetic techniques typically employ conventional parallel synthetic routes, which can only produce one type of pyrrole skeleton, as in the literature "Pd-Catalyzed [3+2]cycloaddition of ketoimines with alkynes via directed sp3 C–H bond activation".

[0005] The palladium(II)-catalyzed ketoimine [3+2] cycloaddition reaction is disclosed in (Doi:10.1039 / C4CC04676E). It is evident that existing synthetic methods for compounds containing the pyrrole skeleton rarely overcome substrate / reaction condition limitations, failing to achieve tunable divergent synthesis of multifunctional pyrrole skeletons under mild conditions. In recent years, chemists have begun to incorporate synthetic efficiency into the consideration of synthetic methods for compounds containing the pyrrole skeleton, which also has guiding significance for the development of methods for synthesizing pyrrole drug intermediates. Therefore, developing efficient synthetic strategies for pyrrole skeleton compounds sets a higher standard for innovative methods and presents significant challenges.

[0006] Due to their abundant sources and economic feasibility, alkynyl aldehydes have become promising raw materials for the synthesis of pyrroles. The Gevorgyan group (Kel'in, AV; Sromek, AW; Gevorgyan, VA Novel Cu-Assisted Cycloisomerization of Alkynyl Imines: Efficient Synthesis of Pyrroles and Pyrrole-Containing Heterocycles. J. Am. Chem. Soc. 2001, 123, 2074–2075. Doi: 10.1021 / ja0058684) first synthesized the pyrrole skeleton using the propargyl and carbonyl groups of alkynyl aldehydes as C4 synthons. Through a copper-catalyzed cycloisomerization strategy, they synthesized the pyrrole skeleton using alkynyl imines and allene intermediates.

[0007]

[0008] Subsequently, Wang's group (Wei, L.; Xu, S.-M.; Jia, Z.; Tao, H.-Y.; Wang, C.-JA new entry to highly functionalized pyrroles via a cascade reaction of α-amino esters and alkynals. Chem. Commun. 2020, 56, 9691–9694. Doi:10.1039 / D0CC02964E) developed a base-mediated cycloisomerization pathway to synthesize functionalized pyrroles by reacting readily available acetylacetic aldehydes as C3 synthons with amphiphilic α-amino acid ester hydrochlorides.

[0009]

[0010] These strategies employ parallel synthesis methods, offering advantages such as simplicity, efficiency, and atom economy in synthesizing a class of pyrrole skeleton molecules. Furthermore, acetylacetines exhibit significant reactivity in these reactions. However, the development of acetylacetines as building blocks for pyrrole synthesis still holds great potential, including the ability to utilize the carbonyl carbon and α-position reaction site of acetylacetines as C2 synthons. Further exploration is needed to fully exploit substrate sites and efficiently construct various types of pyrrole skeletons under mild conditions. Summary of the Invention

[0011] The purpose of this invention is to provide a method for the controlled, divergent synthesis of functionalized pyrrole skeleton compounds.

[0012] This invention provides a method for synthesizing pyrrole skeleton compounds, comprising the following steps:

[0013]

[0014] or

[0015]

[0016] In a solvent, raw material 1, raw material 2, metal catalyst and phosphine ligand are mixed and reacted to obtain a reaction mixture containing an intermediate; the reaction mixture undergoes a nucleophilic reaction with a nucleophile to obtain pyrrole skeleton compound 1 or pyrrole skeleton compound 2.

[0017] When synthesizing pyrrole skeleton compound 1

[0018] R 1Selected from substituted or unsubstituted 6- to 10-membered aryl groups and substituted or unsubstituted 6- to 10-membered heteroaryl groups; the substituents of the aryl or heteroaryl groups are selected from: C1- to C6 alkyl groups, C1- to C6 alkoxy groups, and halogens;

[0019] R 2 Selected from substituted or unsubstituted 6- to 10-membered aryl groups and substituted or unsubstituted 6- to 10-membered heteroaryl groups; the substituents of the aryl or heteroaryl groups are selected from: C1- to C6 alkyl groups, C1- to C6 alkoxy groups, and halogens;

[0020] R 3 and R 4 The connection forms a substituted or unsubstituted structure. The The substituents are selected from: C1 to C6 alkyl groups;

[0021] n is 1, 2, 3, 4 or 5;

[0022] The nucleophile is an acid compound, ethanol, or indole;

[0023] In pyrrole skeleton compound 1, Nu is the group remaining after the carboxyl group of the linked nucleophile is dehydrogenated;

[0024] When synthesizing pyrrole skeleton compound 2

[0025] R 1 Selected from substituted or unsubstituted 6- to 10-membered aryl groups and substituted or unsubstituted 6- to 10-membered heteroaryl groups; the substituents of the aryl or heteroaryl groups are selected from: C1- to C6 alkyl groups, C1- to C6 alkoxy groups, and halogens;

[0026] R 2’ Selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, and halogen;

[0027] R 3 and R 4 The connection forms a substituted or unsubstituted structure. The The substituents are selected from: C1 to C6 alkyl groups;

[0028] R 5 Selected from hydrogen, hydroxyl, -NHR 3’ ;

[0029] R 3’ Selected from -C(O)OR 4’ ;

[0030] R 4’ Selected from C1 to C6 alkyl groups;

[0031] Ring A is an intermediate and R 1 When the connected double keys are opened, they connect with R. 5The formed substituted or unsubstituted 5- or 6-membered heterocyclic alkyl group; the substituents of the heterocyclic alkyl group are selected from: -C(O)OR 4’ ;

[0032] The nucleophile is raw material 1.

[0033] Furthermore, when synthesizing pyrrole skeleton compound 1, it includes the following steps: reacting raw material 1, raw material 2, metal catalyst and phosphine ligand in a solvent to obtain a reaction mixture containing an intermediate, and the reaction mixture undergoes a nucleophilic reaction with a nucleophile;

[0034] The molar ratio of raw material 1 to raw material 2 is 1:(1~5);

[0035] And / or, the volume molar ratio of the solvent to raw material 1 is 1 mL: (0.05–0.1) mmol;

[0036] And / or, the amount of the metal catalyst is 8 to 10% of the amount of raw material 1;

[0037] And / or, the amount of the phosphine ligand is 10-12% of the amount of the raw material 1;

[0038] And / or, the molar ratio of the raw material 1 to the nucleophile is 1:(1-5);

[0039] And / or, the reaction temperature of the mixture of raw material 1, raw material 2, metal catalyst and phosphine ligand is 20-60°C and the reaction time is 6-20 hours.

[0040] And / or, the nucleophilic reaction is carried out at a temperature of 20–60°C for a reaction time of 1–10 hours.

[0041] Furthermore, when synthesizing pyrrole skeleton compound 1,

[0042] The molar ratio of raw material 1 to raw material 2 is 1:2;

[0043] And / or, the volume molar ratio of the solvent to raw material 1 is 1 mL: 0.05 mmol;

[0044] And / or, the amount of the metal catalyst is 10% of the amount of raw material 1;

[0045] And / or, the amount of the phosphine ligand is 12% of the amount of the raw material 1;

[0046] And / or, the molar ratio of raw material 1 to nucleophile is 1:1.2;

[0047] And / or, the pyrrole skeleton compound 1 is obtained by rapid silica gel chromatography purification.

[0048] Furthermore, when synthesizing pyrrole skeleton compound 1,

[0049] The metal catalyst is selected from silver catalysts or nickel catalysts;

[0050] The phosphine ligand is selected from...

[0051] The solvent is selected from dichloromethane, dichloroethane, trichloromethane, tetrahydrofuran, toluene, or ethanol;

[0052] Preferably, the metal catalyst is selected from silver acetate, silver oxide, silver carbonate, and bis(1,5-cyclooctadiene)nickel.

[0053] Furthermore, when synthesizing pyrrole skeleton compound 1,

[0054] The metal catalyst is selected from silver oxide;

[0055] The phosphine ligand is selected from...

[0056] The solvent is selected from chloroform or ethanol.

[0057] Preferably, when ethanol is used as a solvent, it acts as both a solvent and a nucleophile, thus directly causing a nucleophilic reaction.

[0058] Furthermore, when synthesizing pyrrole skeleton compound 1,

[0059] R 1 The substituent is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidinyl, or substituted or unsubstituted pyridazinyl; the substituent of the phenyl, naphthyl, pyridyl, pyrimidinyl, or pyridazinyl is selected from: C1-C6 alkyl, C1-C6 alkoxy, or halogen.

[0060] R 2 The substituent is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidinyl, or substituted or unsubstituted pyridazinyl; the substituent of the phenyl, naphthyl, pyridyl, pyrimidinyl, or pyridazinyl is selected from: C1-C6 alkyl, C1-C6 alkoxy, or halogen.

[0061] R 3 and R 4 Connection formation

[0062] The nucleophile is PhCO2H,

[0063] Ethanol or indole;

[0064] In pyrrole skeleton compound 1, Nu is the group remaining after the carboxyl group of the linked nucleophile is dehydrogenated.

[0065] Furthermore, the synthesis of pyrrole skeleton compound 2 includes the following steps: in a solvent, raw material 1, raw material 2, metal catalyst and phosphine ligand undergo a nucleophilic reaction;

[0066] The molar ratio of raw material 1 to raw material 2 is 1:(1~5);

[0067] And / or, the volume molar ratio of the solvent to raw material 1 is 1 mL: (0.05–0.1) mmol;

[0068] And / or, the amount of the metal catalyst is 8 to 10% of the amount of raw material 1;

[0069] And / or, the amount of the phosphine ligand is 10-12% of the amount of the raw material 1;

[0070] And / or, the nucleophilic reaction is carried out at a temperature of 20–60°C for a reaction time of 1–20 hours.

[0071] Furthermore, when synthesizing pyrrole skeleton compound 2,

[0072] The molar ratio of raw material 1 to raw material 2 is 1:2;

[0073] And / or, the volume molar ratio of the solvent to raw material 1 is 1 mL: 0.05 mmol;

[0074] And / or, the amount of the metal catalyst is 10% of the amount of raw material 1;

[0075] And / or, the amount of the phosphine ligand is 12% of the amount of the raw material 1;

[0076] And / or, the pyrrole skeleton compound 2 is obtained by rapid silica gel chromatography purification;

[0077] Preferably, an acidic additive is added during the nucleophilic reaction to promote the reaction; the molar ratio of the acidic additive to raw material 1 is (0-1.2):1;

[0078] More preferably, the acidic additive is TsOH.

[0079] Furthermore, when synthesizing pyrrole skeleton compound 2,

[0080] The metal catalyst is selected from silver catalysts or nickel catalysts;

[0081] The phosphine ligand is selected from...

[0082] The solvent is selected from dichloromethane, dichloroethane, trichloromethane, tetrahydrofuran, toluene, or ethanol;

[0083] Preferably, the metal catalyst is selected from silver acetate, silver oxide, silver carbonate, and bis(1,5-cyclooctadiene)nickel;

[0084] More preferably, the metal catalyst is selected from silver oxide;

[0085] The ligands are selected from

[0086] The solvent is selected from chloroform or toluene.

[0087] Furthermore, when synthesizing pyrrole skeleton compound 2,

[0088] R 1 The substituent is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidinyl, or substituted or unsubstituted pyridazinyl; the substituent of the phenyl, naphthyl, pyridyl, pyrimidinyl, or pyridazinyl is selected from: C1-C6 alkyl, C1-C6 alkoxy, or halogen.

[0089] R 2’ Selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, and halogen;

[0090] R 3 and R 4 Connection formation

[0091] R 5 Selected from hydrogen, hydroxyl, -NHR 3’ ;

[0092] R 3’ Selected from C(O)OR 4’ ;

[0093] R 4’ Selected from C1 to C6 alkyl groups;

[0094] Ring A is an intermediate and R 1 When the connected double keys are opened, they connect with R. 5 The formed substituted or unsubstituted 5- or 6-membered heterocyclic alkyl group; the substituents of the heterocyclic alkyl group are selected from: -C(O)OR 4’ ;

[0095] The nucleophile is raw material 1.

[0096] The compounds and derivatives provided in this invention can be named according to the IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstracts Service, Columbus, OH) nomenclature system.

[0097] Regarding the definition of terms used in this invention: Unless otherwise stated, the initial definitions provided for groups or terms herein apply to the groups or terms used throughout this specification; for terms not specifically defined herein, the meanings that a person skilled in the art would give them should be given based on the disclosure and context.

[0098] "Substitution" refers to the replacement of hydrogen atoms in a molecule by other different atoms or molecules.

[0099] The minimum and maximum carbon atom content in hydrocarbon groups are indicated by a prefix, for example, the prefix C. a ~C b Alkyl indicates any alkyl group containing "a" to "b" carbon atoms. Therefore, for example, "C1 to C6 alkyl" refers to an alkyl group containing 1 to 6 carbon atoms; "C1 to C6 alkoxy" refers to an alkoxy group containing 1 to 6 carbon atoms.

[0100] "Alkyl" refers to a saturated hydrocarbon chain with a specified number of carbon atoms. For example, C1-C6 alkyl refers to an alkyl group with 1 to 6 carbon atoms, that is, alkyl groups with 1, 2, 3, 4, 5, or 6 carbon atoms. Alkyl groups can be straight-chain or branched. Representative branched alkyl groups have one, two, or three branches. Alkyl groups include methyl, ethyl, propyl (n-propyl and isopropyl), butyl (n-butyl, isobutyl, and tert-butyl), pentyl (n-pentyl, isopentyl, and neopentyl), and hexyl, etc.

[0101] "Cycloalkyl" refers to saturated or unsaturated all-carbon monocyclic or polycyclic (including fused, spiro, or bridged rings) that do not possess a conjugated π-electron system, such as, but not limited to:

[0102] "Heterocyclic alkyl" refers to a cycloalkyl group in which at least one carbon atom on the ring is replaced by a heteroatom, which is O, N, or S, including but not limited to:

[0103]

[0104] "Aryl" refers to an all-carbon monocyclic or polycyclic ring (including fused rings, spirocyclic or bridged rings) with a conjugated π-electron system, such as, but not limited to, phenyl, naphthyl, phenanthryl, anthracene, fluorenyl, and indene. The aromatic ring may be fused to other cyclic groups (including saturated and unsaturated rings), but cannot contain heteroatoms such as O, N, or S. Furthermore, the point of attachment to the parent group must be on a carbon atom of a ring with a conjugated π-electron system, such as, but not limited to, [other types of rings].

[0105] "Heteroaryl" refers to an aryl group in which at least one carbon atom on the ring of a conjugated π-electron system is replaced by a heteroatom, which is O, N, or S, including but not limited to:

[0106]

[0107] "Acid compounds" refer to compounds containing carboxyl groups.

[0108] In this invention, "room temperature" refers to a temperature of 20–30°C.

[0109] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0110]

[0111] This invention provides a novel and innovative method for synthesizing pyrrole derivatives under mild conditions via metal catalysis (silver catalysis), utilizing acetylacetonate as a C2 synthon and combining it with HOMO-enriched enamine as a nitrogen-containing amphiphilic reagent. This multi-step process involves propynylation, hydroamination, and vinyl addition, forming a common intermediate called a azeotropic quaternary ammonium salt. This intermediate exhibits significant reactivity in the late-stage functionalization of the pyrrole skeleton, resulting in pyrrole products with specific functionalizations or polycyclic fused pyrrole skeletons. Furthermore, the silver-catalyzed autotandem approach employed in this invention demonstrates high efficiency, excellent chemoselectivity, mild reaction conditions, and a broad substrate range.

[0112] This invention utilizes the highly reactive intermediate aza-rich quaternary ammonium salt to achieve a multifunctional silver-catalyzed autocatalytic tandem reaction involving enamines, acetylacetonates, and various nucleophiles. By adjusting the catalytic conditions, this method achieves flexible and switchable regioselectivity, enabling intermolecular or intramolecular nucleophilic attacks. The highly efficient production process generates a series of site-specific functionalized or polycyclic fused pyrrole products with high chemical control efficiency.

[0113] In summary, this invention provides a novel method for synthesizing functionalized pyrrole skeleton compounds. This method utilizes simple and economical starting materials and employs a one-pot process, resulting in a simple and mild procedure. Through continuous research and screening, this invention demonstrates that enamines and acetylacetonates can form highly reactive intermediates, such as aza-rich quaternary ammonium salts, in situ under specific catalysts and ligands. These intermediates are compatible with various nucleophiles, enabling intermolecular and intramolecular nucleophilic reactions with them. This allows for the efficient construction of various pyrrole skeleton compounds with specific functionalization or polycyclic fusion at specific sites, exhibiting excellent chemoselectivity. The pyrrole skeleton compounds obtained by this method are of high purity and yield. This invention can effectively advance the synthesis of pyrrole skeleton compounds and has promising application prospects.

[0114] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0115] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Detailed Implementation

[0116] The raw materials and equipment used in the specific embodiments of the present invention are all known products, obtained by purchasing commercially available products.

[0117] Nuclear magnetic resonance (NMR) spectra were recorded on DMSO-d6 and CDCl3 using a JEOL 600 NMR instrument. Proton chemical shifts are reported in parts per million (δ-scale). 1 H NMR chemical shifts are reported in ppm, with the internal TMS signal at 0.0 ppm as the standard. 13 C10 NMR chemical shifts are given using CDCl3 or DMSO-d6 as internal standards (CDCl3: δ = 77.20 ppm, DMSO-d6: δ = 39.50 ppm). Data are reported as follows: chemical shifts [multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiply, br s = broad peak)], coupling constant (J) (Hz), integral]. High-resolution mass spectrometry (HRMS) was obtained using an Agilent P / N G1969-90010. HRMS was performed with the molecular ion [M+Na]. + Or [M+H] + Report. X-ray diffraction experiments were performed on an Agilent Gemini, and the resulting data were stored at the Cambridge Crystallography Data Centre. In each case, the excess of the optical isomer was determined by HPLC analysis on a chiral stationary phase compared with the true racemate, using a Daicel Chiralpak AD-H column (250 × 4.6 mm). UV detection was performed at 254 nm. Column chromatography was performed on a mixture of ethyl acetate (EtOAc) and petroleum ether (PE) using silica gel (200–300 mesh). Thin-layer chromatography was performed on glass-supported silica gel plates; the product was visualized using UV light. All reagents and solvents were commercially available and used without further purification. Unless otherwise specified, all reagents were commercially available and used without further purification. Alternative substrates enamine 1 and acetylene 2 were prepared according to the literature.

[0118] Example 1: Synthesis method of functionalized pyrrole skeleton compounds 3a-3z and 3aa-3ae of the present invention. The general synthesis method is as follows:

[0119]

[0120] A mixture of 1 (0.1 mmol, 1.0 equiv) and 2 (0.2 mmol, 2.0 equiv) was added to chloroform (2.0 mL), followed by the addition of Ag₂O (2.3 mg, 10% of the molar amount of 1) and BINAP (7.5 mg, 12% of the molar amount of 1) at room temperature. The reaction mixture was reacted for 12 hours at room temperature. When the reaction was complete (monitored by TLC), A (0.12 mmol) was added to the reaction mixture, and the reaction was continued at room temperature for 2 hours until the reaction was complete (monitored by TLC). The reaction mixture was then purified by silica gel rapid chromatography (PE / EA = 10 / 1, v / v) to give pure product 3.

[0121] The specific compounds synthesized are as follows:

[0122] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl benzoate(3a)

[0123]

[0124] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 37.0 mg of compound 3a (yellow solid) was synthesized, with a yield of 82% and a purity greater than 99%. Melting point: 174.6-175.5℃; 1 H NMR (600MHz, CDCl3) δ7.98(d,J=8.4Hz,2H),7.57(t,J=7.2Hz,1H),7.49–7.39(m,4H),7.33–7.28(m,6H),7.25( d,J=8.4Hz,1H),7.16(d,J=7.8Hz,1H),6.86(s,1H),6.55(s,1H),2.43–2.35(m,4H),1.10(s,3H),1.07(s,3H). 13C NMR (150MHz, CDCl3) δ193.8,165.0,145.0,137.9,136.4,134.3,133.1,129.7,129.7,129.5,129.1,128.4,12 8.3,128.3,128.1,127.7,127.2,119.0,107.0,70.6,52.0,36.4,35.5,28.7,28.5.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 30 H 28 NO3 450.2064; Found450.2054.

[0125] (6,6-dimethyl-4-oxo-1-(o-tolyl)-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl benzoate(3b)

[0126]

[0127] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 32.8 mg of compound 3b (white solid) was synthesized, with a yield of 71% and a purity greater than 99%. Melting point: 181.2-184.0℃; 1 H NMR (600MHz, CDCl3) δ7.96(d,J=6.60Hz,2H),7.57(t,J=7.2Hz,1H),7.43(t,J=7.8Hz,2H),7.34(t,J=7.8Hz,1H),7.30–7.28(m,6H),7.14(d,J= 7.2Hz,1H),7.06(d,J=7.2Hz,1H),6.79(s,1H),6.58(s,1H),2.39–2.33 (m,3H),2.18(d,J=16.8Hz,1H),1.93(s,3H),1.09(s,3H),1.07(s,3H). 13C NMR (150MHz, CDCl3) δ193.9,164.8,145.1,138.0,136.7,135.4,133.9,133.3,131.3,129.8,128.7,128.6,1 28.5,128.4,127.4,127.1,119.1,107.0,70.6,52.2,36.2,35.7,29.3,28.2,17.4.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 31 H 30 NO3 464.2220; Found 464.2214.

[0128] (1-(2-methoxyphenyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl benzoate(3c)

[0129]

[0130] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 34.0 mg of compound 3c (white solid) was synthesized, with a yield of 71% and a purity greater than 99%. Melting point: 154.0-154.6℃; 1 H NMR (600MHz, CDCl3) δ7.93(d,J=6.6Hz,2H),7.53(t,J=7.8Hz,1H),7.39(t,J =7.8Hz,2H),7.34–7.30(m,3H),7.29–7.26(m,3H),7.18(dd,J=7.8,1.8Hz,1 H),7.02(t,J=7.8Hz,1H),6.91(s,1H),6.68(d,J=8.4Hz,1H),6.47(s,1H),3 .50(s,3H),2.38–2.32(m,2H),2.29–2.25(m,2H),1.07(s,3H),1.03(s,3H). 13C NMR (150MHz, CDCl3) δ194.0,164.7,155.2,146.7,137.9,134.2,133.1,130.9,130.0,129.8,129.5,128.4,128.3,12 8.3,127.2,125.0,120.9,118.8,111.8,107.5,70.3,55.4,52.3,36.1,35.6,28.9,28.6.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 31 H 29 NO4Na 502.1989; Found502.1984.

[0131] (6,6-dimethyl-4-oxo-1-(p-tolyl)-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl benzoate(3d)

[0132]

[0133] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 20.0 mg of compound 3d (white solid) was synthesized, with a yield of 43% and a purity greater than 99%. Melting point: 178.9-179.4℃; 1 H NMR (600MHz, CDCl3) δ7.96(d,J=6.6Hz,2H),7.55(t,J=7.8Hz,1H),7.41(t,J=7.8Hz,2H),7.32–7.27(m,5H),7.22(d,J=7.8Hz,1H),7.10(d,J= 7.8Hz,1H),7.05(d,J=7.8Hz,1H),7.00(d,J=7.8Hz,1H),6.81(s,1H), 6.50(s,1H),2.46–2.35(m,4H),2.35(s,3H),1.07(s,3H),1.04(s,3H). 13C NMR (150MHz, CDCl3) δ194.0,165.2,145.2,139.4,138.2,134.6,133.9,133.2,130.2,130.0,129.8,128.6,128. 5,128.4,128.0,127.6,127.3,119.1,107.0,70.8,52.2,36.6,35.7,28.9,28.7,21.3.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 31 H 30 NO3 464.2220; Found464.2221.

[0134] (6,6-dimethyl-4-oxo-1-(o-tolyl)-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl benzoate(3e)

[0135]

[0136] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 46.6 mg of compound 3e (white solid) was synthesized, with a yield of 87% and a purity greater than 99%. Melting point: 174.7-175.5℃; 1 H NMR (600MHz, CDCl3) δ7.97(d,J=7.2Hz,2H),7.53(t,J=7.2Hz,1H),7.45(dd,J=7.8,1.2Hz,1H),7.39(t,J=8.4Hz,3H),7.34–7.33(m,2H ),7.29–7.27(m,3H),7.25–7.21(m,2H),6.84(s,1H),6.50(s,1H),2.38–2.35(m,3H),2.27(d,J=16.8Hz,1H),1.11(s,3H),1.06(s,3H). 13C NMR (150MHz, CDCl3) δ193.9,164.9,145.6,137.8,136.0,133.8,133.8,133.2,131.0,130.1,130.0,129.6,128.7 ,128.6,128.3,127.5,123.8,119.3,107.7,70.3,52.2,36.2,35.7,29.3,28.3.HRMS(ESI-TOF)m / z:[M+H]+Calcd forC 31 H 27 BrNO3 528.1169 ( 78 Br), 530.1148( 80 Br); Found 528.1174 ( 78 Br), 530.1152( 80 Br).

[0137] (1-(4-chlorophenyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl benzoate(3f)

[0138]

[0139] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 41.0 mg of compound 3f (white solid) was synthesized, with a yield of 85% and a purity greater than 99%. Melting point: 167.2-167.9℃; 1 H NMR (600MHz, CDCl3) δ7.96(d,J=6.6Hz,2H),7.56(t,J=7.8Hz,1H),7.44–7.40(m,3H),7.29(s,5H),7.22(d,J=7.2Hz,1H),7.13(d,J =9.0Hz,1H),7.07(d,J=8.4Hz,1H),6.83(s,1H),6.53(s,1H),2.38–2.35(m,3H),2.31(d,J=16.8Hz,1H),1.07(s,3H),1.05(s,3H). 13C NMR (150MHz, CDCl3) δ193.8,165.2,145.0,137.9,135.4,135.1,134.4,133.4,129.9,129.8,129.8,12 8.7,128.6,128.6,127.3,119.4,107.4,70.7,52.1,36.5,35.7,28.9,28.7.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 31 H 27 ClNO3 484.1674 ( 35 Cl), 486.1644 ( 37 Cl); Found 484.1665 ( 35 Cl), 486.1644 ( 37 Cl).

[0140] (1-(4-bromophenyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl benzoate(3g)

[0141]

[0142] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 3g of compound (white solid) was synthesized (33.0mg), with a yield of 61% and a purity greater than 99%. Melting point: 171.5-172.3℃; 1 H NMR (600MHz, CDCl3) δ7.96(d,J=6.6Hz,2H),7.56(t,J=7.2Hz,2H),7.43(t,J=7.8Hz,2H),7.37(d,J=7.8Hz,1H),7.29(s,5H), 7.04(dd,J=37.2,7.8Hz,2H),6.83(s,1H),6.53(s,1H),2.36(d,J=16.8Hz,3H),2.38–2.30(m,1H),1.07(s,3H),1.05(s,3H). 13CNMR (150MHz, CDCl3) δ193.8,165.2,144.9,137.9,135.6,134.4,133.4,132.9,129.8,128.7,128. 6,128.6,127.3,123.4,119.4,107.4,70.7,52.1,36.5,35.7,28.9,28.7.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 31 H 27 BrNO3 528.1169 ( 78 Br), 530.1148( 80 Br); Found 528.1159 ( 78 Br), 530.1138( 80 Br).

[0143] (6,6-dimethyl-1-(naphthalen-1-yl)-4-oxo-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl benzoate(3h)

[0144]

[0145] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 48.0 mg of compound 3h (white solid) was synthesized, with a yield of 96% and a purity greater than 99%. Melting point: 199.1-199.8℃; 1 H NMR(600MHz, CDCl3)δ7.86(d,J=8.4Hz,1H),7.70(d,J=7.2Hz,1H),7.53–7.48(m,3H),7.40–7.37(m,2H),7.40–7.29(m,4H),7.26–7.22(m,4 H),7.18(t,J=7.8Hz,2H),6.82(s,1H),6.53(s,1H),2.38(s,2H),2.31(d,J=16.2Hz,1H),2.12(d,J=16.8Hz,1H),1.03(s,3H),1.00(s,3H). 13C NMR (150MHz, CDCl3) δ194.0,164.5,146.5,137.9,135.3,134.2,133.0,132.7,130.8,130.0,129.4,129.2,128.5,128.4,128.3 ,128.0,127.8,127.3,126.9,126.1,125.4,122.7,119.1,107.6,70.3,52.3,36.0,35.7,29.1,28.1.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 34 H 30 NO3500.2220; Found 500.2212.

[0146] (6,6-dimethyl-4-oxo-1-(pyridin-2-yl)-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl benzoate(3i)

[0147]

[0148] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 33.0 mg of compound 3i (white solid) was synthesized, with a yield of 73% and a purity greater than 99%. Melting point: 173.4-173.9℃; 1 H NMR (600MHz, CDCl3) δ8.45(d,J=3.0Hz,1H),7.78(d,J=7.8Hz,2H),7.61(t,J=7.8Hz,1H),7.43(t,J=7.2Hz,1H),7.32–7.27(m,4H),7 .24–7.17(m,4H),7.15–7.12(m,1H),7.12(s,1H),6.33(s,1H),2.57(d,J=16.8Hz,1H),2.38–2.25(m,3H),1.04(s,3H),0.97(s,3H). 13C NMR (150MHz, CDCl3) δ193.9,165.0,150.0,149.8,144.3,138.5,137.8,134.2,133.1,129.6,128.4,128.4 ,128.2,127.3,123.5,121.3,119.5,108.2,70.9,52.0,36.8,35.6,29.2,28.1.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 29 H 27 N2O3 451.2016; Found 451.2021.

[0149] (4-oxo-1-phenyl-1,4,5,6,7,8-hexahydrocyclohepta[b]pyrrol-2-yl)(phenyl)methyl benzoate(3j)

[0150]

[0151] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 30.0 mg of compound 3j (white solid) was synthesized, with a yield of 69% and a purity greater than 99%. Melting point: 187.1-187.8℃; 1 H NMR(600MHz, CDCl3)δ7.88(d,J=7.8Hz,2H),7.46(t,J=7.2Hz,1H),7.38–7.29(m,4H),7.21–7.13(m,7H), 7.04(d,J=7.8Hz,1H),6.65(s,1H),6.54(s,1H),2.65–2.63(m,2H),2.54–2.46(m,2H),1.82–1.74(m,4H). 13 C NMR (150MHz, CDCl3) δ197.6,165.1,141.8,138.1,136.9,133.2,133.0,130.0,129.8,129.6,129.6,129.3,12 8.9,128.5,128.5,128.5,128.4,127.3,123.4,110.6,70.8,43.3,27.4,25.5,22.6.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 29 H 26NO3 436.1907; Found 458.1721.

[0152] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(o-tolyl)methyl benzoate(3k)

[0153]

[0154] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 37.0 mg of compound 3k (white solid) was synthesized, with a yield of 80% and a purity greater than 99%. Melting point: 187.4-188.2℃; 1 H NMR (600MHz, CDCl3) δ7.95(d,J=6.6Hz,2H),7.55(t,J=7.2Hz,1H),7.47(t,J=7.8Hz,1H),7.42–7.37(m,4H),7.24(s,2H),7.20–7.14(m,3 H),7.10(d,J=7.8Hz,1H),6.96(s,1H),6.37(s,1H),2.38(d,J=9.0Hz,2H),2.36(d,J=1.8Hz,2H),2.20(s,3H),1.08(s,3H),1.06(s,3H). 13 C NMR (150MHz, CDCl3) δ193.9,165.1,145.2,136.5,136.3,135.5,133.6,133.2,130.5,129.9,129.8,129.7,129.4,128. 5,128.4,128.2,127.5,126.7,126.3,119.2,107.9,67.7,52.2,36.6,35.7,28.8,28.7,19.2.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 31 H 30 NO3 464.2220; Found464.2221.

[0155] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(3-metho xyphenyl)methyl benzoate(3l)

[0156]

[0157] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 38.8 mg of compound 3l (white solid) was synthesized, with a yield of 81% and a purity greater than 99%. Melting point: 186.7-187.5℃; 1 H NMR(600MHz,DMSO-d6)δ7.83(d,J=6.6Hz,2H),7.64(t,J=7.2Hz,1H),7.53–7 .48(m,4H),7.42–7.39(m,1H),7.31–7.28(m,3H),6.96(d,J=7.8Hz,1H),6.92 (d,J=6.0Hz,2H),6.86(s,1H),6.10(s,1H),3.72(s,3H),2.51(d,J=1.8Hz,2 H), 2.31 (d, J = 16.2Hz, 2H), 2.22 (d, J = 16.2Hz, 1H), 1.02 (s, 3H), 0.96 (s, 3H). 13 C NMR(150MHz,DMSO-d6)δ192.3,164.2,159.1,144.8,139.5,135.9,133.5,133.5,129.5,129.1,128.9,128.9,1 28.7,118.7,118.1,113.5,112.5,106.5,69.8,55.1,51.4,35.6,35.0,28.4,27.6.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 31 H 29 NO4Na502.1989; Found 502.1984.

[0158] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(2-fluoro phenyl)methyl benzoate(3m)

[0159]

[0160] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 49.0 mg of compound 3m (white solid) was synthesized, with a yield of 99% and a purity greater than 99%. Melting point: 198.5-199.3℃; 1 H NMR (600MHz, CDCl3) δ7.95(d,J=7.2Hz,2H),7.55(t,J=7.8Hz,1H),7.48(t,J=7.8Hz,1H),7.45–7.38(m,4H),7.30–7.27(m,2H ),7.24(d,J=10.2Hz,2H),7.12–7.09(m,2H),7.01(t,J=9.0Hz,1H),6.46(s,1H),2.43–2.35(m,4H),1.08(s,3H),1.05(s,3H). 13 C NMR (150MHz, CDCl3) δ193.9, 164.8, 159.9 (d, J = 247.5Hz), 145.3, 136.3, 133.3, 133.2,130.1(d,J=7.5Hz),129.9,129.8,129.7,129.4,128.5,128.3(d,J=3.0Hz ),128.1,127.7,125.6(d,J=13.5Hz),124.5(d,J=3.0Hz),119.2,115.7(d,J=21. 0Hz),107.6,64.5,64.5,52.2,36.6,35.7,28.9,28.7.HRMS(ESI-TOF)m / z:[M+H] + Calcdfor C 30 H 27 FNO3 468.1969; Found468.1967.

[0161] (2-chlorophenyl)(6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-ind ol-2-yl)methyl benzoate(3n)

[0162]

[0163] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 47.0 mg of compound 3n (white solid) was synthesized, with a yield of 97% and a purity greater than 99%. Melting point: 179.9-180.5℃; 1H NMR(600MHz, CDCl3)δ7.86(d,J=7.2Hz,2H),7.46(t,J=7.2Hz,1H),7.42–7.40(m,2H),7.34–7.28(m,3H),7.24–7.20 (m,2H),7.16–7.13(m,4H),7.02(s,1H),6.21(s,1H),2.31(d,J=3.0Hz,2H),2.27(s,2H),0.99(s,3H),0.97(s,3H). 13 C NMR (150MHz, CDCl3) δ193.9,164.8,145.3,136.3,136.0,133.4,132.8,132.8,130.0,129.8,129.7,129.7,129.6,129.6 ,129.5,128.5,128.0,127.8,127.7,127.2,119.3,108.2,67.4,52.2,36.6,35.7,28.8,28.8.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 30 H 27 ClNO3 484.1674 ( 35 Cl), 486.1644 ( 37 Cl); Found 484.1664 ( 35 Cl), 486.1652 ( 37 Cl).

[0164] (3-chlorophenyl)(6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-ind ol-2-yl)methyl benzoate(3o)

[0165]

[0166] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 49.0 mg of compound 3o (white solid) was synthesized, with a yield of 99% and a purity greater than 99%. Melting point: 158.4-159.0℃; 1H NMR (600MHz, CDCl3) δ7.86 (d, J=7.2Hz, 2H), 7.47 (t, J=7.8Hz, 1H), 7.37–7.29 (m, 4H), 7. 19–7.04(m,8H),6.70(s,1H),6.42(s,1H),2.30–2.23(m,4H),0.98(s,3H),0.96(s,3H). 13 C NMR (150MHz, CDCl3) δ193.9,165.0,145.3,140.1,136.4,134.5,133.7,133.5,129.9,129.9,129.7,129.7,129.6,129.4 ,128.7,128.6,128.2,127.9,127.4,125.4,119.2,107.3,70.0,52.2,36.5,35.7,28.8,28.7.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 30 H 27 ClNO3 484.1674 ( 35 Cl), 486.1644 ( 37 Cl); Found484.1664( 35 Cl), 486.1651( 37 Cl).

[0167] (3-bromophenyl)(6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)methyl benzoate(3p)

[0168]

[0169] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 49.0 mg of compound 3p (white solid) was synthesized, with a yield of 93% and a purity greater than 99%. Melting point: 149.4-150.2℃; 1H NMR (600MHz, CDCl3) δ7.87(d,J=6.6Hz,2H),7.48(t,J=7.2Hz,1H),7.39–7.30(m,6H),7.19(d,J=7. 8Hz,2H),7.14–7.04(m,4H),6.70(s,1H),6.43(s,1H),2.31–2.25(m,4H),0.99(s,3H),0.97(s,3H). 13 C NMR (150MHz, CDCl3) δ193.9,165.0,145.3,140.3,136.4,133.7,133.5,131.6,130.3,130.2,129.9,129.7,129.7,129.6 ,129.5,128.6,128.2,127.9,125.8,122.6,119.2,107.3,70.0,52.2,36.5,35.7,28.8,28.7.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 30 H 27 BrNO3 528.1169 ( 78 Br), 530.1148( 80 Br); Found528.1160( 78 Br), 530.1145( 80 Br).

[0170] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(4-fluoro phenyl)methyl benzoate(3q)

[0171]

[0172] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 40.0 mg of compound 3q (white solid) was synthesized, with a yield of 86% and a purity greater than 99%. Melting point: 155.8-156.3℃; 1H NMR (600MHz, CDCl3) δ7.87(d,J=8.4Hz,2H),7.48(t,J=7.2Hz,1H),7.37–7.30(m,4H),7.22–7.18(m,3H),7.15(d,J=7.8Hz ,1H),7.02(d,J=7.8Hz,1H),6.89(t,J=8.4Hz,2H),6.74(s,1H),6.45(s,1H),2.32–2.25(m,4H),1.00(s,3H),0.98(s,3H). 13 C NMR (150MHz, CDCl3) δ193.9, 165.1, 162.7 (d, J = 244.5Hz), 161.9, 145.2, 136.5, 134.2, 133.9 (d, J = 3.0Hz), 133.4, 129.8, 129.7 (d, J = 3.0Hz), 129.4 ,129.2(d,J=9.0Hz),128.5,128.2(d,J=55.5Hz),119.2,115.6(d,J=21.0 Hz),106.9,70.2,52.2,36.5,35.7,28.8,28.7.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 30 H 27 FNO3 468.1969; Found468.1960.

[0173] (4-bromophenyl)(6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)methyl benzoate(3r)

[0174]

[0175] The structure of 1 is The structure of 2 is The structure of A is PhCO₂H. Using the above synthetic method, 43.0 mg of compound 3r (white solid) was synthesized, with a yield of 82% and a purity greater than 99%. Melting point: 160.4-161.0℃; 1H NMR (600MHz, CDCl3) δ7.88(d,J=7.8Hz,2H),7.50(t,J=7.8Hz,1H),7.38–7.32(m,6H),7.23(d,J=7.8Hz,1H),7.15(d,J=8.4H z,1H),7.10(d,J=9.0Hz,2H),7.05(d,J=8.4Hz,1H),6.72(s,1H),6.45(s,1H),2.34–2.27(m,4H),1.01(s,3H),0.99(s,3H). 13 C NMR (150MHz, CDCl3) δ193.9,165.1,145.3,137.2,136.4,133.8,133.4,131.8,129.8,129.7,129.6,129.4,12 9.0,128.6,128.2,127.8,122.5,119.2,107.1,70.2,52.2,36.5,35.7,28.8,28.7.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 30 H 27 BrNO3 528.1169 ( 78 Br), 530.1148( 80 Br); Found 528.1162( 78 Br), 530.1146( 80 Br).

[0176] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl 3-methylbenzoate(3s)

[0177]

[0178] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 37.0 mg of compound 3s (white solid), with a yield of 80% and a purity greater than 99%. Melting point: 171.3-172.1℃; 1H NMR (600 MHz, CDCl3) δ7.70 (d, J = 7.2 Hz, 2H), 7.38 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 7.8 Hz, 1H), 7.29 (d, J = 7.2 Hz,1H),7.25–7.21(m,7H),7.16(d,J=7.8 Hz,1H),7.07(d,J=7.8Hz,1H),6.77(s,1H),6.47(s,1H),2.33(t,J=8.4 Hz,4H),2.30–2.27(m,3H),1.01(s,3H),0.99(s,3H). 13 C NMR(150 MHz, CDCl3)δ194.0,165.3,145.1,138.3,138.1,136.5,134.6,134.1,130.3,129.8,129.6,129.3,128.6,128.4,12 8.4,128.3,127.9,127.3,127.0,119.2,107.1,70.6,52.2,36.6,35.7,28.9,28.7,21.4.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 31 H 29 NO3Na 486.2040; Found486.2048.

[0179] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl 4-methoxybenzoate(3t)

[0180]

[0181] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 47.4 mg of compound 3t (white solid), with a yield of 99% and a purity greater than 99%. Melting point: 183.1-184.0℃; 1H NMR (600 MHz, CDCl3) δ7.91 (d, J = 9.0 Hz, 2H), 7.43 (t, J = 7.8 Hz, 1H), 7.38 (t, J = 7.2 Hz, 1H), 7.30–7.27 (m, 6H), 7.22 (d, J = 7.8 Hz,1H),7.12(d,J=7.8 Hz,1H),6.88(d,J=9.0Hz,2H),6.80(s,1H),6.50(s,1H),3.85(s,3H),2.40–2.37(m,1H),2.34(d,J=16.2 Hz,4H),1.07(s,3H),1.05(s,3H). 13 C NMR(150 MHz, CDCl3)δ194.0,164.8,163.6,145.1,138.3,136.6,134.7,131.9,129.6,129.2,128.5,128.4,128.3,12 7.9,127.3,122.3,119.1,113.7,106.9,70.4,55.6,52.2,36.5,35.7,28.8,28.7.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 31 H 29 NO4Na 502.1989; Found502.1981.

[0182] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl 3-fluorobenzoate(3u)

[0183]

[0184] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 46.2 mg of compound 3u (white solid), with a yield of 99% and a purity greater than 99%. Melting point: 178.3-178.9℃; 1H NMR (600MHz, CDCl3) δ7.74(d,J=7.8Hz,1H),7.60(d,J=9.0Hz,1H),7.45(t,J=7.8Hz,1H),7.40–7.37(m,2H),7.29(s,6H),7.25–7 .23(m,1H),7.20(d,J=7.8Hz,1H),7.14(d,J=8.4Hz,1H),6.83(s,1H),6.50(s,1H),2.41–2.32(m,4H),1.08(s,3H),1.05(s,3H). 13 C NMR(150MHz, CDCl3)δ193.9,164.0(d,J=3.0Hz),163.4,161.8,145.3,137.7,13 6.5,134.1,132.0(d,J=7.5Hz),130.2,130.1,129.7(d,J=18.0Hz),129.4,128.7 ,128.6,128.0(d,J=51.0Hz),127.3,125.6(d,J=3.0Hz),120.4,120.3,119.2,11 6.7,116.6,107.4,71.2,52.2,36.5,35.7,28.9,28.6.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 30 H 27 FNO3 468.1969; Found468.1659.

[0185] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl(E)-but-2-enoate(3v)

[0186]

[0187] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 34.0 mg of compound 3v (white solid), with a yield of 82% and a purity greater than 99%. Melting point: 181.7-182.5℃; 1H NMR(600MHz, CDCl3)δ7.44(s,3H),7.28–7.27(m,1H),7.25–7.24(m,2H),7.22–7.20(m,2H),7.09–7.08(m,1H),6.92–6.86(m,1H), 6.61(s,1H),6.44(s,1H),5.74(dd,J=15.6,1.8Hz,1H),2.39–2.32(m,5H),1.84(dd,J=7.2,1.8Hz,3H),1.06(s,3H),1.04(s,3H). 13 C NMR (150MHz, CDCl3) δ193.9,165.0,145.6,145.0,138.1,136.6,134.6,129.6,129.3,128.5,128.3,128. 2,127.9,127.2,122.3,119.1,106.8,70.0,52.2,36.5,35.7,28.8,28.7,18.2.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 27 H 28 NO3 414.2064; Found 414.2056.

[0188] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl cinnamate(3w)

[0189]

[0190] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 43.0 mg of compound 3w (white solid), with a yield of 90% and a purity greater than 99%. Melting point: 163.5-163.8℃; 1 H NMR(600MHz, CDCl3)δ7.51(d,J=16.2Hz,1H),7.44–7.37(m,5H),7.39–7.32(m,3H),7.25–7.21(m,6H),7.09(d ,J=7.8Hz,1H),6.65(s,1H),6.41(s,1H),6.27(d,J=16.2Hz,1H),2.36–2.27(m,4H),1.02(s,3H),0.99(s,3H).13 C NMR (150MHz, CDCl3) δ193.9,165.4,145.5,145.1,138.0,136.6,134.5,134.4,130.6,129.7,129.7,129.3,129.1,12 8.6,128.4,128.3,127.9,127.2,119.2,117.6,107.1,70.2,52.2,36.6,35.7,28.8,28.6.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 32 H 29 NO3Na498.2040; Found498.2032.

[0191] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl 2-(p-tolyl)acetate(3x)

[0192]

[0193] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 27.0 mg of compound 3x (white solid), with a yield of 57% and a purity greater than 99%. Melting point: 163.9-164.7℃; 1 H NMR (600MHz, CDCl3) δ7.39–7.36(m,2H),7.29(t,J=7.8Hz,1H),7.19–7.17(m,3H),7.09–7.07(m,3H),7.03(d,J=7.8Hz ,3H),6.97(d,J=8.4Hz,2H),6.51(s,1H),6.31(s,1H),3.40–3.34(m,2H),2.33–2.23(m,7H),1.01(s,3H),0.97(s,3H). 13CNMR (150MHz, CDCl3) δ193.9,170.3,145.0,137.9,136.9,136.6,134.3,130.5,129.8,129.7,129.4,129.4,129.3,128. 5,128.4,128.1,127.9,127.2,119.2,107.2,70.6,52.2,40.8,36.6,35.7,28.9,28.6,21.3.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 32 H 31 NO3Na500.2196;Found 500.2190.

[0194] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl(1r,3R,5S)-adamantane-1-carboxylate(3y)

[0195]

[0196] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 53.0 mg of compound 3y (white solid), with a yield of 99% and a purity greater than 99%. Melting point: 195.6-196.3℃; 1 H NMR (600MHz, CDCl3) δ7.43–7.35(m,3H),7.24–7.22(m,1H),7.19–7.17(m,3H),7.10–7.08(m,2H),7.00(d,J=7.2Hz,1H),6.49(s,1H),6 .37(s,1H),2.35–2.24(m,4H),1.91(s,3H),1.70(d,J=3.0Hz,6H),1.67–1.61(m,4H),1.58(d,J=10.2Hz,3H),1.01(s,3H),0.97(s,3H). 13C NMR (150MHz, CDCl3) δ194.0,176.1,144.8,138.6,136.6,134.7,129.7,129.2,128.5,128.2,127.1, 119.2,106.6,69.9,52.2,40.8,38.8,36.6,36.6,35.7,29.0,28.6,28.0.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 34 H 38 NO3 508.2846; Found 508.2839.

[0197] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl ferroceneate(3z)

[0198]

[0199] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 46.0 mg of compound 3z (white solid), with a yield of 83% and a purity greater than 99%. Melting point: 174.8-175.5℃; 1 H NMR (600MHz, CDCl3) δ7.35(t,J=6.0Hz,2H),7.31–7.29(m,1H),7.26-7.24(m,4H),7.22–7.21(m,1H),7.19–7.17(m,1H),7.01(d,J=5 .4Hz,1H),6.67(s,1H),6.54(s,1H),4.73–4.66(m,2H),4.32–4.30(m,2H),3.94(s,5H),2.34–2.26(m,4H),1.01(s,3H),0.99(s,3H). 13C NMR (150MHz, CDCl3) δ194.0,170.3,145.0,138.5,136.6,134.6,129.7,129.6,129.3,128.5,128.5,128.3,128.0,12 7.6,119.2,106.8,71.5,71.4,70.8,70.3,70.2,69.9,69.8,52.2,36.6,35.7,28.8,28.7.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 34 H 31 FeNO3Na 580.1546; Found 580.1537.

[0200] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate(3aa)

[0201]

[0202] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 42.0 mg of compound 3aa (white solid), with a yield of 61% and a purity greater than 99%. Melting point: 149.8-150.7℃; 1 H NMR (600MHz, CDCl3) δ7.57(d,J=8.4Hz,2H),7.40(d,J=8.4Hz,2H),7.34–7.33(m,2H),7.25– 7.21(m,1H),7.19–7.14(m,3H),7.07(d,J=6.6Hz,2H),6.97–6.94(m,2H),6.81(d,J=9.0Hz, 1H),6.72(d,J=2.4Hz,1H),6.59(dd,J=9.0,2.4Hz,1H),6.53(s,1H),6.34(s,1H),3.64(s,3 H),3.49–3.43(m,2H),2.33–2.24(m,4H),2.20(d,J=17.4Hz,4H),0.99(s,3H),0.95(s,3H). 13CNMR (150MHz, CDCl3) δ193.9,193.9,169.3,168.5,156.2,145.1,139.5,137.8, 136.5,136.0,134.1,134.0,131.4,130.9,130.6,129.7,129.6,129.3,129.3,12 8.5,128.5,127.9,127.8,127.1,119.2,115.1,112.3,112.2,107.1,101.2,70.9 ,55.7,52.2,52.1,36.5,35.7,30.5,28.8,28.6,13.5.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 42 H 37 ClN2O5H 645.2464( 35 Cl), 687.2434 ( 37 Cl); Found 645.2454 ( 35 Cl), 687.2442( 37 Cl).

[0203] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoate(3ab)

[0204]

[0205] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 55.8 mg of compound 3ab (yellow semi-solid), with a yield of 89% and a purity greater than 99%. 1 H NMR (600MHz, CDCl3) 1H NMR (600MHz, CDCl3) δ7.39–7.31(m,3H),7.23–7.19(m,3H),7.17–7.14(m,2H),7.08–7.02(m,1H),6.90(d d,J=15.0,11.4Hz,1H),6.55(s,1H),6.34(s,1H),6.21(d,J=15.0Hz,1H),6.17(d,J=15.0Hz,1H),6.08(s 1H),6.06(s,1H),5.62(s,1H),2.35–2.22(m,5H),2.12(s,3H),1.97–1.93(m,4H),1.92(s,3H ),1.64(s,3H),1.59–1.50(m,2H),1.45–1.36(m,2H),0.99(s,3H),0.97(s,3H),0.96(s,6H). 13 C NMR (150MHz, CDCl3) δ192.8,164.3,152.8,143.9,138.9,137.1,136.6,136. 2,135.4,133.8,133.7,130.3,129.1,128.5,128.4,128.0,127.9,127.3,12 7.1,126.12,126.08,117.9,116.6,105.7,68.2,51.0,38.6,35.4,34.5,33. 2,32.1,27.9,27.6,27.5,20.7,18.2,12.8,11.9,HRMS(ESI-TOF)m / z:[M+Na] + Calcd forC 43 H 49 NO3Na 650.3610; Found 650.3604.

[0206] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl-2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate(3ac)

[0207]

[0208] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 57.0 mg of compound 3ac (white solid), with a yield of 91% and a purity greater than 99%. Melting point: 190.7-191.2℃; 1 H NMR(600MHz, CDCl3)δ7.35(t,J=7.8Hz,1H),7.23(d,J=8.4Hz,2H),7.22–7.20(m ,1.0H),7.19–7.18(m,2H),7.17–7.15(m,2H),7.10(d,J=9.0Hz,1H),7.09–7.02 (m,3H),6.99(d,J=8.4Hz,1H),6.90–6.86(m,2H),6.56(s,1H),6.46–6.43(m,2H ),6.25(s,1H),3.60–3.54(m,2H),2.33–2.20(m,5H),1.00(s,3H),0.95(s,3H). 13 CNMR (150MHz, CDCl3) δ193.9,170.6,145.3,142.9,138.0,137.5,136.3,133.9,131.1,129.8,129.6,129.3,128.9,128.6,128.5,128. 2,128.0,127.6,127.1,124.2,124.1,122.3,119.1,118.7,108.2,70.8,52.2,38.6,36.5,35.6,28.9,28.5.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 37 H 32 Cl2N2O3Na 645.1682 ( 35 Cl), 647.1653 ( 37 Cl); Found 645.1675 ( 35 Cl), 647.1655 ( 37 Cl).

[0209] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl 4-([1,1'-biphenyl]-4-yl)-4-oxobutanoate(3ad)

[0210]

[0211] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 55.2 mg of compound 3ad (white solid), with a yield of 95% and a purity greater than 99%. Melting point: 193.1-193.8℃; 1 H NMR (600MHz, CDCl3) δ7.94–7.89(m,2H),7.62–7.57(m,2H),7.56–7.52(m,2H),7.48 –7.42(m,1H),7.42–7.36(m,4H),7.32(td,J=7.2,1.3Hz,1H)7.26(d,J=7.2Hz,1H),7 .23–7.19(m,3H),7.17–7.13(m,2H),7.09–7.04(m,1H),6.53(s,1H),6.34(s,1H),3. 14–3.07(m,2H),2.59(q,J=6.7Hz,2H),2.37–2.20(m,4H),1.00(s,3H),0.97(s,3H); 13 C NMR (150MHz, CDCl3) δ195.5,192.1,169.7,144.2,143.2,138.1,136.0,134.7,133.4,132.4,127.90,127.86,127.4,127.2,126.9,126. 7,126.5,126.4,125.9,125.52,125.51,125.3,117.3,105.4,68.6,50.3,34.7,33.8,31.4,27.0,26.7,26.4.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 39 H 35 NO4Na 604.2464; Found 604.2464.

[0212] (6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydro-1H-indol-2-yl)(phenyl)methyl 4-(N,N-dipropylsulfamoyl)benzoate(3ae)

[0213]

[0214] The structure of 1 is The structure of 2 is The structure of A is The above synthetic method yielded 33.0 mg of compound 3ae (white solid), with a yield of 54% and a purity greater than 99%. Melting point: 176.7-177.6℃; 1 H NMR (600MHz, CDCl3) δ7.94 (d, J = 9.0 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.34 (t, J = 7. 8Hz,1H),7.28(t,J=7.2Hz,1H),7.20(s,4H),7.18–7.15(m,2H),7.10(d,J=7.8Hz ,1H),7.02(d,J=7.8Hz,1H),6.74(s,1H),6.41(s,1H),3.00–2.98(m,4H),2.31– 2.21(m,4H),1.47–1.41(m,5H),0.98(s,3H),0.94(s,3H),0.77(t,J=7.2Hz,6H). 13 C NMR (150MHz, CDCl3) δ194.0,163.8,145.3,144.6,137.5,136.5,133.9,133.1,130.4,129.8,129.7,129.4,128.8,128.7, 128.1,127.8,127.4,127.1,119.2,107.2,71.5,52.2,50.1,36.5,35.7,28.9,28.6,22.1,11.3.HRMS(ESI-TOF)m / z:[M+H] + Calcd forC 36 H 41 N2O5S 635,2556; Found 635,2550.

[0215] Comparing the preparation methods of all compounds in Example 1, it was found that R involved in phenylpropyne aldehyde... 1 When substituents are used, electron-deficient substituents exhibit higher reactivity than electron-donating groups.

[0216] Example 2: Synthesis method of functionalized pyrrole skeleton compounds 4a-4i of the present invention

[0217] The general synthesis method is as follows:

[0218]

[0219] A mixture of 1 (0.1 mmol, 1.0 equiv) and 2 (0.2 mmol, 2.0 equiv) was added to chloroform (2.0 mL), followed by the addition of Ag₂O (2.3 mg, 10% of the molar amount of 1) and BINAP (7.5 mg, 12% of the molar amount of 1) at room temperature. The reaction mixture was reacted for 12 hours at room temperature. When the reaction was complete (monitored by TLC), TsOH (22.8 mg, 1.2 equiv) was added to the reaction mixture at room temperature, and the reaction was continued for another 2 hours at room temperature until complete (monitored by TLC). The reaction mixture was then purified by silica gel rapid chromatography (PE / EA = 10 / 1, v / v) to give pure product 4.

[0220] The specific compounds synthesized are as follows:

[0221] 3,3-dimethyl-10-phenyl-2,3,4,10-tetrahydro-1H-indolo[1,2-a]indol-1-one(4a)

[0222]

[0223] The structure of 1 is The structure of 2 is The above synthetic method yielded 25.5 mg of compound 4a (pale yellow solid), with a yield of 78% and a purity greater than 99%. Melting point: 246.2-246.7℃; 1 H NMR (600MHz, CDCl3) δ7.49(t,J=7.8Hz,1H),7.34(t,J=7.2Hz,1H),7.30(d,J=7.8Hz,1H),7.20–7.13(m,2H),7.0 7–6.99(m,4H),6.31(d,J=7.8Hz,1H),5.53(s,1H),2.44–2.32(m,2H),2.14–2.05(m,2H),0.97(d,J=33.6Hz,6H). 13 C NMR (150MHz, CDCl3) δ193.6,144.7,143.1,136.8,133.0,129.6,129.4,129.1,128.6,128.3,12 7.9,127.5,126.0,119.1,115.8,53.1,39.0,36.8,36.0,30.3,26.9.HRMS(ESI-TOF)m / z:[M+H] + Calcdfor C 23 H 22NO 328.1696; Found 328.1696.

[0224] 6-methoxy-3,3-dimethyl-10-phenyl-2,3,4,10-tetrahydro-1H-indolo[1,2-a]indol-1-one(4b)

[0225]

[0226] The structure of 1 is The structure of 2 is The above synthetic method yielded 18.9 mg of compound 4b (pale yellow solid), with a yield of 53% and a purity greater than 99%. Melting point: 240.3-241.2℃; 1 H NMR (600MHz, CDCl3) δ7.32–7.26(m,2H),7.17(s,2H),7.04(t,J=7.2Hz,1H),6.96(s,3H),6.53(d,J= 8.4Hz,1H),5.49(s,1H),3.17(s,3H),2.40–2.30(m,2H),2.11–2.01(m,2H),0.94(d,J=28.2Hz,6H). 13 C NMR (150MHz, CDCl3) δ193.6,155.3,146.1,142.5,132.7,130.3,130.0,129.4,126.9,125.4,125. 3,120.6,118.8,115.6,111.5,55.0,53.1,39.2,36.1,35.8,30.1,27.1.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 24 H 24 NO2 358.1802; Found 358.1798.

[0227] 3,3,8-trimethyl-10-phenyl-2,3,4,10-tetrahydro-1H-indolo[1,2-a]indol-1-one(4c)

[0228]

[0229] The structure of 1 is The structure of 2 is The above synthetic method yielded 15.0 mg of compound 4c (pale yellow solid), with a yield of 44% and a purity greater than 99%. Melting point: 164.2-165.1℃; 1 H NMR(600MHz, CDCl3)δ7.26(s,1H),7.14(d,J=6.6Hz,3H),7.01(s,3H),6.83(d,J=7.8Hz,1H),6 .19(d,J=7.8Hz,1H),5.49(s,1H),2.37(s,5H),2.11(t,J=13.8Hz,2H),0.95(d,J=31.8Hz,6H). 13 CNMR (150MHz, CDCl3) δ193.6,144.9,143.3,138.6,134.2,133.2,130.0,129.63,129.59,128.0,127 .7,127.4,125.9,119.2,115.6,53.0,38.9,36.8,35.9,30.2,27.0,21.3.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 24 H 24 NO 342.1850; Found 342.1855.

[0230] 8-chloro-3,3-dimethyl-10-phenyl-2,3,4,10-tetrahydro-1H-indolo[1,2-a]in dol-1-one(4d)

[0231]

[0232] The structure of 1 is The structure of 2 is The above synthetic method yielded 24.9 mg of compound 4d (pale yellow solid), with a yield of 69% and a purity greater than 99%. Melting point: 305.2-306.3℃; 1 H NMR(600MHz, CDCl3) δ7.46(d,J=8.4Hz,1H),7.24–7.16(m,3H),7.05(d,J=3.6Hz,3H),7.00(d,J=9.0Hz,1H) ,6.20(d,J=8.4Hz,1H),5.47(d,J=3.6Hz,1H),2.37(t,J=16.8Hz,2H),2.10(m,2H),0.97(d,J=38.4Hz,6H). 13C NMR (150MHz, CDCl3) δ193.6,144.6,142.9,135.3,134.8,132.9,129.7,129.66,129.60,129.3,1 29.2,127.7,126.2,119.2,116.0,53.0,38.9,36.7,36.0,30.2,27.0.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 23 H 21 ClNO362.1306( 35 Cl), 364.1277( 37 Cl); Found 362.1316( 35 Cl).

[0233] 3,3-dimethyl-10-(m-tolyl)-2,3,4,10-tetrahydro-1H-indolo[1,2-a]indol-1-one(4e)

[0234]

[0235] The structure of 1 is The structure of 2 is The above synthetic method yielded 21.2 mg of compound 4e (pale yellow solid), with a yield of 62% and a purity greater than 99%. Melting point: 233.2-223.6℃; 1 H NMR (600MHz, CDCl3) δ7.52(t,J=7.8Hz,1H),7.38(t,J=7.2Hz,1H),7.32(d,J=7.8Hz,1H ),7.11(t,J=7.8Hz,1H),6.93(d,J=7.8Hz,1H),6.90(t,J=7.8Hz,1H),6.82(d,J=6.0Hz ,2H),6.40(d,J=7.8Hz,1H),5.50(s,1H),2.43(d,J=16.4Hz,1H),2.34(d,J=15.6Hz,1H ),2.12(s,3H),2.10(d,J=6.0Hz,1H),2.08(d,J=7.2Hz,1H),0.99(s,3H),0.93(s,3H). 13C NMR (150MHz, CDCl3) δ193.5,144.6,143.0,137.1,136.6,133.3,130.4,129.5,129.0,128.6,128.5,128. 1,127.3,126.7,126.6,118.8,115.8,53.0,38.9,36.8,35.9,30.3,27.0,21.6.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 24 H 24 NO 342.1850; Found 342.1843.

[0236] 3,3-dimethyl-10-(p-tolyl)-2,3,4,10-tetrahydro-1H-indolo[1,2-a]indol-1-on e(4f)

[0237]

[0238] The structure of 1 is The structure of 2 is The above synthetic method yielded 18.1 mg of compound 4f (pale yellow solid), with a yield of 53% and a purity greater than 99%. Melting point: 164.2-165.1℃; 1 H NMR (600MHz, CDCl3) δ7.48(t,J=7.8Hz,1H),7.35(t,J=7.8Hz,1H),7.29(d,J=7.8Hz,1H),7.06(t,J=7.8Hz,1H),7.00(d,J=7.8Hz,2H) ,6.81(d,J=7.8Hz,2H),6.36(d,J=7.8Hz,1H),5.49(s,1H),2.43–2.31(m,2H),2.21(s,3H),2.15–2.05(m,2H),0.96(d,J=34.8Hz,6H). 13 C NMR (150MHz, CDCl3) δ193.7,144.8,144.7,140.2,136.9,135.3,133.2,129.43,129.40,129.0,128.6,128. 4,128.2,128.0,119.3,115.7,53.10,53.08,38.5,36.8,36.0,30.3,27.0,21.2.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 24H 24 NO 342.1850; Found 342.1855.

[0239] 10-(4-methoxyphenyl)-3,3-dimethyl-2,3,4,10-tetrahydro-1H-indolo[1,2-a]indol-1-one(4g)

[0240]

[0241] The structure of 1 is The structure of 2 is The above synthetic method yielded 4g of compound (pale yellow solid) with a yield of 50% and a purity greater than 99%. Melting point: 196.9-197.6℃; 1 H NMR (600MHz, CDCl3) δ7.47(d,J=8.4Hz,1H),7.41(d,J=8.4Hz,2H),7.19–7.15(m,2H),7.15–7.09(m,1H),6.93(d,J=9.0Hz,2H),6.12(s,1H),5.8 6(s,1H),3.83(s,3H),3.13(d,J=16.3Hz,1H),2.96(d,J=16.2Hz,1H),2 .49(d,J=15.6Hz,1H),2.33(d,J=16.0Hz,1H),1.24(s,3H),1.08(s,3H). 13 C NMR (150MHz, CDCl3) δ193.7,157.8,157.4,144.8,136.9,135.6,133.1,130.5,129.4,129.1,128.6,128. 3,127.9,119.4,115.7,112.9,112.6,55.3,53.1,38.1,36.8,36.0,30.3,27.0.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 24 H 24 NO2358.1802; Found 358.1808.

[0242] 10-(2-fluorophenyl)-3,3-dimethyl-2,3,4,10-tetrahydro-1H-indolo[1,2-a]in dol-1-one(4h)

[0243]

[0244] The structure of 1 is The structure of 2 is The above synthetic method yielded 17.3 mg of compound 4h (pale yellow solid), with a yield of 50% and a purity greater than 99%. Melting point: 349.9-350.8℃; 1 H NMR (600MHz, CDCl3) δ7.52(t,J=7.2Hz,1H),7.40(t,J=7.2Hz,1H),7.32(d,J=7.8 Hz,1H),7.22(t,J=7.8Hz,1H),7.06(t,J=7.8Hz,1H),7.01–6.95(m,1H),6.90(t, J=7.2Hz,1H),6.60(t,J=9.6Hz,1H),6.31(d,J=7.8Hz,1H),5.76(s,1H),2.31(d, J=16.8Hz,1H),2.17(d,J=16.2Hz,1H),2.07–1.95(m,2H),0.90(d,J=14.4Hz,6H). 13 C NMR (150MHz, CDCl3) δ 193.0, 161.7 (d, J = 247.5Hz), 145.1, 136.8, 132.7, 130.2, 129.9, 129.8 (d, J = 4.5Hz), 128.9, 128.6 (d, J = 33.0Hz), 128.5, 127. 7(d,J=6.0Hz),123.2(d,J=3.2Hz),117.2,115.5,114.7(d,J=23.6Hz),52 .6,36.7,35.5,31.77(d,J=2.9Hz),30.1,27.1.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 23 H 21 NO 346.1607; Found 346.1602.

[0245] 10-(3-chlorophenyl)-3,3-dimethyl-2,3,4,10-tetrahydro-1H-indolo[1,2-a]in dol-1-one(4i)

[0246]

[0247] The structure of 1 is The structure of 2 is The above synthetic method yielded 22.1 mg of compound 4i (pale yellow solid), with a yield of 61% and a purity greater than 99%. Melting point: 308.4-308.9℃; 1 H NMR (600MHz, CDCl3) δ7.54(t,J=7.2Hz,1H),7.42(t,J=7.8Hz,1H),7.31(d,J=8.4Hz,1H),7.16(t,J=7.8Hz,1H),7.03–6.96(m,2H),6.96–6. 90(m,2H),6.46(d,J=7.8Hz,1H),5.49(s,1H),2.46(d,J=16.8Hz,1H),2.34(d,J=15.6Hz,1H),2.14–2.02(m,2H),1.01(s,3H),0.93(s,3H). 13 C NMR (150MHz, CDCl3) δ193.5,144.91,144.90,136.7,133.4,132.5,129.7,129.43,129.37,129.0,128.7, 128.4,127.9,127.8,126.3,118.4,115.7,52.9,38.7,36.7,35.9,30.2,27.0.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 23 H 21 NO362.1306( 35 Cl), 364.1277( 37 Cl); Found 362.1310 ( 35 Cl), 364.1285 ( 37 Cl).

[0248] Example 2 explored further reactions for synthesizing polycyclic fused pyrrole skeletons by introducing nucleophilic sites at the ortho position of the N-benzene ring.

[0249] Example 3: Synthesis method of functionalized pyrrole skeleton compounds 5a-5e of the present invention

[0250] The general synthesis method is as follows:

[0251]

[0252] A mixture of 1 (0.1 mmol, 1.0 equiv) and 2 (0.2 mmol, 2.0 equiv) was added to toluene (2.0 mL), and Ag₂O (10% of the amount of 1) and ligand L3 (12% of the amount of 1) were added at 60 °C. The reaction mixture was reacted at 60 °C for 4 hours. When the reaction was complete (monitored by TLC), the reaction mixture was purified by silica gel rapid chromatography (PE / EA = 20 / 1, v / v) to give pure product 5.

[0253] The specific compounds synthesized are as follows:

[0254] 10,10-dimethyl-6-phenyl-6,9,10,11-tetrahydro-8H-benzo[5,6][1,4]oxazino[4,3-a]indol-8-one(5a)

[0255]

[0256] The structure of 1 is The structure of 2 is The above synthetic method yielded 27.1 mg of compound 5a (yellow solid), with a yield of 79% and a purity greater than 99%. Melting point: 133.4-134.2℃; 1 H NMR (600MHz, CDCl3) δ7.48(d,J=7.2Hz,3H),7.41(d,J=6.6Hz,3H),7.18(d,J=4.8Hz,2H),7.15–7.09(m,1H),6.11(s,1H),5.92( s,1H),3.13(d,J=16.2Hz,1H),2.96(d,J=16.2Hz,1H),2.49(d,J=15.6Hz,1H),2.33(d,J=16.2Hz,1H),1.24(s,3H),1.08(s,3H). 13 C NMR (150MHz, CDCl3) δ194.1,148.3,139.8,136.7,131.2,129.3,128.8,128.0,127.0,126.6,12 2.7,121.3,119.2,118.0,103.4,76.7,51.6,39.0,35.9,30.4,27.5.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 23 H 21NO3Na 366.1465; Found 366.1473.HPLC (DaicelChiralpak AD-H, n-hexane / 2-propanol=70:30, 1.0mL / min, at254nm): t R =5.607min(major),t R =6.400min(minor);65.5:34.5er.

[0257] 6-(4-methoxyphenyl)-10,10-dimethyl-6,9,10,11-tetrahydro-8H-benzo[5,6][1,4]oxazino[4,3-a]indol-8-one(5b)

[0258]

[0259] The structure of 1 is The structure of 2 is The above synthetic method yielded 26.1 mg of compound 5b (yellow solid), with a yield of 70% and a purity greater than 99%. Melting point: 220.2-220.7℃; 1 H NMR (600MHz, CDCl3) δ7.47(d,J=8.4Hz,1H),7.41(d,J=9.0Hz,2H),7.19–7.15(m,2H),7.15–7.09(m,1H),6.93(d,J=8.4Hz,2H),6.12(s,1H),5.8 6(s,1H),3.83(s,3H),3.13(d,J=16.2Hz,1H),2.96(d,J=16.2Hz,1H),2 .49(d,J=15.6Hz,1H),2.33(d,J=15.6Hz,1H),1.24(s,3H),1.08(s,3H). 13 C NMR (150MHz, CDCl3) δ194.0,160.5,148.4,139.7,131.4,129.7,128.8,127.0,126.5,122.6,121.4 ,119.2,118.0,114.2,103.4,76.5,55.5,51.6,39.0,35.9,30.5,27.5.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 24 H 23 NO3Na 396.1570; Found 396.1561.

[0260] 6-(4-bromophenyl)-10,10-dimethyl-6,9,10,11-tetrahydro-8H-benzo[5,6][1,4]oxazino[4,3-a]indol-8-one(5c)

[0261]

[0262] The structure of 1 is The structure of 2 is The above synthetic method yielded 37.1 mg of compound 5c (yellow solid), with a yield of 88% and a purity greater than 99%. Melting point: 195.4-196.8℃; 1 H NMR (600MHz, CDCl3) δ7.54(d,J=8.4Hz,2H),7.47(d,J=7.8Hz,1H),7.35(d,J=8.4Hz,2H),7.21–7.16(m,2H),7.14–7.10(m,1H),6.11(d,J=0.6Hz,1H) ,5.91(s,1H),3.11(d,J=16.8Hz,1H),2.97(d,J=16.2Hz,1H),2.48(d,J=1 6.2Hz,1H),2.35(d,J=15.6Hz,1H),1.65(s,1H),1.23(s,3H),1.09(s,3H). 13 C NMR (150MHz, CDCl3) δ194.0,147.9,139.9,135.8,132.0,130.5,129.7,127.0,126.7,123.4,12 2.9,121.4,119.3,118.1,103.4,75.9,51.6,39.0,35.9,30.2,27.7.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 23 H 20 BrNO2Na444.0570( 78 Br), 446.0549( 80 Br); Found444.0575( 78 Br), 446.0559( 80 Br).

[0263] ethyl 10,10-dimethyl-8-oxo-6-phenyl-8,9,10,11-tetrahydroindolo[1,2-a]quinoxaline-5(6H)-carboxylate(5d)

[0264]

[0265] The structure of 1 is The structure of 2 is The above synthetic method yielded 33.1 mg of compound 5d (yellow solid), with a yield of 80% and a purity greater than 99%. Melting point: 179.6-180.1℃; 1 H NMR (600MHz, CDCl3) δ7.68(s,1H),7.37(d,J=9.6Hz,1H),7.19–7.111(m,5H),7.09(d,J=7.2Hz,2H),6.83(s,1H),6.67(s,1H),4.39(s,2H),3. 17(d,J=16.3Hz,1H),2.89(d,J=16.8Hz,1H),2.59(d,J=16.2Hz,1H),2.33(d,J=15.6Hz,1H),1.38(t,J=7.2Hz,3H),1.29(s,3H),1.03(s,3H). 13 C NMR (150MHz, CDCl3) δ194.2,154.1,139.3,138.0,130.6,129.7,129.4,128.5,127.8,127.0,126.8,125. 8,125.5,121.4,118.6,103.2,63.1,54.4,51.7,39.3,36.1,31.5,26.4,14.7.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 26 H 26 N2O3Na437.1836; Found 437.1841.

[0266] tert-butyl 10,10-dimethyl-8-oxo-6-phenyl-8,9,10,11-tetrahydroindolo[1,2-a]quinoxaline-5(6H)-carboxylate(5e)

[0267]

[0268] The structure of 1 is The structure of 2 is The above synthetic method yielded 34.0 mg of compound 5e (yellow solid), with a yield of 78% and a purity greater than 99%. Melting point: 196.7-197.5℃; 1 H NMR (600MHz, CDCl3) δ7.77–7.57(m,1H),7.38(d,J=1.2Hz,1H),7.19–7.10(m,5H),7.10–7.05(m,2H),6.76(s,1H),6.65(s,1H),3.1 7(d,J=16.2Hz,1H),2.90(d,J=16.2Hz,1H),2.59(d,J=16.0Hz,1H),2.33(d,J=16.0Hz,1H),1.59(s,9H),1.29(s,3H),1.04(s,3H). 13 C NMR (150MHz, CDCl3) δ194.2,152.8,139.1,138.2,130.7,129.5,128.4,127.5,126.9,126.6,125.4,1 24.9,121.2,118.4,102.9,82.6,51.6,39.1,36.0,31.3,28.4,26.9,26.3.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 26 H 27 N2O3 465.2154; Found465.2146.

[0269] Example 3 shows that the electron-rich ligand L3 exhibits stronger activity, thus successfully synthesizing product 5 with a high yield.

[0270] Example 4: Synthesis method of functionalized pyrrole skeleton compounds 6a-6c of the present invention

[0271] The general synthesis method is as follows:

[0272]

[0273] A mixture of 1a (0.1 mmol, 1.0 equiv) and 2 (0.2 mmol, 2.0 equiv) was added to ethanol (2.0 mL). Ag₂O (10% of the amount of 1a) and BINAP (12% of the amount of 1a) were added at room temperature, and the reaction was carried out for 6 hours at room temperature. When the reaction was complete (monitored by TLC), the reaction mixture was purified by silica gel rapid chromatography (PE / EA = 12 / 1, v / v) to give pure products 6a-6c.

[0274] The specific compounds synthesized are as follows:

[0275] 2-(ethoxy(phenyl)methyl)-6,6-dimethyl-1-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one(6a)

[0276]

[0277] The structure of 1 is The structure of 2 is The nucleophile was EtOH. Using the above synthetic method, 36.9 mg of compound 6a (yellow solid) was synthesized, with a yield of 99% and a purity greater than 99%. Melting point: 110.2-110.8℃; 1 H NMR (600MHz, CDCl3) δ7.53–7.48(m,3H),7.41(s,1H),7.33–7.29(m,1H),,7.29–7.27(m,4H),7.27–7.20(m,3H),6.17(s,1H),5.04 (s,1H),3.26–3.20(m,1H),2.94–2.86(m,1H),2.41–2.33(m,2H),2.33–2.30(m,2H),1.04(d,J=10.2Hz,6H),0.97(t,J=6.6Hz,3H). 13 C NMR (150MHz, CDCl3) δ194.0,145.0,139.4,137.3,136.9,129.4,129.0,128.9,128.5,128.0,127. 8,127.3,118.9,106.6,76.2,64.5,52.2,36.7,35.6,28.8,28.7,15.2.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 25 H 27 NO2Na 396.1934; Found 396.1925.

[0278] 2-(ethoxy(o-tolyl)methyl)-6,6-dimethyl-1-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one(6b)

[0279]

[0280] The structure of 1 is The structure of 2 is The nucleophile was EtOH. Using the above synthetic method, 34.8 mg of compound 6b (yellow solid) was synthesized, with a yield of 90% and a purity greater than 99%. Melting point: 215.1-215.7℃; 1 H NMR (600MHz, CDCl3) δ7.50–7.57(m,4H),7.49(d,J=7.2Hz,1H),7.22(t,J=6.6,2H),7.18(t,J=7.2Hz,1H),7.08(d,J=7.8Hz,1H),6.05(s,1 H),5.13(s,1H),3.29–3.21(m,1H),2.87–2.78(m,1H),2.38(s,2H),2.31(s,2H),2.07(s,3H),1.05(d,J=3.6Hz,6H),0.98(t,J=7.2Hz,3H). 13 C NMR (150MHz, CDCl3) δ194.0,144.9,137.3,137.2,136.0,135.6,130.4,129.5,129.4,129.1,129.0,127.7,127.5 ,126.31,126.29,119.0,106.6,72.9,64.8,52.2,36.7,35.6,28.9,28.6,19.0,15.3.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 26 H 29 NO2Na 410.2091; Found 410.2082.

[0281] 2-(ethoxy(2-fluorophenyl)methyl)-6,6-dimethyl-1-phenyl-1,5,6,7-tetrahy dro-4H-indol-4-one(6c)

[0282]

[0283] The structure of 1 is The structure of 2 is The nucleophile was EtOH. Using the above synthetic method, 38.5 mg of compound 6c (yellow solid) was synthesized, with a yield of 99% and a purity greater than 99%. Melting point: 148.7-149.4℃; 1H NMR (600MHz, CDCl3) δ7.56–7.48(m,4H),7.46(d,J=8.4Hz,1H),7.26(t,J=1 3.8Hz,2H),7.17(t,J=7.8Hz,1H),6.97(t,J=9.0Hz,1H),6.15(s,1H),5.39( s,1H),3.26–3.18(m,1H),2.91–2.83(m,1H),2.41(d,J=16.2Hz,1H),2.35(d ,J=16.8Hz,1H),2.31(s,2H),1.05(d,J=10.8Hz,6H),0.95(t,J=7.6Hz,3H). 13 C NMR (150MHz, CDCl3) δ194.0,161.3,159.7,145.0,137.1,135.7,129.5(d,J=7.5Hz),129.1,128.7,128.3(d,J=3.0Hz),126.7,(d,J=13.5Hz),124. 5(d,J=4.5Hz),118.9,115.3(d,J=21.0Hz),106.4,69.1(d,J=3.5Hz),64.9,52.2,36.6,35.6,28.8(d,J=16.5Hz),15.1.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 25 H 26 FNO2Na414.1996;Found 414.1987.

[0284] Example 5: Synthesis method of the functionalized pyrrole skeleton compound 6d-6f of the present invention

[0285] The general synthesis method is as follows:

[0286]

[0287] A mixture of 1a (0.1 mmol, 1.0 equiv) and 2 (0.2 mmol, 2.0 equiv) was added to CHCl3 (2.0 mL). Ag2O (10% of the amount of 1a) and BINAP (12% of the amount of 1a) were added at room temperature, and the reaction was allowed to proceed for 6 hours at room temperature. After the reaction was complete (monitored by TLC), indole 3 (14.0 mg, 1.2 equiv) was added to the reaction mixture at room temperature, and the reaction was allowed to proceed for another 2 hours at room temperature until the reaction was complete (monitored by TLC).

[0288] The reaction mixture was then purified by silica gel column chromatography (PE / EA = 10 / 1, v / v) to obtain the pure product 6d-6f.

[0289] 2-((1H-indol-3-yl)(phenyl)methyl)-6,6-dimethyl-1-phenyl-1,5,6,7-tetrahy dro-4H-indol-4-one(6d)

[0290]

[0291] The structure of 1 is The structure of 2 is The structure of 3 is The above synthetic method yielded 44.0 mg of compound 6d (yellow solid), with a yield of 99% and a purity greater than 99%. Melting point: 225.6-226.3℃; 1 H NMR (600MHz, CDCl3) δ8.15(s,1H),7.36(d,J=3.6Hz,2H),7.31(d,J=7.8Hz,2H),7.22(d,J=7.8Hz,1H),7.21–7.13(m,4H),7.16–7.08(m,2 H),7.05(d,J=6.0Hz,2H),6.98(t,J=7.2Hz,1H),6.84(d,J=7.8Hz,1H),6.59(s,1H),6.28(s,1H),5.25(s,1H),2.36(s,4H),1.06(s,6H). 13 C NMR (150MHz, CDCl3) δ194.2,144.1,142.4,138.6,137.0,136.7,129.4,129.3,128.8,128.6,128.4,128.3,128.0,126.7,12 6.6,123.9,122.1,119.5,119.3,119.0,118.1,111.3,105.4,52.2,40.9,36.7,35.8,28.8,28.8.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 31 H 29 N2O3445.2274; Found 445.2268.

[0292] 2-((1H-indol-3-yl)(p-tolyl)methyl)-6,6-dimethyl-1-phenyl-1,5,6,7-tetrahy dro-4H-indol-4-one(6e)

[0293]

[0294] The structure of 1 is The structure of 2 is The structure of 3 is The above synthetic method yielded 45.1 mg of compound 6e (yellow solid), with a yield of 92% and a purity greater than 99%. Melting point: 251.9-252.7℃; 1 H NMR(600MHz, CDCl3)δ8.14(s,1H),7.48–7.30(m,4H),7.22(d,J=8.4Hz,1H),7.17–7.07(m,2H),7.05–6.94( m,5H),6.91(d,J=7.8Hz,1H),6.63(s,1H),6.30(s,1H),5.23(s,1H),2.37(s,3H),2.32(s,3H),1.08(s,6H). 13 C NMR (150MHz, CDCl3) δ194.0,143.8,139.3,138.7,136.9,136.6,135.9,129.2,129.1,128.9,128.6,128.3,128.1,127.8,126.6 ,123.6,121.9,119.3,119.2,118.8,118.2,111.1,105.1,52.1,40.3,36.6,35.6,28.7,21.0.HRMS(ESI-TOF)m / z:[M+Na]+Calcd for C32H30N2ONa 481.2250; Found 481.2248.

[0295] 2-((3-bromophenyl)(1H-indol-3-yl)methyl)-6,6-dimethyl-1-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one(6f)

[0296]

[0297] The structure of 1 is The structure of 2 is The structure of 3 is The above synthetic method yielded 38.1 mg of compound 6f (yellow solid), with a yield of 83% and a purity greater than 99%. Melting point: 227.1-228.2℃; 1 H NMR(600MHz, CDCl3)δ8.23(s,1H),7.42–7.36(m,1H),7.38–7.29(m,3H),7.29(d,J=7.8Hz,1H),7.22–7.15(m,2H),7.17–7.11(m,1H),7.09(s,1 H),7.05(t,J=7.8Hz,1H),6.99(t,J=7.2Hz,2H),6.87(s,1H),6.61(s,1 H),6.27(s,1H),5.22(s,1H),2.42–2.31(m,4H),1.07(d,J=6.6Hz,6H). 13 C NMR (150MHz, CDCl3) δ194.1,144.7,144.1,137.7,136.7,136.6,131.4,129.9,129.6,129.4,129.3,128.8,128.1,127.8,127.1,126.4,123 .7,122.3,122.2,119.5,119.0,118.9,117.1,111.2,105.4,77.3,77.0,76.8,52.0,40.5,36.5,35.6,28.8,28.5.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 31 H 28 BrN2O523.1380; Found 523.1375.

[0298] Examples 4 and 5 investigated the effects of nucleophiles other than carboxylic acids on the reaction.

[0299] The following specific experimental examples demonstrate the beneficial effects of the present invention.

[0300] Experimental Example 1: Optimization of reaction conditions based on Example 1

[0301] Taking the synthesis of compound 3a as an example, the reaction conditions (catalyst, ligand and solvent) were optimized.

[0302] Catalysts: Silver acetate (AgOAc), silver oxide (Ag2O), silver carbonate (Ag2CO3), bis(1,5-cyclooctadiene)nickel (Ni(COD)2);

[0303] Ligands:

[0304] Solvents: dichloromethane (DCM), dichloroethane (DCE), chloroform (CHCl3), tetrahydrofuran (THF), and toluene.

[0305]

[0306] A mixture of 1a (0.1 mmol, 1.0 equiv) and 2a (0.2 mmol, 2.0 equiv) was added to a solvent (1.0 mL). A catalyst (10% of the molar amount of 1a) and a ligand (12% of the molar amount of 1a) were added at room temperature, and the reaction was carried out for 12 hours at room temperature. When the reaction was complete (monitored by TLC), PhCO₂H (0.12 mmol, 1.2 equiv) was added to the reaction mixture, and the reaction was carried out for 2 hours at room temperature until the reaction was complete (monitored by TLC). The reaction mixture was then purified by silica gel chromatography (PE / EA = 10 / 1, v / v) to give the target compound 3a and byproduct 3a', respectively.

[0307] The selection of catalysts, ligands and solvents is shown in Table 1. The yield and purity of compound 3a and the yield of byproduct 3a' are also shown in Table 1.

[0308] Table 1. Selection of catalyst, ligand and solvent, and yield and purity of compound 3a, and yield of byproduct 3a'.

[0309]

[0310] In Table 1, a ligand “-” indicates that no ligand is used; a yield (3a) “-” indicates that 3a cannot be generated.

[0311] Taking the synthesis of compound 3a as an example, the results in Table 1 show that:

[0312] (1) Without the use of ligands in the reaction, the target product—pyrrole skeleton compound (3a)—cannot be formed. In this case, the reaction leads to the O-selective attack of the alkyne group by the enamine, mainly forming compound 3a'. However, when ligands are used in the reaction, pyrrole skeleton compound (3a) is mainly formed, and compound 3a' is hardly formed. This result indicates that changes in the steric hindrance or electronic effects of the catalyst may affect the chemoselectivity, highlighting the important role of ligands in metal catalysis and their decisive influence on whether the target product is formed.

[0313] (2) This invention compared the effects of different metal catalysts on the reaction and found that all different metal catalysts could enable the reaction to proceed and generate the target product. Among them, silver acetate (AgOAc) and silver oxide (Ag2O) were used as metal catalysts, resulting in higher yields of the target product.

[0314] (3) This invention compared the effects of different ligands on the reaction and found that different ligands could all enable the reaction to proceed and generate the target product. However, the yield of compound 3a obtained by bisphosphine ligands L1, L2 and electron-rich phosphine ligand L3 was only 45-50%, which was lower than that of ligand BINAP.

[0315] (4) This invention compares the effects of different solvents on the reaction and finds that different solvents have a relatively small effect on the reaction, but the yield of the target product is the highest when CHCl3 is used.

[0316] (5) The present invention also compared the effects of different amounts of solvent on the reaction. The study found that different amounts of solvent have a certain effect on the yield of the target product. When the amount of solvent is 2 mL, the yield of compound 3a can be increased to 82%.

[0317] Therefore, for the reaction in Example 1, the yield of the pyrrole compounds was optimal when the metal catalyst was Ag2O, the ligand was BINAP, and the solvent was CHCl3 (2 mL).

[0318] Experimental Example 2: Optimization of reaction conditions based on Example 3

[0319] Taking the synthesis of compound 5a as an example, the reaction conditions (ligand, solvent and reaction temperature) were optimized.

[0320] Ligands:

[0321] Solvents: dichloromethane (DCM), dichloroethane (DCE), chloroform (CHCl3), and toluene.

[0322] Reaction temperatures: room temperature (RT), 40°C, and 60°C.

[0323]

[0324] A mixture of 1c (0.1 mmol, 1.0 equiv) and 2a (0.2 mmol, 2.0 equiv) was added to a solvent (2.0 mL). Ag₂O (10% of the amount of 1c) and a ligand (12% of the amount of 1c) were added at the reaction temperature, and the reaction was carried out for 4 hours. When the reaction was complete (monitored by TLC), the reaction mixture was purified by silica gel rapid chromatography (PE / EA = 20 / 1, v / v) to give pure product 5a.

[0325] The selection of ligands, solvents and reaction temperatures are shown in Table 2, and the yield and purity of the obtained compound 5a are also shown in Table 2.

[0326] Table 2. Selection of ligands, solvents, and reaction temperatures, and yield and purity of compound 5a

[0327]

[0328]

[0329] Taking the synthesis of compound 5a as an example, the results in Table 2 show that:

[0330] (1) This experimental example compared the effects of different ligands on the reaction and found that different ligands could all enable the reaction to proceed and generate the target product. The electron-rich phosphine ligand L3 yielded a higher yield of compound 5a.

[0331] (2) This experimental example compares the effects of different solvents on the reaction and found that the yield of compound 5a was higher in DCM, CHCl3 and toluene solvent.

[0332] (3) This experimental example compares the effect of different reaction temperatures on the reaction. As the reaction temperature increases, the yield of compound 5a increases.

[0333] In summary, this invention provides a novel method for synthesizing functionalized pyrrole skeleton compounds. This method utilizes simple and economical starting materials and employs a one-pot process, resulting in a simple and mild procedure. Through continuous research and screening, this invention demonstrates that enamines and acetylacetonates can form highly reactive intermediates, such as aza-rich quaternary ammonium salts, in situ under specific catalysts and ligands. These intermediates are compatible with various nucleophiles, enabling intermolecular and intramolecular nucleophilic reactions with them. This allows for the efficient construction of various pyrrole skeleton compounds with specific functionalization or polycyclic fusion at specific sites, exhibiting excellent chemoselectivity. The pyrrole skeleton compounds obtained by this method are of high purity and yield. This invention can effectively advance the synthesis of pyrrole skeleton compounds and has promising application prospects.

Claims

1. A method for synthesizing a pyrrole skeleton compound, characterized in that: It includes the following steps: or In a solvent, raw material 1, raw material 2, a metal catalyst and a phosphine ligand are mixed and reacted to obtain a reaction mixture containing an intermediate; the reaction mixture undergoes a nucleophilic reaction with a nucleophilic reagent to obtain a pyrrole skeleton compound 1 or a pyrrole skeleton compound 2; When synthesizing the pyrrole skeleton compound 1, R 1 is selected from substituted or unsubstituted 6-10 membered aryl groups, substituted or unsubstituted 6-10 membered heteroaryl groups; the substituents of the aryl or heteroaryl groups are selected from: C1-C6 alkyl, C1-C6 alkoxy, halogen; R 2 is selected from substituted or unsubstituted 6-10 membered aryl groups, substituted or unsubstituted 6-10 membered heteroaryl groups; the substituents of the aryl or heteroaryl groups are selected from: C1-C6 alkyl, C1-C6 alkoxy, halogen; R 3 and R 4 Connect to form substituted or unsubstituted Said The substituents are selected from: C1-C6 alkyl; n is 1, 2, 3, 4 or 5; The nucleophile is an acid compound, ethanol or indole; In the pyrrole skeleton compound 1, Nu is the group remaining after the carboxyl group of the attached nucleophile is dehydrogenated; When synthesizing pyrrole skeleton compound 2, R 1 is selected from substituted or unsubstituted 6-10 membered aryl groups, substituted or unsubstituted 6-10 membered heteroaryl groups; the substituents of the aryl or heteroaryl groups are selected from: C1-C6 alkyl, C1-C6 alkoxy, halogen; R 2’ Selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen; R 3 and R 4 Connect to form substituted or unsubstituted Said The substituents are selected from: C1-C6 alkyl; R 5 Selected from hydrogen, hydroxyl, -NHR 3’ ; R 3’ selected from -C(O)OR 4’ ; R 4’ Selected from C1-C6 alkyl; Ring A is an intermediate with R 1 The double bond connected to R is opened 5 A substituted or unsubstituted 5-6 membered heterocycloalkyl is formed; the substituent of the heterocycloalkyl is selected from: -C(O)OR 4’ ; The nucleophile is raw material 1.

2. The synthesis method according to claim 1, characterized in that: When synthesizing the pyrrole skeleton compound 1, it includes the following steps: in a solvent, raw material 1, raw material 2, a metal catalyst and a phosphine ligand are mixed and reacted to obtain a reaction mixture containing an intermediate, and the reaction mixture undergoes a nucleophilic reaction with a nucleophilic reagent; The molar ratio of raw material 1 to raw material 2 is 1:(1-5); and / or, the volume molar ratio of the solvent to the raw material 1 is 1 mL: (0.05-0.1) mmol; and / or, the amount of the metal catalyst substance is 8-10% of the amount of the raw material 1 substance; and / or, the amount of the phosphine ligand substance is 10-12% of the amount of the raw material 1; and / or, the molar ratio of the raw material 1 to the nucleophilic reagent is 1:(1-5); And / or, the reaction temperature after the raw material 1, raw material 2, metal catalyst and phosphine ligand are mixed is 20 to 60° C., and the reaction time is 6 to 20 hours; And / or, the temperature of the nucleophilic reaction is 20 to 60° C., and the reaction time is 1 to 10 hours.

3. The synthesis method according to claim 2, characterized in that: When synthesizing the pyrrole skeleton compound 1, The molar ratio of raw material 1 to raw material 2 is 1:2; And / or, the volume molar ratio of the solvent to the raw material 1 is 1 mL: 0.05 mmol; and / or, the amount of the metal catalyst substance is 10% of the amount of the raw material 1 substance; and / or, the amount of the phosphine ligand substance is 12% of the amount of the raw material 1; and / or, the molar ratio of the raw material 1 to the nucleophilic reagent is 1:1.2; And / or, the pyrrole skeleton compound 1 is purified by silica gel flash chromatography.

4. The synthesis method according to any one of claims 1 to 3, characterized in that: When synthesizing the pyrrole skeleton compound 1, The metal catalyst is selected from a silver catalyst or a nickel catalyst; The phosphine ligand is selected from The solvent is selected from dichloromethane, dichloroethane, chloroform, tetrahydrofuran, toluene or ethanol; Preferably, the metal catalyst is selected from silver acetate, silver oxide, silver carbonate, and bis(1,5-cyclooctadiene)nickel.

5. The synthesis method according to claim 4, characterized in that: When synthesizing the pyrrole skeleton compound 1, The metal catalyst is selected from silver oxide; The phosphine ligand is selected from The solvent is selected from chloroform or ethanol.

6. The synthesis method according to any one of claims 1 to 3, characterized in that: When synthesizing the pyrrole skeleton compound 1, R 1 is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidyl, substituted or unsubstituted pyridazinyl; the substituent of the phenyl, naphthyl, pyridyl, pyrimidyl or pyridazinyl is selected from: C1-C6 alkyl, C1-C6 alkoxy, halogen; R 2 is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidyl, substituted or unsubstituted pyridazinyl; the substituent of the phenyl, naphthyl, pyridyl, pyrimidyl or pyridazinyl is selected from: C1-C6 alkyl, C1-C6 alkoxy, halogen; R 3 and R 4 Connection Formation The nucleophile is PhCO2H, Ethanol or indole; In the pyrrole skeleton compound 1, Nu is the group remaining after the carboxyl group of the connected nucleophilic reagent is dehydrogenated.

7. The synthesis method according to claim 1, characterized in that: When the pyrrole skeleton compound 2 is synthesized, it includes the following steps: in a solvent, raw material 1, raw material 2, a metal catalyst and a phosphine ligand undergo a nucleophilic reaction; The molar ratio of raw material 1 to raw material 2 is 1:(1-5); and / or, the volume molar ratio of the solvent to the raw material 1 is 1 mL: (0.05-0.1) mmol; and / or, the amount of the metal catalyst substance is 8-10% of the amount of the raw material 1 substance; and / or, the amount of the phosphine ligand substance is 10-12% of the amount of the raw material 1; And / or, the temperature of the nucleophilic reaction is 20 to 60° C., and the reaction time is 1 to 20 hours.

8. The synthesis method according to claim 7, characterized in that: When synthesizing pyrrole skeleton compound 2, The molar ratio of raw material 1 to raw material 2 is 1:2; And / or, the volume molar ratio of the solvent to the raw material 1 is 1 mL: 0.05 mmol; and / or, the amount of the metal catalyst substance is 10% of the amount of the raw material 1 substance; and / or, the amount of the phosphine ligand substance is 12% of the amount of the raw material 1; And / or, the pyrrole skeleton compound 2 is purified by silica gel flash chromatography; Preferably, an acidic additive is added during the nucleophilic reaction to promote the reaction; the molar ratio of the acidic additive to the raw material 1 is (0-1.2):1; More preferably, the acidic additive is TsOH.

9. The synthesis method according to any one of claims 1, 7 to 8, characterized in that: When synthesizing pyrrole skeleton compound 2, The metal catalyst is selected from a silver catalyst or a nickel catalyst; The phosphine ligand is selected from The solvent is selected from dichloromethane, dichloroethane, chloroform, tetrahydrofuran, toluene or ethanol; Preferably, the metal catalyst is selected from silver acetate, silver oxide, silver carbonate, bis(1,5-cyclooctadiene)nickel; More preferably, the metal catalyst is selected from silver oxide; The ligand is selected from The solvent is selected from chloroform or toluene.

10. The synthesis method according to any one of claims 1, 7 to 8, characterized in that: When synthesizing pyrrole skeleton compound 2, R 1 is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidyl, substituted or unsubstituted pyridazinyl; the substituent of the phenyl, naphthyl, pyridyl, pyrimidyl or pyridazinyl is selected from: C1-C6 alkyl, C1-C6 alkoxy, halogen; R 2’ Selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen; R 3 and R 4 Connection Formation R 5 Selected from hydrogen, hydroxyl, -NHR 3’ ; R 3’ selected from C(O)OR 4’ ; R 4’ Selected from C1-C6 alkyl; Ring A is an intermediate with R 1 The double bond connected to R is opened 5 A substituted or unsubstituted 5-6 membered heterocycloalkyl is formed; the substituent of the heterocycloalkyl is selected from: -C(O)OR 4’ ; The nucleophile is raw material 1.

Images