A method for synthesizing a β-pyridone derivative

Abstract

This invention discloses a method for synthesizing β-pyridone derivatives, which is based on the photocatalytic β-C(sp) synthesis of 1-(o-iodoaryl)alkyl-1-one and cyanoaryl hydrocarbons induced by iodoaryl hydrocarbons via halogen atom transfer (XAT) and hydrogen atom transfer (HAT). 3 )-H arylation involves the generation of an aryl intermediate mediated by a diethylaminoethyl radical, followed by the formation of a distal alkyl radical intermediate from 1,5-HAT, and coupling with a cyanoaromatic hydrocarbon (the corresponding cyanoaromatic hydrocarbon radical intermediate generated via photoreduction). This method is applicable to a wide range of inactive, long-range C(sp) arylation. 3 The presence of H bonds provides a novel synthetic route for constructing derivatives such as β-pyridones. The method of this invention can be carried out at room temperature, with mild and simple reaction conditions, a wide range of substrate adaptability, and high yields of the target product.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical synthesis technology, specifically relating to a method for synthesizing a β-pyridone derivative. Background Technology

[0002] β-Pyridone derivatives have wide applications in pharmaceuticals, agricultural chemistry, and organic synthesis. For example, prior art WO2006 / 041037A1 discloses a pyridine derivative having the following formula (1). In the formula, A represents a substituted phenyl or naphthyl group, X represents an O atom, and R1-R4 are hydrogen or lower alkyl groups, indicating that this type of β-pyridone derivative can be used as a therapeutic agent, especially as an inhibitor of C17-20 lyases. The patent document describes two methods for preparing the pyridinium derivatives: one involves using an aromatic ketone as a starting material, first converting it to an enol, then reacting it with a pyridin-4-one compound via an aldol reaction, followed by dehydration elimination and catalytic hydrogenation to obtain the target product; the other involves using an aromatic ketone as a starting material, reacting it with pyridin-4-carboxaldehyde via an aldol condensation, followed by dehydration elimination and double bond addition to obtain the target product. The above methods have lengthy synthetic routes, high reaction costs, and low overall yields, making them unsuitable for industrial production. Therefore, developing a convenient method for synthesizing β-pyridone derivatives is of significant practical importance.

[0003] Jiangwei Wen et al. reported the site-selective hydrogenation and pyridylation of acetylacetones / enones under electrocatalytic conditions to prepare β-pyridinones (Org. Chem. Front., 2023, 10, 193-202; Adv. Synth. Catal. 2022, 364, 845-854); Zhiyong Jiang et al. reported the catalytic asymmetric reduction of aziridines with 4-cyanopyridine to prepare β-pyridinones under DPZ, phosphate ester ligand, HE-1, and light irradiation conditions (J. Am. Chem. Soc., 2022, 144, 7805-7814). MacMillan's group reported a radical-mediated β-C(sp3)-H arylation reaction of ketones and aldehydes using electron-deficient cyanoaromatics as aryl coupling agents, through synergistic photoredox and enamine catalysis, via radical-radical coupling, thus constructing β-aryl ketones and aldehydes (Science, 2013, 339, 1593-1596). While these methods are relatively efficient, they require pre-designed reaction substrates with specific structures, limiting their general applicability.

[0004] Site-selective functionalization of inert C(sp3)-H bonds to specifically enhance molecular complexation and modify abundant hydrocarbon feedstocks into valuable compounds is an important research topic in the field of drug synthesis. In contrast to the widely studied arylation of α-position C(sp3)-H bonds in carbonyl compounds, the direct arylation of β-position or more advanced C(sp3)-H bonds in carbonyl compounds remains largely imperfect. Furthermore, due to competing reactions, such as the more acidic arylation of α-C(sp3)-H bonds, site-selective control remains a significant challenge. This invention reports for the first time the direct β-CH arylation of o-iodoaryl alkyl ketones with cyano(hetero)aromatics via visible light-mediated photoredox halogen atom transfer (XAT) and 1,5-hydrogen atom transfer (HAT) processes. In this process, the photoreduction / deprotonation of triethylamine generates a diethylaminoethyl radical, which serves as a halogen atom transfer agent for activating the aryl iodine to undergo XAT and generate aryl radicals. Subsequently, 1,5-HAT is directed to provide a long-range β-sp3-carbon center radical and radical-radical coupling. This iodoaryl directional HAT strategy is applicable to the β-C(sp3)-H arylation of alkanols and their derivatives, the distal C(sp3)-H arylation of alkanes or alkyl ethers, and the α-C(sp3)-H arylation of esters for the assembly of various functionalized aromatics and heteroaromatics, and is particularly suitable for the preparation of a series of β-pyridone derivatives. Summary of the Invention

[0005] The purpose of this invention is to provide a novel method for synthesizing β-pyridone derivatives. This method involves the direct β-CH arylation of o-iodoaryl alkyl ketones with cyano(hetero)aromatic hydrocarbons via visible light-mediated photoredox halogen atom transfer (XAT) and 1,5-hydrogen atom transfer (HAT) processes. This method has advantages such as mild and simple reaction conditions, readily available starting materials, a wide range of substrate adaptability, and high yield of the target product.

[0006] A method for synthesizing a β-pyridone derivative according to the present invention includes the following steps:

[0007] Compounds of Formula 1, Formula 2, a photocatalyst, an organic amine, a base, and an organic solvent were added to a reactor. The atmosphere inside the reactor was then replaced with an inert atmosphere, and the reaction was carried out under stirring at room temperature and under light. After the reaction was complete, the β-pyridone derivative of Formula 3 was obtained through purification. The reaction formula is as follows:

[0008]

[0009] In the above reaction formula, m and n are integers of 1, 2, 3 or 4.

[0010] Each R1 may be the same or different, and is independently selected from hydrogen, halogen, CN, and C. 1-20 Alkyl, Halogenated C1-20 Alkyl, C 1-20 Alkyl group.

[0011] Indicates a double bond, a single bond, or no bond; Y is selected from O, S, OR. a , or does not exist; where R a For hydrogen, C 1-20 Alkyl, C 1-20 Acyl group.

[0012] Z is selected from CH2, O, or S.

[0013] R2 and R3 are independently selected from hydrogen and C. 1-20 Alkyl, C 6-20 Aryl, C 6-20 Aryl-C 1-20 Alkyl, substituted C 6-20 Aryl groups, or R2 and R3 atoms, are linked together and together with the carbon atoms connecting R2 and R3, they form C. 3-8 Metacyclic group; wherein the substituted C 6-20 The substituents of the aryl group are selected from halogens, C 1-6 Alkyl, C 1-6 Alkyl group; the condition is that R2 and R3 are not simultaneously selected from hydrogen.

[0014] X is selected from N or CR b ;where R b It is an electron-withdrawing group, selected from CN, NO2, CF3, -COOR c -SO2R d ;where R c R d Selected independently from C 1-6 Alkyl, C 6-20 Aryl.

[0015] Each R4 may be the same or different, and is independently selected from hydrogen, halogen, CN, and C. 1-20 Alkyl, Halogenated C 1-20 Alkyl, C 1-20 Alkoxy, C 6-20 Aryl, C 2-20 heteroaryl, substituted C 6-20 Aryl, C 6-20 arylethynyl; wherein the substituted C 6-20 The substituents of the aryl group are selected from halogens, C 1-6 Alkyl, C 1-6 Alkyl group.

[0016] Preferably, m and n are integers of 1 or 2.

[0017] Each R1 may be the same or different, and is independently selected from hydrogen, fluorine, chlorine, bromine, iodine, CN, and C.1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkyl group.

[0018] Indicates a double bond, a single bond, or no bond; Y is selected from O, S, OR. a , or does not exist; where R a For hydrogen, C 1-6 Alkyl, C 1-20 Acyl group.

[0019] Z is selected from CH2, O, or S.

[0020] R2 and R3 are independently selected from hydrogen and C. 1-10 Alkyl, C 6-14 Aryl, C 6-14 Aryl-C 1-6 Alkyl, substituted C 6-14 Aryl groups, or R2 and R3 atoms, are linked together and together with the carbon atoms connecting R2 and R3, they form C. 3-8 The substituted carbocyclic group; wherein the C 6-14 The substituents of the aryl group are selected from fluorine, chlorine, bromine, iodine, and C. 1-6 Alkyl, C 1-6 Alkyl group; the condition is that R2 and R3 are not simultaneously selected from hydrogen.

[0021] X is selected from N or CR b ;where R b It is an electron-withdrawing group, selected from CN, NO2, CF3, -COOR c -SO2R d ;where R c R d Selected independently from C 1-6 Alkyl, C 6-20 Aryl.

[0022] Each R4 may be the same or different, and is independently selected from hydrogen, fluorine, chlorine, bromine, iodine, CN, and C. 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, C 6-14 Aryl, C 2-14 heteroaryl, substituted C 6-14 Aryl, C 6-14 arylethynyl; wherein the substituted C 6-14 The substituents of the aryl group are selected from fluorine, chlorine, bromine, iodine, and C. 1-6 Alkyl, C 1-6 Alkyl group.

[0023] More preferably, m and n are integers of 1 or 2.

[0024] Each R1 may be the same or different, and is independently selected from hydrogen, fluorine, chlorine, methyl, methoxy, and trifluoromethyl.

[0025] Indicates a double bond, a single bond, or no bond; Y is selected from O, S, OR. a , or does not exist; where R a For hydrogen, acetyl,

[0026] Z is selected from CH2, O, or S.

[0027] R2 and R3 are independently selected from hydrogen, methyl, ethyl, isopropyl, n-propyl, n-decyl, phenyl, benzyl, phenethyl, p-methylphenyl, or R2 and R3 are connected to each other and together with the carbon atoms connecting R2 and R3 to form a cyclohexyl group.

[0028] X is selected from N or CR b ;where R b It is an electron-withdrawing group, selected from CN, -COOR c -SO2R d ;where R c R d Selected independently from methyl.

[0029] Each R4 may be the same or different, and is independently selected from hydrogen, fluorine, chlorine, bromine, iodine, CN, methyl, ethyl, methoxy, phenyl, phenylethynyl, thiophene, p-methoxyphenyl, and p-chlorophenyl.

[0030] The photocatalyst is selected from either fac-Ir(ppy)3 or Ir(ppy)2(dtbbpy)PF6; preferably fac-Ir(ppy)3.

[0031] The organic amine is selected from either triethylamine or diisopropylethylamine, preferably triethylamine.

[0032] The organic base is selected from any one or more of NaOAc, KOAc, K2CO3 or Na2CO3, preferably NaOAc.

[0033] The organic solvent is selected from any one or more of DMSO, DMF, NMP, and acetonitrile, preferably DMSO.

[0034] In this document, the C 1-20 Alkyl groups are preferably C 1-12 Alkyl, more preferably C 1-6Alkyl groups. Examples of the aforementioned alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, undecyl, dodecyl, etc. In this document, the alkoxy, haloalkyl, C... 6-20 Aryl-C 1-20 The alkyl group in alkyl has the same definition as the aforementioned alkyl.

[0035] In this document, the C 1-20 An acyl group refers to an acyl group having 1-20 carbon atoms. It can be straight-chain, branched, or cyclic, and can be saturated or unsaturated. Preferably, it does not contain other atoms. Exemplary acyl groups can be acetyl, propionyl, etc. wait.

[0036] In this article, the C mentioned 6-20 Aryl, substituted C 6-20 The aryl group in the aryl group is preferably C. 6-14 Aryl groups, exemplary aryl groups include phenyl, naphthyl, anthraceneyl, phenanthryl, indene, fluorene, etc. In this document, the C... 6-20 Aryl-C 1-20 Alkyl, C 6-20 The aryl group in arylethynyl group has the same definition as the aforementioned aryl group.

[0037] In this article, the C mentioned 2-20 heteroaryl, C 2-20 The heteroaryl group in the heteroaryl group is preferably C. 2-14 Heteroaryl groups, such as thienyl, furanyl, indolyl, pyridyl, quinolinyl, pyrimidinyl, benzothienyl, benzofuranyl, etc.

[0038] According to the aforementioned synthesis method of the present invention, the molar ratio of the compound shown in Formula 1, the compound shown in Formula 2, the photocatalyst, the organic amine, and the base is 1:(0.8-1.2):(0.005-0.02):(1-3):(1-3). Preferably, the molar ratio of the compound shown in Formula 1, the compound shown in Formula 2, the photocatalyst, the organic amine, and the base is 1:1:0.01:2:2.

[0039] According to the synthesis method described above, the inert atmosphere is a nitrogen atmosphere or an argon atmosphere, preferably an argon atmosphere.

[0040] According to the synthesis method described above, the illumination conditions are provided by a 3-30W blue LED lamp, preferably by an 18W blue LED lamp.

[0041] According to the synthesis method described above, the reaction time of the stirring reaction is 4 to 48 hours, preferably 8 to 24 hours, and more preferably 12 hours.

[0042] According to the aforementioned synthesis method of the present invention, the purification process includes the following operations: concentrating the reaction solution under vacuum, diluting it with diethyl ether, washing it with saturated brine, combining the organic phases and drying it with anhydrous sodium sulfate, concentrating it to obtain the residue, and separating the residue by silica gel column chromatography to obtain the β-pyridone derivative shown in Formula 3.

[0043] Compared with the prior art, the method of the present invention has the following significant advantages:

[0044] This invention reports for the first time a photocatalytic β-C(sp3)-H arylation of iodoaryl-induced 1-(o-iodoaryl)alkyl-1-ones with cyanoaryl hydrocarbons via halogen atom transfer (XAT) and hydrogen atom transfer (HAT). The method involves the generation of an aryl intermediate mediated by a diethylaminoethyl radical, followed by the guidance of 1,5-HAT to form a distal alkyl radical intermediate, which is then coupled to a cyanoaryl hydrocarbon (the corresponding cyanoaryl radical intermediate generated via photoreduction). This method is applicable to a wide range of inactive, long-range C(sp3)-H bonds, providing a novel synthetic route for constructing derivatives such as β-pyridones.

[0045] The method of the present invention can be carried out at room temperature, the reaction conditions are mild and simple, the substrate range is wide, and the yield of the target product is high. Attached Figure Description

[0046] Figure 1 Diffraction pattern of single crystal structure of compound 3aa

[0047] Figure 2 This is a schematic diagram of the reaction mechanism of the present invention. Detailed Implementation

[0048] The present invention will be further described in detail below with reference to specific embodiments. Unless otherwise specified, the methods used herein are conventional methods in the art, and the reagents and raw materials used are obtained through conventional commercial channels and / or prepared by conventional methods.

[0049] Example 1 of the preparation of reaction raw materials

[0050]

[0051] A mixture of 50 mmol of 2-iodobenzaldehyde compounds and 50 mL of THF was cooled to 0 °C under nitrogen protection. The corresponding Grignard reagent (1.5 eq) was added dropwise. The reaction mixture was stirred at 0 °C for 1.5–3 hours, quenched with saturated ammonium chloride, extracted with ethyl acetate, washed with 50 mL of brine, dried over anhydrous sodium sulfate, and separated by silica gel column chromatography to obtain benzyl alcohol intermediate A. DMP (1.5 eq) was added to a 0.1 M dichloromethane solution of benzyl alcohol intermediate A (1 eq) at 0 °C. The mixture was then stirred at room temperature until complete. After the reaction, the mixture was filtered, extracted with ethyl acetate, concentrated, and the residue was separated by silica gel column chromatography to obtain compound 1.

[0052] Example 2 of the preparation of reaction raw materials

[0053]

[0054] A mixture of NaH (60% mineral oil suspension, 1.5-3 eq) and anhydrous THF (0.56 M NaH concentration) was added to a dry round-bottom flask and cooled to 0°C. A solution of 2-iodophenylmethanol (1 eq) in anhydrous THF (0.78 M) was added dropwise and stirred for 2 hours. Subsequently, the corresponding bromide (1.1-1.7 eq) was added dropwise, and the mixture was heated to room temperature and stirred for 2-16 hours. The reaction was monitored by TLC until it was complete. The reaction was quenched at 0°C with saturated ammonium chloride or H2O (20 mL). The mixture was extracted with ethyl acetate, and the organic phases were combined and washed with brine. The organic phases were dried with sodium sulfate, filtered, concentrated under vacuum, and the residue was separated by silica gel column chromatography to obtain the corresponding compound 2.

[0055] Examples 1-19: Optimization of Reaction Conditions

[0056] Using the compound shown in Formula 1a and p-cyanopyridine shown in Formula 2a as starting materials, β-pyridone derivatives shown in Formula 3aa were prepared by photocatalytic β-C(sp3)-H arylation via halogen atom transfer (XAT) and hydrogen atom transfer (HAT). The effects of different synthetic conditions on the yield of the target product were investigated, and the results are as follows:

[0057] Table 1 shows the reaction formulas as follows:

[0058]

[0059] Table 1:

[0060]

[0061]

[0062] aStandard reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), fac-Ir(ppy)3 (1 mol%), Et3N (2 equiv), NaOAc (2 equiv), DMSO (0.1 M; 2 mL), 18 W blue LEDs, argon, room temperature, reaction time 12 h; b 1a (1mmol) and 24h.

[0063] Taking Example 1 as an example, the typical experimental procedure is as follows:

[0064] Compounds 1a (0.2 mmol), 2a (0.2 mmol, 1 eq), fac-Ir(ppy)3 (1 mol%), Et3N (2 equiv), NaOAc (2 equiv), and DMSO (2 mL, 0.1 M) were added to a Schlenk sealed reactor. The atmosphere inside the reactor was then purged three times with argon. The reactor was then placed at room temperature and irradiated with an 18 W blue LED lamp (the light source was about 5 cm away from the reactor) with stirring for 12 hours. The reaction mixture was monitored by TLC and / or GC-MS to indicate that the reactants had been completely consumed. After the reaction was complete, the mixture was concentrated under vacuum, diluted with diethyl ether, washed with saturated brine, and the combined organic phases were dried over anhydrous sodium sulfate. The mixture was then concentrated under vacuum, and the residue was subjected to silica gel column chromatography (eluting buffer: PE / EA = 10:1 to 4:1) to give 33.8 mg of product 3aa, with a yield of 71%. 1 HNMR(500MHz,Chloroform-d)δ(ppm)8.48(d,J=6.5Hz,2H),7.85-7.83(m,2H),7. 54-7.51(m,1H),7.43-7.40(m,2H),7.27-7.25(m,2H),3.36(s,2H),1.49(s,6H); 13 C NMR (125MHz, Chloroform-d) δ (ppm) 197.76, 157.89, 149.72, 137.70, 132.99, 128.54, 127.89, 120.85, 50.02, 37.16, 28.69.

[0065] Substrate Expansion Experiment 1: Preparation of a Series of β-Pyridone Derivatives

[0066]

[0067] Product structure characterization:

[0068] Compound 3ba: 33 mg, 66% yield; R f =0.2(PE / EA=4:1);Yellow oil; 11H NMR (400 MHz, Chloroform-d) δ (ppm) 8.42 - 8.41 (m, 2H), 7.69 - 7.67 (m, 2H), 7.20 - 7.18 (m, 2H), 7.13 (d, J = 8.0 Hz, 2H), 3.26 (s, 2H), 2.31 (s, 3H), 1.40 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ (ppm) 197.43, 158.07, 149.68, 143.89, 135.12, 129.24, 128.06, 120.90, 49.84, 37.14, 28.76, 21.63。

[0069] Compound 3ca: 42 mg, 78% yield; R f = 0.3 (PE / EA = 3:1); Brown oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.49 (d, J = 6.5 Hz, 2H), 7.84 - 7.81 (m, 2H), 7.27 - 7.26 (m, 2H), 6.90 - 6.87 (m, 2H), 3.85 (s, 3H), 3.30 (s, 2H), 1.48 (s, 6H); 13 13C NMR (125 MHz, Chloroform-d) δ (ppm) 196.31, 163.45, 158.14, 149.64, 130.79, 130.22, 120.89, 113.67, 55.45, 49.62, 37.23, 28.72。

[0070] Compound 3da: 29 mg, 57% yield; R f = 0.2 (PE / EA = 5:1); Brown oil; 1 1H NMR (400 MHz, Chloroform-d) δ (ppm) 8.41 (d, J = 6.4 Hz, 2H), 7.57 - 7.53 (m, 1H), 7.43 - 7.37 (m, 1H), 7.19 - 7.17 (m, 2H), 7.10 - 6.98 (m, 2H), 3.34 (d, J = 2.4 Hz, 2H), 1.39 (s, 6H); 1313C NMR (100 MHz, Chloroform-d) δ (ppm) 196.34 (d, J = 3.8 Hz), 162.71, 160.19, 157.86, 149.60, 134.44 (d, J = 8.9 Hz), 130.36 (d, J = 2.6 Hz), 126.53 (d, J = 13.1 Hz), 124.52 (d, J = 3.4 Hz), 120.89, 116.57 (d, J = 23.9 Hz), 55.20 (d, J = 7.0 Hz), 37.2 (d, J = 1.4 Hz), 28.78; 19 19F NMR (376 MHz, Chloroform-d) δ (ppm) -108.89.

[0071] Compound 3ea: 26.4 mg, 43% yield; R f = 0.15 (PE / EA = 5:1); Light brown oil; 1 1H NMR (400 MHz, Chloroform-d) δ (ppm) 8.43 (d, J = 6.4 Hz, 2H), 7.87 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H), 7.20–7.18 (m, 2H), 3.32 (s, 2H), 1.43 (s, 6H); 13 13C NMR (101 MHz, Chloroform-d) δ (ppm) 196.76, 157.50, 149.81, 140.11, 134.36 (d, J = 32.5 Hz) 128.23, 125.69 - 125.61 (m), 120.81, 50.37, 37.14, 28.69.; 19 19F NMR (376 MHz, Chloroform-d) δ (ppm) -63.11.

[0072] Compound 3fa: 31 mg, 62% yield; R f = 0.2 (PE / EA = 4:1); Colorless oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.48 (d, J = 7.0 Hz, 2H), 7.64 - 7.63 (m, 2H), 7.35–7.28 (m, 2H), 7.26–7.24 (m, 2H), 3.35 (s, 2H), 2.37 (s, 3H), 1.48 (s, 6H); 13¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 197.98, 158.03, 149.62, 138.34, 137.72, 133.74, 128.44, 128.40, 125.11, 120.89, 50.09, 37.16, 28.70, 21.29。

[0073] Compound 3ga: 37 mg, 69% yield; R f = 0.15 (PE / EA = 3:1); Yellow oil; 1 ¹H NMR (500 MHz, Chloroform-d) δ (ppm) 8.49 (d, J = 6.0 Hz, 2H), 7.44 - 7.42 (m, 1H), 7.36–7.29 (m, 2H), 7.27–7.30 (m, 2H), 7.27 - 7.25 (m, 2H), 3.81 (s, 3H), 3.35 (s, 2H), 1.48 (s, 6H); 13 ¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 197.55, 159.82, 158.02, 149.61, 138.98, 129.50, 120.88, 120.54, 119.54, 112.17, 55.40, 50.11, 37.15, 28.73。

[0074] Compound 3ha: 47 mg, 78% yield; R f = 0.1 (PE / EA = 3:1); Brown oil; 1 ¹H NMR (500 MHz, Chloroform-d) δ (ppm) 8.50 (d, J = 6.5 Hz, 2H), 7.49 - 7.47 (m, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.28–7.26 (m, 2H), 6.83 (d, J = 8.5 Hz, 1H), 3.93 (s, 3H), 3.88 (s, 3H), 3.32 (s, 2H), 1.48 (s, 6H); 13 ¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 196.31, 158.15, 153.34, 149.65, 149.09, 130.92, 122.62, 120.88, 110.12, 109.88, 56.06, 55.94, 49.48, 37.23, 28.76。

[0075] Compound 3ia: 45 mg, 81% yield; R f= 0.1 (PE / EA = 4:1); Colorless oil; 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 8.44 (d, J = 5.0 Hz, 2H), 7.68 - 7.66 (m, 2H), 7.48–7.45 (m, 1H), 7.34 - 7.31 (m, 2H), 7.26 (d, J = 3.0 Hz, 2H), 3.21 (s, 2H), 2.26 - 2.20 (m, 2H), 1.89 - 1.84 (m, 2H), 1.63 - 1.58 (m, 2H), 1.49 - 1.34 (m, 4H); 13 C NMR (125 MHz, Chloroform-d) δ (ppm) 198.35, 155.38, 149.58, 137.99, 132.81, 128.37, 127.86, 122.32, 49.76, 41.24, 35.83, 26.03, 22.23。

[0076] Compound 3ja: 18.5 mg, 41% yield; R f = 0.2 (PE / EA = 3:1); Colorless oil; 1 H NMR (400 MHz, Chloroform-d) δ (ppm) 8.51 (d, J = 6.4 Hz, 2H), 7.93–7.91 (m, 2H), 7.59 - 7.54 (m, 1H), 7.44 - 7.44 (m, 2H), 7.21 - 7.19 (m, 2H), 3.56 - 3.48 (m, 1H), 3.34 - 3.18 (m, 2H), 1.35 (d, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, Chloroform-d) δ (ppm) 198.08, 155.49, 149.87, 136.87, 133.29, 128.69, 128.01, 122.43, 45.88, 34.75, 21.31。

[0077] Compound 3ka: 25 mg, 53% yield; R f = 0.2 (PE / EA = 5:1); Brown oil; 11H NMR (500 MHz, Chloroform-d) δ (ppm) 8.50 (d, J = 3.5 Hz, 2H), 7.7.90 - 7.88 (m, 2H), 7.57 - 7.53 (m, 1H), 7.46 - 7.42 (m, 2H), 7.16 (d, J = 4.5 Hz, 2H), 3.31 - 3.24 (m, 3H), 1.84 - 1.76 (m, 1H), 1.70 - 1.62 (m, 1H), 0.83 (t, J = 7.0 Hz, 3H); 13 13C NMR (125 MHz, Chloroform-d) δ (ppm) 198.13, 153.77, 149.84, 136.99, 133.16, 128.62, 127.95, 123.16, 44.44, 42.19, 28.70, 11.85.

[0078] Compound 3la: 31 mg, 45% yield; R f = 0.3 (PE / EA = 3:1); Brown oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.49 (d, J = 5.0 Hz, 2H), 7.89 (d, J = 8.0 Hz, 2H), 7.55 (t, J = 7.5 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.17 (d, J = 5.0 Hz, 2H), 3.36–3.24 (m, 3H), 1.76 - 1.59 (m, 2H), 1.30 - 1.21 (m, 16H), 0.87 (t, J = 7.0 Hz, 3H); 13 13C NMR (125 MHz, Chloroform-d) δ (ppm) 198.17, 154.21, 149.82, 137.00, 133.19, 128.65, 127.98, 123.16, 44.87, 40.56, 35.82, 31.89, 29.71, 29.56, 29.48, 29.42, 29.30, 27.33, 22.67, 14.10.

[0079] Compound 3ma: 14 mg, 27% yield; R f = 0.3 (PE / EA = 2:1); Colorless oil; 1HNMR(500MHz, Chloroform-d) δ(ppm) 8.45 (d, J = 4.0Hz, 2H), 7.87 (d, J = 8.0Hz, 2H), 7.55 - 7.52 (m, 1H), 7.45 - 7.41 (m, 2H), 7.11 (d, J = 4.5Hz, 2H), 3.37 (d, J = 7.0Hz, 2H), 3.20–3.15 (m, 1H), 1.99 - 1.92 (m, 1H), 0.99 - 0.98 (m, 3H), 0.81 - 0.79 (m, 3H); 13 C NMR(125MHz, Chloroform-d) δ(ppm) 198.39, 152.84, 149.51, 137.05, 133.11, 128.61, 127.91, 123.82, 47.11, 41.45, 32.77, 20.61, 20.30.

[0080] Compound 3na and 3n’a: 3na: 3na' = 1.5:1 (the ratio was determined by 1 H NMR), 42mg, 71% yield,; R f = 0.2 (PE / EA = 3:1); White powder, m.p. 135 - 139°C (uncorrected); 1 HNMR(400MHz, Chloroform-d) δ(ppm) 8.50 (d, J = 5.2Hz, 2H), 8.44 (d, J = 5.2Hz, 1.3H), 7.87 - 7.83 (m, 3.4H), 7.55 - 7.51 (m, 1.8H), 7.44 - 7.39 (m, 3.6H), 7.33 - 7.29 (m, 2.3H), 7.25 - 7.15 (m, 7.4H), 7.10 - 7.05 (m, 2.8H), 4.01 (t, J = 8.0Hz, 1H), 3.68 (p, J = 7.2Hz, 0.72H), 3.40 - 3.28 (m, 1.4H), 3.05 - 2.99 (m, 0.8H), 2.93 (t, J = 7.2Hz, 2.8H), 2.53 - 2.47 (m, 2.5H); 1313C NMR (101 MHz, Chloroform-d) δ (ppm) 199.44, 197.93, 153.46, 153.18, 149.96, 149.76, 142.39, 138.80, 136.82, 136.77, 133.29, 133.17, 129.18, 128.89, 128.67, 128.62, 128.41, 127.98, 127.96, 127.03, 126.49, 123.21, 123.18, 49.81, 43.15, 42.28, 36.41, 28.98。

[0081] Compounds 3oa and 3o’a: 3oa:3oa' = 4:1 (the ratio was determined by 1 1H NMR), 30 mg, 48% yield,; R f f = 0.3 (PE / EA = 3:1); colorless oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.53 (d, J = 5.0 Hz, 2H), 8.48 (d, J = 5.0 Hz, 0.5H), 7.91 - 7.85 (m, 2.7H), 7.56 - 7.52 (m, 1.5H), 7.46 - 7.41 (m, 2.9H), 7.31 - 7.28 (m, 0.8H), 7.26 - 7.14 (m, 5.6H), 7.10 - 7.03 (m, 2.5H), 3.94 - 3.91 (m, 0.25H), 3.44 - 3.37 (m, 1H), 3.34 - 3.26 (m, 2.1H), 3.00 - 2.97 (m, 0.84H), 2.55 - 2.44 (m, 2.4H), 2.22 - 1.93 (m, 4H), 1.76 - 1.71 (m, 0.8H); 13 13C NMR (126 MHz, Chloroform-d) δ 197.84, 153.66, 149.91, 149.78, 141.32, 136.88, 133.22, 128.73, 128.64, 128.59, 128.42, 128.26, 127.94, 127.86, 126.79, 126.00, 123.21, 50.84, 44.89, 40.20, 38.19, 37.24, 34.47, 33.53, 29.68, 22.55; 13¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 197.84, 153.66, 149.91, 149.78, 141.32, 136.88, 133.22, 128.73, 128.64, 128.59, 128.42, 128.26, 127.94, 127.86, 126.79, 126.00, 123.21, 50.84, 44.89, 40.20, 38.19, 37.24, 34.47, 33.53, 29.68, 22.55。

[0082] Compound 3pa: 44 mg, 76% yield; R f = 0.2 (PE / EA = 5:1); Brown oil; 1 ¹H NMR (500 MHz, Chloroform-d) δ (ppm) 8.48 (d, J = 5.5 Hz, 2H), 7.93 (d, J = 8.0 Hz, 2H), 7.55 (t, J = 7.5 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.31–7.17 (m, 7H), 4.81 (t, J = 7.5 Hz, 1H), 3.79 - 3.68 (m, 2H); 13 ¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 197.16, 152.93, 149.96, 142.51, 136.78, 133.34, 128.84, 128.70, 128.01, 127.88, 126.98, 123.16, 45.30, 43.91。

[0083] Compound 3qa: 45 mg, 75% yield; R f = 0.1 (PE / EA = 5:1); Brown oil; 1 ¹H NMR (500 MHz, Chloroform-d) δ (ppm) 8.48 (d, J = 5.0 Hz, 2H), 7.95 - 7.93 (m, 2H), 7.58 - 7.55 (m, 1H), 7.45 (t, J = 8.0 Hz, 2H), 7.18 (d, J = 6.0 Hz, 2H), 7.15 - 7.10 (m, 4H), 4.77 (t, J = 7.0 Hz, 1H), 3.78 - 3.67 (m, 2H), 2.30 (s, 3H); 13¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 197.26, 153.27, 149.87, 139.49, 136.80, 136.61, 133.32, 129.52, 128.69, 128.02, 127.71, 123.14, 44.93, 43.96, 20.96。

[0084] Compound 3ab: 27 mg, 54% yield; R f = 0.15 (PE / EA = 5:1); Yellow oil; 1 ¹H NMR (500 MHz, Chloroform-d) δ (ppm) 8.36 (d, J = 5.5 Hz, 1H), 7.85 - 7.83 (m, 2H), 7.54–7.50 (m, 1H), 7.42 - 7.39 (m, 2H), 7.07 - 7.05 (m, 1H), 3.34 (s, 2H), 2.51 (s, 3H), 1.46 (s, 6H); 13 ¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 197.94, 158.20, 158.15, 148.96, 137.75, 132.95, 128.50, 127.90, 120.35, 117.94, 50.03, 37.09, 28.68, 24.56。

[0085] Compound 3ac: 36 mg, 57% yield; R f = 0.2 (PE / EA = 10:1); Brown oil; 1 ¹H NMR (500 MHz, Chloroform-d) δ (ppm) 8.57 (d, J = 5.0 Hz, 1H), 7.93 - 7.91 (m, 2H), 7.85 - 7.83 (m, 2H), 7.68 (d, J = 2.0 Hz, 1H), 7.51 - 7.48 (m, 1H), 7.46 - 7.42 (m, 2H), 7.40 - 7.37 (m, 3H), 7.22 - 7.20 (m, 1H), 3.39 (s, 2H), 1.53 (s, 6H); 13 ¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 197.94, 158.78, 157.61, 149.50, 139.87, 137.77, 133.00, 128.76, 128.64, 128.54, 127.98, 127.93, 127.12, 125.66, 119.43, 118.11, 50.12, 37.48, 28.76。

[0086] Compound 3ad: 44 mg, 64% yield; R f = 0.2 (PE / EA = 10:1); Brown oil; 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 8.52 (d, J = 5.0 Hz, 1H), 7.88 - 7.83 (m, 4H), 7.61 (s, 1H), 7.52 - 7.48 (m, 1H), 7.40 - 7.37 (m, 2H), 7.16–7.15 (m, 1H), 6.98 - 6.95 (m, 2H), 3.84 (s, 3H), 3.38 (s, 2H), 1.53 (s, 6H); 13 C NMR (125 MHz, Chloroform-d) δ (ppm) 198.02, 160.33, 158.52, 157.28, 149.45, 137.80, 132.97, 132.58, 128.52, 128.31, 127.93, 118.77, 117.26, 114.03, 55.33, 50.09, 37.45, 28.73。

[0087] Compound 3ae: 40 mg, 58% yield; R f = 0.2 (PE / EA = 10:1); Brown oil; 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 8.55 (d, J = 5.0 Hz, 1H), 7.86 - 7.83 (m, 4H), 7.63 (s, 1H), 7.53 - 7.50 (m, 1H), 7.42–7.40 (m, 4H), 7.23 - 7.22 (m, 1H), 3.40 (s, 2H), 1.54 (s, 6H); 13 C NMR (125 MHz, Chloroform-d) δ (ppm) 197.87, 158.87, 156.41, 149.66, 138.37, 137.71, 134.89, 133.07, 128.81, 128.75, 128.58, 128.38, 127.92, 119.71, 117.85, 50.11, 37.47, 28.84。

[0088] Compound 3af: 28 mg, 43% yield; R f = 0.2 (PE / EA = 10:1); Yellow oil; 11H NMR (500 MHz, Chloroform-d) δ (ppm) 8.45 (d, J = 5.0 Hz, 1H), 7.86 - 7.85 (m, 2H), 7.63 (s, 1H), 7.55 - 7.50 (m, 2H), 7.42 - 7.39 (m, 2H), 7.37–7.36 (m, 1H), 7.14 - 7.08 (m, 2H), 3.39 (s, 2H), 1.52 (s, 6H); 13 13C NMR (125 MHz, Chloroform-d) δ (ppm) 197.83, 158.68, 152.58, 149.46, 145.22, 137.74, 133.00, 128.55, 127.91, 127.83, 127.27, 124.31, 119.32, 116.10, 50.02, 37.35, 28.66.

[0089] Compound 3ag: 22 mg, 32% yield; R f = 0.1 (PE / EA = 4:1); Brown oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.49 (d, J = 5.0 Hz, 1H), 7.87 - 7.85 (m, 2H), 7.61 - 7.58 (m, 2H), 7.55 - 7.52 (m, 2H), 7.44 - 7.41 (m, 2H), 7.37 - 7.34 (m, 3H), 7.23 - 7.21 (m, 1H), 3.38 (s, 2H), 1.50 (s, 6H); 13 13C NMR (125 MHz, Chloroform-d) δ (ppm) 197.52, 158.38, 149.92, 143.36, 137.61, 133.06, 132.03, 128.81, 128.57, 128.33, 127.90, 124.46, 122.46, 120.19, 89.15, 88.63, 49.99, 37.15, 28.61.

[0090] Compound 3ah: 32 mg, 65% yield; R f = 0.2 (PE / EA = 10:1); Brown oil; 11H NMR (500 MHz, Chloroform-d) δ (ppm) 8.33 (d, J = 5.5 Hz, 1H), 8.24 (s, 1H), 7.86 - 7.84 (m, 2H), 7.54 - 7.51 (m, 1H), 7.41 (t, J = 8.0 Hz, 2H), 7.22 (d, J = 5.0 Hz, 1H), 3.52 (s, 2H), 2.44 (s, 3H), 1.54 (s, 6H); 13 13C NMR (125 MHz, Chloroform-d) δ (ppm) 197.76, 154.92, 152.94, 147.75, 137.48, 133.01, 130.36, 128.58, 127.82, 121.37, 48.92, 38.32, 29.12, 20.25.

[0091] Compound 3ai: 27 mg, 50% yield; R f = 0.2 (PE / EA = 4:1); Brown oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.49 (d, J = 6.0 Hz, 2H), 7.85 - 7.83 (m, 2H), 7.54 - 7.51 (m, 1H), 7.41 (t, J = 7.5 Hz, 2H), 7.26 (d, J = 2.0 Hz, 1H), 3.36 (s, 2H), 1.49 (s, 6H); 13 13C NMR (125 MHz, Chloroform-d) δ (ppm) 197.80, 157.98, 149.69, 137.71, 133.03, 128.57, 127.92, 120.90, 50.04, 37.19, 28.72.

[0092] Compound 3aj: 22 mg, 42% yield; R f = 0.2 (PE / EA = 3:1); Yellow oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.49 (d, J = 6.0 Hz, 2H), 7.85 - 7.83 (m, 2H), 7.54 - 7.51 (m, 1H), 7.41 (t, J = 7.5 Hz, 2H), 7.26 (d, J = 2.0 Hz, 1H), 3.36 (s, 2H), 1.49 (s, 6H); 13C NMR (125MHz, Chloroform-d) δ (ppm) 197.80, 157.98, 149.69, 137.71, 133.03, 128.57, 127.92, 120.90, 50.04, 37.19, 28.72.

[0093] Substrate Expansion Experiment 2: Preparation of a Series of Similar Compounds

[0094]

[0095]

[0096] Product structure characterization:

[0097] Compound 3ra: 35 mg, 72% yield; R f =0.1(PE / EA=3:1);Yellow oil; 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.45-8.43(m,2H),7.29-7.20(m,5H),7.19-7.17(m,2H),4 .49-4.46(m,1H),2.29(s,1H),2.20-2.15(m,1H),2.03-1.99(m,1H),1.45(s,3H),1.32(s,3H); 13 CNMR(125MHz,Chloroform-d)δ(ppm)158.44,149.55,149.48,145.70,128.50,127.50,127.47,125.65,121.46,72.16,52.62,37.65,29.35,28.35

[0098] Compound 3sa: 29 mg, 51% yield; R f =0.2(PE / EA=4:1); Brown oil; 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.52(d,J=5.5Hz,2H),7.30-7.22(m,5H),7.19(d,J=7.5Hz,2H ),5.73-5.71(m,1H),2.48-2.44(m,1H),1.99-1.96(m,1H),1.65(s,3H),1.40(s,3H),1.35(s,3H); 1313C NMR (125 MHz, Chloroform-d) δ (ppm) 169.81, 157.65, 149.59, 141.39, 128.51, 127.89, 126.11, 121.31, 72.99, 50.01, 37.19, 29.99, 27.18, 20.70。

[0099] Compound 3ta: dr = 1.5:1; 54 mg, 58% yield; R f = 0.2 (PE / EA = 3:1); Yellow oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.53 (s, 2H), 7.36 - 7.29 (m, 5.51H), 7.26 - 7.19 (m, 4H), 7.18 - 7.16 (m, 1.21H), 7.13 - 7.11 (d, J = 5.5 Hz, 1.3H), 5.58 - 5.54 (m, 1H), 3.97 - 3.85 (m, 1H), 2.79 - 2.71 (m, 1.08H), 2.51–2.43 (m, 1.42H), 2.08 - 2.00 (m, 32.72H), 1.95 - 1.93 (m, 3.65H), 1.70 - 1.67 (m, 3.60H), 1.61 - 1.54 (m, 9.86H); 13 13C NMR (125 MHz, Chloroform-d) δ (ppm) 170.84, 170.59, 153.07, 152.88, 149.90, 142.10, 141.84, 140.29, 140.00, 128.94, 128.91, 128.54, 128.25, 128.17, 127.89, 127.83, 127.11, 127.09, 126.89, 126.68, 74.10, 74.03, 48.91, 48.87, 47.29, 47.16, 42.43, 41.51, 41.34, 36.73, 32.90, 28.61。

[0100] Compound 3ua: dr = 5:1; 26 mg, 31% yield; R f = 0.1 (PE / EA = 4:1); Brown oil; 11H NMR (400 MHz, Chloroform-d) δ (ppm) 8.56 - 8.54 (m, 2H), 8.46 - 8.45 (m, 0.4H), 7.25 - 7.20 (m, 2.4H), 7.16 - 7.06 (m, 5H), 6.99 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 6.83 - 6.79 (m, 2H), 5.66 - 5.63 (m, 1H), 5.49 - 5.46 (m, 0.2H), 3.51 - 3.45 (m, 0.2H), 3.10 - 3.05 (m, 1H), 2.91 (d, J = 25.7 Hz, 0.67H), 2.47 - 2.41 (m, 2.8H), 2.35–2.22 (m, 1.5H), 2.02 - 1.78 (m, 2.8H), 1.43–1.26 (m, 11.5H), 1.14 (d, J = 2.8 Hz, 1.2H), 0.91 - 0.86 (m, 8.6H); 13 13C NMR (100 MHz, Chloroform-d) δ (ppm) 173.48, 173.20, 157.94, 157.75, 149.70, 149.61, 141.75, 141.36, 140.61, 140.34, 137.39, 137.33, 129.53, 129.26, 129.14, 128.50, 128.22, 127.79, 127.49, 127.45, 127.25, 127.03, 125.93, 125.48, 121.37, 121.19, 74.08, 73.20, 50.39, 49.95, 45.21, 45.05, 45.00, 44.73, 42.88, 37.27, 37.25, 37.17, 35.93, 30.26, 30.20, 29.82, 29.72, 28.88, 27.76, 27.28, 22.43, 22.41, 22.37, 22.35, 20.77, 18.19, 17.70.

[0101] Compound 3wa: 48.2 mg, 87% yield; R f = 0.4 (PE / EA = 5:1); Brown oil; 1 1H NMR (400 MHz, Chloroform-d) δ (ppm) 8.54 (d, J = 5.6 Hz, 2H), 7.38 - 7.32 (m, 8H), 7.31–7.27 (m, 4H), 5.39 (s, 1H), 4.58 - 4.48 (m, 2H); 1313C NMR (100 MHz, Chloroform-d) δ (ppm) 151.17, 149.87, 140.49, 137.80, 128.80, 128.53, 128.28, 127.86, 127.78, 127.42, 121.73, 81.19, 70.68。

[0102] Compound 3xa: 30 mg, 43% yield; R f = 0.1 (PE / EA = 6:1); Yellow oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.53 (d, J = 5.0 Hz, 2H), 7.48 - 7.46 (m, 6H), 7.38 - 7.32 (m, 8H), 7.31 - 7.28 (m, 3H), 4.16 (s, 2H); 13 13C NMR (126 MHz, Chloroform-d) δ (ppm) 154.15, 149.56, 142.11, 138.50, 129.00, 128.36, 128.15, 127.76, 127.36, 127.02, 来22.79, 86.38, 66.01。

[0103] Compound 3ya: 48.2 mg, 35% yield; R f = 0.2 (PE / EA = 4:1); Brown oil; 1 1H NMR (500 MHz, Chloroform-d) δ (ppm) 8.52 (d, J = 6.5 Hz, 2H), 7.32 - 7.23 (m, 10H), 7.20 - 7.19 (m, 2H), 4.85 (s, 1H), 3.56 (s, 2H); 13 13C NMR (125 MHz, Chloroform-d) δ (ppm) 150.10, 149.99, 139.40, 137.34, 128.96, 128.80, 128.54, 128.45, 127.74, 127.25, 123.49, 52.25, 36.57。

[0104] Compound 3za: 11 mg, 20% yield; R f = 0.2 (PE / EA = 10:1); Colorless oil; 1 There is a small error in the original text where "来22.79" in line 9 should be "122.79", and this has been corrected in the translation.HNMR (500 MHz, Chloroform-d) δ 8.54 (d, J = 6.0 Hz, 2H), 7.37 - 7.35 (m, 2H), 7.30 - 7.28 (m, 2H), 7.26 - 7.22 (m, 5H), 6.99 - 6.96 (m, 1H), 6.91 - 6.88 (m, 2H), 4.52 - 4.46 (m, 3H); 13 C NMR (126 MHz, Chloroform-d) δ 158.38, 150.59, 149.88, 139.91, 129.53, 128.83, 128.38, 127.33, 123.74, 121.26, 114.72, 70.00, 49.99.

[0105] Compound 3wb: 47 mg, 82% yield; R f = 0.2 (PE / EA = 6:1); Brown oil; 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 8.41 (d, J = 5.0 Hz, 1H), 7.36 - 7.27 (m, 10H), 7.16 (s, 1H), 7.09 (d, J = 5.5 Hz, 1H), 5.35 (s, 1H), 4.62–4.44 (m, 2H), 2.51 (s, 3H); 13 C NMR (125 MHz, Chloroform-d) δ (ppm) 158.59, 151.40, 149.23, 140.69, 137.88, 128.74, 128.51, 128.17, 127.82, 127.78, 127.37, 121.14, 118.93, 81.35, 70.70, 24.55.

[0106] Compound 3wc: 37 mg, 53% yield; R f = 0.3 (PE / EA = 10:1); Brown oil; 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 8.64 (d, J = 5.0 Hz, 1H), 7.00 - 7.96 (m, 2H), 7.77 (s, 1H), 7.48 - 7.44 (m, 2H), 7.42 - 7.38 (m, 9H), 7.35 - 7.30 (m, 2H), 7.27 - 7.25 (mz, 1H), 5.47 (s, 1H), 4.64 - 4.55 (m, 2H); 13¹³C NMR (126 MHz, Chloroform-d) δ (ppm) 157.74, 151.93, 149.76, 140.58, 139.45, 137.84, 128.96, 128.76, 128.69, 128.50, 128.22, 127.82, 127.78, 127.39, 127.04, 120.29, 118.54, 81.46, 70.77。

[0107] Compound 3wg: 38 mg, 51% yield; R f = 0.4 (PE / EA = 5:1); Brown oil; 1 ¹H NMR (500 MHz, Chloroform-d) δ (ppm) 8.56 - 8.50 (m, 1H), 7.62 - 7.57 (m, 3H), 7.39 - 7.31 (m, 14H), 7.27 - 7.26 (m, 1H), 5.40 (s, 1H), 4.61–4.51 (m, 2H); 13 ¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 151.65, 150.11, 143.55, 140.20, 137.68, 132.10, 128.97, 128.87, 128.55, 128.40, 127.91, 127.83, 127.46, 125.04, 122.34, 120.86, 88.21, 88.87, 80.99, 70.76。

[0108] Compound 3wh: 50 mg, 71% yield; R f = 0.3 (PE / EA = 5:1); Brown oil; 1 ¹H NMR (500 MHz, Chloroform-d) δ (ppm) 8.49 (d, J = 5.0 Hz, 1H), 8.34 (s, 1H), 7.53 (d, J = 5.0 Hz, 1H), 7.36 - 7.26 (m, 10H), 5.51 (s, 1H), 4.52 (q, J = 12.0 Hz, 2H), 2.13 (s, 3H); 13 ¹³C NMR (125 MHz, Chloroform-d) δ (ppm) 151.20, 148.50, 147.91, 139.23, 137.78, 130.85, 128.58, 128.46, 128.12, 127.87, 127.81, 127.80, 121.10, 78.95, 70.79, 16.27。

[0109] Compound 3wj: 34 mg, 57% yield; R f = 0.2 (PE / EA = 5:1); Brown oil; 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 7.39 - 7.34 (m, 8H), 7.33 - 7.29 (m, 2H), 6.99 (s, 2H), 5.33 (s, 1H), 4.58 - 4.50 (m, 2H), 2.50 (s, 6H); 13 C NMR (126 MHz, Chloroform-d) δ (ppm) 157.91, 151.63, 140.87, 137.95, 128.69, 128.49, 128.08, 127.79, 127.31, 118.29, 81.46, 70.69, 24.57。

[0110] Compound 3wk: 37 mg, 62% yield; R f = 0.2 (PE / EA = 30:1); Yellow oil; 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 7.61 (d, J = 8.0 Hz, 2H), 7.52 - 7.50 (m, 2H), 7.40 - 7.35 (m, 8H), 7.34 - 7.31 (m, 2H), 5.49 (s, 1H), 4.61 - 4.51 (m, 2H); 13 C NMR (125 MHz, Chloroform-d) δ (ppm) 147.74, 140.74, 137.77, 132.23, 128.78, 128.50, 128.19, 127.84, 127.75, 127.53, 127.28, 118.80, 111.23, 81.77, 70.74。

[0111] Compound 3wl: 33 mg, 50% yield; R f = 0.2 (PE / EA = 20:1); Brown oil; 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 7.99 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.37 - 7.27 (m, 10H), 5.47 (s, 1H), 4.57 - 4.51 (m, 2H), 3.89 (s, 3H); 13CNMR(125MHz,Chloroform-d)δ(ppm)166.92,147.41,141.41,138.08,129.76,129. 32,128.59,128.44,127.84,127.74,127.70,127.23,126.93,82.13,70.67,52.03.

[0112] Compound 3wm: 35mg, 51% yield; R f =0.2(PE / EA=2:1); Brown oil; 1 HNMR(500MHz,Chloroform-d)δ(ppm)7.91-7.88(m,2H),7.61m 7.60(m,2H),7.39-7.30(m,10H),5.51(s,1H),4.61-4.51(m,2H),3.03(s,3H); 13 C NMR(125MHz,Chloroform-d)δ(ppm)148.71,140.81,139.51,137.76,128.78,1 28.51,128.18,127.85,127.77,127.73,127.54,127.26,81.74,70.76,44.52.

[0113] The embodiments described above are merely preferred embodiments of the present invention, and not an exhaustive list of all possible implementations of the present invention. Any obvious modifications made by those skilled in the art without departing from the principles and spirit of the present invention should be considered to be included within the scope of protection of the claims of the present invention.

Claims

1. A method for synthesizing a β-pyridone derivative, characterized in that, Includes the following steps: Compounds of Formula 1, Formula 2, a photocatalyst, an organic amine, a base, and an organic solvent were added to a reactor. The atmosphere inside the reactor was then replaced with an inert atmosphere, and the reaction was carried out under stirring at room temperature and under light. After the reaction was complete, the β-pyridone derivative of Formula 3 was obtained through purification. The reaction formula is as follows: ； In the above reaction formula, m and n are integers of 1, 2, 3 or 4; Each R1 may be the same or different, and is independently selected from hydrogen, halogen, CN, and C. 1-20 Alkyl, Halogenated C 1-20 Alkyl, C 1-20 Alkoxy; Indicates a double bond, a single bond, or no bond; Y is selected from O, S, OR. a , or does not exist; where R a For hydrogen, C 1-20 Alkyl, C 1-20 Acyl group; Z is selected from CH2, O, or S; R2 and R3 are independently selected from hydrogen and C. 1-20 Alkyl, C 6-20 Aryl, C 6-20 Aryl-C 1-20 Alkyl, substituted C 6-20 Aryl groups, or R2 and R3 atoms, are linked together and together with the carbon atoms connecting R2 and R3, they form C. 3-8 Metacyclic group; wherein the substituted C 6-20 The substituents of the aryl group are selected from halogens, C 1-6 Alkyl, C 1-6 Alkyl group; the condition is that R2 and R3 are not simultaneously selected from hydrogen; X is selected from N or CR b ;where R b It is an electron-withdrawing group, selected from CN, NO2, CF3, -COOR c -SO2R d ;where R c R d Selected independently from C 1-6 Alkyl, C 6-20 Aryl; Each R4 may be the same or different, and is independently selected from hydrogen, halogen, CN, and C. 1-20 Alkyl, Halogenated C 1-20 Alkyl, C 1-20 Alkoxy, C 6-20 Aryl, C 2-20 heteroaryl, substituted C 6-20 Aryl, C 6-20 arylethynyl; wherein the substituted C 6-20 The substituents of the aryl group are selected from halogens, C 1-6 Alkyl, C 1-6 Alkoxy; The photocatalyst is selected from fac The organic amine is selected from either -Ir(ppy)3 or Ir(ppy)2(dtbbpy)PF6; the organic amine is selected from either triethylamine or diisopropylethylamine; the base is selected from either or more of NaOAc, KOAc, K2CO3 or Na2CO3; the organic solvent is selected from either or more of DMSO, DMF, NMP, and acetonitrile.

2. The synthesis method according to claim 1, characterized in that, m and n are integers of 1 or 2; Each R1 may be the same or different, and is independently selected from hydrogen, fluorine, chlorine, bromine, iodine, CN, and C. 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy; Indicates a double bond, a single bond, or no bond; Y is selected from O, S, OR. a , or does not exist; where R a For hydrogen, C 1-6 Alkyl, C 1-20 Acyl group; Z is selected from CH2, O, or S; R2 and R3 are independently selected from hydrogen and C. 1-10 Alkyl, C 6-14 Aryl, C 6-14 Aryl-C 1-6 Alkyl, substituted C 6-14 Aryl groups, or R2 and R3 atoms, are linked together and together with the carbon atoms connecting R2 and R3, they form C. 3-8 The substituted carbocyclic group; wherein the C 6-14 The substituents of the aryl group are selected from fluorine, chlorine, bromine, iodine, and C. 1-6 Alkyl, C 1-6 Alkyl group; the condition is that R2 and R3 are not simultaneously selected from hydrogen; X is selected from N or CR b ;where R b It is an electron-withdrawing group, selected from CN, NO2, CF3, -COOR c -SO2R d ;where R c R d Selected independently from C 1-6 Alkyl, C 6-20 Aryl; Each R4 may be the same or different, and is independently selected from hydrogen, fluorine, chlorine, bromine, iodine, CN, and C. 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, C 6-14 Aryl, C 2-14 heteroaryl, substituted C 6-14 Aryl, C 6-14 arylethynyl; wherein the substituted C 6-14 The substituents of the aryl group are selected from fluorine, chlorine, bromine, iodine, and C. 1-6 Alkyl, C 1-6 Alkyl group.

3. The synthesis method according to claim 2, characterized in that, m and n are integers of 1 or 2; Each R1 may be the same or different, and is independently selected from hydrogen, fluorine, chlorine, methyl, methoxy, and trifluoromethyl. Indicates a double bond, a single bond, or no bond; Y is selected from O, S, OR. a , or does not exist; where R a For hydrogen, acetyl, , ; Z is selected from CH2, O, or S; R2 and R3 are independently selected from hydrogen, methyl, ethyl, isopropyl, n-propyl, n-decyl, phenyl, benzyl, phenethyl, p-methylphenyl, or R2 and R3 are connected to each other and together with the carbon atoms connecting R2 and R3 to form a cyclohexyl group. X is selected from N or CR b ;where R b It is an electron-withdrawing group, selected from CN, -COOR c -SO2R d ;where R c R d Independently selected from methyl; Each R4 may be the same or different, and is independently selected from hydrogen, fluorine, chlorine, bromine, iodine, CN, methyl, ethyl, methoxy, phenyl, phenylethynyl, thiophene, p-methoxyphenyl, and p-chlorophenyl.

4. The synthesis method according to any one of claims 1-3, characterized in that, The photocatalyst is selected from fac -Ir(ppy)3; the organic amine is selected from triethylamine; the base is selected from NaOAc; the organic solvent is selected from DMSO.

5. The synthesis method according to any one of claims 1-3, characterized in that, The molar ratio of the compound shown in Formula 1, the compound shown in Formula 2, the photocatalyst, the organic amine, and the base is 1: (0.8~1.2): (0.005~0.02): (1~3): (1~3).

6. The synthesis method according to claim 5, characterized in that, The molar ratio of the compound shown in Formula 1, the compound shown in Formula 2, the photocatalyst, the organic amine, and the base is 1:1:0.01:2:

2.

7. The synthesis method according to any one of claims 1-3, characterized in that, The inert atmosphere is either a nitrogen atmosphere or an argon atmosphere.

8. The synthesis method according to any one of claims 1-3, characterized in that, The lighting conditions are provided by 3~30W blue LED lights.

9. The synthesis method according to any one of claims 1-3, characterized in that, The reaction time for the stirring reaction is 4 to 48 hours.

10. The synthesis method according to any one of claims 1-3, characterized in that, The purification process includes the following steps: the reaction solution is concentrated under vacuum, diluted with diethyl ether, washed with saturated brine, the organic phases are combined and dried with anhydrous sodium sulfate, the residue is concentrated, and the residue is separated by silica gel column chromatography to obtain the β-pyridone derivative shown in Formula 3.

Images