A pyridone palladium catalyst, its preparation method and application

Abstract

This invention discloses a pyridone palladium catalyst with the structure shown in Formula I, wherein R1, R2, R3, R4, R5, and R6 are independently selected from H, -CF3, -NO2, -OH, -F, -Cl, -Br, -CN, -CH3, and -OCH3, respectively. R1, R2, R3, R4, R5, and R6 may be the same or different, and R1, R2, R3, R4, R5, and R6 are independently substituted at positions 3, 4, 5, or 6 of the pyridone. This invention discloses the application of the described pyridone palladium catalyst in catalytic coupling reactions and C-H bond functionalization reactions. Using the described pyridone palladium catalyst, a high yield is still maintained even when the reaction feed is increased to the gram level.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and relates to pyridone palladium catalysts, their preparation methods, and applications. Background Technology

[0002] Palladium catalysts possess high catalytic activity and are widely used in various coupling reactions and C-H bond functionalization reactions, attracting widespread attention from scientists. The construction of novel palladium catalysts has become a key topic in synthetic research. In recent years, various types of ligands have been developed, effectively enhancing the catalytic activity of palladium.

[0003] Existing palladium catalysts require significant amounts of metal catalysts or additional ligands for catalyzing coupling reactions and C-H bond functionalization reactions, and their applicability is limited to a single type of reaction. Pyridone ligands exhibit superior ligand acceleration in transition metal-catalyzed C-H bond functionalization reactions; however, for each new system, numerous reaction variables need to be screened, and pyridone ligands exhibit significant specificity, with each ligand suitable for only one type or class of reactions. Furthermore, the ligand role of pyridone ligands in transition metal-catalyzed coupling reactions remains poorly understood. Therefore, developing novel pyridone-palladium catalysts, attempting to combine pyridone and palladium into novel catalysts to effectively reduce catalyst dosage and be applicable to catalyzing various coupling reactions and C-H bond functionalization reactions—achieving a multi-faceted effect—is a pressing technical challenge in this field. Summary of the Invention

[0004] The purpose of this invention is to provide a pyridone palladium catalyst, its preparation method, and its application in catalytic coupling reactions.

[0005] The objective of this invention is achieved through the following technical solution:

[0006] Pyridone palladium catalysts with structures as shown in Formula I:

[0007]

[0008] R1, R2, R3, R4, R5, and R6 are independently selected from H, -CF3, -NO2, -OH, -F, -Cl, -Br, -CN, -CH3, and -OCH3, respectively. R1, R2, R3, R4, R5, and R6 may be the same or different. R1, R2, R3, R4, R5, and R6 are independently substituted at the 3, 4, 5, or 6 positions of the pyridinone.

[0009] In some embodiments of the present invention, the pyridone palladium catalyst is selected from compounds with the following structures:

[0010]

[0011]

[0012] Another object of the present invention is to provide a method for preparing the pyridone palladium catalyst described above, the synthetic route of which is as follows:

[0013]

[0014] The reaction involves, in the presence of a base, reacting pyridone (denoted as L) of Formula II with palladium acetate (Formula III, Pd(OAc)2) in a first solvent to obtain the pyridone palladium catalyst of Formula (I).

[0015] R1, R2, R3, R4, R5, and R6 are as described above.

[0016] R is selected from R1, R2, R3, R4, R5, R6; the pyridone shown in formula (II) is a pyridone in which the 3, 4, 5 or 6 positions are substituted with substituents selected from R1, R2, R3, R4, R5, R6; specifically, the pyridone shown in formula (II) is selected from 2-pyridone, 3-(trifluoromethyl)-2-pyridone, 4-(trifluoromethyl)-2-pyridone, 5-(trifluoromethyl)-2-pyridone, and 6-(trifluoromethyl)-2-pyridone.

[0017] The first solvent is selected from one or a combination of at least two of dichloromethane, 1,2-dichloroethane, or n-hexane.

[0018] The molar ratio of pyridone to base shown in formula (II) is 1:1 to 2:1. The base is selected from Na2CO3; during the synthesis of the pyridone palladium catalyst, the base provides an alkaline environment to facilitate the dissociation of the phenolic hydroxyl groups of the pyridone shown in formula (II).

[0019] In molar quantities, the pyridone shown in formula (II) is in excess relative to palladium acetate; specifically, the molar ratio of pyridone to palladium acetate shown in formula (II) is 2:1 to 3:1.

[0020] The reaction pressure is atmospheric pressure, the reaction temperature is 20-40℃, preferably 30-35℃, and the reaction time is 8-48 hours, preferably 9-24 hours.

[0021] After the reaction is complete, the first organic solvent is removed to obtain a high-purity pyridinone palladium catalyst.

[0022] In some preferred technical solutions, after the reaction is completed, the reaction solution is filtered with diatomaceous earth, the filter cake is washed with a first organic solvent, the filtrates are combined, the first organic solvent is removed, and the reaction product is washed with a second organic solvent. The solid is collected, which is the high-purity pyridinone palladium catalyst.

[0023] The second organic solvent is selected from one or a combination of two of n-hexane and 1,2-dichloroethane; when the second organic solvent is a mixed solvent of n-hexane and 1,2-dichloroethane, the volume ratio of n-hexane to 1,2-dichloroethane is 5:1 to 10:1, specifically a mixed solvent with a volume ratio of n-hexane to 1,2-dichloroethane of 5:1 or 10:1 can be used.

[0024] Another object of the present invention is to provide the application of the pyridone palladium catalyst in catalytic coupling reactions and carbon-hydrogen bond functionalization reactions.

[0025] The pyridone palladium catalysts described above are all suitable for catalyzing coupling reactions. These coupling reactions include the Suzuki coupling reaction, Heck coupling reaction, Negishi coupling reaction, Sonogashira coupling reaction, Buchwald-Hartwig coupling reaction, Stille coupling reaction, Hiyama coupling reaction, and Miyaura Borylation reaction.

[0026] The functionalization reactions of C-H bonds include alkenylation, carbonylation, hydroxylation, cyanation, acetylation, arylation, halogenation (fluorination, chlorination, bromination, and iodination) of C-H bonds, and alkylation.

[0027] The inventors conducted scale-up experiments on the synthesis of several pharmaceutical intermediates using the pyridone palladium catalyst described in this invention. Even when the reaction feed was increased to the gram level, high yields were still maintained. Compared with commonly used palladium acetate catalysts on the market, the described pyridone palladium catalyst exhibits significant advantages.

[0028] Catalytic Suzuki coupling reaction: In a polar solvent and in the presence of a base, the pyridone palladium catalyst described above catalyzes the coupling reaction of phenylboronic acid or its derivatives with a halogen to yield biphenyl compounds.

[0029] The phenylboronic acid derivative is one in which at least one hydrogen atom on the benzene ring of phenylboronic acid is substituted with a halogen, methyl, methoxy, or formyl (-CHO) group, or one in which the CH atom on the benzene ring of phenylboronic acid is substituted with an N group; the halogenated derivative is acetophenone, benzonitrile, nitrobenzene, methyl benzoate, phenol, or carbazole with a halogen substituted at the ortho, meta, or para positions.

[0030] In molar quantities, phenylboronic acid or its derivatives are in excess relative to the halogenated product; specifically, the molar ratio of phenylboronic acid or its derivatives to the halogenated product is 2:1.

[0031] The alkali is selected from K2CO3; the molar ratio of the alkali to the halogenated product is 2:1.

[0032] The polar solvent is selected from ethanol; specifically, 1.0 mL of ethanol is used as the reaction solvent for every 0.1 mmol of halide.

[0033] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to halide is 1:1000 to 1:4000.

[0034] Generally, the pressure for the Suzuki coupling reaction is atmospheric pressure, the reaction temperature is 90–100°C, and the reaction time is 12–24 hours.

[0035] After the Suzuki coupling reaction was completed, ethanol was removed to obtain the crude product. The final product was obtained by column chromatography separation and purification using silica gel thin-layer chromatography or 300-400 mesh silica gel as the stationary phase and a mixed solvent of petroleum ether and ethyl acetate (20:1 to 5:1, v / v) as the mobile phase.

[0036] Catalytic Heck coupling reaction: In a polar solvent and in the presence of a base, the pyridone palladium catalyst catalyzes the coupling reaction of olefins with halobenzenes to yield biphenyl olefin compounds.

[0037] The olefin is a terminal olefin, specifically a styrene, a propenyl ether, or an acrylate in which at least one hydrogen atom at the ortho, meta, or para position is substituted with a halogen or methyl group; the halobenzene is an acetophenone, benzonitrile, nitrobenzene, methyl benzoate, phenol, anisole, or benzaldehyde in which at least one hydrogen atom at the ortho, meta, or para position is substituted with a halogen.

[0038] In molar quantities, the terminal olefin is in excess of the halobenzene; specifically, the molar ratio of the terminal olefin to the halobenzene is 2:1.

[0039] The alkali is selected from K2CO3; the molar ratio of the alkali to the halobenzene is 2:1.

[0040] Generally, the Heck coupling reaction is carried out at atmospheric pressure, at a temperature of 90–100°C, and for a time of 12–24 hours.

[0041] The polar solvent is selected from 1,4-dioxane; specifically, 1.0 mL of 1,4-dioxane is used as the reaction solvent for every 0.1 mmol of halobenzene.

[0042] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to halobenzene is 1:100 to 1:400.

[0043] After the reaction was completed, the polar solvent was removed to obtain the crude product. The crude product was then purified by column chromatography using silica gel thin-layer chromatography or 300-400 mesh silica gel as the stationary phase and a mixed solvent of petroleum ether and ethyl acetate (10:1, v / v) as the mobile phase to obtain the final product.

[0044] Catalytic Sonogashira coupling reaction: In a polar solvent and in the presence of a base, the pyridone palladium catalyst catalyzes the coupling reaction of alkynes with halobenzenes to yield biphenyl alkynes.

[0045] The alkyne is a terminal alkyne, specifically a phenylacetylene or a phenylacetylene in which the hydrogen at the ortho, meta, or para position is replaced by a methyl group; the halobenzene is a nitrobenzene or benzonitrile in which at least one hydrogen at the ortho, meta, or para position is replaced by a halogen.

[0046] In molar quantities, the terminal alkyne is in excess relative to the halobenzene; specifically, the molar ratio of the terminal alkyne to the halobenzene is 3:1.

[0047] The alkali is selected from Bu4NOAc * HOAc; the molar ratio of base to halobenzene is 2:1.

[0048] Generally, the Sonogashira coupling reaction is carried out at atmospheric pressure, at a temperature of 90–100°C, and for 12–24 hours.

[0049] The polar solvent is selected from DMF; specifically, 1.0 mL of DMF is used as the reaction solvent for every 0.1 mmol of halobenzene.

[0050] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to halobenzene is 1:100 to 1:4000.

[0051] After the reaction was completed, the polar solvent was removed to obtain the crude product. The final product was obtained by separating and purifying the crude product using silica gel thin-layer chromatography or 300-400 mesh silica gel as the stationary phase and a mixed solvent of petroleum ether and ethyl acetate (20:1 to 5:1, v / v) as the mobile phase.

[0052] Catalytic Buchwald-Hartwig reaction: In a nonpolar solvent, in the presence of a base and a phosphorus ligand, the pyridone palladium catalyst described above catalyzes the reaction of alcohols or amines with halobenzenes to yield benzidine or diphenyl ether compounds.

[0053] The alcohols are alkyl primary alcohols, specifically methanol, ethanol, n-butanol, and deuterated methanol; the amines are specifically N-methylaniline, aniline, benzylamine, and morpholine; the halobenzenes are benzaldehyde, anisole, trifluoromethylbenzene, benzene, acetonitrile, acetophenone, and benzoate esters, in which at least one hydrogen atom at the ortho, meta, or para position is substituted with a halogen.

[0054] In molar quantities, alcohols or amines are in excess of halobenzenes; specifically, the molar ratio of alcohols to halobenzenes is 3:1; the molar ratio of amines to halobenzenes is 2:1.

[0055] The alkali is selected from Cs2CO3; the molar ratio of the alkali to the halobenzene is 2:1.

[0056] The Buchwald-Hartwig reaction was carried out at atmospheric pressure, at a temperature of 90°C, and for 24 hours.

[0057] The nonpolar solvent is selected from toluene; specifically, 1.0 mL of toluene is used as the reaction solvent for every 0.1 mmol of halobenzene.

[0058] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to halobenzene is 1:100; when alcohols react with halobenzene, the phosphine ligand is BrettPhos, and the molar ratio of phosphine ligand to halobenzene is 2:100; when amines react with halobenzene, the phosphine ligand is XantPhos, and the molar ratio of phosphine ligand to halobenzene is 2:100.

[0059] After the reaction was completed, the nonpolar solvent was removed to obtain the crude product. The final product was obtained by column chromatography separation and purification using silica gel thin-layer chromatography or 300-400 mesh silica gel as the stationary phase and a mixed solvent of petroleum ether and ethyl acetate (10:1 to 3:1, v / v) as the mobile phase.

[0060] Catalytic Miyaura Borylation reaction: In a polar solvent, in the presence of a base and a phosphorus ligand, the pyridone palladium catalyst described above catalyzes the reaction of B2(pin)2 with a halobenzene to yield pinacol phenylboronic acid.

[0061] Halobenzenes are benzaldehyde, anisole, trifluoromethylbenzene, benzene, acetophenone, or benzoate esters in which at least one hydrogen atom at the ortho, meta, or para position is substituted with a halogen.

[0062] In molar amounts, B2(pin)2 (pinaol diboronate) is in excess relative to halobenzene; specifically, the molar ratio of B2(pin)2 to halobenzene is 1.5:1.

[0063] The base is selected from KOAc; the molar ratio of the base to the halobenzene is 2:1.

[0064] The Miyaura Borylation reaction was carried out at atmospheric pressure, at a temperature of 90–100°C, and for 12–24 hours.

[0065] The nonpolar solvent is selected from 1,4-dioxane; specifically, 1.0 mL of 1,4-dioxane is used as the reaction solvent for every 0.1 mmol of halobenzene.

[0066] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to halobenzene is 1:100.

[0067] The phosphine ligand is DavePhos; the molar ratio of the phosphine ligand to the halobenzene is 2:100.

[0068] After the reaction was completed, the solvent was removed to obtain the crude product. The crude product was then purified by column chromatography using silica gel thin-layer chromatography or 300-400 mesh silica gel as the stationary phase and petroleum ether and ethyl acetate (30:1 to 10:1, v / v) as the mobile phase to obtain the final product.

[0069] Catalytic alkenylation reaction of C-H bonds: In a polar solvent, in the presence of an oxidant and an additive, the pyridone palladium catalyst catalyzes the reaction of aromatic hydrocarbons with olefins to yield styrene compounds.

[0070] The olefin is a terminal olefin, specifically it can be acrylate, acrylamide, 1-penten-3-one, N,N-dimethylacrylamide, diethyl vinyl phosphate, diethyl allyl phosphate, phenyl vinyl sulfone, or fluorinated styrene; the aromatic hydrocarbon is N-acetanilide or N-acetanilide in which at least one hydrogen atom at the meta or para position is substituted by fluorine, methyl or methoxy, or o-xylene, o-phenylenediamine, or 1,2,3,4-tetrahydronaphthalene.

[0071] In molar terms, olefins are in excess of aromatics; specifically, the molar ratio of olefins to aromatics is 3:1 to 2:1.

[0072] The oxidant is selected from Ag2CO3, and the molar ratio of the oxidant to the aromatic hydrocarbon is 3:1 to 2:1.

[0073] The additive is selected from PTSA or KOAc; the molar ratio of the additive to the aromatic hydrocarbon is 1:1 to 1:2.

[0074] The alkenylation reaction of carbon-hydrogen bonds is carried out at atmospheric pressure, at a temperature of 90–100 °C, and for a time of 24–36 hours.

[0075] The polar solvent is selected from HFIP (1,1,1,3,3,3-hexafluoro-2-propanol) and AcOH. Specifically, when the polar solvent is a mixture of HFIP and AcOH in a volume ratio of 10:1, 1.0 mL of HFIP and 100 μL of acetic acid are used as the reaction solvent for every 0.1 mmol of aromatic hydrocarbon.

[0076] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to aromatic hydrocarbon is 1:10.

[0077] After the reaction was completed, the polar solvent was removed to obtain the crude product. The crude product was then purified by column chromatography using silica gel thin-layer chromatography or 300-400 mesh silica gel as the stationary phase and petroleum ether and ethyl acetate (20:1 to 1:2, v / v) as the mobile phase to obtain the final product.

[0078] Catalytic CH carbonylation reaction: Using acetonitrile (MeCN) as the reaction solvent, in the presence of an oxidant, the pyridinone palladium catalyst catalyzes the reaction of 2-phenylpyridine with benzaldehyde to obtain benzoyl compounds.

[0079] In molar amounts, benzaldehyde is in excess of 2-phenylpyridine; specifically, the molar ratio of benzaldehyde to 2-phenylpyridine is 3:2.

[0080] The oxidant is selected from TBHP; specifically, the molar ratio of the oxidant to 2-phenylpyridine is 3:1.

[0081] The CH carbonylation reaction is carried out at atmospheric pressure, at a temperature of 25–30 °C, and for a time of 24–36 hours.

[0082] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to 2-phenylpyridine is 10:100.

[0083] After the reaction was completed, acetonitrile was removed to obtain the crude product. The crude product was then purified by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate (10:1, v / v) as the mobile phase to obtain the final product.

[0084] Catalytic CH hydroxylation reaction: Using DCE as the reaction solvent, 2-phenylpyridine reacts with TBHP (tert-butanol peroxide) catalyzed by the pyridone palladium catalyst to obtain phenolic compounds.

[0085] On a molar basis, TBHP is in excess of 2-phenylpyridine; specifically, the molar ratio of TBHP to 2-phenylpyridine is 6:1.

[0086] The CH hydroxylation reaction is carried out at atmospheric pressure, at a temperature of 90–115 °C, and for a time of 12–20 hours.

[0087] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to 2-phenylpyridine is 5:100.

[0088] After the reaction was completed, DCE was removed to obtain the crude product. The final product was obtained by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate (10:1, v / v) as the mobile phase.

[0089] Catalytic CH nitrification reaction: Using DMF as the reaction solvent, in the presence of an oxidant, the pyridone palladium catalyst catalyzes the reaction of 2-phenylpyridine with K3[Fe(CN)6] to obtain benzonitrile compounds.

[0090] The molar ratio of 2-phenylpyridine to K3[Fe(CN)6] is 5:1.

[0091] The oxidant is selected from CuBr2; the molar ratio of the oxidant to 2-phenylpyridine is 1:1.

[0092] The CH nitrification reaction is carried out at atmospheric pressure, at a temperature of 120–130 °C, and for 4–8 hours.

[0093] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to 2-phenylpyridine is 5:100.

[0094] After the reaction was completed, DMF was removed to obtain the crude product. The final product was obtained by column chromatography using silica gel as the stationary phase and petroleum ether-ethyl acetate (10:1, v / v) as the developing solvent.

[0095] Catalytic CH acetylation reaction: In the presence of an oxidant and an additive, the pyridone palladium catalyst described above catalyzes the reaction of N-acetanilide with acetic acid to obtain phenylacetyl compounds.

[0096] The molar ratio of N-acetanilide to acetic acid is 1:20.

[0097] The oxidant is selected from (NH4)2S2O8; the molar ratio of the oxidant to N-acetanilide is 2:1.

[0098] The additive is selected from trifluoroacetic acid, and the molar ratio of the additive to N-acetanilide is 5:1.

[0099] The CH acetylation reaction is carried out at atmospheric pressure, at a temperature of 25–30°C, and for a time of 12–24 hours.

[0100] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to N-acetanilide is 1:10.

[0101] After the reaction was completed, the organic layer was extracted with dichloromethane. The crude product was obtained by removing the dichloromethane. The crude product was purified by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate (1 / 1, v / v) as the mobile phase to obtain the final product.

[0102] Catalytic CH arylation reaction: In the presence of an oxidant and an additive, the pyridone palladium catalyst described above catalyzes the reaction of N-acetanilide with aromatic hydrocarbons to obtain biphenyl compounds.

[0103] The molar ratio of N-acetanilide to aromatic hydrocarbons is 1:20. The aromatic hydrocarbons are selected from o-xylene.

[0104] The oxidant is selected from (NH4)2S2O8; the molar ratio of the oxidant to N-acetanilide is 2:1.

[0105] The additive is selected from trifluoroacetic acid, and the molar ratio of the additive to N-acetanilide is 20:1.

[0106] The CH arylation reaction is carried out at atmospheric pressure, at a temperature of 25–30 °C, and for a time of 12–24 hours.

[0107] The molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to N-acetanilide or N-acetanilide in which at least one hydrogen atom at the meta or para position is substituted by fluorine, methyl or methoxy is 1:10.

[0108] After the reaction was completed, the organic layer was extracted with dichloromethane. The crude product was obtained by removing the dichloromethane. The crude product was purified by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate (2 / 1, v / v) as the mobile phase to obtain the final product.

[0109] Catalytic CH chlorination reaction: Using DCE as the reaction solvent, in the presence of an additive, N-acetanilide and NCS reacted under the catalysis of the aforementioned pyridone palladium catalyst to obtain ortho-chloro N-acetanilide compounds. The molar ratio of N-acetanilide to NCS was 1:2; the additive was selected from Cu(OTf)₂; the molar ratio of the additive to N-acetanilide was 1:2; and the molar ratio of the pyridone palladium catalyst (based on monomer Pd(L)₂) to N-acetanilide was 1:10. The CH chlorination reaction was carried out at atmospheric pressure, at a temperature of 80–90 °C, and for 2–5 hours. After the reaction, DCE was removed to obtain the crude product. The crude product was purified by column chromatography using silica gel as the stationary phase and a mixed solvent of petroleum ether and ethyl acetate (5:1, v / v) as the developing solvent to obtain the final product.

[0110] Catalytic CH bromination reaction: Using DCE as the reaction solvent, in the presence of an additive, N-acetanilide and NBS reacted under the catalysis of the aforementioned pyridone palladium catalyst to obtain ortho-bromo-N-acetanilide compounds. The molar ratio of N-acetanilide to NBS was 1:1.2; the additive was selected from PTSA; the molar ratio of the additive to N-acetanilide was 1:2; and the molar ratio of the pyridone palladium catalyst (based on monomer Pd(L)2) to N-acetanilide was 10:100. The CH bromination reaction was carried out at atmospheric pressure, at a temperature of 80–90 °C, and for 1–2 hours. After the reaction, DCE was removed to obtain the crude product. The crude product was purified by column chromatography using silica gel as the stationary phase and a mixed solvent of petroleum ether and ethyl acetate (5:1, v / v) as the developing solvent to obtain the final product.

[0111] Catalytic CH iodization reaction: Using DCE as the reaction solvent, in the presence of an additive, N-acetanilide and NIS reacted under the catalysis of the aforementioned pyridone palladium catalyst to obtain ortho-iodo-N-acetanilide compounds. The molar ratio of N-acetanilide to NIS was 1:1.5. The additive was selected from PTSA, with a molar ratio of additive to N-acetanilide of 1:2; the molar ratio of pyridone palladium catalyst (based on monomer Pd(L)2) to N-acetanilide was 1:10. The CH iodization reaction was carried out at atmospheric pressure, at a temperature of 80–90 °C, and for 1–2 hours. After the reaction, DCE was removed to obtain the crude product. The crude product was purified by column chromatography using silica gel as the stationary phase and a mixed solvent of petroleum ether and ethyl acetate (5:1, v / v) as the developing solvent to obtain the final product.

[0112] Catalytic CH fluorination reaction: Using acetonitrile as the reaction solvent, in the presence of an additive, 2-phenylquinoxaline reacts with NFSI catalyzed by the aforementioned pyridone palladium catalyst to yield fluoro-2-phenylquinoxaline compounds. The molar ratio of 2-phenylquinoxaline to NFSI is 1:1.5; the additive is selected from TFA, and the molar ratio of the additive to 2-phenylquinoxaline is 2:1; the molar ratio of the pyridone palladium catalyst (based on monomer Pd(L)2) to 2-phenylquinoxaline is 1:10. The CH fluorination reaction is carried out at atmospheric pressure, at a temperature of 90–110 °C, and for 12–24 hours. After the reaction, acetonitrile is removed to obtain the crude product. The crude product is purified by column chromatography using silica gel as the stationary phase and a mixed solvent of petroleum ether and ethyl acetate (10:1, v / v) as the developing solvent to obtain the final product.

[0113] Catalytic CH alkylation reaction: Benzoic acid reacts with dibromomethane in the presence of a base, catalyzed by the aforementioned pyridone palladium catalyst, to yield phthalide compounds. The ratio of benzoic acid to dibromomethane is 0.1 mmol:1 mL; the base is selected from K₂HPO₄; the molar ratio of base to benzoic acid is 3:1; and the molar ratio of pyridone palladium catalyst (based on monomer Pd(L)₂) to benzoic acid is 1:10. The CH alkylation reaction is carried out at atmospheric pressure, at a temperature of 130–140 °C, and for 24–36 hours. After the reaction, the reaction solution is filtered through diatomaceous earth. The filtrate, after removing dibromomethane, yields the crude product. The crude product is then purified by column chromatography using silica gel as the stationary phase and petroleum ether and ethyl acetate (10:1, v / v) as the mobile phase to obtain the final product.

[0114] In some embodiments of the present invention, the reaction raw materials are selected from the following compounds:

[0115]

[0116]

[0117]

[0118] In this article, the term "halogen" generally refers to fluorine, chlorine, bromine, and iodine.

[0119] In this document, the terms "aryl" and "heteroaryl" include monocyclic systems and fused-ring systems (bicyclic or polycyclic systems). A monocyclic system refers to a system existing in the form of only one ring, while a fused-ring system refers to a polycyclic structure formed by two or more rings connected in a fused, spiro, or bridged manner. A fused ring is a fused-ring structure formed by two or more ring structures sharing two adjacent ring atoms (i.e., sharing a bond). A bridged ring is a fused-ring structure formed by two or more ring structures sharing two non-adjacent ring atoms. A spiro ring is a fused-ring structure formed by two or more ring structures sharing a single ring atom. Unless otherwise specified, the aryl and heteroaryl groups defined in this invention by the number of atoms include all monocyclic and fused-ring structures that can be formed.

[0120] In this article, the term “replaced by” means that one or more atoms on a given atom or group are replaced by one or more substituents selected from the given substituents, provided that the replacement does not exceed the normal valence of the given atom.

[0121] The abbreviations used in this article are shown below. For abbreviations mentioned in the article but not listed, they have their usual meaning in the art.

[0122] Pd(OAc)2: Palladium acetate; DMF: N,N-Dimethylformamide; DCM: Dichloromethane; DCE: Dichloroethane; Bu4NOAc*AcOH: Tetrabutylammonium diacetate; BrettPhos: 2-(Dicyclohexylphosphine)-3,6-dimethoxy-2'-4'-6'-tris-1-propyl-11'-biphenyl; XantPhos: 4,5-bis(diphenylphosphine)-9,9-dimethylphosphine 2-Dicyclohexylphosphine-2'-(N,N-dimethylamine)-biphenyl; B2(pin)2: pinacol diboronic acid ester; TBHP: tert-butanol hydroperoxide; PTSA: p-toluenesulfonic acid; NCS: N-chlorosuccinimide; NBS: N-bromosuccinimide; NIS: N-iodosuccinimide; NFSI: N-fluorobis(phenylenesulfonamide); TFA: trifluoroacetic acid. Detailed Implementation

[0123] The technical solutions of the present invention will be clearly and completely described below using embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0124] Example 1: Synthesis of Compound I-1

[0125]

[0126] Under air conditions, DCM (40.0 mL), Na2CO3 (424 mg, 1.0 equiv.), and 2-pyridone (L1, 760 mg, 2.0 equiv.) were added to a round-bottom flask. After reacting at 30 °C for 12 hours, Pd(OAc)2 (896 mg, 4.0 mmol, 1.0 equiv.) was added, and the reaction was continued at 30 °C for 24 hours. After the reaction was completed, the reaction solution was filtered through diatomaceous earth and washed three times with 5.0 mL of DCM each time. The filtrate was collected, and the DCM was removed to obtain an orange powder. The orange powder was washed three times with 5.0 mL of a mixed solvent of n-hexane and 1,2-dichloroethane (n-hexane:1,2-dichloroethane = 10:1, v / v). The filter cake was collected to obtain compound I-1, a pale yellow powder, with a yield of 28%.

[0127] 1 H NMR (500MHz, CDCl3) δ8.11(dd,J=6.3,1.9Hz,1H),7.15(ddd,J=8.7,6.7,1.9Hz,1H),6.59(dd,J=8.6,1.4Hz,1H),6.46(td,J=6.6,1.4Hz,1H); 13C NMR(150MHz, CDCl3)δ172.7,146.4,138.1,117.3,111.9; IR(KBr)ν max :3670,1608,1551,1495,1469,1431,1353,1274,1152,1021,864,771,735,620,528; HRMS(ESI-TOF)m / z Calcd forC 30 H 24 N6O6Pd3[M+H] + :882.8935,found:882.8932.Elemental analysis(%)ofC 30 H 24 N6O6Pd3: C 40.77, H 2.74, N 9.51; found C 39.08, H 2.52, N 9.53.

[0128] Example 2 Synthesis of Compound I-2

[0129]

[0130] Under air conditions, DCM (40.0 mL), Na2CO3 (1272 mg, 3.0 equiv.), and 3-(trifluoromethyl)-2-pyridone (L2, 1956 mg, 3.0 equiv.) were added to a round-bottom flask, and the reaction was carried out at 30 °C for 12 hours. Then, Pd(OAc)2 (896 mg, 4.0 mmol, 1.0 equiv.) was added, and the reaction was carried out at 30 °C for 10 hours. After the reaction was completed, the reaction solution was filtered with diatomaceous earth and washed three times with 5.0 mL of DCM each time. The filtrate was collected, and the DCM was removed to obtain an orange powder. The orange powder was washed three times with 5 mL of a mixed solvent of n-hexane and 1,2-dichloroethane (n-hexane:1,2-dichloroethane = 5:1, v / v) each time. The filter cake was collected to obtain compound I-2, a pale yellow powder, with a yield of 45%.

[0131] 1 H NMR (600MHz, CDCl3) δ8.67(d,J=5.0Hz,2H),8.48(d,J=6.5Hz,1H),7.55(d,J=7.1Hz,1H),7.52(d,J=6.3Hz,2H),6.58–6.51(m,3H); 13C NMR (150MHz, CDCl3) δ169.2,169.0,151.4,151.3,140.6,138.8,137.2,137.00,136.97,136.9,125.4,12 3.8,123.6,122.0,121.7,119.9,117.7,117.5,117.2,117.0,111.7,111.4,111.2,110.7,110.2,105.4; 19 F NMR(470MHz, CDCl3)δ-63.77,-64.72; IR(KBr)ν max :3675,1614,1571,1496,1466,1369,1310,1217,1165,1123,1054,976,892,801,771,680,648,610,542,439cm -1 ;HRMS(ESI-TOF)m / z Calcd for C 36 H 18 F 18 N6O6Pd3[M+Na] + :1312.7997,found:1312.8000;Elemental analysis(%)of C 12 H6F6N2O2Pd: C 33.67, H 1.63, N 6.43; found C 34.50, H1.53, N 6.44.

[0132] Example 3 Synthesis of Compound I-3

[0133]

[0134] Under air conditions, DCM (40.0 mL), Na2CO3 (1272 mg, 3.0 equiv.), and 4-(trifluoromethyl)-2-pyridone (L3, 1956 mg, 3.0 equiv.) were added to a round-bottom flask, and the reaction was carried out at 30 °C for 12 hours. Then, Pd(OAc)2 (896 mg, 4.0 mmol, 1.0 equiv.) was added, and the reaction was carried out at 30 °C for 24 hours. After the reaction was completed, the reaction solution was filtered through diatomaceous earth and washed three times with 5.0 mL of DCM each time. The filtrate was collected, and the DCM was removed to obtain compound I-3, an orange powder, with a yield of 47%.

[0135] 1H NMR (600MHz, CDCl3) δ8.39(d,J=6.5Hz,2H),8.18(d,J=6.6Hz,1H),6.81(s,1H),6.77(dd,J=6.6,2.0Hz,1H),6.72(d,J=5.6Hz,4H). 13 C NMR (150MHz, CDCl3) δ173.1,172.5,147.9,147.3,140.9,140.7,140.6,140.5,123.0,122.9,121.13,121 .05,114.12,114.09,114.07,114.04,113.90,113.87,108.43,108.42,108.40,108.37,108.22,108.20. 19 FNMR(470MHz,CDCl3)δ-65.66,-65.71.IR(KBr)ν max :3424,2927,2855,1634,1553,1499,1451,1346,1292,1273,12401183,1144,1080,1018,936,873,809,797,768,681,608,535,473,428cm -1 .HRMS(ESI-TOF)m / z Calcd for C 36 H 18 F 18 N6O6Pd3[M+H] + :1290.8172,found:1290.8178.Elemental analysis(%)of C 36 H 18 F 18 N6O6Pd3: C 33.67, H 1.63, N 6.43; found: C 33.47, H 1.40, N 6.51.

[0136] Example 4 Synthesis of Compound I-4

[0137]

[0138] Under air conditions, Pd(OAc)₂ (896 mg, 4.0 mmol, 1.0 equiv.), DCM (40.0 mL), Na₂CO₃ (424 mg, 1.0 equiv.), and 5-(trifluoromethyl)-2-pyridone (L₄, 1304 mg, 2.0 equiv.) were added to a round-bottom flask, and the mixture was reacted at 30 °C for 12 hours. After the reaction was completed, the reaction solution was filtered through diatomaceous earth and washed three times with 5 mL of DCM each time. The filtrate was collected, and the DCM was removed to obtain an orange powder. The orange powder was washed three times with a mixed solvent of n-hexane and 1,2-dichloroethane (n-hexane:1,2-dichloroethane = 10:1, v / v) with 5.0 mL each time. The filter cake was collected to obtain compound I-4, a pale yellow powder, with a yield of 28%.

[0139] 1 H NMR (500MHz, CDCl3) δ8.40 (s, 1H), 7.44 (dd, J = 9.0, 2.5Hz, 1H), 6.69 (d, J = 8.9Hz, 1H); 13 C NMR (151MHz, CDCl3) δ173.9,144.7 144.6,135.5,122.5,117.6,116.6,116.4; 19 FNMR(470MHz, CDCl3)δ-61.74,-62.04; IR(KBr)ν max :1670,1633,1543,1437,1367,1329,1293,1245,1175,1118,1077,921,837,638,623,496cm -1 ;HRMS(ESI-TOF)m / z Calcdfor C 36 H 18 F 18 N6O6Pd3[M+Na] + :1312.7997,found:1312.8001.Elemental analysis(%)ofC 12 H6F6N2O2Pd: C 33.67, H1.63, N 6.43; found C 32.93, H 1.65, N 6.97.

[0140] Example 5: Synthesis of Compound I-5

[0141]

[0142] Under air conditions, Pd(OAc)₂ (896 mg, 4.0 mmol, 1.0 equiv.), DCM (40.0 mL), Na₂CO₃ (424 mg, 1.0 equiv.), and 6-(trifluoromethyl)-2-pyridone (L5, 1304 mg, 2.0 equiv.) were added to a round-bottom flask, and the mixture was reacted at 30 °C for 24 hours. After the reaction was completed, the reaction solution was filtered through diatomaceous earth and washed three times with 5 mL of DCM each time. The filtrate was collected, and the DCM was removed to obtain a green powder. This powder was washed three times with 5.0 mL of a mixed solvent of n-hexane and 1,2-dichloroethane (n-hexane:1,2-dichloroethane = 10:1, v / v), and the filter cake was collected to obtain compound I-5, a pale green powder, with a yield of 14%.

[0143] 1 H NMR (600MHz, CDCl3) δ7.12–7.07(m,1H),6.91(d,J=6.9Hz,1H),6.45(d,J=8.7Hz,1H); 13 C NMR(150MHz, CDCl3)δ175.35,144.02,143.80,136.48,122.46,122.04,120.22,111.18; IR(KBr)ν max :3444,3179,3122,3092,2960,2930,2868,2486,1627,1559,1498,1457,1400,1374,1306 ,1246,1183,1146,1128,1079,1011,926,806,763,733,680,631,605,554,537,469,410cm -1 ;HRMS(ESI-TOF)m / z Calcd for C 24 H 12 F 12 N4O4Pd2[M+H] + :860.8809,found:860.8804.Elemental analysis(%)of C 12 H6F6N2O2Pd: C 33.67, H 1.63, N6.43; found C 31.48, H 1.60, N 6.36.

[0144] Example 6 Synthesis of Compound 1

[0145]

[0146] 4-Bromobenzonitrile (18.2 mg, 0.1 mmol, 1.0 equiv.), K2CO3 (27.6 mg, 2.0 equiv.), 3-chlorophenylboronic acid (31.2 mg, 2.0 equiv.), compound I-3 (0.011 mg, calculated as 0.025 mol% of 4-bromobenzonitrile based on the molecular weight of Pd(L3)2 monomer of compound I-3 of 430), and anhydrous ethanol (1.0 mL) were added to a vial, and the vial was placed in ambient air. The mixture was sealed and stirred at 90°C for 24 hours. After cooling to room temperature, EtOAc (1.0 mL) and H2O (1.0 mL) were added, and the layers were separated. The aqueous layer was extracted three times with EtOAc (1.0 mL). The organic layers were combined, washed with saturated brine, dried over MgSO4, filtered, and concentrated under vacuum to obtain the crude product. The crude product was then separated by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 1, yield: 99%. f =0.3.

[0147] 1 H NMR (500MHz, CDCl3) δ7.74(d,J=8.4Hz,2H),7.66(d,J=8.4Hz,2H),7.58–7.55(m,1H),7.46(dt,J=6.9,1.9Hz,1H),7.44–7.37(m,2H); 13 C NMR (125MHz, CDCl3) δ144.2,141.0,135.1,132.7,130.4,128.7,127.8,127.4,125.4,118.7,111.7.

[0148] Example 7 Synthesis of Compound 2

[0149]

[0150] 3-Fluorophenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 2, yield: 99%, R. f =0.3.

[0151] 1H NMR (500MHz, CDCl3) δ7.74(d,J=8.5Hz,2H),7.67(d,J=8.6Hz,2H),7.45(td,J=8.0,5.8Hz,1 H),7.40–7.34(m,1H),7.28(ddd,J=9.9,2.6,1.7Hz,1H),7.12(tdd,J=8.4,2.6,1.0Hz,1H); 13 C NMR (125MHz, CDCl3) δ164.2,162.3,144.34,144.32,141.42,141.36,132.7,130 .75,130.68,127.8,122.93,122.91,118.7,115.6,115.5,114.3,114.1,111.6.

[0152] Example 8 Synthesis of Compound 3

[0153]

[0154] 3-Methylphenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 3, yield: 99%, R. f =0.3.

[0155] 1 H NMR (500MHz, CDCl3) δ7.71(d,J=8.6Hz,2H),7.67(d,J=8.6Hz,2H),7.41–7.33(m,3H),7.24(d,J=7.4Hz,1H),2.43(s,3H); 13 C NMR (125MHz, CDCl3) δ145.9,139.2,138.8,132.5,129.4,129.0,128.0,127.8,124.4,119.0,110.8,21.5.

[0156] Example 9 Synthesis of Compound 4

[0157]

[0158] 3-Methoxyphenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 4, yield: 99%, R. f =0.3.

[0159] 1 H NMR (500MHz, CDCl3) δ7.71(d,J=8.5Hz,2H),7.67(d,J=8.6Hz,2H),7.39(t,J=7.9Hz,1H),7.16(ddd, J=7.7,1.7,0.9Hz,1H),7.10(dd,J=2.5,1.7Hz,1H),6.96(ddd,J=8.3,2.5,0.9Hz,1H),3.87(s,3H); 13 C NMR (125MHz, CDCl3) δ160.2,145.6,140.7,132.6,130.2,127.8,119.7,118.9,113.9,113.1,111.1,55.4.

[0160] Example 10 Synthesis of Compound 5

[0161]

[0162] 4-Methoxyphenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 5, yield: 99%, R. f =0.3.

[0163] 1 H NMR (500MHz, CDCl3) δ7.68(d,J=8.7Hz,2H),7.63(d,J=8.5Hz,2H),7.53(d,J=8.8Hz,2H),7.00(d,J=8.8Hz,2H),3.86(s,3H); 13 C NMR (125MHz, CDCl3) δ160.3,145.3,132.6,131.5,128.4,127.1,119.1,114.6,110.2,55.4.

[0164] Example 11 Synthesis of Compound 6

[0165]

[0166] 4-Methylphenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 6, yield: 99%, R. f =0.3.

[0167] 1H NMR (500MHz, CDCl3) δ7.70(d,J=8.6Hz,2H),7.66(d,J=8.6Hz,2H),7.48(d,J=8.2Hz,2H),7.28(d,J=7.9Hz,2H),2.41(s,3H); 13 C NMR (125MHz, CDCl3) δ145.6,138.8,136.3,132.6,129.9,127.5,127.1,119.0,110.6,21.2.

[0168] Example 12 Synthesis of Compound 7

[0169]

[0170] 4-Chlorophenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 7, yield: 99%, R. f =0.3.

[0171] 1 H NMR (500MHz, CDCl3) δ7.73(d,J=8.5Hz,2H),7.65(d,J=8.4Hz,2H),7.52(d,J=8.6Hz,2H),7.45(d,J=8.6Hz,2H); 13 C NMR (125MHz, CDCl3) δ144.4,137.6,135.0,132.7,129.3,128.5,127.6,118.8,111.3.

[0172] Example 13 Synthesis of Compound 8

[0173]

[0174] 2-Methylphenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 8, yield: 99%. f =0.3.

[0175] 1 H NMR (500MHz, CDCl3) δ7.70(d,J=8.4Hz,2H),7.43(d,J=8.3Hz,2H),7.35–7.25(m,3H),7.18(d,J=6.7Hz,1H),2.25(s,3H); 13C NMR (125MHz, CDCl3) δ146.8,140.0,135.0,132.0,130.7,130.0,129.4,128.3,126.1,119.0,110.8,20.3.

[0176] Example 14 Synthesis of Compound 9

[0177]

[0178] 2-Methoxyphenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 9, yield: 98%. f =0.3.

[0179] 1 H NMR (500MHz, CDCl3) δ7.67(d,J=8.6Hz,2H),7.63(d,J=8.6Hz,2H),7.38(ddd,J=8.3,7.4,1.8Hz,1H) ,7.29(dd,J=7.6,1.7Hz,1H),7.05(td,J=7.5,1.1Hz,1H),7.01(dd,J=8.2,1.1Hz,1H),3.82(s,3H); 13 C NMR (125MHz, CDCl3) δ156.4,143.4,131.8,130.6,130.3,130.0,128.7,121.1,119.2,111.4,110.5,55.6.

[0180] Example 15 Synthesis of Compound 10

[0181]

[0182] 2-Fluorophenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 10, yield: 96%. f =0.3.

[0183] 1 H NMR (500MHz, CDCl3) δ7.73(d,J=8.6Hz,2H),7.66(dd,J=8.5,1.6Hz,2H),7.46–7.35(m,2H),7.28–7.23(m,1H),7.19(ddd,J=10.8,8.2,1.2Hz,1H); 13C NMR (125MHz, CDCl3) δ160.7,158.7,140.5,132.2,130.50,130.47,130.45,130 .4,129.72,129.69,127.2,127.1,124.76,124.73,118.8,116.5,116.4,111.4.

[0184] Example 16 Synthesis of Compound 11

[0185]

[0186] 3-Chlorophenylboronic acid was substituted for phenylboronic acid in Example 6, and 0.1 mol% of compound I-3 was used, with other reaction conditions the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 11, yield: 95%. f =0.3.

[0187] 1 H NMR (500MHz, CDCl3) δ7.72(d,J=8.6Hz,2H),7.68(d,J=8.5Hz,2H),7.59(d,J=7.0Hz,2H),7.48(t,J=7.4Hz,2H),7.42(t,J=7.3Hz,1H); 13 C NMR (125MHz, CDCl3) δ145.7,139.2,132.6,129.1,128.7,127.8,127.2,118.9,111.0.

[0188] Example 17 Synthesis of Compound 12

[0189]

[0190] 3-Chlorophenylboronic acid was replaced with phenylboronic acid in Example 6, and 4-bromobenzonitrile was replaced with 2-bromobenzonitrile in Example 16. 0.1 mol% of compound I-3 was used, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 12, yield: 99%. f =0.3.

[0191] 1 H NMR (500MHz, CDCl3) δ7.76 (dd, J=7.8, 1.4Hz, 1H), 7.64 (td, J=7.7, 1.4Hz, 1H), 7.58–7.54 (m, 2H), 7.53–7.47 (m, 3H), 7.46–7.41 (m, 2H);13 C NMR (125MHz, CDCl3) δ145.5,138.2,133.8,132.8,130.1,128.8,128.7,128.7,127.6,118.7,111.3.

[0192] Example 18 Synthesis of Compound 13

[0193]

[0194] 3-Chlorophenylboronic acid was replaced with phenylboronic acid in Example 6, and 4-bromobenzonitrile was replaced with 3-bromobenzonitrile in Example 6. 0.1 mol% of compound I-1 was used, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 13, yield: 99%. f =0.3.

[0195] 1 H NMR (500MHz, CDCl3) δ7.86 (s, 1H), 7.81 (d, J = 7.8Hz, 1H), 7.62 (dt, J = 7.7, 1.4Hz, 1H), 7.58–7.51 (m, 3H), 7.48 (t, J = 7.5Hz, 2H), 7.41 (t, J = 7.3Hz, 1H); 13 C NMR (125MHz, CDCl3) δ142.5,138.9,131.5,130.72,130.70,129.6,129.1,128.4,127.1,118.9,113.0.

[0196] Example 19 Synthesis of Compound 14

[0197]

[0198] 4-Methylphenylboronic acid replaced 3-chlorophenylboronic acid in Example 6, and 2-bromonitrobenzene replaced 4-bromobenzonitrile in Example 6; other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 14, yield: 99%. f =0.3.

[0199] 1 H NMR (500MHz, CDCl3) δ7.82(d,J=8.0Hz,1H),7.59(t,J=7.4Hz,1H),7.49–7.40(m,2H),7.22(d,J=3.8Hz,4H),2.40(s,3H); 13C NMR (125MHz, CDCl3) δ149.4,138.2,136.3,134.4,132.2,132.0,129.5,127.9,127.8,124.0,21.3.

[0200] Example 20 Synthesis of Compound 15

[0201]

[0202] 3-Chlorophenylboronic acid was replaced with phenylboronic acid in Example 6, and 4-bromophenylacetophenone was replaced with 2-bromobenzonitrile in Example 6. 0.1 mol% of compound I-3 was used, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 15, yield: 99%. f =0.3.

[0203] 1 H NMR (500MHz, CDCl3) δ7.55 (dd, J=7.6, 1.5Hz, 1H), 7.51 (td, J=7.5, 1.5Hz, 1H), 7.46–7.36 (m, 5H), 7.37–7.32 (m, 2H), 2.00 (s, 3H); 13 C NMR (125MHz, CDCl3) δ205.0,140.9,140.8,140.5,130.8,130.3,128.9,128.7,127.9,127.9,127.5,30.5.

[0204] Example 21 Synthesis of Compound 16

[0205]

[0206] 3-Chlorophenylboronic acid was replaced with phenylboronic acid in Example 6, and 4-bromophenylacetophenone was replaced with 3-bromobenzonitrile in Example 6. 0.1 mol% of compound I-3 was used, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 16, yield: 99%. f =0.3.

[0207] 1H NMR(500MHz, CDCl3)δ8.18(s,1H),7.97–7.91(m,1H),7.83–7.76(m,1H),7.62(d,J=7.0H z,2H),7.54(t,J=7.7Hz,1H),7.47(t,J=7.6Hz,2H),7.39(t,J=7.4Hz,1H),2.66(s,3H); 13 C NMR (125MHz, CDCl3) δ198.1,141.8,140.2,137.7,131.8,129.1,129.0,127.8,127.2,127.0,26.8.

[0208] Example 22 Synthesis of Compound 17

[0209]

[0210] 3-Chlorophenylboronic acid was replaced with phenylboronic acid in Example 6, and 4-bromoacetophenone was replaced with 4-bromobenzonitrile in Example 6. 0.1 mol% of compound I-3 was used, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 17, yield: 99%. f =0.3.

[0211] 1 H NMR (500MHz, CDCl3) δ8.03(d,J=8.2Hz,2H),7.69(d,J=8.1Hz,2H),7.63(d,J=6.9Hz,2H),7.47(t,J=7.6Hz,2H),7.40(t,J=7.3Hz,1H),2.64(s,3H); 13 C NMR (125MHz, CDCl3) δ197.8,145.8,139.9,135.9,128.98,128.94,128.3,127.30,127.25,26.7.

[0212] Example 23 Synthesis of Compound 18

[0213]

[0214] 3-Chlorophenylboronic acid was replaced with phenylboronic acid in Example 6, and 4-bromobenzoic acid was replaced with methyl o-bromobenzoate in Example 6. 0.1 mol% of compound I-3 was used, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 18, yield: 99%. f =0.3.

[0215] 1 H NMR (500MHz, CDCl3) δ7.82 (d, J = 7.7Hz, 1H), 7.56–7.49 (m, 1H), 7.39 (qd, J = 11.3, 10.7, 7.2Hz, 5H), 7.34–7.29 (m, 2H), 3.63 (s, 3H); 13 C NMR (125MHz, CDCl3) δ169.2,142.5,141.3,131.3,130.9,130.7,129.8,128.3,128.1,127.3,127.2,52.0.

[0216] Example 24 Synthesis of Compound 19

[0217]

[0218] 3-Chlorophenylboronic acid was replaced with phenylboronic acid in Example 6, and 4-bromobenzonitrile was replaced with 1-bromocarbazole in Example 6. 0.1 mol% of compound I-3 was used, and other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 19, yield: 99%. f =0.3.

[0219] 1 H NMR (500MHz, CDCl3) δ8.28 (s, 1H), 8.10 (d, J = 7.8Hz, 1H), 8.07 (d, J = 7.7Hz, 1H), 7.69 (d, J = 7. 4Hz,2H),7.55(t,J=7.6Hz,2H),7.46–7.39(m,4H),7.32(t,J=7.6Hz,1H),7.27–7.24(m,1H); 13 C NMR (125MHz, CDCl3) δ139.5,139.1,137.3,129.3,128.4,127.6,126.0,125.8,125.1,123.7,123.6,120.5,119.9,119.6,119.5,110.7.

[0220] Example 25 Synthesis of Compound 20

[0221]

[0222] Benzylboronic acid replaced 3-chlorophenylboronic acid in Example 6, 3-bromocarbazole replaced 4-bromobenzonitrile in Example 6, and 0.1 mol% of compound I-3 was used. Other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 5:1 (v / v) as the developing solvent to obtain compound 20, yield: 99%. f =0.3.

[0223] 1 H NMR(500MHz, CDCl3)δ8.29(d,J=1.8Hz,1H),8.12(d,J=7.7Hz,1H),8.06(s,1H),7.71(dd,J=8.2,1.2Hz,2H), 7.67(dd,J=8.4,1.8Hz,1H),7.51–7.44(m,3H),7.46–7.41(m,2H),7.34(t,J=7.4Hz,1H),7.28–7.23(m,1H); 13 C NMR (125MHz, CDCl3) δ142.1,140.0,139.0,133.1,128.78,127.3,126.5,126.1,125.5,123.9,123.5,120.4,119.6,118.9,110.8,110.7.

[0224] Example 26 Synthesis of Compound 21

[0225]

[0226] Benzylboronic acid replaced 3-chlorophenylboronic acid in Example 6, 2-bromophenol replaced 4-bromobenzonitrile in Example 6, and 0.1 mol% of compound I-3 was used. Other reaction conditions were the same as in Example 6. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 21, yield: 89%. f =0.3.

[0227] 1 H NMR (500MHz, CDCl3) δ7.48(p,J=7.0,6.3Hz,4H),7.43–7.37(m,1H),7.25(q,J=5.4,4.8Hz,2H),7.00(t,J=7.7Hz,2H),5.15(s,1H); 13 C NMR (125MHz, CDCl3) δ152.4,137.1,130.3,129.3,129.2,129.1,128.1,127.9,120.9,115.8.

[0228] Example 27 Synthesis of Compound 22

[0229]

[0230] In a vial equipped with a magnetic stir bar, methyl bromobenzoate (21.5 mg, 0.1 mmol, 1.0 equiv), K₂CO₃ (27.6 mg, 2.0 equiv), 2-methylstyrene (2.0 equiv), compound I-2 (0.11 mg, calculated as 0.25 mol% of methyl bromobenzoate based on the molecular weight of Pd(L₂)₂ monomer 430), and 1,4-dioxane (1.0 mL) were added. The vial was sealed under ambient air and stirred at 90 °C for 24 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and EtOAc (1.0 mL) and H₂O (1.0 mL) were added. The layers were separated, and the aqueous layer was extracted three times with EtOAc (1.0 mL). The organic layers were combined, washed with saturated brine, dried with Na₂SO₄, filtered, and concentrated under vacuum to obtain the crude product. The crude product was prepared by hexanes / EtOAc ratio. Separation was performed by silica gel thin-layer chromatography using a 10:1 (v / v) eluent to obtain 22 after oxidation, yield: 98%, R f =0.3.

[0231] 1 H NMR (500MHz, CDCl3) δ8.03(d,J=8.0Hz,2H),7.60(d,J=6.1Hz,1H),7.56(d,J=8.2Hz,2H),7 .44(d,J=16.2Hz,1H),7.25–7.17(m,3H),7.01(d,J=16.2Hz,1H),3.92(s,3H),2.44(s,3H); 13 C NMR (125MHz, CDCl3) δ166.9,142.2,136.2,135.8,130.6,130.1,129.0,128.90,128.89,128.2,126.4,126.3,125.5,52.1,19.9.

[0232] Example 28 Synthesis of Compound 23

[0233]

[0234] 3-Chlorostyrene replaced 2-methylstyrene in Example 27, and other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 23, yield: 83%, R. f =0.3.

[0235] 1 H NMR (500MHz, CDCl3) δ8.03(d,J=8.0Hz,2H),7.55(d,J=8.0Hz,2H),7.52(s,1H),7. 38(d,J=7.5Hz,1H),7.30(t,J=7.7Hz,1H),7.26(s,1H),7.12(s,2H),3.92(s,3H); 13 C NMR (125MHz, CDCl3) δ166.8,141.3,138.7,134.8,130.1,130.0,129.7,129.3,129.0,128.1,126.6,126.5,125.0,52.1.

[0236] Example 29 Synthesis of Compound 24

[0237]

[0238] 4-Fluorostyrene replaced 2-methylstyrene in Example 27, and other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 24, yield: 73%. f =0.3.

[0239] 1 H NMR (500MHz, CDCl3) δ8.02(d,J=8.0Hz,2H),7.54(d,J=8.0Hz,2H),7.50(dd,J=8.4,5.5Hz,2H),7.16(d,J=16.3Hz,1H),7.11–6.99(m,3H),3.92(s,3H); 13 C NMR (125MHz, CDCl3) δ166.9,163.7,161.7,141.7,132.98,132.96,130.1,130.0,129.0,128.4,128.3,127.38,127.36,126.3,115.9,115.7,52.1.

[0240] Example 30 Synthesis of Compound 25

[0241]

[0242] Methyl 3-bromobenzoate replaced methyl p-bromobenzoate in Example 27, and other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 25, yield: 80%. f=0.3.

[0243] 1 H NMR (500MHz, CDCl3) δ8.18(s,1H),7.90(d,J=7.7Hz,1H),7.66(d,J=7.8Hz,1H),7.41( t,J=7.9Hz,3H),7.20–7.12(m,3H),7.07(d,J=16.4Hz,1H),3.94(s,3H),2.36(s,3H); 13 C NMR (125MHz, CDCl3) δ167.1,137.93,137.91,134.2,130.7,130.6,129.9,129.5,128.7,128.3,127.4,126.59,126.57,52.2,21.3.

[0244] Example 31 Synthesis of Compound 26

[0245]

[0246] Ethyl acrylate replaced 2-methylstyrene in Example 27, and 1.0 mol% of compound I-2 was used, with other reaction conditions the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 26, yield: 99%. f =0.3.

[0247] 1 H NMR (500MHz, CDCl3) δ8.05(d,J=8.5Hz,2H),7.70(d,J=16.0Hz,1H),7.58(d,J=8.5Hz,2H), 6.52(d,J=16.1Hz,1H), 4.28(q,J=7.1Hz,2H), 3.93(d,J=2.0Hz,3H), 1.35(t,J=7.1Hz,3H); 13 C NMR (125MHz, CDCl3) δ166.53,166.46,143.2,138.7,131.3,130.1,127.9,120.7,60.8,52.3,14.3.

[0248] Example 32 Synthesis of Compound 27

[0249]

[0250] 4-Bromobenzonitrile replaced methyl p-bromobenzoate in Example 27, and 4-fluorostyrene replaced 2-methylstyrene in Example 27; other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 27, yield: 70%. f =0.3.

[0251] 1 H NMR (500MHz, CDCl3) δ7.63(d,J=8.0Hz,2H),7.56(d,J=8.0Hz,2H),7.50(dd,J=8.4 ,5.3Hz,2H),7.17(d,J=16.3Hz,1H),7.08(t,J=8.5Hz,2H),7.00(d,J=16.3Hz,1H); 13 C NMR (125MHz, CDCl3) δ163.89,161.91,141.7,132.54,132.51,131.2,128.58,128.51,126.8,126.6,126.5,119.0,116.0,115.8,110.7.

[0252] Example 33 Synthesis of Compound 28

[0253]

[0254] 2-Bromobenzonitrile replaced methyl p-bromobenzoate in Example 27, and 1.0 mol% compound I-2,4-methylstyrene replaced 2-methylstyrene in Example 27; other reaction conditions were the same as in Example 26. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 28, yield: 79%. f =0.3.

[0255] 1 H NMR (500MHz, CDCl3) δ7.78(d,J=8.0Hz,1H),7.63(d,J=7.8Hz,1H),7.56(t,J=7.7Hz,1H),7.47(d,J=7.8Hz,2 H),7.40(d,J=16.2Hz,1H),7.30(t,J=7.6Hz,1H),7.24(d,J=15.2Hz,1H),7.19(d,J=7.8Hz,2H),2.37(s,3H); 13C NMR (125MHz, CDCl3) δ140.80,139.0,133.42,133.36,133.1,132.8,129.6,127.3,127.1,125.1,123.0,118.1,111.1,21.4.

[0256] Example 34 Synthesis of Compound 29

[0257]

[0258] 2-Bromonitrobenzene replaced methyl p-bromobenzoate in Example 27, and 4-methylstyrene replaced 2-methylstyrene in Example 27; other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 29, yield: 99%. f =0.3.

[0259] 1 H NMR (500MHz, CDCl3) δ7.94(d,J=8.2Hz,1H),7.75(d,J=7.9Hz,1H),7.61–7.51(m,2H),7.43(d,J =7.7Hz,2H),7.37(t,J=7.5Hz,1H),7.18(d,J=7.8Hz,2H),7.06(d,J=16.1Hz,1H),2.37(s,3H); 13 C NMR (125MHz, CDCl3) δ148.0,138.7,133.9,133.8,133.2,133.0,129.6,128.1,127.7,127.1,124.8,122.4,21.4.

[0260] Example 35 Synthesis of Compound 30

[0261]

[0262] 2-Bromo-4-fluoronitrobenzene replaced methyl p-bromobenzoate in Example 27, 1.0 mol% of compound I-2, and 4-fluorostyrene replaced 2-methylstyrene in Example 27. Other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 30, yield: 70%. f =0.3.

[0263] 1H NMR (500MHz, CDCl3) δ8.06(dd,J=9.1,5.2Hz,1H),7.58–7.50(m,3H),7.41(dd,J=9.5,2.7Hz,1H),7.14–6.98(m,4H); 13 C NMR (125MHz, CDCl3) δ165.9,164.1,163.8,162.1,144.0,136.4,136.3,133.8,132.3,132.3,128 .97,128.90,127.92,127.84,122.70,122.69,122.67,116.0,115.9,115.2,115.0,114.7,114.5.

[0264] Example 36 Synthesis of Compound 31

[0265]

[0266] 4-Bromoanisole replaced methyl p-bromobenzoate in Example 27, 1.0 mol% of compound I-2, and 4-methylstyrene replaced 2-methylstyrene in Example 27; other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 31, yield: 71%. f =0.3.

[0267] 1 H NMR (500MHz, CDCl3) δ7.44(d,J=8.6Hz,2H),7.38(d,J=7.8Hz,2H),7.15(d,J=7.8Hz,2H),7.0 2(d,J=16.3Hz,1H),6.95(d,J=16.3Hz,1H),6.89(d,J=8.6Hz,2H),3.82(s,3H),2.35(s,3H); 13 C NMR (125MHz, CDCl3) δ159.2,137.1,134.9,130.4,129.4,127.6,127.2,126.6,126.2,114.1,55.3,21.3.

[0268] Example 37 Synthesis of Compound 32

[0269]

[0270] 4-Bromo-2,6-difluoroanisole replaced methyl p-bromobenzoate in Example 27, and 4-methylstyrene replaced 2-methylstyrene in Example 27; other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 32, yield: 87%. f =0.3.

[0271] 1 H NMR (500MHz, CDCl3) δ7.37(d,J=8.2Hz,2H),7.17(d,J=7.8Hz,2H),7.06–6.97(m ,2H),6.96(d,J=16.2Hz,1H),6.87(d,J=16.2Hz,1H),4.00(s,3H),2.36(s,3H); 13 C NMR (125MHz, CDCl3) δ156.9,156.8,154.9,154.8,138.1,135.5,133.8,133.01,129.97,129.5,126.6 ,125.30,125.28,125.25,109.91,109.89,109.85,109.8,109.71,109.69,61.91,61.89,61.86,21.3.

[0272] Example 38 Synthesis of Compound 33

[0273]

[0274] methyl p-bromobenzoate was replaced with p-bromoacetophenone in Example 27, and 2-methylstyrene was replaced with 4-methylstyrene in Example 27. Other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 33, yield: 99%. f =0.3.

[0275] 1 H NMR (500MHz, CDCl3) δ7.94(d,J=8.0Hz,2H),7.56(d,J=8.0Hz,2H),7.43(d,J=7 .8Hz,2H),7.22–7.16(m,3H),7.08(d,J=16.3Hz,1H),2.60(s,3H),2.37(s,3H); 13C NMR (125MHz, CDCl3) δ197.5,142.3,138.4,135.8,133.9,131.4,129.6,128.9,126.8,126.5,126.4,26.6,21.4.

[0276] Example 39 Synthesis of Compound 34

[0277]

[0278] methyl p-bromobenzoate was replaced with p-bromobenzaldehyde in Example 27, and 2-methylstyrene was replaced with 4-methylstyrene in Example 27. Other reaction conditions were the same as in Example 27. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 34, yield: 99%. f =0.3.

[0279] 1 H NMR (500MHz, CDCl3) δ9.98 (s, 1H), 7.85 (d, J = 8.3Hz, 2H), 7.63 (d, J = 8.3Hz, 2H), 7.44 (d, J = 8. 2Hz,2H),7.23(d,J=16.5Hz,1H),7.19(d,J=7.9Hz,2H),7.09(d,J=16.2Hz,1H),2.37(s,3H); 13 C NMR (125MHz, CDCl3) δ191.6,143.7,138.6,135.2,133.8,132.2,130.2,129.6,126.9,126.8,126.4,21.3.

[0280] Example 40 Synthesis of Compound 35

[0281]

[0282] Add 2-bromonitrobenzene (20.1 mg, 0.1 mmol, 1.0 equiv.), Bu4NOAc*HOAc (72.2 mg, 2.0 equiv.) as a base, phenylacetylene (30.6 mg, 3.0 equiv.), compound I-3 (0.011 mg, calculated as 0.025 mol% of 2-bromonitrobenzene based on the amount of compound I-3 monomer Pd(L3)2 430), and DMF (1.0 mL) to a vial equipped with a magnetic stir bar. Under sealed atmosphere, the mixture was stirred at 90°C for 24 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and EtOAc (1.0 mL) and H2O (1.0 mL) were added. The layers were separated, and the aqueous layer was extracted three times with EtOAc (1.0 mL). The organic layers were combined, washed with saturated brine, dried with MgSO4, filtered, and concentrated under vacuum to obtain the crude product. The crude product was then separated by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 35, yield: 99%. f =0.6.

[0283] 1 H NMR (500MHz, CDCl3) δ8.07 (dd, J=8.2, 1.3Hz, 1H), 7.71 (dd, J=7.8, 1.5Hz, 1H), 7 .63–7.56(m,3H),7.46(ddd,J=8.7,7.4,1.5Hz,1H),7.38(dd,J=5.1,1.9Hz,3H); 13 CNMR (125MHz, CDCl3) δ149.7,134.6,132.8,132.0,129.3,128.54,128.47,124.73,122.42,118.80,97.17,84.78.

[0284] Example 41 Synthesis of Compound 36

[0285]

[0286] 3-Methylphenylacetylene was used to replace phenylacetylene in Example 40, and other reaction conditions were the same as in Example 40. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to give compound 36, yield: 99%. f =0.3.

[0287] 1H NMR (500MHz, CDCl3) δ8.07(d,J=8.1Hz,1H),7.70(d,J=7.6Hz,1H),7.59(t,J=7.5Hz ,1H),7.49–7.36(m,3H),7.26(t,J=7.6Hz,1H),7.20(d,J=7.4Hz,1H),2.36(s,3H); 13 C NMR (125MHz, CDCl3) δ149.6,138.2,134.6,132.8,132.6,130.2,129.1,128.5,128.4,124.7,122.2,118.9,97.5,84.5,21.2.

[0288] Example 42 Synthesis of Compound 37

[0289]

[0290] 4-Methylphenylacetylene was substituted for phenylacetylene in Example 40, and other reaction conditions were the same as in Example 40. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to give compound 37, yield: 98%. f =0.3.

[0291] 1 H NMR(500MHz, CDCl3)δ8.07(d,J=8.3Hz,1H),7.70(d,J=7.1Hz,1H),7.61–7.55(m,1H ),7.49(d,J=7.8Hz,2H),7.44(t,J=7.8Hz,1H),7.18(d,J=7.7Hz,2H),2.38(s,3H); 13 C NMR (125MHz, CDCl3) δ149.6,139.6,134.5,132.8,132.0,129.3,128.3,124.7,119.3,119.0,97.6,84.3,21.6.

[0292] Example 43 Synthesis of Compound 38

[0293]

[0294] 2-Bromo-4-methyl-1-nitrobenzene was substituted for 2-bromonitrobenzene in Example 40, and other reaction conditions were the same as in Example 40. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to give compound 38, yield: 70%. f =0.3.

[0295] 1 H NMR (500MHz, CDCl3) δ8.01(d,J=8.4Hz,1H),7.60(dd,J=6.8,3.0Hz,2H),7.52(s,1H),7.40–7.35(m,3H),7.26–7.21(m,1H),2.44(s,3H); 13 C NMR (125MHz, CDCl3) δ147.4,144.1,135.0,132.0,129.3,129.2,128.5,124.9,122.6,118.8,96.6,85.2,21.2.

[0296] Example 44 Synthesis of Compound 39

[0297]

[0298] 2-Bromo-4-chloro-1-nitrobenzene was substituted for 2-bromonitrobenzene in Example 40, and other reaction conditions were the same as in Example 40. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to give compound 39, yield: 70%. f =0.3.

[0299] 1 H NMR (500MHz, CDCl3) δ8.05(d,J=8.9Hz,1H),7.70(d,J=2.4Hz,1H),7.62–7.57(m,2H),7.44–7.37(m,4H); 13 C NMR (125MHz, CDCl3) δ147.8,139.4,134.2,132.2,129.7,128.7,128.6,126.2,121.9,120.6,98.7,83.9.

[0300] Example 45 Synthesis of Compound 40

[0301]

[0302] 2-Bromo-4-fluoro-1-nitrobenzene was used to replace 2-bromonitrobenzene in Example 40, and other reaction conditions were the same as in Example 40. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to give compound 45, yield: 80%. f =0.3.

[0303] 1H NMR (500MHz, CDCl3) δ8.15(dd,J=9.1,5.1Hz,1H),7.63–7.58(m,2H),7.39(d,J=7.6Hz,4H),7.14(ddd,J=9.8,7.2,2.8Hz,1H); 13 C NMR (125MHz, CDCl3) δ165.4,163.4,145.8,132.2,129.7,128.5,127.6,12 7.5,121.9,121.7,121.6,121.2,121.0,116.0,115.8,98.7,84.02,84.01.

[0304] Example 46 Synthesis of Compound 41

[0305]

[0306] 2-Bromo-4-fluoro-1-nitrobenzene was substituted for 2-bromonitrobenzene in Example 40, and other reaction conditions were the same as in Example 40. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 41, yield: 89%. f =0.3.

[0307] 1 H NMR (500MHz, CDCl3) δ7.81 (s, 1H), 7.73 (d, J = 7.9Hz, 1H), 7.60 (d, J = 7.9Hz, 1H), 7.56–7.52 (m, 2H), 7.47 (t, J = 7.8Hz, 1H), 7.40–7.35 (m, 3H); 13 C NMR (125MHz, CDCl3) δ135.6,134.9,131.8,131.4,129.3,129.0,128.5,125.0,122.3,118.1,112.9,91.8,86.9.

[0308] Example 47 Synthesis of Compound 42

[0309]

[0310] 2-Bromo-4-fluoro-1-nitrobenzene was substituted for 2-bromonitrobenzene in Example 40, and other reaction conditions were the same as in Example 40. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to obtain compound 42, yield: 96%. f =0.3.

[0311] 1H NMR (500MHz, CDCl3) δ7.66(d,J=8.0Hz,2H),7.63(d,J=8.1Hz,2H),7.60–7.54(m,2H),7.43–7.39(m,2H); 13 C NMR (125MHz, CDCl3) δ132.09,132.07,131.8,129.2,128.5,128.3,122.2,118.6 111.5,93.8,87.7.

[0312] Example 48 Synthesis of Compound 43

[0313]

[0314] Add methyl p-bromobenzoate (21.5 mg, 0.1 mmol, 1.0 equiv.), Cs2CO3 (65.0 mg, 2.0 equiv.), BrettPhos (2.0 mol% based on methyl p-bromobenzoate), methanol (3.0 equiv.), compound I-3 (0.43 mg, calculated as 1.0 mol% of methyl p-bromobenzoate based on the molecular weight of compound I-3 monomer Pd(L3)2 of 430), and 1.0 mL of toluene to a vial equipped with a magnetic stir bar. The mixture was sealed under ambient air and stirred at 90°C for 24 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and EtOAc (1.0 mL) and H2O (1.0 mL) were added. The layers were separated, and the aqueous layer was extracted three times with EtOAc (1.0 mL). The organic layers were combined, washed with saturated brine, dried with MgSO4, filtered, and concentrated under vacuum to obtain the crude product. The crude product was then separated by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 43, yield: 92%. f =0.6.

[0315] 1 H NMR (500MHz, CDCl3) δ8.00(d,J=8.6Hz,2H),6.92(d,J=8.7Hz,2H),3.89(s,3H),3.86(s,3H); 13 C NMR (125MHz, CDCl3) δ166.9,163.3,131.6,122.6,113.6,55.4,51.9.

[0316] Example 49 Synthesis of Compound 44

[0317]

[0318] 4-Bromobenzonitrile replaced methyl p-bromobenzoate in Example 48, and other reaction conditions were the same as in Example 48. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 44, yield: 72%. f =0.3.

[0319] 1 H NMR (500MHz, CDCl3) δ7.59 (d, J = 8.9 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 3.86 (s, 3H); 13 C NMR (125MHz, CDCl3) δ162.9,134.0,119.2,114.8,104.0,55.5.

[0320] Example 50 Synthesis of Compound 45

[0321]

[0322] 4-Bromoacetophenone replaced methyl p-bromobenzoate in Example 48, and other reaction conditions were the same as in Example 48. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 45, yield: 71%. f =0.3.

[0323] 1 H NMR (500MHz, CDCl3) δ7.94 (d, J = 8.9 Hz, 2H), 6.93 (d, J = 8.9 Hz, 2H), 3.87 (s, 3H), 2.56 (s, 3H); 13 C NMR (125MHz, CDCl3) δ196.8,163.5,130.6,130.4,113.7,55.5,26.3.

[0324] Example 51 Synthesis of Compound 46

[0325]

[0326] 2-Bromoanthraquinone replaced methyl p-bromobenzoate in Example 48, and other reaction conditions were the same as in Example 48. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 46, yield: 82%. f =0.3.

[0327] 1H NMR (500MHz, CDCl3) δ8.30(d,J=6.7Hz,2H),8.25(d,J=9.0Hz,1H),7.82–7.73(m,2H),7.72(d,J=1.6Hz,1H),7.28–7.24(m,1H),3.99(s,3H); 13 C NMR (125MHz, CDCl3) δ183.3,182.1,164.4,135.6,134.2,133.69,133.65,133.6,129.8,127.1,121.2,110.0,56.0.

[0328] Example 52 Synthesis of Compound 47

[0329]

[0330] 4-Bromo-2-methylbenzaldehyde replaced methyl p-bromobenzoate in Example 48, and other reaction conditions were the same as in Example 48. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 47, yield: 72%. f =0.3.

[0331] 1 H NMR (500MHz, CDCl3) δ10.12(s,1H),7.76(d,J=8.6Hz,1H),6.84(dd,J=8.6,2.6Hz,1H),6.74(d,J=2.5Hz,1H),3.87(s,3H),2.65(s,3H); 13 C NMR (125MHz, CDCl3) δ191.2,163.7,143.3,134.7,128.0,117.0,111.5,55.4,19.9.

[0332] Example 53 Synthesis of Compound 48

[0333]

[0334] Add p-bromobenzaldehyde (18.5 mg, 0.1 mmol, 1.0 equiv.), Cs2CO3 (65.0 mg, 2.0 equiv.), XantPhos (2.0 mol%), N-methylaniline (2.0 equiv.), compound I-3 (0.43 mg, which is 1.0 mol% of methyl p-bromobenzoate based on the monomer molecular weight of compound I-3 of 430), and toluene (1.0 mL) to a vial equipped with a magnetic stir bar. The mixture was sealed under ambient air and stirred at 90°C for 24 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and EtOAc (1.0 mL) and H2O (1.0 mL) were added. The layers were separated, and the aqueous layer was extracted three times with EtOAc (1.0 mL). The organic layers were combined, washed with saturated brine, dried with MgSO4, filtered, and concentrated under vacuum to obtain the crude product. The crude product was then separated by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 48, yield: 99%. f =0.6.

[0335] 1 H NMR (500MHz, CDCl3) δ9.76 (s, 1H), 7.69 (d, J = 8.9Hz, 2H), 7.43 (dd, J = 8.3, 7.4Hz, 2H),7.27(d,J=7.4Hz,1H),7.27–7.20(m,2H),6.78(d,J=8.9Hz,2H),3.39(s,3H); 13 C NMR (125MHz, CDCl3) δ190.4,153.8,147.0,131.7,130.0,126.8,126.6,126.2,113.5,40.3.

[0336] Example 54 Synthesis of Compound 49

[0337]

[0338] 4-Bromo-2,6-Difluorobenzaldehyde was used to replace p-bromobenzaldehyde in Example 53, with other reaction conditions remaining the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 49, yield: 90%. f =0.3.

[0339] 1H NMR (500MHz, CDCl3) δ10.07(d,J=1.1Hz,1H),7.51–7.43(m,2H),7.35(t,J=7.4Hz,1H),7.21(dd,J=8.5,1.2Hz,2H),6.15(d,J=12.7Hz,2H),3.36(s,3H); 13 C NMR (125MHz, CDCl3) δ183.0,182.94,182.91,165.9,165.8,163.9,163.8,155.1,155.0,145.4,130.4,127.5,126.9,104.7,96.2,96.0,40.5.

[0340] Example 55 Synthesis of Compound 50

[0341]

[0342] 4-Bromo-2-fluorobenzaldehyde replaced p-bromobenzaldehyde in Example 53, and other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 50, yield: 90%. f =0.3.

[0343] 1 H NMR (500MHz, CDCl3) δ10.08(s,1H),7.66(t,J=8.5Hz,1H),7.45(dd,J=8.3,7.4Hz,2H),7.30(d,J=7.5H z,1H),7.25–7.19(m,2H),6.50(ddd,J=8.9,2.4,0.8Hz,1H),6.33(dd,J=14.2,2.3Hz,1H),3.37(s,3H); 13 C NMR (125MHz, CDCl3) δ185.4,185.4,167.5,165.5,155.6,155.5,146.2,130.2, 129.83,129.80,126.9,126.8,114.5,114.4,109.68,109.66,99.4,99.2,40.5.

[0344] Example 56 Synthesis of Compound 51

[0345]

[0346] 4-Bromo-2,6-difluoroanisole replaced p-bromobenzaldehyde in Example 53, and other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 51, yield: 99%. f =0.3.

[0347] 1 H NMR (500MHz, CDCl3) δ7.34(dd,J=8.6,7.4Hz,2H),7.15–7.03(m,3H),6.39(d,J=11.1Hz,2H),3.90(s,3H),3.24(s,3H); 13 C NMR (125MHz, CDCl3) δ157.4,157.3,155.5,155.4,147.9,145.1,145.0,144.9,129.6,129.3,129.2,124.0,123.8,62.2,40.4.

[0348] Example 57 Synthesis of Compound 52

[0349]

[0350] 4-Bromophenylacetonitrile replaced p-bromobenzaldehyde in Example 53, and other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 52, yield: 99%. f =0.3.

[0351] 1 H NMR (500MHz, CDCl3) δ7.45–7.38(m,4H),7.29–7.22(m,1H),7.23–7.17(m,2H),6.72(d,J=9.0Hz,2H),3.34(s,3H); 13 C NMR (125MHz, CDCl3) δ152.0,146.8,133.2,130.1,126.4,126.2,120.3,113.9,99.4,40.1.

[0352] Example 58 Synthesis of Compound 53

[0353]

[0354] 2-Bromoanthraquinone replaced p-bromobenzaldehyde in Example 53, and other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 53, yield: 99%. f =0.3.

[0355] 1 H NMR (500MHz, CDCl3) δ8.28(dd,J=7.5,1.4Hz,1H),8.26–8.21(m,1H),8.09(d,J=8.8Hz,1H),7.75(td,J=7.5,1.6Hz,1H),7.71(td,J=7.5,1 .6Hz,1H),7.57(d,J=2.7Hz,1H),7.49–7.43(m,2H),7.30(t,J=7.5Hz,1H),7.25(d,J=7.1Hz,2H),6.99(dd,J=8.8,2.7Hz,1H),3.48(s,3H); 13 C NMR (125MHz, CDCl3) δ184.0,181.6,153.3,146.6,135.0,134.2,134.0,133.7,133.1,130.2,129.3,126.9,126.6,123.6,118.5,110.3,40.6.

[0356] Example 59 Synthesis of Compound 54

[0357]

[0358] 6-Bromo-3(2H)-benzofuranone replaced p-bromobenzaldehyde in Example 53, and other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 54, yield: 80%. f =0.3.

[0359] 1 H NMR(500MHz, CDCl3)δ7.66(d,J=8.7Hz,1H),7.48–7.41(m,2H),7.28(t,J=7.5Hz,1H),7.22(dd, J=8.5,1.2Hz,2H),6.82(dd,J=8.7,2.2Hz,1H),6.65(d,J=1.5Hz,1H),5.15(s,2H),3.39(s,3H); 13C NMR (125MHz, CDCl3) δ171.5,154.0,149.2,147.1,130.2,126.6,126.5,126.3,115.3,114.2,105.1,69.1,40.6.

[0360] Example 60 Synthesis of Compound 55

[0361]

[0362] Ethyl 4-bromobenzoate replaced p-bromobenzaldehyde in Example 53, and other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 55, yield: 99%. f =0.3.

[0363] 1 H NMR(500MHz, CDCl3)δ7.87(d,J=9.0Hz,2H),7.42–7.35(m,2H),7.23–7.16(m,3H) ,6.77(d,J=9.0Hz,2H),4.32(q,J=7.1Hz,2H),3.36(s,3H),1.36(t,J=7.1Hz,3H); 13 CNMR (125MHz, CDCl3) δ166.8,152.5,147.6,131.0,129.8,125.8,125.2,119.7,114.0,60.3,40.2,14.5.

[0364] Example 61 Synthesis of Compound 56

[0365]

[0366] Methyl 4-bromo-2,6-difluorobenzoate replaced p-bromobenzaldehyde in Example 53, and other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 56, yield: 99%. f =0.3.

[0367] 1 H NMR (500MHz, CDCl3) δ7.44(dd,J=8.3,7.4Hz,2H),7.29(t,J=7.4Hz,1H),7.19(d,J=7.2Hz,2H),6.19(d,J=12.3Hz,2H),3.87(s,3H),3.31(s,3H); 13C NMR (125MHz, CDCl3) δ164.0,163.9,162.6,161.93,161.86,152.9,146.1,130.2,127.8,127.7,98.4,96.94,96.89,96.7,52.0,40.3.

[0368] Example 62 Synthesis of Compound 57

[0369]

[0370] Methyl 4-bromobenzoate replaced p-bromobenzaldehyde in Example 53, and other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 57, yield: 99%. f =0.3.

[0371] 1 H NMR (500MHz, CDCl3) δ7.86(d,J=9.0Hz,2H),7.42–7.36(m,2H),7.20(dtd,J=8.8,2.9,1.1Hz,3H),6.76(d,J=9.0Hz,2H),3.85(s,3H),3.36(s,3H); 13 C NMR (125MHz, CDCl3) δ167.2,152.6,147.5,131.0,129.8,125.9,125.3,119.2,113.8,51.6,40.2.

[0372] Example 63 Synthesis of Compound 58

[0373]

[0374] 4-Bromobenzoate replaced p-bromobenzaldehyde in Example 53, and aniline replaced N-methylaniline in Example 53; other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 58, yield: 86%. f =0.3.

[0375] 1 H NMR (500MHz, CDCl3) δ7.91(d,J=8.9Hz,2H),7.33(dd,J=8.5,7.4Hz,2H),7.19–7.13(m,2H),7.06(t,J=7.4Hz,1H),6.98(d,J=8.8Hz,2H),3.87(s,3H);13 C NMR (125MHz, CDCl3) δ167.0,148.1,140.9,131.5,129.5,123.2,121.2,120.5,114.6,51.7.

[0376] Example 64 Synthesis of Compound 59

[0377]

[0378] Methyl 4-bromobenzoate replaced p-bromobenzaldehyde in Example 53, and morpholine replaced N-methylaniline in Example 53; other reaction conditions were the same as in Example 53. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 59, yield: 72%. f =0.3.

[0379] 1 H NMR (500MHz, CDCl3) δ7.94(d,J=9.0Hz,2H),6.88(d,J=9.0Hz,2H),3.87(d,J=4.9Hz,3H),3.85(d,4H),3.31–3.26(m,4H); 13 C NMR (125MHz, CDCl3) δ167.0,154.1,131.2,120.5,113.6,66.6,51.7,47.8.

[0380] Example 65 Synthesis of Compound 60

[0381]

[0382] Add p-bromobenzaldehyde (18.5 mg, 0.1 mmol, 1.0 equiv.), KOAc (19.6 mg, 2.0 equiv.), DavePhos (based on methyl p-bromobenzoate, 2.0 mol%), B2pin2 (37.8 mg, 1.5 equiv.), and compound I-3 (0.43 mg, calculated as 1% of methyl p-bromobenzoate based on the molecular weight of compound I-3 monomer Pd(L3)2 of 430) to a vial equipped with a magnetic stir bar. 0.0 mol%) and 1,4-Dioxane (1,4-dioxane, 1.0 mL) were sealed under ambient air and stirred at 90 °C for 24 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and EtOAc (1.0 mL) and H2O (1.0 mL) were added. The layers were separated, and the aqueous layer was extracted three times with EtOAc (1.0 mL). The organic layers were combined, washed with saturated brine, dried with MgSO4, filtered, and concentrated under vacuum to obtain the crude product. The crude product was separated by silica gel thin-layer chromatography with hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 60, yield: 85%. f =0.2.

[0383] 1 H NMR (500MHz, CDCl3) δ10.05 (s, 1H), 7.96 (d, J = 8.0Hz, 2H), 7.86 (d, J = 8.1Hz, 2H), 1.36 (s, 12H); 13 C NMR (125MHz, CDCl3) δ192.7,138.1,135.2,128.7,84.3,24.9.

[0384] Example 66 Synthesis of Compound 61

[0385]

[0386] 4-Bromo-2-methylbenzaldehyde was used to replace p-bromobenzaldehyde in Example 65, and other reaction conditions were the same as in Example 65. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 61, yield: 80%. f =0.3.

[0387] 1 H NMR (500MHz, CDCl3) δ10.30 (s, 1H), 7.78 (d, J = 0.9Hz, 2H), 7.70 (s, 1H), 2.67 (s, 3H), 1.36 (s, 12H); 13C NMR (125MHz, CDCl3) δ193.1,139.4,138.0,135.9,132.5,130.9,84.3,24.9,19.3.

[0388] Example 67 Synthesis of Compound 62

[0389]

[0390] Methyl p-bromobenzoate replaced p-bromobenzaldehyde in Example 65, and other reaction conditions were the same as in Example 65. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 62, yield: 90%. f =0.3.

[0391] 1 H NMR (500MHz, CDCl3) δ8.02 (d, J = 7.7Hz, 2H), 7.87 (d, J = 7.7Hz, 2H), 3.92 (s, 3H), 1.36 (s, 12H); 13 C NMR (125MHz, CDCl3) δ167.2,134.7,132.3,128.6,84.2,52.2,24.9.

[0392] Example 68 Synthesis of Compound 63

[0393]

[0394] Ethyl p-bromobenzoate replaced p-bromobenzaldehyde in Example 65, and other reaction conditions were the same as in Example 65. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 63, yield: 92%. f =0.3.

[0395] 1 H NMR (500MHz, CDCl3) δ8.02(d,J=8.3Hz,2H),7.87(d,J=8.3Hz,2H),4.38(q,J=7.1Hz,2H),1.40(t,J=7.1Hz,3H),1.36(s,12H); 13 C NMR (125MHz, CDCl3) δ166.7,134.6,132.7,128.6,84.2,61.0,24.9,14.3.

[0396] Example 69 Synthesis of Compound 64

[0397]

[0398] p-Bromoacetophenone replaced p-bromobenzaldehyde in Example 65, and other reaction conditions were the same as in Example 65. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 64, yield: 70%. f =0.3.

[0399] 1 H NMR (500MHz, CDCl3) δ7.93 (d, J = 8.3Hz, 2H), 7.89 (d, J = 8.4Hz, 2H), 2.61 (s, 3H), 1.36 (s, 12H); 13 C NMR (125MHz, CDCl3) δ198.5,139.0,134.9,127.3,84.2,27.8,24.9.

[0400] Example 70 Synthesis of Compound 65

[0401]

[0402] 2-Bromoanthraquinone replaced p-bromobenzaldehyde in Example 65, and other reaction conditions were the same as in Example 65. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 65, yield: 80%. f =0.3.

[0403] 1 H NMR (500MHz, CDCl3) δ8.75 (s, 1H), 8.36–8.27 (m, 3H), 8.20 (dd, J = 7.6, 1.3Hz, 1H), 7.85–7.76 (m, 2H), 1.39 (s, 12H); 13 C NMR (125MHz, CDCl3) δ183.4,183.2,140.1,135.12,134.2,134.0,133.8,133.62,133.60,132.5,127.3,127.2,127.2,84.6,24.9.

[0404] Example 71 Synthesis of Compound 66

[0405]

[0406] p-Bromoacetophenone replaced p-bromobenzaldehyde in Example 65, and other reaction conditions were the same as in Example 65. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 66, yield: 75%.f =0.3.

[0407] 1 H NMR (500MHz, CDCl3) δ7.88 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H), 1.35 (s, 12H); 13 C NMR (125MHz, CDCl3) δ135.1,131.1,118.9,114.6,84.5,24.9.

[0408] Example 72 Synthesis of Compound 67

[0409]

[0410] In a vial equipped with a magnetic stir bar, add N-acetanilide (13.5 mg, 0.1 mmol, 1.0 equiv.), Ag₂CO₃ (55.0 mg, 2.0 equiv.), PTSA (based on N-acetanilide, p-toluenesulfonic acid, 8.6 mg, 0.5 equiv.), acetic acid (100 μL), methyl acrylate (20.0 mg, 2.0 equiv.), and compound I-2 (4.3 mg, calculated based on the molecular weight of compound I-2 monomer Pd(L₂)₂ of 430, representing N-acetanilide). Aniline (10 mol%) and HFIP (1,1,1,3,3,3-hexafluoro-2-propanol, 1.0 mL) were sealed under ambient air and stirred at 90 °C for 24 hours. After the reaction was completed, the reaction solution was cooled to room temperature, diluted with EtOAc (1.0 mL), filtered through diatomaceous earth, and the filter cake was washed with ethyl acetate (5.0 mL). The organic phases were combined and concentrated under vacuum to obtain the crude product. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to obtain compound 67, yield: 97%. f =0.2.

[0411] 1 H NMR (500MHz, CDCl3) δ7.81(d,J=15.8Hz,1H),7.71(d,J=8.0Hz,1H),7.54(d,J=7.6Hz,1H),7.47(s,1H), 7.37(t,J=7.8Hz,1H),7.19(t,J=7.7Hz,1H),6.39(d,J=15.8Hz,1H),3.80(d,J=0.9Hz,3H),2.22(s,3H); 13C NMR (125MHz, CDCl3) δ168.9,167.2,139.6,135.9,130.8,127.7,127.1,125.9,125.3,120.2,51.8,24.1.

[0412] Example 73 Synthesis of Compound 68

[0413]

[0414] Ethyl acrylate replaced methyl acrylate in Example 72, and other reaction conditions were the same as in Example 72. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to give compound 68, yield: 98%. f =0.2.

[0415] 1 H NMR (500MHz, CDCl3) δ7.82(d,J=15.8Hz,1H),7.71(d,J=8.1Hz,1H),7.55(t,J=11.3Hz,2H),7.37(t,J=7 .8Hz,1H),7.19(t,J=7.7Hz,1H),6.37(s,1H),4.25(q,J=7.1Hz,2H),2.22(s,3H),1.33(t,J=7.2Hz,3H); 13 C NMR (125MHz, CDCl3) δ169.0,166.9,139.4,135.9,130.8,127.7,127.1,125.9,125.4,120.5,60.8,24.1,14.3.

[0416] Example 74 Synthesis of Compound 69

[0417]

[0418] Ethyl acrylate replaced methyl acrylate in Example 72, and other reaction conditions were the same as in Example 72. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to give compound 68, yield: 98%. f =0.2.

[0419] 1H NMR (500MHz, CDCl3) δ7.81(d,J=15.8Hz,1H),7.71(d,J=8.1Hz,1H),7.54(d,J=7.8Hz,2H),7.36(t,J=7.8Hz,1H),7.19(t,J=7.7 Hz,1H),6.38(d,J=15.7Hz,1H),4.19(t,J=6.7Hz,2H),2.21(s,3H),1.72–1.62(m,2H),1.48–1.36(m,2H),0.96(t,J=7.4Hz,3H); 13 C NMR (125MHz, CDCl3) δ169.0,166.9,139.4,135.9,130.8,127.7,127.1,125.9,125.4,120.6,64.7,30.7,24.1,19.2,13.7.

[0420] Example 75 Synthesis of Compound 70

[0421]

[0422] N,N-Dimethylacrylamide replaced methyl acrylate in Example 72, and other reaction conditions were the same as in Example 72. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to give compound 70, yield: 82%. f =0.2.

[0423] 1 H NMR (500MHz, CDCl3) δ7.90 (s, 1H), 7.84 (d, J = 15.4Hz, 2H), 7.51 (d, J = 7.8Hz, 1H), 7.36 (t, J = 7. 8Hz,1H),7.16(t,J=7.7Hz,1H),6.81(d,J=15.2Hz,1H),3.16(s,3H),3.05(s,3H),2.22(s,3H); 13 C NMR (125MHz, CDCl3) δ169.0,166.7,137.5,136.1,130.2,127.9,127.7,125.3,124.8,119.9,37.5,36.0,24.2.

[0424] Example 76 Synthesis of Compound 71

[0425]

[0426] Diethyl vinyl phosphate replaced methyl acrylate in Example 72, and other reaction conditions were the same as in Example 72. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to give compound 71, yield: 78%. f =0.2.

[0427] 1 H NMR(500MHz, CDCl3)δ8.10(s,1H),7.79–7.63(m,2H),7.54(d,J=7.9Hz,1H),7.38(t,J=7.7Hz,1H),7.19( t,J=7.6Hz,1H),6.21(t,J=17.8Hz,1H),4.11(dd,J=8.6,6.0Hz,4H),2.23(s,3H),1.33(t,J=7.1Hz,6H); 13 C NMR (125MHz, CDCl3) δ169.2,144.1,136.0,130.8,127.5,125.7,125.6,116.7,115.2,62.1,62.0,24.0,16.4,16.3.

[0428] Example 77 Synthesis of Compound 72

[0429]

[0430] Phenyl vinyl sulfone replaced methyl acrylate in Example 72, and other reaction conditions were the same as in Example 72. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to give compound 72, yield: 78%. f =0.2.

[0431] 1 H NMR (500MHz, CDCl3) δ7.95(d,J=7.2Hz,2H),7.83(d,J=15.3Hz,1H),7.68(s,1H),7.63(t,J=7.5Hz,1H),7.56(q,J=7.6 ,6.1Hz,3H),7.44(d,J=7.8Hz,1H),7.39(t,J=7.9Hz,1H),7.18(d,J=7.8Hz,1H),6.81(d,J=15.3Hz,1H),2.23(s,3H); 13C NMR (125MHz, CDCl3) δ169.3,140.2,137.9,136.4,133.6,131.7,129.4,128.7,127.8,127.4,127.4,127.3,105.3,24.0.

[0432] Example 78 Synthesis of Compound 73

[0433]

[0434] 2,3,4,5,6-Pentafluorostyrene replaced methyl acrylate in Example 72, and other reaction conditions were the same as in Example 72. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to give compound 73, yield: 88%. f =0.2.

[0435] 1 H NMR (500MHz, DMSO-d6) δ9.75 (s, 1H), 7.82 (d, J = 7.8Hz, 1H), 7.53 (d, J = 16.7Hz, 1H),7.40–7.33(m,2H),7.29–7.23(m,1H),6.98(d,J=16.7Hz,1H),2.06(s,3H); 13 CNMR(150MHz,DMSO-d6)δ169.2,145.5,143.9,138.6,137.0,136.7,134.0,131.5,1 29.7,129.1,127.1,126.4,126.3,123.4,119.4,113.7,112.9,112.8,112.7,23.5.

[0436] Example 79 Synthesis of Compound 74

[0437]

[0438] p-Methylacetanilide replaced acetanilide in Example 72, and ethyl acrylate replaced methyl acrylate in Example 72; other reaction conditions were the same as in Example 72. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to obtain compound 74, yield: 74%. f =0.2.

[0439] 1H NMR (500MHz, CDCl3) δ7.77(d,J=15.8Hz,1H),7.57–7.50(m,1H),7.35(s,2H),7.18(d,J=8.3Hz,1H ),6.37(d,J=15.8Hz,1H),4.25(q,J=7.1Hz,2H),2.33(s,3H),2.21(s,3H),1.33(t,J=7.1Hz,3H); 13 C NMR (125MHz, CDCl3) δ169.0,166.9,139.5,135.8,133.4,131.6,127.9,127.4,125.6,120.3,60.7,24.0,20.9,14.3.

[0440] Example 80 Synthesis of Compound 75

[0441]

[0442] p-Methylacetanilide replaced acetanilide in Example 72, and ethyl acrylate replaced methyl acrylate in Example 72; other reaction conditions were the same as in Example 72. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to obtain compound 75, yield: 81%. f =0.2.

[0443] 1 H NMR (500MHz, CDCl3) δ7.76(d,J=15.9Hz,1H),7.47(d,J=8.8Hz,1H),7.29(s,1H),7.05(d,J=2.9Hz,1H),6.93(dd, J=8.9,2.9Hz,1H),6.37(d,J=15.9Hz,1H),4.27(q,J=7.1Hz,2H),3.81(s,3H),2.20(s,3H),1.33(t,J=7.1Hz,3H); 13 C NMR (125MHz, CDCl3) δ169.3,166.7,157.7,139.4,130.0,129.0,127.8,120.6,116.8,111.3,60.7,55.5,23.8,14.3.

[0444] Example 81 Synthesis of Compound 76

[0445]

[0446] m-Methylacetanilide replaced acetanilide in Example 72, and ethyl acrylate replaced methyl acrylate in Example 72; other reaction conditions were the same as in Example 72. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to obtain compound 76, yield: 98%. f =0.2.

[0447] 1 H NMR (500MHz, CDCl3) δ7.78(d,J=15.8Hz,1H),7.53(s,1H),7.47(s,1H),7.44(d,J=8.1Hz,1H),7.00(d,J=8.0 Hz,1H),6.34(d,J=15.8Hz,1H),4.24(dt,J=7.9,6.6Hz,2H),2.34(s,3H),2.21(s,3H),1.32(t,J=7.1Hz,3H); 13 C NMR (125MHz, CDCl3) δ169.0,167.0,141.5,139.3,135.8,127.9,125.9,124.9,119.4,60.6,24.1,21.5,14.3.

[0448] Example 82 Synthesis of Compound 77

[0449]

[0450] Phthalate (13.8 mg, 0.1 mmol, 1.0 equiv.), Ag₂CO₃ (82.5 mg, 3.0 equiv.), KOAc (9.8 mg, 1.0 equiv.), ethyl acrylate (30.0 mg, 3.0 equiv.), compound I-3 (4.3 mg, calculated as 10 mol% of phthalate based on the molecular weight of Pd(L₃)₂, a monomer of compound I-3, of 430), and HFIP (1.0 mL) were added to a vial equipped with a magnetic stir bar. The vial was sealed under ambient air and stirred at 90 °C for 36 hours. After the reaction was completed, the reaction solution was cooled to room temperature and diluted with EtOAc (1.0 mL). The diluted solution was filtered through diatomaceous earth and washed with ethyl acetate (5.0 mL). The organic phases were combined and concentrated under vacuum to obtain the crude product. The crude product was separated by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 77, yield: 85%. f =0.3.

[0451] 1H NMR(500MHz, CDCl3) δ7.63(d,J=16.0Hz,1H),7.10(dd,J=8.3,2.0Hz,1H),7.06(d,J=2.0Hz,1H),6.8 7(d,J=8.3Hz,1H),6.31(d,J=15.9Hz,1H),4.27(q,J=7.2Hz,2H),3.91(s,6H),1.34(t,J=7.1Hz,3H); 13 C NMR (125MHz, CDCl3) δ167.2,151.1,149.2,144.5,127.5,122.6,116.0,111.1,109.7,60.4,56.0,55.9,14.4.

[0452] Example 83 Synthesis of Compound 78

[0453]

[0454] 1,2,3,4-Tetrahydronaphthalene replaced o-phenylenediamine in Example 82, and other reaction conditions were the same as in Example 82. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 78, yield: 72%. f =0.3.

[0455] 1 H NMR (500MHz, CDCl3) δ7.63(d,J=16.0Hz,1H),7.25(dd,J=7.7,2.0Hz,1H),7.07(d,J=7.9Hz,1H),6.38(d,J=16.0Hz ,1H),4.25(q,J=7.1Hz,2H),2.77(ddd,J=6.8,4.5,2.4Hz,4H),1.80(dq,J=6.7,3.0Hz,4H),1.33(t,J=7.1Hz,3H); 13 C NMR (125MHz, CDCl3) δ167.3,144.9,140.1,137.7,131.8,129.7,129.0,125.0,117.0,60.4,29.5,29.3,23.02,22.99,14.4.

[0456] Example 84 Synthesis of Compound 79

[0457]

[0458] o-xylene replaced o-phenylenedimethyl ether in Example 82, and other reaction conditions were the same as in Example 82. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to give compound 79, yield: 80%. f =0.3.

[0459] 1 H NMR (500MHz, CDCl3) δ7.67(d,J=16.0Hz,1H),7.33(s,1H),7.29(d,J=7.6Hz,3H),7.17(d,J=7 .7Hz,1H),6.41(d,J=16.0Hz,1H),4.28(q,J=7.1Hz,2H),2.30(s,6H),1.36(t,J=7.1Hz,3H); 13 C NMR (125MHz, CDCl3) δ167.3,144.8,139.4,137.1,132.2,130.2,129.3,125.7,117.0,60.4,19.8,19.7,14.4.

[0460] Example 85 Synthesis of Compound 80

[0461]

[0462] 2,3,4,5,6-Pentafluorostyrene replaced ethyl acrylate in Example 82, and other reaction conditions were the same as in Example 82. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent to give compound 80, yield: 80%. f =0.3.

[0463] 1 H NMR(500MHz, CDCl3)δ7.40(d,J=16.8Hz,1H),7.32(s,1H),7.29(d,J=7.4Hz, 2H),7.17(d,J=7.7Hz,1H),6.94(d,J=16.8Hz,1H),2.33(s,3H),2.32(s,3H); 13 C NMR (125MHz, CDCl3) δ137.9,137.1,134.1,130.1,128.1,124.4,120.6,111.4,19.8,19.6.

[0464] Example 86 Synthesis of Compound 81

[0465]

[0466] o-Xylene replaced o-phenylenedimethyl ether in Example 82, and methyl acrylate replaced ethyl acrylate in Example 82; other reaction conditions were the same as in Example 82. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 81, yield: 80%. f =0.3.

[0467] 1 H NMR(500MHz, CDCl3)δ7.65(d,J=16.0Hz,2H),7.29(s,1H),7.27(d,J=1.8Hz,0 H),7.14(d,J=7.7Hz,2H),6.39(d,J=16.0Hz,2H),3.79(s,6H),2.28(s,12H); 13 C NMR (125MHz, CDCl3) δ167.7,145.1,139.5,137.1,132.1,130.2,129.3,125.7,116.5,51.6,19.8,19.7.

[0468] Example 87 Synthesis of Compound 82

[0469]

[0470] o-Xylene replaced o-phenylenedimethyl ether in Example 82, and isobutyl acrylate replaced ethyl acrylate in Example 82; other reaction conditions were the same as in Example 82. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 82, yield: 75%. f =0.3.

[0471] 1 H NMR (500MHz, CDCl3) δ7.64(d,J=16.0Hz,1H),7.30(s,1H),7.28(d,J=1.9Hz,0H),7.14(d,J=7.8Hz,1H),6.40( d,J=16.0Hz,1H),3.98(d,J=6.7Hz,2H),2.28(s,6H),2.01(dt,J=13.4,6.7Hz,1H),0.99(s,3H),0.98(s,3H); 13 C NMR (125MHz, CDCl3) δ167.4,144.8,139.4,137.1,132.2,130.2,129.3,125.7,117.0,70.6,27.9,19.8,19.7,19.2.

[0472] Example 88 Synthesis of Compound 83

[0473]

[0474] o-Xylene replaced o-phenylenedimethyl ether in Example 82, and n-butyl acrylate replaced ethyl acrylate in Example 82; other reaction conditions were the same as in Example 82. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 83, yield: 70%. f =0.3.

[0475] 1 H NMR (500MHz, CDCl3) δ7.63(d,J=16.0Hz,1H),7.30(s,1H),7.27(d,J=1.8Hz,1H),7.14(d,J=7.7Hz,1H),6.39(d, J=16.0Hz,1H),4.20(t,J=6.7Hz,2H),2.28(s,6H),1.73–1.60(m,2H),1.49–1.36(m,2H),0.96(t,J=7.4Hz,3H); 13 C NMR (125MHz, CDCl3) δ167.4,144.7,139.4,137.1,132.2,130.2,129.3,125.7,117.0,64.3,30.8,19.8,19.7,19.2,13.8.

[0476] Example 89 Synthesis of Compound 84

[0477]

[0478] o-Xylene replaced o-phthalic ether in Example 82, and dodecyl 2-acrylate replaced ethyl acrylate in Example 82; other reaction conditions were the same as in Example 82. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 84, yield: 72%. f =0.3.

[0479] 1H NMR (500MHz, CDCl3) δ7.63(d,J=16.0Hz,1H),7.30(s,1H),7.27(s,1H),7.14(d,J=7.7Hz,1H),6.39(d,J=15.7Hz,1H),4.18(t,J=6.8 Hz,2H),2.28(s,6H),2.27–2.21(m,1H),1.69(q,J=7.2Hz,2H),1.39(d,J=7.6Hz,2H),1.27(d,J=10.7Hz,15H),0.88(t,J=6.8Hz,3H); 13 C NMR (125MHz, CDCl3) δ167.4,144.7,139.4,137.1,132.2,130.2,129.3,125.7,117.1 ,64.6,31.9,29.7,29.6,29.6,29.5,29.4,29.3,28.8,27.0,22.7,19.8,19.7,14.1.

[0480] Example 90 Synthesis of Compound 85

[0481]

[0482] o-Xylene replaced o-phthalic acid ether in Example 82, and 2-phenoxyethyl acrylate replaced ethyl acrylate in Example 82; other reaction conditions were the same as in Example 82. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 85, yield: 70%. f =0.3.

[0483] 1 H NMR(500MHz, CDCl3) δ7.70(d,J=16.0Hz,1H),7.36–7.28(m,4H),7.17(d,J=7.7Hz,1H),7.03–6.94( m,3H),6.46(d,J=16.0Hz,1H),4.58(t,J=4.8Hz,2H),4.28(t,J=4.8Hz,2H),2.30(d,J=2.8Hz,6H); 13 C NMR (125MHz, CDCl3) δ167.1,158.6,145.6,139.6,137.2,132.0,130.2,129.5,129.4,125.8,121.2,116.4,114.7,66.0,62.8,19.8,19.7.

[0484] Example 91 Synthesis of Compound 86

[0485]

[0486] A mixture of 2-phenylpyridine (15.5 mg, 0.1 mmol, 1.0 equiv.) and compound I-3 (4.3 mg, calculated as 10 mol% of 2-phenylpyridine based on the molecular weight of Pd(L3)2 monomer of compound I-3 of 430) was added to a dry 10 mL clear vial, followed by 1.0 mL of dry MeCN. Benzaldehyde (15.9 mg, 0.15 mmol, 1.5 equiv.) was then added to the mixture. After purging with nitrogen for 30 seconds, the vial was immediately sealed with a screw cap. TBH was then added to the reaction mixture using a micro-syringe. P (27 mg, 0.3 mmol, 3.0 equiv, 70% hydrogen peroxide tert-butanol) was stirred at room temperature for 36 hours. After the reaction was complete (indicated by TLC), the reaction was quenched with NaHCO3. The reaction solution was poured into water (2 mL), extracted with ethyl acetate (3 × 5.0 mL), the organic layer was washed with water and saturated brine (10.0 mL), dried over anhydrous Na2SO4, the solvent was evaporated under reduced pressure, and the crude product was purified by thin-layer chromatography using petroleum ether and ethyl acetate as eluents to give compound 86 (petroleum ether / ethyl acetate = 10 / 1, v / v), yield: 76%. f =0.3.

[0487] 1 H NMR(500MHz, CDCl3)δ8.36(d,J=4.8Hz,1H),7.77(d,J=8.1Hz,1H),7.71–7.65(m,2H),7.60(ddd,J=7.7,6.7,2.1Hz,1H) ,7.60–7.50(m,3H),7.49(d,J=7.9Hz,1H),7.42–7.34(m,1H),7.27(t,J=7.7Hz,2H),7.01(ddd,J=7.2,4.9,1.2Hz,1H); 13 C NMR (125MHz, CDCl3) δ156.8,149.0,139.58,139.55,137.9,136.4,132.3,130.2,129.5,129.1,128.7,128.6,128.0,122.7,122.0.

[0488] Example 92 Synthesis of Compound 87

[0489]

[0490] 2-Phenyridine (15.5 mg, 0.1 mmol, 1.0 equiv.), compound I-3 (2.15 mg, calculated as 5 mol% of 2-phenylpyridine based on the molecular weight of Pd(L3)2 monomer of compound I-3 of 430), and TBHP (54 mg, 6.0 equiv., 70% aqueous solution of tert-butanol hydroperoxide) were added to DCE (1.0 mL) and sealed in a 25 mL transparent vial. The vial was placed in an oil bath, stirred, and heated to 115 °C for 20 h. The reaction was then cooled to room temperature, quenched with saturated brine (2.0 mL), and extracted with ethyl acetate (3 × 5.0 mL). The organic layers were combined, dried over anhydrous Na2SO4, and the solvent was removed under vacuum. The crude product was purified by thin-layer chromatography to give compound 87 (petroleum ether:ethyl acetate = 10:1, v / v), yield: 50%. f =0.3.

[0491] 1 H NMR (500MHz, CDCl3) δ8.54(dd,J=5.0,0.9Hz,1H),7.95(d,J=8.3Hz,1H),7.86(td,J=8.3,1.8Hz,1H),7.83(dd,J=8.0,1.7H z,1H),7.34(ddd,J=8.6,7.2,1.6Hz,1H),7.29–7.24(m,1H),7.06(dd,J=8.2,1.3Hz,1H),6.94(ddd,J=8.2,7.2,1.3Hz,1H); 13 C NMR (125MHz, CDCl3) δ160.0,157.9,145.8,137.8,131.5,126.1,121.5,119.1,118.8,118.8,118.6.

[0492] Example 93 Synthesis of Compound 88

[0493]

[0494] In a Schlenk reaction tube, 2-phenylpyridine (15.5 mg, 0.1 mmol, 1.0 equiv.), K3[Fe(CN)6] (6.1 mg, 0.02 equiv.), compound I-3 (2.15 mg, calculated as 5 mol% of 2-phenylpyridine based on the molecular weight of the monomer Pd(L3)2 of compound I-3 (430), 22.6 mg, 1.0 equiv.), and dry DMF (1.0 mL) were added. The Schlenk tube was sealed and stirred at 130 °C. The reaction was monitored by thin-layer chromatography (TLC). After the reaction was completed, saturated brine (2.0 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (3 × 5.0 mL). The ethyl acetate extract was concentrated under vacuum. The residue was purified by thin-layer chromatography (petroleum ether:ethyl acetate = 2:1, v / v) to obtain compound 88, yield: 82%. f =0.3.

[0495] 1 H NMR(500MHz, CDCl3)δ8.80(d,J=4.9Hz,1H),7.89–7.84(m,2H),7.84–7.79(m,2H),7.72 (td,J=7.7,1.3Hz,1H),7.53(td,J=7.7,1.2Hz,1H),7.38(ddd,J=7.0,5.0,1.0Hz,1H); 13 C NMR (125MHz, CDCl3) δ155.2,149.9,143.4,136.9,134.1,132.9,130.0,128.8,123.4,123.3,118.7,111.1.

[0496] Example 94 Synthesis of Compound 89

[0497]

[0498] Compound I-3 (4.3 mg, calculated as 10 mol% of N-acetyl-3-toluidine based on the molecular weight of Pd(L3)2 of compound I-3 (430)), (NH4)2S2O8 (45.0 mg, 2.0 equiv.), and N-acetyl-3-toluidine (14.9 mg, 0.1 mmol, 1.0 equiv.) were added to a Schlenk tube. Then, TFA (57.0 mg, 5.0 equiv.) and AcOH (120.0 mg, 20.0 equiv.) were added via syringe. After stirring at room temperature for 24 hours, the reaction solution was diluted with 10.0 mL CH2Cl2, filtered through diatomaceous earth, washed with 10.0 mL CH2Cl2, and the filtrate was collected and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1, v / v) to obtain compound 89, yield: 42%. f =0.3.

[0499] 1 H NMR (500MHz, CDCl3) δ7.96 (s, 1H), 7.14 (s, 1H), 7.02 (d, J = 8.3Hz, 1H), 6.95 (d, J = 7.7Hz, 1H), 2.37 (d, J = 2.8Hz, 6H), 2.19 (s, 3H); 13 C NMR (125MHz, CDCl3) δ168.9,168.2,138.6,136.5,129.2,125.6,123.6,121.6,24.6,21.2,21.1.

[0500] Example 95 Synthesis of Compound 90

[0501]

[0502] Compound I-3 (4.3 mg, calculated as 10 mol% of N-acetyl-3-toluidine based on the molecular weight of the monomer Pd(L3)2 of compound I-3 (430)), (NH4)2S2O8 (45.0 mg, 2.0 equiv.), and N-acetyl-3-toluidine (14.9 mg, 0.1 mmol, 1.0 equiv.) were added to a Schlenk tube. Then, TFA (228.0 mg, 20.0 equiv.) and o-xylene (212.0 mg, 20.0 equiv.) were added via syringe. After stirring at room temperature for 24 hours, the reaction solution was diluted with 10.0 mL CH2Cl2, filtered through diatomaceous earth, washed with 10.0 mL CH2Cl2, and the filtrate was collected and concentrated to obtain the crude product. The crude product was purified by silica gel thin-layer chromatography (petroleum ether:ethyl acetate = 2:1, v / v) to obtain compound 90, yield: 82%. f=0.3.

[0503] 1 H NMR(500MHz, CDCl3)δ8.10(s,1H),7.22(d,J=7.7Hz,1H),7.17(s,1H),7.14–7.05( m,3H),6.96(d,J=7.7Hz,1H),2.39(s,3H),2.32(s,3H),2.31(s,3H),2.01(s,3H); 13 CNMR (125MHz, CDCl3) δ168.2,138.1,137.4,136.2,135.7,134.6,130.6,130.2,129.8,129.4,126.6,125.1,121.9,24.7,21.5,19.8,19.5.

[0504] Example 96 Synthesis of Compound 91

[0505]

[0506] N-acetyl-4-toluidine (14.9 mg, 0.1 mmol, 1.0 equiv.) and dichloroethane (1.0 mL) were added to a pressure tube equipped with a stir bar. The tube was degassed with nitrogen for approximately 10 minutes. Then, compound I-3 (4.3 mg, calculated as 10 mol% of N-acetyl-4-toluidine based on the molecular weight of the monomer Pd(L3)2 of compound I-3 being 430), Cu(OTf)2 (18.1 mg, 0.5 equiv.), and NCS (N-chlorosuccinimide, 26.6 mL) were added. (g, 2.0 equiv.), under nitrogen flow, with a Teflon screw cap installed on the tube, heated to 90°C and stirred at this temperature, monitored by thin-layer chromatography; after the reaction was complete, the reaction solution was cooled to room temperature, the reaction mixture was diluted with ethyl acetate (5 mL), and filtered through diatomaceous earth. The filtrate was washed with saturated brine (5 mL), the organic layer was dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and the crude product was purified by thin-layer chromatography (petroleum ether:ethyl acetate = 5:1, v / v) to give compound 91, yield: 90%, R f =0.3.

[0507] 1 H NMR (500MHz, CDCl3) δ8.21(d,J=8.4Hz,1H),7.55(s,1H),7.20(d,J=2.0Hz,1H),7.09(dd,J=8.4,2.0Hz,1H),2.32(s,3H),2.24(s,3H); 13C NMR (125MHz, CDCl3) δ168.1,134.7,132.0,129.3,128.3,122.5,121.7,24.8,20.6.

[0508] Example 97 Synthesis of Compound 92

[0509]

[0510] In a pressure tube equipped with a stir bar, N-acetyl-4-toluidine (14.9 mg, 0.1 mmol, 1.0 equiv.) and dichloroethane (1.0 mL) were degassed with nitrogen for approximately 10 minutes. Then, compound I-3 (4.3 mg, calculated as 10 mol% of N-acetyl-4-toluidine based on the molecular weight of compound I-3 monomer Pd(L3)2 of 430), PTSA (p-toluenesulfonic acid, 8.6 mg, 0.5 equiv.), and NBS (N-bromosuccinimide, 21.2 mg) were added. (mg, 1.2 equiv.), under nitrogen flow, with a Teflon screw cap installed on the tube, heated to 90°C and stirred at this temperature, monitored by thin-layer chromatography. After the reaction was complete, the reaction solution was cooled to room temperature, diluted with ethyl acetate (5 mL), and filtered through diatomaceous earth. The filtrate was washed with saturated brine (5 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by thin-layer chromatography (petroleum ether:ethyl acetate = 5:1, v / v) to give compound 92, yield: 80%. f =0.3.

[0511] 1 H NMR (500MHz, CDCl3) δ8.18(d,J=8.4Hz,1H),7.53(s,1H),7.37(s,1H),7.13(d,J=7.7Hz,1H),2.32(s,3H),2.24(s,3H); 13 C NMR (125MHz, CDCl3) δ168.1,135.3,133.2,132.4,129.0,121.9,113.2,24.8,20.5.

[0512] Example 98 Synthesis of Compound 93

[0513]

[0514] In a pressure tube equipped with a stir bar, N-acetyl-4-toluidine (14.9 mg, 0.1 mmol, 1.0 equiv.) and dichloroethane (1.0 mL) were degassed with nitrogen for approximately 10 minutes. Then, compound I-3 (4.3 mg, calculated as 10 mol% of N-acetyl-4-toluidine based on the molecular weight of compound I-3 monomer Pd(L3)2 of 430), PTSA (p-toluenesulfonic acid, 8.6 mg, 0.5 equiv.), and NIS (N-iodosuccinimide, 33.6 mg, 0.5 equiv.) were added. (mg, 1.5 equiv.), under nitrogen flow, with a Teflon screw cap on the tube, heated to 90°C and stirred at this temperature, monitored by thin-layer chromatography; after the reaction was complete, the reaction solution was cooled to room temperature, diluted with ethyl acetate (5 mL), and filtered through diatomaceous earth. The filtrate was washed with saturated brine (5 mL); the organic layer was dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and the crude product was purified by thin-layer chromatography (petroleum ether:ethyl acetate = 5:1, v / v) to give compound 93, yield: 82%, R f =0.3.

[0515] 1 H NMR (500MHz, CDCl3) δ8.03(d,J=9.9Hz,1H),7.63(s,1H),7.35(s,1H),7.16(d,J=8.3Hz,1H),2.30(s,3H),2.24(s,3H); 13 C NMR (125MHz, CDCl3) δ168.2,139.0,136.1,135.8,129.9,122.1,90.3,24.7,20.3.

[0516] Example 99 Synthesis of Compound 94

[0517]

[0518] 2-Phenylacetin (20.6 mg, 0.1 mmol, 1.0 equiv.), N-fluorobis(benzenesulfonamide) (47.3 mg, 1.5 equiv.), compound I-3 (4.3 mg, calculated as 10 mol% of 2-phenylquinoxalin based on the molecular weight of Pd(L3)2 monomer of compound I-3 of 430), TFA (trifluoroacetic acid, 22.8 mg, 2.0 equiv.), and CH3CN (1.0 mL) were added sequentially to a 10.0 mL test tube. The tube was sealed and stirred at 110 °C until the reaction was complete (TLC monitoring). The solvent was evaporated to obtain the crude product, which was then purified directly by thin-layer chromatography (petroleum ether:ethyl acetate = 10:1, v / v) to give compound 94, yield: 50%. f =0.3.

[0519] 1 H NMR(500MHz, CDCl3)δ9.35(d,J=3.1Hz,1H),8.23–8.16(m,2H),8.15(td,J=7.7,1.8Hz,1H),7.87–7 .78(m,2H),7.53(dddd,J=8.3,7.1,5.0,1.8Hz,1H),7.39(td,J=7.6,1.2Hz,1H),7.32–7.24(m,1H); 13 C NMR (125MHz, CDCl3) δ161.8,159.8,149.28,149.25,146.0,145.9,142.6,141.4,132 .0,131.9,131.51,131.49,130.3,130.0,129.7,129.2,125.1,125.0,116.6,116.4.

[0520] Example 100 Synthesis of Compound 95

[0521]

[0522] Compound I-3 (4.3 mg, calculated as 10 mol% of benzoic acid based on the molecular weight of Pd(L3)2 monomer 430) was added to a 10 mL reaction tube equipped with a magnetic stir bar. Then, K2HPO4 (13.8 mg, 1.0 equiv.), benzoic acid (12.2 mg, 0.1 mmol, 1.0 equiv.), and dibromomethane (1.0 mL) were added. The reaction tube was sealed with a Teflon tube, and the reaction mixture was stirred at 140 °C for 36 h. After the reaction was complete, the reaction solution was filtered through diatomaceous earth, and the filtrate was concentrated under vacuum to obtain the crude product. This crude product was purified by thin-layer chromatography (petroleum ether:ethyl acetate = 10:1, v / v) to give compound 95, yield: 45%. f =0.3.

[0523] 1 H NMR (500MHz, CDCl3) δ7.96 (d, J = 7.7Hz, 1H), 7.71 (td, J = 7.5, 1.1Hz, 1H), 7.57 (td, J = 7.5, 0.8Hz, 1H), 7.52 (d, J = 7.8Hz, 1H), 5.35 (s, 2H); 13 C NMR (125MHz, CDCl3) δ171.1,146.5,134.0,129.1,125.83,125.81,122.1,69.6.

[0524] Example 101 Synthesis of Compound 96

[0525]

[0526] 2-Bromobenzonitrile (1274 mg, 7.0 mmol, 1.0 equiv.), K2CO3 (1932 mg, 2.0 equiv.), 4-tolueneboronic acid (1890 mg, 2.0 equiv.), compound I-3 (3.01 mg, calculated as 0.1 mol% of 2-bromobenzonitrile based on the molecular weight of Pd(L3)2 monomer of compound I-3 of 430), and ethanol / water (20 mL, ethanol:water = 2:1 v / v) were placed in a microwave-safe bottle equipped with a magnetic stir bar. The bottle cap was placed on a ring. The mixture was stirred at 90°C for 24 hours in ambient air. After the reaction was completed, the reaction solution was cooled to room temperature, and ethyl acetate (10 mL) and water (10 mL) were added. The mixture was allowed to separate into layers. The aqueous layer was extracted three times with ethyl acetate (10 mL). The organic layers were combined and washed with saturated brine (10 mL). The organic layer was concentrated under vacuum to obtain the crude product. The crude product was purified using 200-300 mesh silica gel as the stationary phase and petroleum ether / ethyl acetate as the mobile phase (petroleum ether:ethyl acetate = 20:1, v / v) to give compound 96, yield: 95%. f =0.3.

[0527] 1 H NMR (500MHz, CDCl3) δ7.74 (dd, J=7.7, 1.4Hz, 1H), 7.62 (td, J=7.7, 1.4Hz, 1H), 7.50 (dd, J=8.0, 1.2Hz,1H),7.49–7.42(m,2H),7.41(td,J=7.6,1.3Hz,1H),7.29(d,J=7.7Hz,2H),2.42(s,3H); 13 C NMR (125MHz, CDCl3) δ145.6,138.7,135.3,133.7,132.7,130.0,129.4,128.6,127.3,118.8,111.3,21.2.

[0528] Example 102 Synthesis of Compound 97

[0529]

[0530] 2-Bromo-4-fluoro-1-nitrobenzene (657 mg, 3.0 mmol, 1.0 equiv.), K2CO3 (828 mg, 2.0 equiv.), 3,4-dichlorophenylboronic acid (1140 mg, 2.0 equiv.), compound I-3 (1.29 mg, calculated as 0.1 mol% of 2-bromo-4-fluoro-1-nitrobenzene based on the molecular weight of the monomer Pd(L3)2 of compound I-3 of 430), and toluene / water (2:1, v / v, 10 mL) were placed in a microwave-safe bottle equipped with a magnetic stir bar. In the reaction, the bottle cap was left in ambient air, and the mixture was stirred at 90°C for 24 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and ethyl acetate (10 mL) and water (10 mL) were added. The mixture was allowed to separate into layers. The aqueous layer was extracted three times with ethyl acetate (10 mL), and the organic layers were combined. The organic layer was washed with saturated brine (10 mL), and the organic layer was concentrated under vacuum to obtain the crude product. The crude product was purified using 200-300 mesh silica gel as the stationary phase and petroleum ether / ethyl acetate (petroleum ether:ethyl acetate = 20:1, v / v) as the mobile phase to obtain compound 97, yield: 95%. f =0.3.

[0531] 1 H NMR (500MHz, CDCl3) δ8.04(dd,J=9.0,5.0Hz,1H),7.53(d,J=8.3Hz,1H),7.44(d,J=2.1Hz,1H ),7.24(ddd,J=9.0,7.3,2.8Hz,1H),7.15(dd,J=8.3,2.1Hz,1H),7.12(dd,J=8.5,2.8Hz,1H); 13 C NMR (125MHz, CDCl3) δ165.1,163.0,144.8,137.4,137.3,136.6,133.3,133.1,130.7,129.7,127.4,127.3,127.1,119.0,118.8,116.1,115.9.

[0532] Example 103 Synthesis of Compound 98

[0533]

[0534] 2-Nitroiodobenzene (1245 mg, 5.0 mmol, 1.0 equiv.), K2CO3 (1380 mg, 2.0 equiv.), 3,4,5-trifluorophenylboronic acid (1759 mg, 2.0 equiv.), compound I-3 (6.45 mg, calculated as 0.1 mol% of 2-nitroiodobenzene based on the molecular weight of compound I-3 monomer Pd(L3)2 of 430), and ethanol / water (20 mL, ethanol:water = 2:1 v / v) were placed in a microwave-safe bottle equipped with a magnetic stir bar. The mixture was sealed under ambient air and stirred at 90°C for 24 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and ethyl acetate (10 mL) and water (10 mL) were added. The mixture was allowed to separate into layers. The aqueous layer was extracted three times with ethyl acetate (10 mL). The organic layers were combined and washed with saturated brine (10 mL). The organic layer was concentrated under vacuum to obtain the crude product. The crude product was purified using 200-300 mesh silica gel as the stationary phase and petroleum ether / ethyl acetate (petroleum ether:ethyl acetate = 20:1, v / v) as the mobile phase to give compound 98, yield: 97%. f =0.3.

[0535] 1 H NMR (500MHz, CDCl3) δ7.96(dd,J=8.1,1.4Hz,1H),7.68(td,J=7.6,1.3Hz,1H),7.61–7.54(m,1H),7.41(dd,J=7.7,1.4Hz,1H),7.00–6.92(m,2H); 13 C NMR (125MHz, CDCl3) δ152.22,152.19,152.14,152.11,150.22,150.19,150.14,150.11,148.8,141.0,140.9,140.8,139.0,138 .9,138.7,133.56,133.56,133.53,133.50,133.45,133.43,133.39,132.7,131.7,129.4,124.5,112.70,112.66,112.6,112.5.

[0536] Example 104 Synthesis of Compound 99

[0537]

[0538] 2-Nitrobromobenzene (1414 mg, 7.0 mmol, 1.0 equiv.), K2CO3 (1932 mg, 2.0 equiv.), boric acid (2180 mg, 2.0 equiv.), compound I-3 (3.01 mg, calculated as 0.1 mol% of 2-nitrobromobenzene based on the molecular weight of compound I-3 monomer Pd(L3)2 of 430), and ethanol / water (20.0 mL, ethanol:water = 2:1 v / v) were placed into a microwave-safe bottle equipped with a magnetic stir bar and microwaved under ambient air. Under sealed atmosphere, the mixture was stirred at 90°C for 24 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and ethyl acetate (10 mL) and water (10 mL) were added. The mixture was allowed to separate into layers. The aqueous layer was extracted three times with ethyl acetate (10 mL). The organic layers were combined and washed with saturated brine (10 mL). The organic layer was concentrated under vacuum to obtain the crude product. The crude product was purified using 200-300 mesh silica gel as the stationary phase and petroleum ether / ethyl acetate (petroleum ether:ethyl acetate = 20:1, v / v) as the mobile phase to obtain compound 99, yield: 92%. f =0.3.

[0539] 1 H NMR (500MHz, CDCl3) δ7.91 (dd, J=8.1, 1.3Hz, 1H), 7.65 (td, J=7.6, 1.3Hz, 1H), 7.5 6–7.51(m,1H),7.50(d,J=8.6Hz,1H),7.43(d,J=8.5Hz,2H),7.28(d,J=8.4Hz,2H); 13 C NMR (125MHz, CDCl3) δ149.1,138.5,135.9,135.3,134.5,132.5,131.9,129.3,129.1,128.9,128.6,128.3,124.3.

[0540] Example 105 Synthesis of Compound 100

[0541]

[0542] 2-Bromobenzonitrile (7.0 mmol, 1.0 equiv.), K2CO3 (1932 mg, 2.0 equiv.), 4-formylphenylboronic acid (2098 mg, 2.0 equiv.), compound I-3 (3.01 mg, calculated as 0.1 mol% of 2-bromobenzonitrile based on the molecular weight of compound I-3 monomer Pd(L3)2 430), and DMF (20.0 mL) were placed into a microwave-safe bottle equipped with a magnetic stir bar, sealed in ambient air, and incubated at 90 °C. After stirring for 24 hours, the reaction solution was cooled to room temperature, and ethyl acetate (10 mL) and water (10 mL) were added. The mixture was allowed to separate into layers. The aqueous layer was extracted three times with ethyl acetate (10 mL). The organic layers were combined and washed with saturated brine (10 mL). The organic layer was concentrated under vacuum to obtain the crude product. The crude product was purified using 200-300 mesh silica gel as the stationary phase and petroleum ether / ethyl acetate as the mobile phase (petroleum ether:ethyl acetate = 10:1, v / v) to give compound 100, yield: 91%. f =0.3.

[0543] 1 H NMR (500MHz, CDCl3) δ10.12(s,1H),8.04(d,J=8.3Hz,2H),7.84(dd,J=7.8,1.4 Hz,1H),7.76(d,J=8.3Hz,2H),7.73(td,J=7.7,1.4Hz,1H),7.59–7.50(m,2H); 13 C NMR (125MHz, CDCl3) δ191.7,144.0,143.9,136.2,134.0,133.1,130.1,130.0,129.6,128.5,118.2,111.3.

[0544] Example 106 Synthesis of Compound 101

[0545]

[0546] 3-Bromobenzaldehyde (1295 mg, 7.0 mmol, 1.0 equiv.), K2CO3 (1932 mg, 2.0 equiv.), 2-fluoro-3-pyridineboronic acid (1973 mg, 2.0 equiv.), compound I-3 (3.01 mg, calculated as 0.1 mol% of 3-bromobenzaldehyde based on the molecular weight of the monomer Pd(L3)2 of compound I-3 of 430), and DMF (20.0 mL) were placed in a reaction flask equipped with a magnetic stir bar. The reaction mixture was sealed in ambient air and stirred at 90°C for 24 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and ethyl acetate (10 mL) and water (10 mL) were added. The mixture was allowed to separate into layers. The aqueous layer was extracted three times with ethyl acetate (10 mL). The organic layers were combined and washed with saturated brine (10 mL). The organic layer was concentrated under vacuum to obtain the crude product. The crude product was purified using 200-300 mesh silica gel as the stationary phase and petroleum ether / ethyl acetate as the mobile phase (petroleum ether:ethyl acetate = 5:1, v / v) to give compound 101, yield: 91%. f =0.3.

[0547] 1 H NMR(500MHz, CDCl3)δ10.10(s,1H),8.32–8.18(m,1H),8.08(d,J=1.7Hz,1H),7.96–7.91(m ,2H),7.86(dq,J=7.7,1.6Hz,1H),7.66(t,J=7.7Hz,1H),7.34(ddd,J=7.5,4.8,1.8Hz,1H); 13 C NMR (125MHz, CDCl3)δ 13 C NMR (125MHz, CDCl3) δ191.8,161.3,159.4,147.3,147.1,140.73,140.69,136.9,135 .0,134.9,134.68,134.65,129.9,129.8,129.7,129.5,122.7,122.4,122.07,122.0.

[0548] Example 107 Synthesis of Compound 102

[0549]

[0550] 2-Bromo-4-chloro-1-nitrobenzene (708 mg, 3.0 mmol, 1.0 equiv.), K2CO3 (828 mg, 2.0 equiv.), ethyl acrylate (900 mg, 3.0 equiv.), compound I-2 (6.45 mg, calculated as 0.5 mol% of 2-bromo-4-chloro-1-nitrobenzene based on the molecular weight of Pd(L2)2 monomer 430), and 1,4-dioxane (10.0 mL) were placed in a microwave-safe bottle equipped with a magnetic stir bar. The reaction mixture was sealed under ambient air and stirred at 90°C for 24 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and ethyl acetate (10 mL) and water (10 mL) were added. The mixture was allowed to separate into layers. The aqueous layer was extracted three times with ethyl acetate (10 mL). The organic layers were combined and washed with saturated brine (10 mL). The organic layer was concentrated under vacuum to obtain the crude product. The crude product was purified using 200-300 mesh silica gel as the stationary phase and petroleum ether / ethyl acetate (petroleum ether:ethyl acetate = 5:1, v / v) as the mobile phase to give compound 102, yield: 93%. f =0.3.

[0551] 1 H NMR (500MHz, CDCl3) δ8.08(d,J=15.7Hz,1H),8.03(d,J=8.7Hz,1H),7.60(d,J=2.3 Hz,1H),7.50(dd,J=8.7,2.3Hz,1H),4.30(q,J=7.1Hz,2H),1.35(t,J=7.1Hz,3H); 13 C NMR (125MHz, CDCl3) δ165.4,146.4,140.1,138.7,132.6,130.1,129.1,127.5,124.5,61.1,14.2.

[0552] Example 108 Synthesis of Compound 103

[0553]

[0554] 5-Bromo-2-methoxypyridine (1316 mg, 7.0 mmol, 1.0 equiv.), K2CO3 (1932 mg, 2.0 equiv.), tert-butyl acrylate (3584 mg, 4.0 equiv.), compound I-3 (15.05 mg, calculated as 0.5 mol% of 5-bromo-2-methoxypyridine based on the molecular weight of compound I-2 monomer Pd(L2)2 of 430), and 1,4-dioxane (20.0 mL) were placed in a microwave-safe bottle equipped with a magnetic stir bar. The reaction mixture was sealed under ambient air and stirred at 90°C for 24 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and ethyl acetate (10 mL) and water (10 mL) were added. The mixture was allowed to separate into layers. The aqueous layer was extracted three times with ethyl acetate (10 mL). The organic layers were combined and washed with saturated brine (10 mL). The organic layer was concentrated under vacuum to obtain the crude product. The crude product was purified using 200-300 mesh silica gel as the stationary phase and petroleum ether / ethyl acetate (petroleum ether:ethyl acetate = 2:1, v / v) as the mobile phase to give compound 103, yield: 90%. f =0.3.

[0555] 1 H NMR(500MHz, CDCl3) δ8.28(d,J=2.4Hz,1H),7.77(dd,J=8.7,2.5Hz,1H),7.55(d,J=1 6.0Hz,1H),6.77(d,J=8.7Hz,1H),6.29(d,J=16.0Hz,1H),3.99(s,3H),1.55(s,8H); 13 C NMR (125MHz, CDCl3) δ166.1,165.1,148.0,139.8,136.4,124.1,119.3,111.5,80.6,53.8,28.2.

[0556] Example 109 Synthesis of Compound 104

[0557]

[0558] 2-Nitroiodobenzene (1245 mg, 5.0 mmol, 1.0 equiv.), Cs₂CO₃ (3250 mg, 2.0 equiv.), XantPhos (28.9 mg, 1.0 mol%), 2-aminopyridine (940 mg, 2.0 equiv.), compound I-3 (10.75 mg, calculated as 0.5 mol% of 2-nitroiodobenzene based on the molecular weight of the monomer Pd(L₃)₂ of compound I-3 (430)), and toluene (10.0 mL) were loaded into a microsphere equipped with a magnetic stir bar. In a flask, sealed under ambient air, the mixture was stirred at 90°C for 24 hours. After the reaction was complete, the reaction solution was cooled to room temperature, and ethyl acetate (10 mL) and water (10 mL) were added. The mixture was allowed to separate into layers. The aqueous layer was extracted three times with ethyl acetate (10 mL). The organic layers were combined and washed with saturated brine (10 mL). The organic layer was concentrated under vacuum to obtain the crude product. The crude product was purified using 200-300 mesh silica gel as the stationary phase and petroleum ether / ethyl acetate (petroleum ether:ethyl acetate = 2:1, v / v) as the mobile phase to give compound 104, yield: 99%. f =0.3.

[0559] 1 H NMR(500MHz, CDCl3)δ10.14(s,1H),8.74(dd,J=8.7,1.3Hz,1H),8.37–8.31(m,1H),8.22(dd,J=8.5, 1.7Hz,1H),7.64(ddd,J=8.2,7.4,2.0Hz,1H),7.56(ddd,J=8.7,7.0,1.7Hz,1H),6.97–6.91(m,3H); 13 C NMR (125MHz, CDCl3) δ153.6,147.8,138.8,138.2,135.7,135.0,126.3,119.9,119.8,117.8,113.8.

[0560] Synthesis of Compound 14 in Comparative Example 1

[0561]

[0562] Palladium acetate (47% Pd content) replaced compound I-3 (24.7% Pd content calculated as monomer Pd(L3)2) in Example 19, and other reaction conditions were the same as in Example 19. Compound 14 was obtained by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent, with a yield of 10%.

[0563] Synthesis of Compound 28 in Comparative Example 2

[0564]

[0565] Palladium acetate (47% Pd content) replaced compound I-2 (24.7% Pd content calculated as monomer Pd(L2)2) in Example 33, and other reaction conditions were the same as in Example 33. Separation by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent yielded compound 28 in 16% yield.

[0566] Synthesis of Compound 35 in Comparative Example 3

[0567]

[0568] Palladium acetate (47% Pd content) replaced compound I-3 (24.7% Pd content calculated as monomer Pd(L3)2) in Example 40, and other reaction conditions were the same as in Example 40. Separation by silica gel thin-layer chromatography using hexanes / EtOAc 20:1 (v / v) as the developing solvent yielded compound 35 in 66% yield.

[0569] Synthesis of Compound 43 in Comparative Example 4

[0570]

[0571] Palladium acetate (47% Pd content) replaced compound I-3 (24.7% Pd content calculated as monomer Pd(L3)2) in Example 48, and other reaction conditions were the same as in Example 48. Compound 43 was obtained by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent, with a yield of 57%.

[0572] Synthesis of Compound 68 in Comparative Example 5

[0573]

[0574] Palladium acetate (47% Pd content) replaced compound I-3 (24.7% Pd content calculated as monomer Pd(L3)2) in Example 73, and other reaction conditions were the same as in Example 73. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 2:1 (v / v) as the developing solvent to obtain compound 68 in 80% yield.

[0575] Synthesis of Compound 79 in Comparative Example 6

[0576]

[0577] Palladium acetate (47% Pd content) replaced compound I-3 (24.7% Pd content calculated as monomer Pd(L3)2) in Example 84, and other reaction conditions were the same as in Example 84. Separation was performed by silica gel thin-layer chromatography using hexanes / EtOAc 10:1 (v / v) as the developing solvent to obtain compound 79, yield: 30%.

Claims

1. A pyridinone palladium catalyst having a structure as shown in Formula I: Formula I wherein: R1, R2, R3, R4, R5, R6 are each independently selected from H, -CF3, -NO2, -OH, -F, -Cl, -Br, -CN, -CH3, -OCH3, R1, R2, R3, R4, R5, R6 are the same or different, R1, R2, R3, R4, R5, R6 are each independently substituted at the 3, 4, 5 or 6 position of the pyridinone. ； wherein 2. A pyridinone palladium catalyst having a structure selected from the group consisting of: Formula II Formula III Formula IV Formula V The synthesis route is as follows: 。 3. A process for the preparation of the pyridinone palladium catalyst of claim 1, characterized by: comprising: reacting a pyridinone having a structure as shown in Formula II and palladium acetate in a first solvent in the presence of a base to obtain a pyridinone palladium catalyst having a structure as shown in Formula I; ； R1, R2, R3, R4, R5, R6 are as defined in claim 1; R is selected from R1, R2, R3, R4, R5, R6; the pyridinone having a structure as shown in Formula (II) is a pyridinone substituted at the 3, 4, 5 or 6 position with a substituent selected from R1, R2, R3, R4, R5, R6. The first solvent is selected from one or a combination of at least two of dichloromethane, 1,2-dichloroethane or n-hexane.

4. The method of preparing a pyridinone palladium catalyst according to claim 3, characterized in that: The molar ratio of the pyridinone to the base is 1:1 to 2:1; the base is selected from Na2CO3; 5. The method for preparing the pyridone palladium catalyst according to claim 3, characterized in that: The pyridinone having a structure as shown in Formula (II) is in excess of the palladium acetate in terms of molar amount. The reaction temperature is 20 to 40 °C.

6. The method for preparing the pyridone palladium catalyst according to claim 3, characterized in that: The reaction temperature is 30 to 35 °C.

7. The method of preparing a pyridinone palladium catalyst according to claim 6, characterized in that: After the reaction is completed, the first organic solvent is removed to obtain the pyridinone palladium catalyst; 8. The method for preparing the pyridone palladium catalyst according to claim 3, characterized in that: or after the reaction is completed, the reaction solution is filtered using diatomite, the filter cake is washed with the first organic solvent, the filtrates are combined, the first organic solvent is removed, the reaction product is then washed with a second organic solvent, and the solid is collected to obtain the pyridinone palladium catalyst; The second organic solvent is selected from one or a combination of at least two of n-hexane and 1,2-dichloroethane.

9. Use of the pyridinone palladium catalyst as defined in claim 1 or 2 in catalyzing a coupling reaction, a functionalization reaction of a carbon-hydrogen bond. The coupling reaction includes Suzuki coupling, Heck coupling, Negishi coupling, Sonogashira coupling, Buchwald-Hartwig coupling, Stille coupling, Hiyama coupling and Miyaura Borylation.

10. Use according to claim 9, characterised in that: The functionalization reaction of a carbon-hydrogen bond includes alkenylation of a carbon-hydrogen bond, carbonylation of a carbon-hydrogen bond, hydroxylation of a carbon-hydrogen bond, cyanation of a carbon-hydrogen bond, acetylation of a carbon-hydrogen bond, arylation of a carbon-hydrogen bond, halogenation of a carbon-hydrogen bond and alkylation of a carbon-hydrogen bond.

11. Use according to claim 9, characterised in that: ​

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