A method for preparing a C2-arylated or alkenylated quinoline compound

Abstract

The application discloses a preparation method of a C2-arylated or alkenylated quinoline compound. + -O ‑ After cross-coupling reaction of the quinoline compound and an arylated, heteroarylated or alkenylated boronic acid ester compound, a corresponding C2-arylated or alkenylated quinoline compound can be obtained; the method two comprises the following steps: after the cross-coupling reaction, oxidation reaction is carried out with an oxidizing agent, and a corresponding C2-arylated or alkenylated quinoline N + -O ‑ Compound can be obtained. The preparation method uses a more inexpensive copper catalytic system, a mild and stable organic boronic acid ester, and can efficiently realize C2-arylation or alkenylation of the quinoline compound at room temperature, can tolerate various functional groups, and has good substrate universality.

Description

Technical Field

[0001] This invention relates to the field of organic chemistry, and specifically to a method for preparing C2-arylated or alkenylated quinoline compounds. Background Technology

[0002] Nitrogen-containing heterocyclic compounds, as an important class of organic skeletons, have been widely used in the synthesis of bioactive molecules, advanced materials, and pesticide intermediates. In recent years, nitrogen-containing aromatic heterocyclic drugs have been the most common among FDA-approved drugs. Functionalized quinolines and their derivatives have high medicinal value, particularly in antibacterial and antimalarial activity. For example, quinoline amides such as falcator are effective in treating cystic fibrosis caused by gene mutations in humans; pirvidin, an N-methylammonium salt anthelmintic, treats helminthiasis by interfering with the respiratory enzyme system of worms; finasteride, a fluoroquinolone antibiotic, is clinically used for acute otitis externa caused by bacterial infection; other drugs, such as the NK3 receptor antagonist talnetant and SB-222200, can be used to treat central nervous system diseases such as schizophrenia; 3-amino-substituted SB-222200 and GSK172981 are more potent drugs for treating mental illnesses; and rutin, a naturally extracted alkaloid, is widely used to treat angiogenesis or Alzheimer's disease. (References: Smith, P.; Wyman, P.; Dawson, L. Bioorg. Med. Chem. Lett. 2009, 19, 837-840. Rodrigues, T.; Reker, D.; Schneider, G. Angew. Chem. Int. Ed. 2015, 54, 10516-10520). Quinoline is a heterocyclic organic compound formed by the fusion of a benzene ring and a pyridine ring, possessing certain unique properties. Introducing a nitrogen-containing heterocycle into the drug skeleton can improve the drug's selectivity to the target by altering its polarity, thereby enhancing its physiological activity. It can also prolong the duration of action and improve bioavailability through hydrogen bonding with target proteins or amino acids at the active site. The introduction of sterically hindered groups such as the quinoline ring can also improve the drug's metabolic stability.

[0003] Due to the unique properties of quinoline compounds, the efficient synthesis of quinoline derivatives is of great significance in drug development and structural modification. However, because the nitrogen atom in the pyridine ring has a high electronegativity, the π electron cloud shifts to the nitrogen atom, reducing the electron cloud density on the ring. Therefore, the aromaticity of the pyridine ring is weaker than that of the benzene ring. In summary, electrophilic or nucleophilic aromatic substitution reactions of the pyridine ring are challenging. Currently, the main approach is to introduce different substituents onto the nitrogen atom to enhance the reactivity of quinoline compounds. Among these, quinoline oxynitrides have high reactivity, readily available starting materials, and the ability to undergo subsequent transformations, making them widely used in the synthesis of quinoline derivatives.

[0004] Due to the unique advantages and important roles of quinoline derivatives, the synthesis of functionalized quinoline compounds has attracted widespread attention from organic chemists. In particular, the synthesis of 2-functionalized quinoline derivatives has been extensively reported in recent years. Traditional methods for synthesizing 2-functionalized substituted quinoline derivatives require the use of equivalent metal reagents or activators (acid anhydrides or acyl chlorides), and these reactions often require high temperatures. These demanding reaction conditions result in poor substrate universality, low regioselectivity, and low yields. Therefore, developing mild and efficient 2-functionalization methods for quinolines is of great significance for biomedicine, advanced materials, and other related fields.

[0005] Organoboron compounds possess advantages such as chemical stability, unique reactivity, low toxicity, good functional group tolerance, and the ability to undergo various transformation reactions, leading to their increasingly widespread application in organic synthesis. Boron, located in Group IIIA of the second period of the periodic table, has three valence electrons in its outermost shell. Neutral boron atoms have six valence electrons and one empty p orbital, making them relatively electron-deficient and exhibiting Lewis acidity, allowing them to accept lone pairs of electrons to form complexes. The earliest synthesized organoboron compounds, B₂X₄ (X = F, Cl, Br, I), were highly sensitive to water and oxygen, and their preparation conditions were demanding, significantly limiting their application in organic synthesis methodologies. With increasingly in-depth research into organoboron chemistry, organic chemists have discovered a variety of more stable organoboron molecules that are insensitive to water and oxygen. Among these, organoboronate esters are easy to prepare and chemically stable, making them a research hotspot for organic chemists. Currently, commonly used organoboron reagents include: symmetrical structures such as B2pin2, B2neop2, B2dmpd2, B2dmp2, and B2cat2, and asymmetrical structures such as BpinBdan and BpinB(Mes)2. Organoboron reagents can be used as functional group transfer agents to achieve structural modification of various skeletal fragments, or they can directly introduce boron-containing groups into active molecules, thereby obtaining a series of active molecule analogs through various transformation reactions. Therefore, applying organoboron compounds to methodological research is of great significance for the mild and efficient synthesis of complex drug structural fragments.

[0006] Transition metal-catalyzed cross-coupling reactions are a powerful means of constructing C-C bonds. Traditional synthetic methods require noble metal catalysts or highly toxic organotin reagents, which does not align with the development principles of green chemistry. Professor Akira Suzuki's research group used mild organoboron esters to replace highly toxic organotin reagents in palladium-catalyzed cross-coupling reactions, thus opening up new avenues for C-C bond construction. Subsequently, chemists have developed nickel- or copper-catalyzed coupling reactions, hydroboration reactions, and their transformation reactions involving organoboron compounds. Copper, located in Group IB of the fourth period of the periodic table with atomic number 29, is abundant in nature and has low toxicity, making it a cost-effective alternative to noble metals. The common valence states of copper are +1 and +2, with monovalent copper being the most extensively studied. Copper-catalyzed reaction modes mainly include the following four types: 1. Coupling reactions: Copper can directly catalyze the coupling reactions of nucleophiles and electrophiles. 2. Substitution and addition reactions: Under copper catalysis, C-C bonds can be constructed by reacting organocopper intermediates with halogenated or unsaturated substrates in situ. 3. Reduction reaction: The reduction of unsaturated substrates is achieved through the on-site generation of copper-hydrogen species. 4. Changes in the valence state of copper are mediated through single-electron transfer, leading to free radical reactions. Combining copper catalysis with organoboron compounds can develop more novel reaction modes, enabling the functionalization of quinoline compounds at the 2-position.

[0007] In 1965, Kato's group first reported the 2-arylation reaction of pyridine oxynitrides, but this reaction used an equivalent amount of metal reagent. Although this reaction had certain limitations, it solved the long-standing problem of the difficulty in functionalizing pyridine (References: (a) Kato, T.; Yamanaka, H. J. J. J. G. Chem. 1965, 30, 910. (b) Kato, T.; Yamanaka, H.; Adachi, T.; Hiranuma, H. J. J. G. Chem. 1967, 32, 3788.). In 2015, Hirano's group reported the coupling reaction of pyridine oxynitrides with oxazoles, avoiding the use of an equivalent amount of metal reagent, but the substrate generality was poor (References: Odani, R.; Hirano, K.; Satoh, T.; Miura, M. J. J. G. Chem. 2015, 80, 2384.). Further optimization of the reaction conditions was achieved, but high temperatures were still required to drive the reaction, and the excessively high temperatures significantly limited the substrate range. Wu's group achieved the coupling reaction of quinoline oxynitrides with other heterocyclic compounds under metal-free conditions, but the reaction temperature was high (References: Chen, X.; Cui, X.; Yang, F.; Wu, Y. Org. Lett. 2015, 17, 1445.). In 2015 and 2019, Antonchick's group achieved the coupling reaction of quinoline oxynitrides or pyridine oxynitrides with highly reactive alkyl or arylboronic acids or benzylsilanes, respectively, but this required a high temperature of 110 °C (References: (a) Bering, L.; Antonchick, AP Org. Lett. 2015, 17, 3134. (b) Puthanveedu, M.; Polychronidou, V.; Antonchick, AP Org. Lett. 2019, 21, 3407.).

[0008] In addition, quinoline oxynitrides can also couple with unsaturated substrates, but the reaction conditions are quite harsh. In 2008, Chang's group reported a palladium-catalyzed coupling reaction of quinoline oxynitrides with 40 equiv of olefins at a high temperature of 130 °C. The C2 olefin-substituted product could also be deoxygenated to generate quinoline products under mild conditions (References: Cho, SH; Hwang, SJ; Chang, SJ, Am. Chem. Soc. 2008, 130, 9254.). The following year, Cui's group used NMP as a solvent and achieved the yield of C2 olefin-substituted products without additional oxidants in a Pd(OAC)2 catalytic system. However, this reaction required a high temperature of 110 °C, and the use of NMP solvent made the post-processing operation complex and difficult to purify (References: Wu, J.; Cui, X.; Chen, L.; Jiang, G.; Wu, YJ, Am. Chem. Soc. 2009, 131, 13888.). In 2017, Ge's research group utilized the in-situ generated CuH intermediate to achieve the C2-position olefination reaction of quinoline oxynitrides, subsequently synthesizing a series of quinoline-substituted chiral allene products. This reaction requires the addition of a metal reagent (EtO)₂MeSiH as a transfer agent, and the reaction must be carried out at a low temperature of 5°C, making the reaction conditions quite harsh. (References: Yu, S.; Sang, H.; Ge, S. Angew. Chem. Int. Ed. 2017, 56, 15896.). In 2022, Liu's research group employed a Cu, B₂pin₂ system to catalyze the coupling reaction of quinoline oxynitrides with aryl alkynes, which can yield a single product species. Due to substrate limitations, the Cu-Bpin active intermediate generated by Cu and B2Pin2 undergoes selective addition with unsaturated substrate alkynes to form alkenyl copper species. Furthermore, the Bpin group retained on the alkenyl copper intermediate can be desorbed, resulting in only the C2-branched quinoline olefin product (Reference: Linjuan Jiang, Hui Hu, Yuanhong Liu, Angew. Chem. Int. Ed. 2022.).

[0009] Therefore, traditional synthetic methods use precious metal catalysts, which are relatively expensive; the reaction temperature is high (above 100℃); the reaction requires an equivalent amount of metal reagent or activating reagent, making the reaction conditions quite harsh; the substrate universality is poor, and the yield is low. Given the limitations of the 2-position arylation reaction of quinoline oxynitrides, we need to further enrich the methods for the functionalization of quinoline or quinoline oxynitrides at the C2 position. Summary of the Invention

[0010] The technical problem to be solved by this invention is to overcome the shortcomings of existing methods for preparing C2-functionalized quinoline compounds. A method for preparing C2-arylated or alkenylated quinoline compounds is proposed. This method uses a more inexpensive copper catalytic system and a mild and stable organoboroester ester to efficiently achieve the C2-arylation or alkenylation reaction of quinoline compounds at room temperature. It can tolerate a variety of functional groups and has good substrate versatility.

[0011] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0012] This invention provides a method for preparing C2-arylated or alkenylated quinoline compounds, which is either Method 1 or Method 2.

[0013] Method 1 includes the following steps:

[0014] In a solvent, in the presence of a copper complex and a base, quinoline N + -O - After cross-coupling reactions of such compounds with arylated, heteroarylated, or alkenylated borate esters, the corresponding C2-position (the N) is obtained. + -O - Quinoline compounds that are (ortho-)arylated or alkenylated can be used;

[0015] Method 2 includes the following steps:

[0016] Following the cross-coupling reaction, an oxidation reaction is carried out with an oxidant to obtain the corresponding C2-arylated or alkenylated quinoline N. + -O - Compounds of the same type are acceptable;

[0017] The copper complex is a mixture (in-situ mixture) of copper salt catalyst and phosphine ligand or a complex formed by the two.

[0018] In one embodiment of the present invention, the cross-coupling reaction is carried out under the protection of an inert gas, which may be one or more of nitrogen, helium, argon or neon.

[0019] In one embodiment of the present invention, the alkali is an organic alkali or an inorganic alkali;

[0020] The organic base is preferably an alkali metal alkoxide or a heterocyclic amine compound, and the alkali metal alkoxide is preferably a primary alkali metal alkoxide or a tertiary alkali metal alkoxide; the tertiary alkali metal alkoxide is preferably KO. t Bu, NaO t Bu or LiO tBu; the alkali metal primary alkoxide is preferably NaOMe or KOMe; the heterocyclic amine compound is preferably DMAP or MTBD; the organic base is preferably KO t Bu;

[0021] The inorganic base is preferably an alkali metal phosphate, alkali metal carbonate, or alkali metal bicarbonate; the alkali metal phosphate is preferably K3PO4; the alkali metal carbonate is preferably Na2CO3 or K2CO3; and the alkali metal bicarbonate is preferably NaHCO3 or KHCO3.

[0022] The amount of alkali used can be the amount conventionally used in the art; the preferred amount in this invention is quinoline N. + -O - The molar ratio of the compound to the base is 1:0.5-1:5, more preferably 1:0.8-1:1.5, for example 1:1.

[0023] The copper complex can be a copper complex conventionally used in this type of coupling reaction in the art. It can participate in the reaction in the form of a metal complex of a conventionally applicable copper salt catalyst and a conventionally applicable ligand, which is well-known in the art and may not require the addition of other ligands. Alternatively, a conventionally applicable copper salt catalyst and a conventionally applicable ligand may be coordinated in situ in the reaction system before participating in the reaction. The copper salt catalyst is a monovalent or divalent copper salt, preferably selected from one or more of CuCl, CuCl2, CuBr, Cu(acac)2, Cu(OTf)2, Cu(OAc)2, Cu(MeCN)4PF6, and CuTc; more preferably one or more of CuCl, CuCl2, CuBr, CuTc, Cu(acac)2, Cu(OTf)2, and Cu(MeCN)4PF6; for example, CuCl2, CuBr, or CuTc.

[0024] The amount of the copper complex can be the amount conventionally used in this type of reaction in the art; the preferred embodiment of the present invention is the quinoline N. + -O - The molar ratio of the compound to the copper salt catalyst is 1:0.01-1:1, more preferably 1:0.02-1:0.50, and even more preferably 1:0.05-1:0.12.

[0025] In one embodiment of the present invention, the phosphine ligand is selected from monodentate phosphine ligands and bidentate phosphine ligands; the monodentate phosphine ligand is preferably triphenylphosphine (PPh3), tricyclohexylphosphine (PCy3), 2-(di-tert-butylphosphine)biphenyl (Johnphos), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (XPhos), 2-dicyclohexylphosphine-2,6-dimethoxy-1,1-biphenyl (SPhos), or 2-(dicyclohexylphosphine)-3,6 One or more of 2-dicyclohexylphosphine-2,6-dimethoxy-1,1-biphenyl (Brettphos) or 2-(di-1-adamantylphosphine)dimethylaminophenyl (Me-dalphos); preferably one or more of 2-dicyclohexylphosphine-2,6-dimethoxy-1,1-biphenyl (SPhos), 2-(di-1-adamantylphosphine)dimethylaminophenyl (Me-dalphos), or tricyclohexylphosphine (PCy3);

[0026] The preferred bidentate phosphine ligands are 1,2-bis(diphenylphosphine)ethane (dppe), 1,3-bis(diphenylphosphine)propane (dppp), 1,4-bis(diphenylphosphine)butane (dppb), 1,2-bis(diphenylphosphino)benzene (dppbz), 1,1'-bis(diphenylphosphine)ferrocene (dppf), 9,9-dimethyl-4,5-bisdiphenylphosphineoxanthracene (xantphos), 9,9-dimethyl-4,5-bisdicyclohexylphosphineoxanthracene (Cyxantphos), bis(2-diphenylphosphine) ether (DPEPhos), 1,2-bis(dicyclohexylphosphino)ethane (Dcype), 1,1'-binaphthyl-2,2'-bisdiphenylphosphine (±BINAP), bisdiphenylphosphinemethane (dppm), and 4,5-bis(di-tert-butylphosphine)-9,9-dimethyloxanthracene (...). t One or more of 1,1'-binaphthyl-2,2'-bis(3,5-dimethyl)phosphine]-4,4-di-1,3-benzoxantphosphine (R-DM-Segphosphine); preferably 1,1'-binaphthyl-2,2'-bis(diphenylphosphine)phosphine (±BINAP), 1,2-bis(diphenylphosphine)benzene (dppbz), 1,2-bis(diphenylphosphine)ethane (dppe), R-5,5-bis(3,5-dimethyl)phosphine]-4,4-di-1,3-benzoxantphosphine (R-DM-Segphosphine); One or more of the following: R-DM-Segphos, 1,4-bis(diphenylphosphine)butane (dppb), 1,1'-bis(diphenylphosphine)ferrocene (dppf), bis(2-diphenylphosphine) ether (DPEPhos), or 9,9-dimethyl-4,5-bis(diphenylphosphine)oxanthracene (xantphos), for example, 9,9-dimethyl-4,5-bis(diphenylphosphine)oxanthracene (xantphos) or bis(2-diphenylphosphine) ether (DPEPhos).

[0027] The molar ratio of the copper salt catalyst to the phosphine ligand can be a conventional molar ratio for this type of coupling reaction in the art; the preferred molar ratio of the present invention is 1:0.5-1:10, more preferably 1:0.5-1:5, and even more preferably 1:1, 1:1.2 or 1:2.

[0028] The quinoline N + -O - The molar ratio of the compound to the arylated, heteroarylated, or alkenylated borate ester can be the conventional molar ratio for this type of reaction in the art; preferably, it is 1:0.1-1:10, more preferably 1:0.5-1:2.0, and even more preferably 1:1-1:1.6, for example, 1:1.3 or 1:1.5.

[0029] The solvent can be any solvent conventionally used in this coupling reaction in the art, and does not participate in the reaction; the present invention preferably uses one or more of aromatic solvents and ether solvents; the aromatic solvent is preferably one or more of benzene, toluene and xylene; the ether solvent is preferably one or more of diethyl ether, 1,4-dioxane and tetrahydrofuran; the solvent is more preferably one or more of toluene, tetrahydrofuran and 1,4-dioxane, such as tetrahydrofuran.

[0030] The amount of solvent used can be the amount conventionally used in this type of coupling reaction in the art; preferably, the molar volume ratio of the arylated, heteroarylated or alkenylated borate ester compound to the solvent is 0.01-1 mmol / mL, more preferably 0.1-0.5 mmol / mL, for example 0.2 mmol / mL.

[0031] The reaction temperature of the cross-coupling reaction can be the conventional temperature for this type of cross-coupling reaction in the art; in this invention, it can be -100℃ to 500℃, preferably 0℃ to 100℃, more preferably 0℃ to 50℃, and even more preferably room temperature, such as 25℃.

[0032] The reaction temperature of the oxidation reaction can be the conventional temperature for this type of oxidation reaction in the art; in this invention, it can be -100℃ to 500℃, preferably 0℃ to 100℃, more preferably 0℃ to 50℃, and even more preferably room temperature, such as 25℃.

[0033] The reaction process of the cross-coupling reaction can be monitored using conventional monitoring methods (e.g., TLC, HPLC, or NMR) used in this type of cross-coupling reaction in the art. The reaction endpoint is generally defined as the disappearance or cessation of reaction of the arylated, heteroarylated, or alkenylated borate ester compounds. For example, the reaction time of the cross-coupling reaction can be 0.1-200 h, preferably 6-36 h; for example, 10 h, 16 h, or 24 h.

[0034] In one aspect of the present invention, the oxidant is 1,4-benzoquinone or O2, such as air or oxygen.

[0035] In one aspect of the present invention, the arylated quinoline N at the C2 position... + -O - In this class of compounds, the oxidant is preferably 1,4-benzoquinone, and the quinoline N + -O - The molar ratio of the compound to the oxidant is preferably 1:1.8-1:3, for example 1:2.

[0036] In one aspect of the present invention, the alkenylated quinoline N at the C2 position... + -O - In this type of compound, the oxidant is preferably air.

[0037] In one embodiment of the present invention, the borate ester compound has a borate ester group of Bpin (pinacol borate) or Bneop (neopentane glycol borate).

[0038] The oxidation reaction can be monitored using conventional monitoring methods in the art (e.g., TLC, HPLC, or NMR), and the reaction endpoint is generally defined as when the product no longer increases. For example, the reaction time of the oxidation reaction can be 0.1-24 h, such as 0.5 h, 1 h, 1.5 h, 16 h, or 24 h.

[0039] In one aspect of the present invention, after the reaction is completed, the following post-processing step is preferably included: after the reaction is completed, the mixture is filtered, and the filtrate is separated by column chromatography to obtain the compound;

[0040] The column chromatography separation can be performed using conventional methods for this type of operation in the art. The eluent is preferably a mixture of alkane and ester solvents or a mixture of haloalkane and alcohol solvents. The volume ratio of the alkane solvent to the ester solvent is preferably 100:1 to 1:1; the alkane solvent is preferably petroleum ether; the ester solvent is preferably ethyl acetate. Similarly, the volume ratio of the haloalkane solvent to the alcohol solvent is preferably 100:1 to 1:1; the haloalkane solvent is preferably dichloromethane; the alcohol solvent is preferably methanol.

[0041] In one aspect of the present invention, the preparation method is as follows:

[0042] Option 1: In a solvent, in the presence of a copper complex and a base, quinoline N containing the structural fragment shown in Formula IIa is... + -O -The compound undergoes a cross-coupling reaction as shown below with an alkenyl borate ester containing the structural fragment shown in Formula III-1a to generate the corresponding C2-alkenylated quinoline compound containing the structural fragment shown in Formula I-1a, or further undergoes an oxidation reaction to generate the corresponding C2-alkenylated quinoline N containing the structural fragment shown in Formula I-1b. + -O - Compounds of this type are sufficient;

[0043]

[0044] Option 2: In a solvent, in the presence of a copper complex and a base, quinoline N containing the structural fragment shown in Formula IIa is... + -O - The compounds undergo cross-coupling reactions as shown below with arylated or heteroarylated borate esters containing the structural fragment shown in Formula III-2a to generate corresponding quinoline compounds with C2-arylated segments containing the structural fragment shown in Formula I-2a, or further undergo oxidation reactions to generate corresponding quinoline N containing C2-arylated segments containing the structural fragment shown in Formula I-2b. + -O - Compounds of this type are sufficient;

[0045]

[0046] Wherein, R is a borate ester group;

[0047] Ar is an unsubstituted or substituted aryl group, or an unsubstituted or substituted heteroaryl group.

[0048] In one embodiment of the present invention, in the preparation method,

[0049] The proposed solution is as follows:

[0050] In a solvent, in the presence of a copper complex and a base, quinoline N as shown in Formula II is... + -O - The compounds undergo cross-coupling reactions as shown in Formula III-1 with the alkenyl borate esters to generate the corresponding C2-alkenylated quinoline compounds as shown in Formula I-1A, or undergo further oxidation reactions to generate the corresponding C2-alkenylated quinoline N as shown in Formula I-1B. + -O - Compounds of this type are sufficient;

[0051]

[0052] The second scheme is as follows:

[0053] In a solvent, in the presence of a copper complex and a base, quinoline N as shown in Formula II is... + -O - The compounds undergo cross-coupling reactions as shown below with arylated or heteroarylated borosilicate esters as represented by Formula III-2 to generate the corresponding C2-arylated quinoline compounds as represented by Formula I-2A, or further undergo oxidation reactions to generate the corresponding C2-arylated quinoline N as represented by Formula I-2B. + -O - Compounds of this type are sufficient;

[0054]

[0055] n is selected from any integer between 0 and [M-1], where M represents the quinoline N shown in Equation II. + -O - The maximum number of substitutions on a class of compounds, for example, n can be 0, 1 or 2;

[0056] m is selected from any integer between 0 and [M-1], where M represents the maximum number of substitutions on Ar. For example, m can be 0, 1, or 2.

[0057] R 1 R 2 and R 3 The group is hydrogen, halogen, -C(=O)-O-, or may be a group formed by linking one or more substituents selected from the following: alkyl, alkoxy, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; when a group is formed by linking multiple substituents, the substituents may be the same or different (when a group is formed by linking multiple substituents, the number and position of the substituents are not limited, as long as such linking produces a stable compound; when a substituent linking two ring systems is present, it may be a fused, bridged bicyclic system); the substituent is optionally connected by one or more R 1-1 replace;

[0058] R 1-1 It can be a substituent that is conventional in the art, as long as it does not affect the reaction, such as halogen, haloalkyl or ether (e.g. silyl ether-Si-O-).

[0059] In one aspect of the present invention, the R 1 R 2 and R 3 In this context, the alkyl group is independently C1-C2. 10 Straight-chain or branched alkyl groups; for example, straight-chain or branched alkyl groups of C1-C6, or straight-chain or branched alkyl groups of C1-C4.

[0060] In one aspect of the present invention, the R1 R 2 and R 3 In this context, the alkoxy group is independently C1-C. 10 Straight-chain or branched alkoxy groups; for example, straight-chain or branched alkoxy groups of C1-C6, and also straight-chain or branched alkoxy groups of C1-C4.

[0061] In one aspect of the present invention, the R 1 R 2 and R 3 In this context, the alkenyl group is independently C2-C. 10 Straight-chain or branched alkenyl groups; for example, C2-C4 straight-chain or branched alkenyl groups.

[0062] In one aspect of the present invention, the R 1 R 2 and R 3 In this context, the alkynyl group is independently C2-C. 10 Straight-chain or branched alkynyl groups; for example, C2-C4 straight-chain or branched alkynyl groups.

[0063] In one aspect of the present invention, the R 1 R 2 and R 3 In this context, the heteroalkyl group is independently C1-C2. 10 Straight-chain or branched heteroalkyl groups; for example, C1-C4 straight-chain or branched heteroalkyl groups.

[0064] In one aspect of the present invention, the R 1 R 2 and R 3 In this context, the cycloalkyl group is independently a 3-15 membered cycloalkyl group; for example, a 3-6 membered cycloalkyl group.

[0065] In one aspect of the present invention, the R 1 R 2 and R 3 In this context, the heterocyclic alkyl group is independently a 3-10 membered heterocyclic alkyl group; for example, a 3-6 membered heterocyclic alkyl group.

[0066] In one embodiment of the present invention, the Ar and R... 1 R 2 and R 3 In this context, the aryl group is independently C6-C. 10 Aryl, preferably phenyl or naphthyl.

[0067] In one embodiment of the present invention, the Ar and R... 1 R 2 and R 3In this context, the heteroaryl group is a 5-14-membered heteroaryl group, preferably a 5-10-membered heteroaryl group, containing 1, 2, 3, or 4 heteroatoms or heteroatomic groups selected from N, O, S, S(=O), or S(=O)2; preferably furanyl, pyrroloyl, thiophenyl, thiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, or indoleyl; more preferably furanyl or indoleyl, for example...

[0068] In one embodiment of the present invention, when Ar is a substituted aryl group or a substituted heteroaryl group, the substituent is a halogen, OH, CN, a straight-chain or branched alkyl group of C1-C6, or a straight-chain or branched alkoxy group of C1-C6; preferably a straight-chain or branched alkyl group of C1-C6.

[0069] In one aspect of the present invention, when Ar is a substituted aryl group and a substituted heteroaryl group, and the substituent is a halogen, the halogen is fluorine, chlorine, bromine or iodine.

[0070] In one aspect of the present invention, when Ar is a substituted aryl group and a substituted heteroaryl group, and the substituent is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is a C1-C4 straight-chain or branched alkyl group, preferably methyl, ethyl, propyl, isopropyl or tert-butyl, for example methyl.

[0071] In one aspect of the present invention, when Ar is a substituted aryl group or a substituted heteroaryl group, and the substituent is a C1-C6 straight-chain or branched alkoxy group, it is preferably a methoxy, ethoxy, propoxy, or isopropoxy group.

[0072] In one aspect of the present invention, R 1 They may be the same or different, each independently selected from hydrogen, halogen, C1-C4 straight-chain or branched alkyl, C1-C4 straight-chain or branched alkoxy, and C6-C 10 aryl; or any two adjacent R 1 Together with the carbon atom it is attached to, it forms a 6-10 membered aromatic ring.

[0073] In one aspect of the present invention, R 2 They may be the same or different, and each is independently selected from C1-C6 straight-chain or branched alkyl, 3-6 membered cycloalkyl, -(C1-C4)alkylene-(R a ), C1-C6 straight-chain or branched alkoxy groups and C6-C 10 Aryl;

[0074] R a for C6-C 10 Aryl or halogen-substituted C1-C6 straight-chain or branched alkyl groups;

[0075] R 2-1 R 2-2 and R 2-3 Independently C1-C6 straight-chain or branched alkyl or C6-C 10 Aryl.

[0076] In one aspect of the present invention, R 3 They may be the same or different, and each is independently selected from hydrogen, halogen, C1-C6 straight-chain or branched alkyl, C1-C6 straight-chain or branched alkoxy, and -C(=O)-OR. b ;

[0077] R b Selected from 3-15 membered cycloalkyl groups or containing one or more R groups b-1 Substituted 3-15 membered cycloalkyl groups; R b-1 It is a C1-C6 straight-chain or branched alkyl group.

[0078] In one aspect of the present invention, when R 1 When the halogen is halogen, the halogen is fluorine, chlorine, bromine or iodine, preferably chlorine or bromine.

[0079] In one aspect of the present invention, when R 1 When the alkyl group is a C1-C4 straight-chain or branched alkyl group, the C1-C4 straight-chain or branched alkyl group is a C1-C3 straight-chain or branched alkyl group, preferably methyl, ethyl, propyl or isopropyl, for example methyl.

[0080] In one aspect of the present invention, when R 1 When the alkoxy group is a C1-C4 straight-chain or branched alkoxy group, the C1-C4 straight-chain or branched alkoxy group is a C1-C3 straight-chain or branched alkoxy group, preferably methoxy, ethoxy, propoxy or isopropoxy, such as methoxy.

[0081] In one aspect of the present invention, when R 1 For C6-C 10 In the aryl case, the C6-C 10 The aryl group is a benzene ring or a naphthalene ring, for example, a benzene ring.

[0082] In one aspect of this invention, when any two adjacent R 1 When it forms a 6-10 membered aromatic ring together with the carbon atom attached to it, the 6-10 membered aromatic ring is a benzene ring or a naphthalene ring, such as a benzene ring.

[0083] In one embodiment of the present invention, when n is 1, R 1 It can be hydrogen, bromine, chlorine, methyl, phenyl, or methoxy, preferably methyl or bromine.

[0084] In one aspect of the present invention, when R 2When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl, ethyl, propyl, isopropyl, or... n Bu or t Bu, preferred n Bu or t Bu.

[0085] In one aspect of the present invention, when R 2 When the alkyl group is a 3-6 membered cycloalkyl group, the 3-6 membered cycloalkyl group is cyclopropyl, cyclobutyl or cyclopentyl, for example cyclopropyl.

[0086] In one aspect of the present invention, when R 2 -(C1-C4)alkylene-(R a When ), the -(C1-C4) alkylene group is independently -CH2-, -CH2CH2-, -CH(CH3)-, -CH(CH3)CH2- or -C(CH3)2-, for example -CH2CH2-.

[0087] In one aspect of the present invention, when R 2-1 R 2-2 and R 2-3 When independently a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl, ethyl, propyl or tert-butyl, for example methyl or tert-butyl.

[0088] In one aspect of the present invention, when R 2-1 R 2-2 and R 2-3 Independently for C 6-10 When aryl, the C 6-10 The aryl group is phenyl or naphthyl, for example, phenyl.

[0089] In one aspect of the present invention, when R a For C6-C 10 When the aryl group is present, the C6-C 10 The aryl group is phenyl or naphthyl, for example, phenyl.

[0090] In one aspect of the present invention, when R a When the halogen is a halogen-substituted C1-C6 straight-chain or branched alkyl group, the halogen is fluorine, chlorine, or bromine, such as chlorine.

[0091] In one aspect of the present invention, when R a When the C1-C6 straight-chain or branched alkyl group is halogen-substituted, the C1-C6 straight-chain or branched alkyl group is methyl, ethyl, or propyl, for example, methyl.

[0092] In one aspect of the present invention, when R 2 -(C1-C4)alkylene-(Ra When )-, the R mentioned a for Phenyl or -CH2Cl.

[0093] In one aspect of the present invention, when R 2 When the alkoxy group is a straight-chain or branched alkoxy group of C1-C6, the straight-chain or branched alkoxy group of C1-C6 is preferably a straight-chain or branched alkoxy group of C1-C3, and more preferably a methoxy, ethoxy, propoxy or isopropoxy group, such as ethoxy.

[0094] In one aspect of the present invention, when R 2 For C6-C 10 In the aryl case, the C6-C 10 The aryl group is a benzene ring or a naphthalene ring, for example, a benzene ring.

[0095] In one aspect of the present invention, R 2 for- n Bu, cyclopropyl, - t Bu、 -CH2CH2Ph, -CH2CH2CH2Cl -OCH2CH3 or phenyl.

[0096] In one aspect of the present invention, when R 3 When the halogen is halogen, the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.

[0097] In one aspect of the present invention, when R 3 When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is a C1-C4 straight-chain or branched alkyl group, preferably methyl, ethyl, propyl, isopropyl or tert-butyl, for example methyl or tert-butyl.

[0098] In one aspect of the present invention, when R 3 When the alkoxy group is a straight-chain or branched alkoxy group of C1-C6, the straight-chain or branched alkoxy group of C1-C6 is a straight-chain or branched alkoxy group of C1-C3, preferably methoxy, ethoxy, propoxy or isopropoxy, such as methoxy.

[0099] In one aspect of the present invention, when R b When the alkyl group is a 3-15 membered cycloalkyl group, the 3-15 membered cycloalkyl group is a 6-12 membered cycloalkyl group, preferably.

[0100] In one aspect of the present invention, when R b-1When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is a C1-C4 straight-chain or branched alkyl group, preferably methyl, ethyl, propyl, isopropyl or tert-butyl, such as methyl.

[0101] In one embodiment of the present invention, when m is 1, R 3 It is hydrogen, fluorine, chlorine, bromine, methyl, tert-butyl, methoxy,

[0102]

[0103] In one aspect of the present invention, the quinoline N as shown in Formula II is described. + -O - The class of compounds has any of the following structures:

[0104]

[0105] In one aspect of the present invention, the alkenyl borate ester compound as shown in Formula III-1 has any of the following structures:

[0106]

[0107] In one aspect of the present invention, the arylated or heteroarylated borate ester compound as shown in Formula III-2 has any of the following structures:

[0108] In one aspect of the present invention, the C2-alkenylated quinoline compound as shown in Formula I-1A has any of the following structures:

[0109] In one aspect of the present invention, the C2-alkenylated quinoline N as shown in Formula I-1B is described. + -O - The class of compounds has any of the following structures:

[0110]

[0111] In one aspect of the present invention, the C2-arylated quinoline compound as shown in Formula I-2A has the following structure:

[0112]

[0113] In one aspect of the present invention, the C2-arylated quinoline N as shown in Formula I-2B is described. + -O - The class of compounds has any of the following structures:

[0114]

[0115] Definitions of Terms

[0116] In structural fragments This refers to the connection between the structural segment and other segments in the molecule through this site.

[0117] The term "multiple" refers to 2, 3, 4, or 5.

[0118] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0119] The term "alkyl" refers to a straight-chain or branched alkyl group having a specified number of carbon atoms (e.g., C1 to C6). Alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, etc.

[0120] The term "alkoxy" refers to an -O-alkyl group, wherein the alkyl group is as described above. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, tert-butoxy, isobutoxy, sec-butoxy, pentoxy, etc.

[0121] The term "alkenyl" refers to a straight-chain or branched, unsaturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C2 to C6) and having one or more (e.g., 1, 2, or 3) carbon-carbon sp groups. 2 Double bond. Alkenyl groups include, but are not limited to: vinyl groups, wait.

[0122] The term "alkynyl" refers to a straight-chain or branched, unsaturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C2 to C6) and having one or more (e.g., 1, 2, or 3) carbon-carbon sp groups. 3 Triple bond. Alkynyl groups include, but are not limited to: ethynyl, wait.

[0123] The term "heteroalkyl" refers to an alkyl group as defined above that contains one or more heteroatoms or heterogroups selected from N, O, S, S(=O), or S(=O)2.

[0124] The term "cycloalkyl" refers to a saturated, monocyclic or polycyclic (such as bicyclic) non-aromatic hydrocarbon group. For example, "C3-C..." 12"Cycloalkyl" or "3-12 membered cycloalkyl" refers to a cycloalkyl group having 3-12 ring carbon atoms (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12). Common cycloalkyl groups include (but are not limited to) monocyclic cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.; or bicyclic cycloalkyl groups, including fused rings, bridged rings, or spiro rings, such as bicyclic [1.1.1]pentyl, bicyclic [2.2.1]heptyl, bicyclic [3.2.1]octyl, bicyclic [5.2.0]nonyl, etc.

[0125] The term "heterocyclic alkyl" refers to a stable, saturated monocyclic or polycyclic (e.g., bicyclic, tricyclic or more bridging, fused, or spirocyclic) heterocyclic hydrocarbon group consisting of at least one carbon atom and a specified number of heteroatoms or heteroatom groups, which may be connected to the rest of the molecule via a single bond through any suitable carbon atom or heteroatom. For example, a stable 3- to 30-membered (preferably 3- to 20-membered, more preferably 3- to 10-membered, most preferably 3- to 7-membered) saturated heterocyclic hydrocarbon group consisting of 2 to 29 carbon atoms (preferably 2 to 19, more preferably 2 to 9, and most preferably 2 to 6) and 1 to 6 heteroatoms or heteroatom groups selected from N, O, S, S(=O), and S(=O)2; preferably a 4- to 10-membered saturated monocyclic or polycyclic (e.g., bicyclic, tricyclic, or more ring-bridged, fused-ring, or spirocyclic systems) heterocyclic hydrocarbon group containing 1, 2, 3, or 4 heteroatoms or heteroatom groups independently selected from N, O, S, S(=O), and S(=O)2. The ring system of a heterocyclic alkyl bicyclic may include one or more heteroatoms in one or two rings; and is saturated.

[0126] The term "aryl" or "aromatic ring" refers to an aromatic ring having a specified number of carbon atoms (e.g., C6 to C7). 10 An aryl group is a cyclic group consisting solely of carbon atoms, which may be monocyclic or polycyclic, and at least one ring is aromatic (conforming to Hückel's rule). An aryl group is linked to other segments of the molecule via an aromatic or non-aromatic ring. Aryl groups include, but are not limited to, phenyl and naphthyl groups.

[0127] The term "heteroaryl" refers to a cyclic, unsaturated monovalent group having a specified number of ring atoms (e.g., 5 to 10), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatom (one or more of N, O, and S). It can be monocyclic or polycyclic, with the monocyclic rings sharing two atoms and one bond, and (at least one ring / each ring) is aromatic. Heteroaryl groups are attached to the rest of the molecule via carbon atoms or heteroatoms; they can be attached to the rest of the molecule via a ring with or without heteroatoms; or they can be attached to the rest of the molecule via an aromatic ring or a non-aromatic ring.

[0128] The term "halogenated alkyl" refers to the alkyl group described above, in which one or more hydrogen atoms are replaced by halogens.

[0129] The term "ether group" refers to a product in which the hydrogen atom in the hydroxyl group of an alcohol or phenol is replaced by a hydrocarbon group (including alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl), an aromatic group (including aryl or heteroaryl), or a silicon atom.

[0130] The term "alkylene" refers to a saturated divalent hydrocarbon group obtained by removing two hydrogen atoms from a saturated straight-chain or branched hydrocarbon group; that is, one hydrogen atom in the alkyl group is replaced, as defined above. Examples of alkylene groups include methylene (-CH2-), ethylene {including -CH2CH2- or -CH(CH3)-}, isopropylene {including -CH(CH3)CH2- or -C(CH3)2-}, etc.

[0131] "Room temperature" is 15-40℃, for example, 25℃.

[0132] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention. All reagents and raw materials used in the present invention are commercially available.

[0133] The significant advantages of this invention are: it utilizes an inexpensive copper-catalyzed system to prepare C2-position arylated or alkenylated quinoline compounds with various functional group substitutions, offering advantages such as readily available raw materials, mild conditions, high reaction efficiency, functional group compatibility, and good substrate universality. This preparation method provides better application prospects and practical value for the industrial synthesis of C2-position functionalized quinoline compounds. Detailed Implementation

[0134] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0135] Preparation Example 1:

[0136]

[0137] Under air atmosphere, 4-carboxyphenylboronic acid pinacol ester (893.1 mg, 3.6 mmol), 2-adamantaneol (456.7 mg, 3.0 mmol), DCC (742.8 mg, 3.6 mmol), DMAP (18.3 mg, 5 mol%), and DCM (10 mL) were added to a reaction flask. The reaction mixture was allowed to react overnight at room temperature. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 30:1 as the eluent. The product was a white solid, 501 mg, in yield of 44%.1 H NMR(400MHz, CDCl3)δ8.06(d,J=8.0Hz,2H),7.88(d,J=8.4Hz,2H),5.19(s,1H),2.18-2 .15(m,4H),1.89(t,J=10.0Hz,6H),1.78(s,2H),1.64(d,J=12.4Hz,2H),1.36(s,12H); 13 C NMR (100MHz, CDCl3) δ165.82,134.59,133.29,128.50,84.08,77.55,37.35,36.31,31.99,31.96,27.27,26.98,24.81.

[0138] Preparation Example 2:

[0139]

[0140] Under air atmosphere, pinacol 4-carboxyphenylboronic acid (893.1 mg, 3.6 mmol), borneol (462.8 mg, 3.0 mmol), DCC (742.8 mg, 3.6 mmol), DMAP (18.3 mg, 5 mol%), and DCM (10 mL) were added to the reaction flask. The reaction mixture was allowed to react overnight at room temperature. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 30:1 as the eluent. The product was a white solid, 715 mg, in 62% yield. 1 H NMR (400MHz, CDCl3) δ8.03(d,J=8.0Hz,2H),7.88(d,J=8.0Hz,2H),5.13(dt,J1=8.8Hz,J2=3.2Hz 1H),2.52-2.44(m,1H),2.18-2.11(m,1H),1.83-1.77(m,1H),1.74(t,J=4.4Hz,1 H),1.36(s,14H),1.13(dd,J1=13.6Hz,J2=3.6Hz,1H),0.97(s,3H),0.92(s,6H). 13 C NMR (100MHz, CDCl3) δ166.78,134.61,133.03,128.44,84.07,80.55,49.05,47.83,44.94,36.84,28.04,27.34,24.81,19.68,18.87,13.57.

[0141] Preparation Example 3:

[0142]

[0143] Under an Ar atmosphere, Pd(OAc)₂ (34.0 mg, 5 mol%), PPh₃ (78.7 mg, 10 mol%), CsOPiv (772.3 mg, 3.3 mmol), B₂pin₂ (1.90 g, 7.5 mmol), bromobiphenyl (699.3 mg, 3 mmol), and 1,4-dioxane (25 mL) were added to a reaction flask. After reacting at 90 °C for 6 h, the reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 50:1 as the eluent. The product was a white solid, 660 mg, with a yield of 79%. 1 HNMR (400MHz, CDCl3) δ7.89 (d, J=8.0Hz, 2H), 7.62-7.60 (m, 4H), 7.45 (t, J=8.0Hz, 2H), 7.36-7.33 (m, 1H), 1.36 (s, 12H). 13 C NMR (100MHz, CDCl3) δ143.87,141.01,135.24,128.75,127.53,127.21,126.44,83.80,24.86.

[0144] Preparation Example 4:

[0145]

[0146] Under an Ar atmosphere, 3-butyn-1-ol (20 mmol, 1.40 g) and THF (17 mL) were added to a reaction flask, followed by 60% NaH (20 mmol, 800 mg), TBAI (1.6 mmol, 591 mg), and BnBr (24 mmol, 4.10 g) at 0 °C. The system was allowed to react overnight at room temperature. The reaction was then quenched with NH4Cl solution, extracted with EA, and the organic phases were combined. The solutions were washed successively with water and saturated NaCl solution, dried over anhydrous Na2SO4, filtered, and concentrated to obtain the crude product, which can be directly used in the next reaction step.

[0147] In a nitrogen-filled glove box, ZrCp₂HCl (2 mmol, 515.7 mg) was added to a 4 mL sample vial. After capping, the vial was removed from the glove box. Under an Ar atmosphere, THF (20 mL) was added, and the system was cooled to 0 °C. 3-Alkyneoxymethylbenzene (20 mmol, 3.20 g), HBpin (24 mmol, 3.07 g), and Et₃N (2 mmol, 202.4 mg) were added. The system was reacted overnight at 60 °C. The reaction system was cooled to 0 °C, and water was slowly added to quench the reaction until no bubbles were generated. The mixture was extracted with EA, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 40:1 as the eluent. The product was a colorless liquid, 3.08 g, with a yield of 53%. 1 H NMR (400MHz, CDCl3): δ7.33-7.26(m,5H),6.63(dt,J=17.6,6.4Hz,1H),5.53(d,J=1 7.6Hz,1H),4.51(s,2H),3.55(t,J=6.8Hz,2H),2.49(q,J=6.4Hz,2H),1.26(s,12H). 13 C NMR (100MHz, CDCl3): δ150.4,138.3,128.3,127.6,127.5,83.0,72.9,68.8,36.1,24.7.

[0148] Preparation Example 5:

[0149]

[0150] In a nitrogen-filled glove box, ZrCp₂HCl (1 mmol, 257.9 mg) was added to a 4 mL sample vial. After capping, the vial was removed from the glove box. Under an Ar atmosphere, THF (10 mL) was added, and the system was cooled to 0 °C. 4-Phenylenyne (10 mmol, 1.30 g), HBpin (12 mmol, 1.54 g), and Et₃N (1 mmol, 101.2 mg) were added. The system was reacted overnight at 60 °C. The reaction system was cooled to 0 °C, and water was slowly added to quench the reaction until no bubbles were generated. The mixture was extracted with EA, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 40:1 as the eluent. The product was 1.35 g of a colorless liquid, with a yield of 52%. 1H NMR (400MHz, CDCl3): δ7.29-7.25(m,2H),7.19-7.15(m,3H),6.71(dt,J1=18. 0,J2=6.0Hz,1H),2.74(t,J=7.2Hz,2H),2.47(q,J=8.4Hz,2H),1.26(s,12H). 13 C NMR (100MHz, CDCl3): δ153.4,141.7,128.27,128.26,125.8,83.0,37.4,34.5,24.7.

[0151] Preparation Example 6:

[0152]

[0153] In a nitrogen-filled glove box, ZrCp₂HCl (1 mmol, 257.9 mg) was added to a 4 mL sample vial. After capping, the vial was removed from the glove box. Under an Ar atmosphere, THF (10 mL) was added, and the system was cooled to 0 °C. 1-Hexyne (10 mmol, 821.5 mg), HBpin (12 mmol, 1.54 g), and Et₃N (1 mmol, 101.2 mg) were added. The system was reacted overnight at 60 °C. The reaction system was cooled to 0 °C, and water was slowly added to quench the reaction until no bubbles were generated. The mixture was extracted with EA, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 100:1). The product was 1.14 g of a colorless liquid, with a yield of 54%. 1 H NMR (400MHz, CDCl3): δ6.56 (dt, J=18.0, 6.4Hz, 1H), 5.35 (d, J=17.6Hz, 1H), 2 .08(q,J=7.2Hz,1H),1.36-1.22(m,4H),1.19(s,12H),0.81(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3): δ154.7,82.8,35.4,30.3,26.7,22.2,13.8.

[0154] Preparation Example 7:

[0155]

[0156] In a nitrogen-filled glove box, ZrCp₂HCl (0.5 mmol, 128.9 mg) was added to a 4 mL sample vial. After capping, the vial was removed from the glove box. Under an argon atmosphere, THF (5 mL) was added, and the system was cooled to 0 °C. Cyclopropylacetylene (5 mmol, 330.5 mg), HBpin (6 mmol, 767.9 mg), and Et₃N (0.5 mmol, 50.6 mg) were added. The system was reacted overnight at 60 °C. The reaction system was cooled to 0 °C, and water was slowly added to quench the reaction until no bubbles were generated. The mixture was extracted with EA, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated, and subjected to silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 50:1). The product was a colorless liquid, 612 mg, with a yield of 63%. 1 H NMR (400MHz, CDCl3): δ6.00 (dd, J1=17.8, J2=9.2Hz, 1H), 5.42 (d, J=17.6Hz, 1H) ,1.48-1.42(m,1H),1.18(s,12H),0.74(q,J=8.0Hz,2H),0.46(q,J=6.0Hz,2H). 13 C NMR (100MHz, CDCl3): δ158.6, 82.8, 24.7, 17.0, 7.8.

[0157] Preparation Example 8:

[0158]

[0159] In a nitrogen-filled glove box, ZrCp₂HCl (0.5 mmol, 128.9 mg) was added to a 4 mL sample vial. After capping, the vial was removed from the glove box. Under an Ar atmosphere, THF (5 mL) was added, and the system was cooled to 0 °C. 3,3-Dimethyl-1-butyne (5 mmol, 410.8 mg), HBpin (6 mmol, 767.9 mg), and Et₃N (0.5 mmol, 50.6 mg) were added. The system was reacted overnight at 60 °C. The reaction system was cooled to 0 °C, and water was slowly added to quench the reaction until no bubbles were generated. The mixture was extracted with EA, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 40:1 as the eluent. The product was a white solid, 574 mg, with a yield of 55%. 1 H NMR (400MHz, CDCl3): δ6.57 (d, J = 18.4Hz, 1H), 5.28 (d, J = 18.4Hz, 1H), 1.20 (s, 12H), 0.95 (s, 9H). 13C NMR (100MHz, CDCl3): δ164.3, 82.9, 34.9, 28.7, 24.7.

[0160] Preparation Example 9:

[0161]

[0162] In a nitrogen-filled glove box, ZrCp₂HCl (1.5 mmol, 386.8 mg) was added to a 4 mL sample vial. After capping, the vial was removed from the glove box. Under an Ar atmosphere, THF (10 mL) was added, and the system was cooled to 0 °C. 5-Chloropentyne (15 mmol, 1.54 g), HBpin (16.5 mmol, 2.11 g), and Et₃N (1.5 mmol, 151.8 mg) were added. The system was reacted at 60 °C for 6 h. The reaction system was cooled to 0 °C, and water was slowly added to quench the reaction until no more bubbles were generated. Extraction was performed using EA, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 50:1 as the eluent. The product was 2.12 g of a colorless liquid, yield 61%. 1 H NMR (400MHz, CDCl3): δ6.59 (dt, J1=17.6, J2=6.4Hz, 1H), 5.49 (dd, J1=18.0, J2=1.2H z,1H),3.54(t,J=6.8Hz,1H),2.31(d,J=6.8Hz,2H),1.94-1.87(m,2H),1.27(s,12H). 13 C NMR (100MHz, CDCl3): δ152.1,83.1,44.3,32.7,31.0,24.7.

[0163] Preparation Example 10:

[0164]

[0165] In a nitrogen-filled glove box, ZrCp₂HCl (0.2 mmol, 51.6 mg) was added to a 4 mL sample vial. After capping, the vial was removed from the glove box. Under an Ar atmosphere, THF (2 mL) was added, and the system was cooled to 0 °C. 4-(tert-butyldimethoxy)-1-butyne (2 mmol, 368.7 mg), HBpin (2.4 mmol, 307.2 mg), and Et₃N (0.2 mmol, 20.2 mg) were added. The system was reacted overnight at 60 °C. The reaction system was cooled to 0 °C, and water was slowly added to quench the reaction until no bubbles were generated. Extraction was performed using EA, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 50:1 as the eluent. The product was a colorless liquid, 450.8 mg, with a yield of 72%. 1 H NMR (400MHz, CDCl3): δ6.70 (dt, J1=18.0, J2=6.8Hz, 1H), 5.60 (d, J=18.0 1H),3.80(t,J=6.8Hz,2H),2.49(q,J=6.8Hz,2H),1.37(s,12H),0.99(s,9H),0.15(s,6H). 13 C NMR (100MHz, CDCl3): δ150.6,83.0,62.2,39.4,25.9,24.7,18.3,5.31.

[0166] Preparation Example 11:

[0167]

[0168] In a nitrogen-filled glove box, ZrCp₂HCl (0.5 mmol, 128.9 mg) was added to a 4 mL sample vial. After capping, the vial was removed from the glove box. Under an Ar atmosphere, THF (5 mL) was added, and the system was cooled to 0 °C. 4-(tert-butyldiphenylsiloxy)-1-butyne (5 mmol, 1.54 mg), HBpin (6 mmol, 767.9 mg), and Et₃N (0.5 mmol, 50.6 mg) were added. The system was reacted overnight at 60 °C. The reaction system was cooled to 0 °C, and water was slowly added to quench the reaction until no bubbles were generated. Extraction was performed using EA, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 50:1 as the eluent. The product was 1.22 g of a colorless liquid, yield 56%. 1H NMR (400MHz, CDCl3): δ7.66 (d, J=7.2Hz, 4H), 7.43-7.35 (m, 6H), 6.60 (dt, J1=18.0, J2=6.4Hz, 1H) ,5.48(d,J=18.4Hz,1H),3.73(t,J=6.8Hz,2H),2.43(q,J=6.8Hz,2H),1.25(s,12H),1.04(s,9H). 13 C NMR (100MHz, CDCl3): δ150.6,135.5,133.8,129.5,127.6,83.0,62.9,39.1,26.8,24.7,19.2.

[0169] Preparation Example 12:

[0170]

[0171] Under an Ar atmosphere, phenylacetylene (20 mmol, 2.04 g), HBpin (26 mmol, 3.33 mg), and DIBAL-H (2 mmol, 2 mL) were added to a reaction flask, and the system was then reacted at 90 °C for 4 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 50:1 as the eluent, yielding 3.16 g of a yellow liquid, with a yield of 69%. 1 HNMR (400MHz, CDCl3): δ7.49 (d, J = 6.8 Hz, 2H), 7.40 (d, J = 18.8 1H), 7.35-7.29 (m, 3H), 6.17 (d, J = 18.4 Hz, 1H), 1.31 (s, 12H). 13 C NMR (100MHz, CDCl3): δ149.5,137.4,128.9,128.5,127.0,83.3,24.8.

[0172] Preparation Example 13:

[0173]

[0174] Under an Ar atmosphere, Pd(OAc)₂ (112.3 mg, 5 mol%), PPh₃ (393.4 mg, 15 mol%), K₂CO₃ (5.53 g, 40 mmol), phenylboronic acid (1.83 g, 15 mmol), 4-bromoquinoline (2.08 g, 10 mmol), and EtOH / H₂O / Tol (5 / 10 / 20 mL) were added to the reaction flask. The mixture was reacted at 95 °C for 16 h. The mixture was extracted with EA, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na₂SO₄, filtered, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate eluent of 50:1 to 20:1. The crude product obtained could be directly used for the next reaction.

[0175] Under air atmosphere, 85% m-CPBA (1.52 g, 7.5 mmol) and DCM (10 mL) were added to the reaction flask. 4-Phenylenol (1.03 g, 5 mmol) was added at 0 °C. The system was then reacted at room temperature for 18 h. The reaction was quenched with 2 M NaOH solution, extracted with DCM, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na2SO4, filtered, concentrated, and subjected to silica gel column chromatography with dichloromethane:methanol = 50:1 to 20:1 as the eluent. The product was 1.22 g of white solid, with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ8.86(d,J=8.8Hz,1H),8.59(d,J=6.0Hz,1H),7.95(d,J=8.4Hz, 1H),7.78(t,J=8.0Hz,1H),7.60(t,J=8.0Hz,1H),7.56-7.48(m,5H),7.25(d,J=6.4Hz 1H). 13 C NMR (100MHz, CDCl3) δ144.45,138.81,136.89,134.93,130.17,129.48,128.69,128.60,128.55,126.63,121.23,120.00.

[0176] Preparation Example 14:

[0177]

[0178] Under air atmosphere, 85% m-CPBA (1.52 g, 7.5 mmol) and DCM (10 mL) were added to the reaction flask. 4-Methylquinoline (716 mg, 5 mmol) was added at 0 °C. The system was then reacted at room temperature for 18 h. The reaction was quenched with 2 M NaOH solution, extracted with DCM, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na2SO4, filtered, concentrated, and subjected to silica gel column chromatography with dichloromethane:methanol = 50:1 to 20:1 as the eluent. The product was a white solid, 730 mg, with a yield of 92%. 1 H NMR (400MHz, CDCl3) δ8.80(d,J=8.8Hz,1H),8.43(d,J=6.0Hz,1H),7.96(d,J=8.4Hz,1H),7.76(t,J=8.0Hz,1H),7.67(t,J=7.2Hz,1H),2.65(s,3H). 13 C NMR (100MHz, CDCl3) δ140.72,134.83,134.62,129.92,129.64,128.32,124.59,121.25,120.10,18.17.

[0179]

[0180] Under air atmosphere, 8-methylquinoline (716.0 mg, 5 mmol), 85% m-CPBA (1.42 g, 7.0 mmol), and DCM (10 mL) were added to a reaction flask. After reacting at room temperature for 7 h, the reaction was quenched with 2 M NaOH solution, extracted with DCM, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na2SO4, filtered, concentrated, and subjected to silica gel column chromatography with dichloromethane as the eluent. The product was a light brown solid, 401 mg, with a yield of 50%. 1 H NMR (400MHz, CDCl3) δ8.40 (d, J = 5.6Hz, 1H), 7.65-7.62 (m, 2H), 7.45-7.41 (m, 2H), 7.17 (dd, J1 = 8.0Hz, J2 = 6.0Hz, 1H), 3.19 (s, 3H). 13 C NMR (100MHz, CDCl3) δ141.12,137.08,133.29,133.19,132.23,127.86,126.62,126.39,120.45,24.70.

[0181] Preparation Example 16:

[0182]

[0183] Under air atmosphere, 7-methylquinoline (716.0 mg, 5 mmol), 85% m-CPBA (1.52 g, 7.0 mmol), and DCM (10 mL) were added to a reaction flask. After reacting overnight at room temperature, the reaction was quenched with 2 M NaOH solution, extracted with DCM, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na2SO4, filtered, concentrated, and subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 3:1 to ethyl acetate:methanol = 3:1. The product was a pale yellow solid, 646 mg, with a yield of 81%. 1 H NMR (400MHz, CDCl3) δ8.55(s,1H),8.50(d,J=6.0Hz,1H),7.75(d,J=8.4Hz,1H),7.70(d ,J=8.0Hz,1H),7.46(d,J=8.4Hz,1H),7.17(dd,J1=7.8Hz,J2=6.8Hz,1H),2.59(s,3H). 13 C NMR (100MHz, CDCl3) δ141.38,135.51,130.73,128.79,127.71,125.77,119.81,118.52,21.89.

[0184] Preparation Example 17:

[0185]

[0186] Under air atmosphere, 7,8-benzoquinoline (10 mmol, 1.79 g), DCM (20 mL), and 85% m-CPBA (3.05 g, 15.0 mmol) were added to a reaction flask. After reacting at room temperature for 7 h, the reaction was quenched with 2 M NaOH solution, extracted with DCM, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na2SO4, filtered, concentrated, and subjected to silica gel column chromatography with ethyl acetate:methanol = 30:1 to 20:1 as the eluent. The product was a pale yellow solid, 1.61 g, with a yield of 82%. 1 H NMR (400MHz, CDCl3): δ10.85(d,J=7.6Hz,1H),8.66(d,J=6.4Hz,1H),7.92(d, J=6.4Hz,1H),7.90-7.73(m,4H),7.62(d,J=8.8Hz,1H),7.38(t,J=7.6Hz,1H). 13C NMR (100MHz, CDCl3): δ139.2,138.4,134.0,131.1,130.5,129.0,128.2,128.0,127.7,125.9,125.7,124.9,121.2.

[0187] Preparation Example 18:

[0188]

[0189] Under air atmosphere, 4-chloro-7-methoxyquinoline (5 mmol, 968.2 mg), DCM (25 mL), and m-CPBA (7.5 mmol, 1.29 g) were added to a reaction flask. After reacting at room temperature for 7 h, the reaction was quenched with NaHCO3 solution, extracted with DCM, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na2SO4, filtered, concentrated, and subjected to silica gel column chromatography with ethyl acetate:methanol in a ratio of 10:1 to 5:1 to 2:1. The product was a white solid, 932.1 mg, with a yield of 89%. 1 HNMR (400MHz, CDCl3): δ8.43 (d, J=6.8Hz, 1H), 8.09-8.07 (m, 2H), 7.36 (dd, J1=9.2, J2=2.0Hz, 1H), 7.24 (d, J=6.4Hz, 1H), 4.03 (s, 3H). 13 C NMR (100MHz, CDCl3): δ162.4,143.4,135.7,130.2,126.5,122.9,122.6,118.5,98.7,56.1.

[0190] Preparation Example 19:

[0191]

[0192] Under air atmosphere, 5-chloroquinoline (20 mmol, 3.30 g), DCM (50 mL), and m-CPBA (26 mmol, 5.28 g) were added to a reaction flask. After reacting at room temperature for 16 h, the reaction was quenched with 2 M NaOH solution, extracted with DCM, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na2SO4, filtered, concentrated, and subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 2:1 to ethyl acetate:methanol = 2:1. The product was a pale yellow solid, 2.40 g, with a yield of 67%. 1HNMR (400MHz, CDCl3): δ8.70(d,J=8.4Hz,1H),8.57(d,J=6.0Hz,1H),8.11(d,J=8.8H z,1H),7.72(d,J=7.6Hz,1H),7.67(t,J=8.4Hz,1H),7.40(dd,J1=8.8,J2=6.0Hz,1H). 13 CNMR (100MHz, CDCl3): δ142.5,135.9,132.1,129.8,128.9,128.7,122.3,121.6,118.9.

[0193] Preparation Example 20:

[0194]

[0195] Under air atmosphere, 6-bromoquinoline (20 mmol, 4.16 g), DCM (20 mL), and m-CPBA (24 mmol, 4.87 g) were added to the reaction flask. After reacting at room temperature for 18 h, the reaction was quenched with 2 M NaOH solution, extracted with DCM, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na2SO4, filtered, concentrated, and subjected to silica gel column chromatography with ethyl acetate:methanol = 10:1 as the eluent. The product was a white solid, 3.40 g, with a yield of 76%. 1 H NMR (400MHz, CDCl3): δ8.62(d,J=9.2Hz,1H),8.51(d,J=6.0Hz,1H),8.04(d,J=2.0 Hz,1H),7.82(dd,J1=9.4,J2=2.0Hz,1H),7.64(d,J=8.4Hz,1H),7.35-7.30(m,1H). 13 C NMR (100MHz, CDCl3): δ140.3,135.7,135.6,133.6,131.5,130.0,124.4,123.2,122.2,121.7.

[0196] Preparation Example 21:

[0197]

[0198] Under air atmosphere, 7-bromoquinoline (5 mmol, 1.04 g), DCM (20 mL), and 85% m-CPBA (7.5 mmol, 1.52 g) were added to the reaction flask. After reacting at room temperature for 18 h, the reaction was quenched with 2 M NaOH solution, extracted with DCM, and the organic phases were combined and washed successively with water and saturated NaCl solution. The mixture was dried over anhydrous Na2SO4, filtered, concentrated, and subjected to silica gel column chromatography with ethyl acetate:methanol = 10:1 as the eluent. The product was a white solid, 967.2 mg, with a yield of 86%. 1 H NMR (400MHz, CDCl3): δ8.95 (s, 1H), 8.53 (d, J = 4.8Hz, 1H), 7.74-7.71 (m, 3H), 7.35-7.29 (m, 1H). 13 C NMR (100MHz, CDCl3): δ141.8,136.1,132.4,129.4,129.1,125.5,125.1,122.5,121.3.

[0199] Example 1 Compound (3a)

[0200]

[0201] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1a (43.5 mg, 0.3 mmol), and 2a (91.8 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and subjected to silica gel column chromatography with dichloromethane:methanol = 100:1 as the eluent. The crude product was then subjected to plate chromatography (eluent: petroleum ether:ethyl acetate = 1:1) to give 47.8 mg of a white solid, yield 72%. mp 131.5-132.8℃. 1 H NMR (400MHz, CDCl3) δ8.86(d,J=8.8Hz,1H),7.97(d,J=7.6Hz,2H),7.84(d,J=8.4Hz,1H),7.78-7.71(m,2H),7.61(t,J=7.6Hz,1H),7.53-7.44(m,4H). 13C NMR (100MHz, CDCl3) δ144.91,142.20,133.38,130.44,129.49,129.42,128.29,128.17,127.87,125.14,125.0 7,123.19,120.14.IR(neat):2925,2849,1560,1491,1450,1351,1309,1206,889,817,779,754,735,701,766cm -1 .

[0202] Example 2 Compound (3a)

[0203]

[0204] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1a (43.5 mg, 0.3 mmol), and 2a (91.8 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with dichloromethane:methanol = 70:1 as the eluent, yielding 47.1 mg of a white solid, with a yield of 71%. 1 H NMR (400MHz, CDCl3) δ8.86(d,J=8.8Hz,1H),7.97(d,J=7.6Hz,2H),7.84(d,J=8.4Hz,1H),7.78-7.71(m,2H),7.61(t,J=7.6Hz,1H),7.53-7.44(m,4H). 13 C NMR (100MHz, CDCl3) δ144.91,142.20,133.38,130.44,129.49,129.42,128.29,128.17,127.87,125.14,125.0 7,123.19,120.14.IR(neat):2925,2849,1560,1491,1450,1351,1309,1206,889,817,779,754,735,701,766cm -1 .

[0205] Compound (3b) of Example 3

[0206]

[0207] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1b (67.2 mg, 0.3 mmol), and 2a (91.8 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and subjected to silica gel column chromatography with dichloromethane:methanol = 100:1 to 50:1 as the eluent. The crude product was then subjected to plate chromatography (eluent: petroleum ether:ethyl acetate = 1:1) to give 47.1 mg of a white solid, yield 52%. mp 171.1-172.6℃. 1 H NMR (400MHz, CDCl3) δ8.72(d,J=9.6Hz,1H),8.01(d,J=2.0Hz,1H),7.96-7.94(m ,2H),7.82(dd,J1=9.2,J2=2.0Hz,1H),7.63(d,J=8.8Hz,1H),7.53-7.45(m,4H). 13 C NMR (100MHz, CDCl3) δ145.17,141.08,133.72,132.98,130.63,129.87,129.71,129.44,128.30,124.47,123.7 8,122.74,122.27.IR(neat):3058,2917,2852,1552,1336,1308,1246,1069,894,873,813,773,745,696,670cm -1

[0208] Example 4 Compound (3c)

[0209]

[0210] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1c (47.8 mg, 0.3 mmol), and 2a (91.8 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and subjected to silica gel column chromatography with dichloromethane:methanol = 100:1 to 50:1 as the eluent. The crude product was then subjected to plate chromatography (with dichloromethane:methanol = 50:1 as the eluent) to obtain 53.2 mg of a white solid, with a yield of 75%. mp 113.1-114.5℃. 1 H NMR (400MHz, CDCl3) δ8.91(d,J=8.4Hz,1H),7.96(t,J=7.2Hz,3H),7.77(t,J=7 .6Hz,1H),7.65(t,J=7.2Hz,1H),7.52-7.43(m,3H),7.32(s,1H),2.66(s,3H). 13 C NMR (100MHz, CDCl3) δ144.22,141.64,133.47,133.44,130.11,129.52,129.31,128.99,128.12,128.05,124.47,12 3.66,120.69,18.21.IR(neat):3050,2923,2852,1383,1338,1306,1237,1204,1186,1146,860,768,755,696,666cm -1

[0211] Compound of Example 5 (3d)

[0212]

[0213] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2a (91.8 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and subjected to silica gel column chromatography with dichloromethane:methanol = 100:1 as the eluent. The crude product was then subjected to plate chromatography (eluent:petroleum ether:ethyl acetate = 1:1), and the product was a white solid, 59.7 mg, with a yield of 85%. mp 154.8-155.9℃. 1 H NMR (400MHz, CDCl3) δ8.66(s,1H),7.96(d,J=7.2Hz,2H),7.72(d,J=8.0Hz,1H),7.68(d,J=8.8Hz,1H),7.52-7.39(m,5H),2.59(s,3H). 13 C NMR (100MHz, CDCl3) δ144.89,142.10,141.42,133.57,130.34,129.46,129.29,128.11,127.60,127.56,124.99 ,122.23,119.18,22.04.IR(neat):2922,2853,1493,1350,1308,1219,1169,1144,889,841,775,733,692,675cm -1

[0214] Example 6 Compound (3e)

[0215]

[0216] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1e (67.2 mg, 0.3 mmol), and 2a (91.8 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with dichloromethane:methanol = 50:1 as the eluent. The product was a pale yellow solid, 27.3 mg, with a yield of 30%. mp 178.5-179.6℃. 1 H NMR (400MHz, CDCl3) δ9.05 (s, 1H), 7.97-7.95 (m, 2H), 7.72-7.70 (m, 3H), 7.55-7.48 (m, 4H). 13 C NMR (100MHz, CDCl3) δ145.64,142.68,133.00,132.04,129.78,129.48,129.23,128.34,128.15,125.16,124.75 ,123.64,123.11.IR(neat):2921,2852,1490,1446,1347,1320,1304,1241,1114,1072,894,879,845,734,688cm -1 .HRMS(EI)m / z:[MH] + Calcd for C 15 H9BrNO 297.9862; Found 297.9861.

[0217] Compound (3f) of Example 7

[0218]

[0219] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1a (67.2 mg, 0.3 mmol), and 2b (91.8 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 32.8 mg, yield 46.5%. mp 115.5-116.0℃. 1 H NMR (400MHz, CDCl3) δ8.85(d,J=9.2Hz,1H),7.90(d,J=8.4Hz,2H),7.83(d,J=8.0Hz,1H),7.78 -7.70(m,2H),7.61(t,J=8.0Hz,1H),7.49(d,J=8.8Hz,1H),7.32(d,J=8.0Hz,2H),2.42(s,3H). 13 C NMR (100MHz, CDCl3) δ145.04,142.20,139.67,130.44,129.42,129.35,128.90,128.19,127.86,125.22,123.19 ,120.15,21.41.IR(neat):2920,2847,1500,1339,1328,1304,1219,1205,1187,1108,889,803,770,759,733cm -1

[0220] Example 8 Compound (3g)

[0221]

[0222] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1a (43.5 mg, 0.3 mmol), and 2c (91.8 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate at a ratio of 2:1 to 1:1 as the eluent. The product was a pale yellow solid, 36.2 mg, in yield of 48%. mp 119.7–120.8 °C. 1 H NMR(400MHz, CDCl3)δ8.85(d,J=8.8Hz,1H),8.04-8.00(m,2H),7.82(d,J=8.0Hz,1H),7.78-7.74(m, 1H),7.71(d,J=8.8Hz,1H),7.62-7.58(m,1H),7.50(d,J=8.8Hz,1H),7.05-7.01(m,2H),3.87(s,3H). 13 CNMR (100MHz, CDCl3) δ160.45,144.62,142.25,131.34,130.40,129.18,128.04,127.82,125.58,125.17,123.01,12 0.09,113.62,55.30.IR(neat):3082,2920,2829,1600,1500,1330,1292,1250,1177,1107,1026,887,810,749,735cm -1

[0223] Example 9 Compound (3h)

[0224]

[0225] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2b (98.1 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 64.3 mg, in yield of 86%. mp 123.3-124.3℃. 1 H NMR (400MHz, CDCl3) δ8.66(s,1H),7.89(d,J=8.0Hz,2H),7.72(d,J=8.4Hz,1H),7.67(d ,J=8.8Hz,1H),7.42(t,J=8.8Hz,2H),7.32(d,J=8.0Hz,2H),2.60(s,3H),2.42(s,3H). 13 C NMR (100MHz, CDCl3) δ145.01,142.08,141.35,139.47,130.61,130.19,129.36,128.82,127.56,127.41,125.04,122.1 7,119.16,22.03,21.34.IR(neat):3082,2909,2844,1506,1348,1309,1244,1218,1166,1112,887,838,820,764,738cm -1 .HRMS(EI)m / z:[MH] + Calcdfor C 17 H 14 NO 248.1070; Found 248.1070.

[0226] Example 10 Compound (3i)

[0227]

[0228] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2c (105.3 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 70 mg, in 88% yield. mp 150.1-151.3℃. 1 H NMR (400MHz, CDCl3) δ8.65(s,1H),8.01(d,J=8.8Hz,2H),7.70(d,J=8.4Hz,1H),7.65(d ,J=8.8Hz,1H),7.42(d,J=8.8Hz,2H),7.02(d,J=9.2Hz,2H),3.86(s,3H),2.59(s,3H). 13 C NMR (100MHz, CDCl3) δ160.33,144.56,142.21,141.33,131.09,130.07,127.55,127.24,125.75,125.01,122.01,119.12 ,113.54,55.25,22.05.IR(neat):3006,2920,2836,1598,1504,1340,1288,1247,1213,1183,1165,1022,833,821,742cm -1 .HRMS(EI)m / z:[M] + Calcdfor C 17 H 15 NO2 265.1097; Found 265.1094.

[0229] Example 11 Compound (3j)

[0230]

[0231] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2d (126.1 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 59.9 mg, yield 64%. mp 163.1-164.6℃. 1 H NMR (400MHz, CDCl3) δ8.67 (s, 1H), 8.07 (d, J = 8.4Hz, 2H), 7.74-7.70 (m, 3H), 7.66(t,J=8.4Hz,3H),7.47-7.42(m,4H),7.36(t,J=7.2Hz,1H),2.60(s,3H). 13 C NMR (100MHz, CDCl3) δ144.57,142.17,142.07,141.47,140.37,132.41,130.36,129.94,128.75,127.62,127.58,127.54,127.07,12 6.81,125.03,122.10,119.20,21.98.IR(neat):3056,3024,2912,2857,1485,1347,1218,1166,1114,889,831,770,738,756,685cm -1 .HRMS(EI)m / z:[MO] + Calcd forC 22 H 17 N 295.1356; Found 295.1356.

[0232] Example 12 Compound (3k)

[0233]

[0234] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2e (85.5 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 68.1 mg, yield 96%. mp 159.1-160.1℃. 1 H NMR (400MHz, CDCl3) δ8.67(s,1H),7.97(d,J=7.6Hz,2H),7.73(d,J=8.0Hz,1H),7.68(d,J=8.4Hz,1H),7.53-7.40(m,5H),2.60(s,3H). 13 C NMR (100MHz, CDCl3) δ144.88,142.02,141.40,133.51,130.31,129.42,129.26,128.07,127.56,127.51,125.06,12 2.17,119.11,22.00.IR(neat):3069,3045,2969,1350,1308,1245,1219,1164,1144,1116,889,841,775,747,693cm -1

[0235] Example 13 Compound (3l)

[0236]

[0237] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2f (99.9 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 65.5 mg, in yield of 86%. mp 182.2-184.1℃. 1 H NMR (400MHz, CDCl3) δ8.63(s,1H),7.99(dd,J1=8.4,J2=5.6Hz,2H),7.73(d,J=8.8Hz,1H),7.68( d,J=8.8Hz,1H),7.45(d,J=8.0Hz,1H),7.39(d,J=8.8Hz,1H),7.18(t,J=8.4Hz,2H),2.59(s,3H). 13 C NMR (100MHz, CDCl3) δ 162.97 (d, J = 249.3Hz), 143.89, 141.97, 141.59, 131.58 (d, J = 8.4Hz), 130.41, 129.46 (d, J = 3.4Hz), 127.61, 127.49, 125. 21,121.88,119.02,115.14(d,J=21.6Hz),22.00.IR(neat):3061,2920 ,1504,1327,1300,1248,1221,1159,1145,891,849,825,813,741,658cm -1 .HRMS(EI)m / z:[M] + Calcd for C 16 H 12 FNO 253.0897; Found 253.0891.

[0238] Example 14 Compound (3m)

[0239]

[0240] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1 d (47.7 mg, 0.3 mmol), and 2 g (107.3 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 62.1 mg, yield 77%. mp 192.7-193.8℃. 1 H NMR (400MHz, CDCl3) δ8.62 (s, 1H), 7.94-7.92 (m, 2H), 7.72 (d, J = 8.0Hz, 1H), 7.67(d,J=8.8Hz,1H),7.47-7.44(m,3H),7.37(d,J=8.8Hz,1H),2.59(s,3H). 13 C NMR (100MHz, CDCl3) δ143.69,142.05,141.62,135.25,131.89,130.85,130.53,128.34,127.64,127.59,125.11,12 1.79,119.08,22.04.IR(neat):3058,2917,1488,1339,1326,1297,1220,1144,1089,1013,896,850,822,764,735cm -1 .HRMS(EI)m / z:[MH] + Calcd for C 16 H 11 ClNO 268.0524; Found 268.0527.

[0241] Example 15 Compound (3n)

[0242]

[0243] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1 day (47.7 mg, 0.3 mmol), and 2 h (127.3 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 61.6 mg, in yield of 65%. mp 200.1-200.9℃. 1 H NMR (400MHz, CDCl3) δ8.62 (s, 1H), 7.87-7.85 (m, 2H), 7.73 (d, J = 8.4Hz, 1H), 7.68 (d, J = 8.8 Hz,1H),7.63-7.61(m,2H),7.46(dd,J=8.4,1.2Hz,1H),7.38(d,J=8.8Hz,1H),2.60(s,3H). 13 CNMR (100MHz, CDCl3) δ143.77,142.10,141.68,132.38,131.33,131.09,130.58,127.68,127.63,125.15,123.66,12 1.75,119.10,22.08.IR(neat):3056,2909,1486,1338,1325,1297,1220,1143,1099,1070,1009,890,849,818,733cm -1 .HRMS(EI)m / z:[M] + Calcd forC 16 H 12 BrNO 313.0097; Found 313.0089.

[0244] Example 16 Compound (3o)

[0245]

[0246] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2i (117.1 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 63.7 mg, yield 73%. mp 138.8-140.1℃. 1 H NMR (400MHz, CDCl3) δ8.66(s,1H),7.94(d,J=8.0Hz,2H),7.70(d,J=8.4Hz,1H),7.65(d ,J=8.8Hz,1H),7.53(d,J=8.0Hz,2H),7.42(d,J=8.4Hz,2H),2.59(s,3H),1.37(s,9H). 13 C NMR (100MHz, CDCl3) δ152.50,144.88,142.16,141.28,130.58,130.17,129.20,127.55,127.42,125.11,124.90,122.19,11 9.18,34.71,31.11,22.03.IR(neat):2961,2852,1501,1366,1339,1328,1309,1246,1219,1144,1121,892,843,826,732cm -1 .HRMS(EI)m / z:[M] + Calcd for C 20 H 21 NO 291.1618; Found 291.1612.(nyr-2-84)

[0247] Example 17 Compound (3p)

[0248]

[0249] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2j (114.4 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 43.1 mg, yield 50%. mp 175.5-176.8℃. 1 H NMR (400MHz, CDCl3) δ8.68 (s, 1H), 8.42 (s, 1H), 8.09 (d, J = 8.8Hz, 1H), 7.94-7.85 (m ,3H),7.71(d,J=8.4Hz,1H),7.67(d,J=8.8Hz,1H),7.54-7.42(m,4H),2.59(s,3H). 13 C NMR (100MHz, CDCl3) δ144.90,142.14,141.50,133.50,132.95,131.15,130.39,129.49,128.53,127.64,127.60,127.53,127.48,126.96,12 6.42,126.16,125.14,122.42,119.13,22.11.IR(neat):3056,2915,2849,1364,1330,1317,1251,1210,1129,892,870,838,817,763,754cm -1 .HRMS(EI)m / z:[MO] + Calcd for C 20 H 15 N 269.1199; Found 269.1197.

[0250] Example 18 Compound (3q)

[0251]

[0252] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2k (172.0 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 98.0 mg, yield 79%. mp 207.4-208.6℃. 1 H NMR (400MHz, CDCl3) δ8.65 (s, 1H), δ8.22 (d, J = 8.0Hz, 2H), δ8.05 (d, J = 8.0Hz, 2H), 7.74 (dd, J1 = 16.0Hz, J2 = 8.4Hz, 2H), δ7.48 (d, J = 8.4Hz, 1 H), δ7.43(d,J=8.8Hz,1H),5.22(s,1H),2.61(s,3H),2.19(d,J=12.4Hz,4H),1,91.(t,J=10.4Hz,6H),1.79(s,2H),1.66(d,J=12.8Hz,2H); 13 C NMR (100MHz, CDCl3) δ165.26,144.01,142.20,141.71,137.80,131.61,130.75,129.49,129.34,127.83,127.71,125.08,122.00,119.24,77 .69,37.33,36.30,31.93,27.25,26.96,22.10.IR(neat):2914,2851,1713,1343,1266,1120,1099,1040,1015,986,839,777,758,737,706cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 27 H 28 NO3414.2064; Found 414.2060.

[0253] Example 19 Compound (3r)

[0254]

[0255] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2l (172.9 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was changed from petroleum ether:ethyl acetate = 20:1 to dichloromethane:methanol = 100:1. The product was a white solid, 97.2 mg, yield 78%. mp 186.1-187.8℃. 1 H NMR (400MHz, CDCl3) δ8.04 (s, 1H), δ8.19 (d, J = 8.4Hz, 2H), δ8.05 (d, J = 8.8Hz, 2H), 7.73 (dd, J1 = 15.6H z,J2=8.0Hz,2H),δ7.46(d,J=8.4Hz,1H),δ7.42(d,J=8.4Hz,1H),5.17(dt,J1=9.2Hz,J2=2.0Hz,1H),2 .60(s,3H),2.53-2.47(m,1H),2.19-2.14(m,1H),1.86-1.79(m,1H),1,75.(t,J=4.4Hz,1H),1.47-1. 37(m,1H),1.35-1.32(m,1H),1.16(dd,J1=13.8Hz,J2=3.6Hz,1H),0.98(s,3H),0.93(d,J=5.6Hz,6H); 13 C NMR (100MHz, CDCl3) δ166.11,143.81,142.05,141.57,137.75,131.20,130.6 3,129.39,129.17,127.72,127.63,124.99,121.85,119.08,80.55,48.96,47. 72,44.81,36.74,27.93,27.23,22.00,19.56,18.75,13.47.IR(neat):2951, 2912,2873,1712,1299,1279,1270,1213,1106,1019,835,778,756,735,702cm -1 .HRMS(ESI)m / z:[M+H]+ Calcd for C 27 H 30 NO3 416.2220; Found 416.2218.

[0256] Example 20 Compound (3s)

[0257]

[0258] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2m (116.6 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with dichloromethane:methanol = 70:1 as the eluent. The product was a white solid, 80.2 mg, with a yield of 92%. 1 HNMR (400MHz, CDCl3) δ9.20 (s, 1H), 8.65 (s, 1H), 8.04-8.01 (m, 2H), 7.65 (d, J= 8.4Hz,2H),7.40(d,J=7.2Hz,1H),7.34-7.25(m,3H),3.85(s,3H),2.58(s,3H). 13 C NMR (100MHz, CDCl3) δ142.1,141.2,141.1,136.7,135.3,128.9,127.4,126.4,125.4,125.0,122.2,120.9,120.3,119.8,118.5,110.1,106 .4,33.2,22.1.IR(neat):3045,2914,1602,1531,1506,1476,1390,1369,1347,1302,1219,1124,1085,818,733cm-1.HRMS(ESI)m / z:[M+H] + Calcd for C 19 H 17 N2O 289.1335; Found 289.1332.

[0259] Example 21 Compound (3t)

[0260]

[0261] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1d (47.7 mg, 0.3 mmol), and 2n (87.3 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and reacted at room temperature for 24 h. Then, 1,4-benzoquinone (64.9 mg, 0.6 mmol) was added to the reaction system, and the reaction was continued at room temperature for 1.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with dichloromethane:methanol = 70:1 as the eluent. The product was a white solid, 50.0 mg, with a yield of 74%. 1 H NMR (400MHz, CDCl3) δ9.39 (s, 1H), 8.61 (s, 1H), 7.68 (dd, J1=17.0Hz, J2=8.0 Hz,2H),7.57-7.55(m,2H),7.41(d,J=8.0Hz,1H),6.92(s,1H),2.60(s,3H). 13 C NMR (100MHz, CDCl3) δ147.1,142.7,142.0,141.5,138.7,129.9,127.6,126.1,125.1,119.0,118.7,118.0,108.5,22.1 .IR(neat):3144,2917,2835,2705,2600,1333,1323,1162,1027,869,836,801,785,761,739cm-1.HRMS(ESI)m / z:[M+H] + Calcd forC 14 H 12 NO2226.0863; Found 226.0860.

[0262] Example 22 Compound (3u)

[0263]

[0264] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. tBu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1f (47.7 mg, 0.3 mmol), and 2a (91.8 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and allowed to react at room temperature for 24 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 20:1 as the eluent. The product was a pale yellow liquid, 33.8 mg, with a yield of 51%. 1 H NMR (400MHz, CDCl3) δ8.25(d,J=7.2Hz,2H),8.13(d,J=8.8Hz,1H),7.86(d,J=8.4Hz,1H),7.6 3(d,J=8.4Hz,1H),7.56-7.49(m,3H),7.45-7.44(m,1H),7.38(t,J=7.2Hz,1H),2.90(s,3H). 13 CNMR(100MHz, CDCl3)δ155.49,147.15,139.84,137.65,136.88,129.64,129.18,128.73,127.44,127.07,125.98,12 5.35,118.14,17.86.IR(neat):3040,2915,1597,1560,1508,1488,1421,1322,1281,1073,1024,833,764,712,690cm -1 .

[0265] Example 23 Compound (3t-1)

[0266]

[0267] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2m⁻¹ (0.45 mmol, 129.7 mg), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 1:2 as the eluent. The product was a pale yellow solid, 71.1 mg, yield 77%. mp 92.2-92.8℃. 1H NMR (400MHz, CDCl3): δ8.76(d,J=8.4Hz,1H),7.75(d,J=8.4Hz,1H),7.70(t,J=7.2Hz,1H),7.59-7.51(m,2H),7.49-7.43(m,2H) ,7.37-7.32(m,4H),7.29-7.28(m,1H),6.83(dt,J=16.4,7.2Hz,1H),4.55(s,2H),3.67(t,J=6.4Hz,2H),2.70(q,J=6.8Hz,2H). 13 C NMR (100MHz, CDCl3): δ143.6,141.5,138.0,136.7,130.2,128.7,128.2,127.8,127.7,127.55,127.48,124.7,123.3 ,119.8,119.0,72.8,69.0,33.9.IR(neat):2864,1641,1560,1453,1353,1236,1116,1098,1077,973,815,731,696cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 20 H 20 NO2306.1489; Found 306.1484.

[0268] Example 24 Compound (3t-1)

[0269]

[0270] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2m⁻¹ (0.45 mmol, 129.7 mg), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 1:2 as the eluent. The product was a pale yellow solid, 62.2 mg, in yield of 68%. 1H NMR (400MHz, CDCl3): δ8.76(d,J=8.4Hz,1H),7.75(d,J=8.4Hz,1H),7.70(t,J=7.2Hz,1H),7.59-7.51(m,2H),7.49-7.43(m,2H) ,7.37-7.32(m,4H),7.29-7.28(m,1H),6.83(dt,J=16.4,7.2Hz,1H),4.55(s,2H),3.67(t,J=6.4Hz,2H),2.70(q,J=6.8Hz,2H). 13 C NMR (100MHz, CDCl3): δ143.6,141.5,138.0,136.7,130.2,128.7,128.2,12 7.8,127.7,127.55,127.48,124.7,123.3,119.8,119.0,72.8,69.0,33.9.

[0271] Example 25 Compound (3u-1)

[0272]

[0273] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2m⁻¹ (0.45 mmol, 129.7 mg), and 1c (0.3 mmol, 47.8 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 1:2 as the eluent. The product was a pale yellow liquid, 70.0 mg, with a yield of 73%. 1 H NMR (400MHz, CDCl3): δ8.81(d,J=8.8Hz,1H),7.84(d,J=8.0Hz,1H),7.70(t,J=7.6Hz,1H),7.56(t,J=7.6Hz,1H),7.44(d,J=16.4Hz ,1H),7.36-7.28(m,6H),6.82(dt,J1=16.4,J2=7.2Hz,1H),4.55(s,2H),3.68(t,J=6.4Hz,2H),2.70(q,J=6.4Hz,2H),2.58(s,3H). 13CNMR (100MHz, CDCl3): δ142.8,140.9,138.0,136.5,132.9,129.8,128.3,128.2,127.54,127.46,124.3,123.2,120.3,119 .2,72.8,69.0,33.9,18.2.IR(neat):2856,1734,1641,1560,1454,1390,1229,1213,1144,1093,1029,971,758,728,697cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 21 H 22 NO2320.1645; Found 320.1643.

[0274] Example 26 Compound (3v)

[0275]

[0276] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2 m-1 (0.45 mmol, 129.7 mg), and 1 g (0.3 mmol, 66.4 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 1:1 as the eluent. The product was a white solid, 81.3 mg, yield 71%. mp 126.3–127.8 °C. 1 H NMR (400MHz, CDCl3): δ8.87(d,J=8.4Hz,1H),7.84(d,J=8.0Hz,1H),7.73(t,J=7.6Hz,1H),7.50-7.46(m,8H),7 .33-7.25(m,5H),6.82(dt,J1=16.4,J2=6.4Hz,1H),4.54(s,2H),3.67(t,J=5.6Hz,2H),2.70(d,J=6.0Hz,2H). 13CNMR (100MHz, CDCl3): δ143.0,141.6,138.0,137.4,137.1,136.8,130.1,129.4,128.6,128.4,128.3,127.8,127.6,127.5,127.3,126.3,123 .3,120.2,119.4,72.9,69.0,34.0.IR(neat):2854,1635,1551,1387,1359,1340,1305,1216,1124,1074,1027,992,974,779,751,730,702cm - 1 .HRMS(ESI)m / z:[M+H] + Calcd for C 26 H 24 NO2 382.1802; Found 382.1799.

[0277] Example 27 Compound (3w)

[0278]

[0279] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2 m⁻¹ (0.45 mmol, 129.7 mg), and 1 d (0.3 mmol, 47.8 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 1:1 as the eluent. The product was a pale yellow solid, 73.6 mg, yield 77%. mp 76.6–77.9 °C. 1 H NMR (400MHz, CDCl3): δ8.57(s,1H),7.65(d,J=8.0Hz,1H),7.54(d,J=8.8Hz,1H),7.48(s,1H),7.42(d,J=9.2Hz,2H),7.38-7.32 (m,5H),7.29-7.27(m,1H),6.80(dt,J=16.4,6.4Hz,1H),4.55(s,2H),3.67(t,J=6.8Hz,2H),2.70(d,J=6.4Hz,2H),2.56(s,3H). 13C NMR (100MHz, CDCl3): δ143.8,141.5,141.2,138.1,136.4,129.9,128.3,127.6,127.5,126.9,124.7,123.4,118.9,118.0,72.9, 69.1,33.9,22.0.IR(neat):2852,1599,1557,1453,1356,1339,1242,1144,1117,1102,1074,1029,980,971,900,831,733,697cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 21 H 22 NO2 320.1645; Found 320.1638.

[0280] Example 28 Compound (3x)

[0281]

[0282] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2 m⁻¹ (0.45 mmol, 129.7 mg), and 1 h (0.3 mmol, 53.9 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was stirred in air for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 1:1 as the eluent. The product was a pale yellow solid, 62.5 mg, yield 61%, mp 75.6-77.9 °C. 1 H NMR (400MHz, CDCl3): δ8.71-8.69(m,1H),7.96(d,J=9.2Hz,1H),7.62-7.57(m,3H),7.41(d,J=16.4Hz,1H),7.36-7.3 3(m,4H),7.29-7.27(m,1H),6.89(dt,J=16.4,6.8Hz,1H),4.56(s,2H),3.69(t,J=5.6Hz,2H),2.71(q,J=6.8Hz,2H). 13C NMR (100MHz, CDCl3): δ144.0,142.7,138.0,137.8,131.8,129.8,128.3,128.1,127.63,127.59,127.0,123.0,121.1,119.9,119.1,7 2.9,69.0,34.1.IR(neat):2919,2851,1637,1511,1496,1453,1355,1339,1242,1116,1097,1074,1028,974,881,806,793,731,696cm - 1 .HRMS(ESI)m / z:[M+H] + Calcd for C 20 H 19 NO2Cl 340.1099; Found 340.1093.

[0283] Example 29 Compound (3y)

[0284]

[0285] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2m⁻¹ (0.45 mmol, 129.7 mg), and 1b (0.3 mmol, 67.2 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 1:2 as the eluent. The product was a pale yellow solid, 65.6 mg, yield 57%. mp 109.8–110.4 °C. 1 H NMR (400MHz, CDCl3): δ8.62(d,J=9.2Hz,1H),7.91(s,1H),7.76(d,J=9.2Hz,1H),7.52-7.47(m,2H),7.42-7.32(m ,5H),7.30-7.27(m,1H),6.89(dt,J=16.4,6.8Hz,1H),4.55(s,2H),3.68(t,J=6.4Hz,2H),2.70(q,J=6.4Hz,2H). 13C NMR (100MHz, CDCl3): δ143.9,140.4,138.1,137.4,133.4,129.9,129.8,128.3,127.62,127.56,123.4,123.0,122.2,121 .9,120.3,72.9,69.0,34.0.IR(neat):2919,2848,1641,1549,1497,1451,1346,1238,1123,983,897,823,805,732,691cm -1 .HRMS(ESI)m / z:[M+H] + Calcd forC 20 H 19 NO2Br 384.0594; Found384.0589.

[0286] Example 30 Compound (3z)

[0287]

[0288] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2n-1 (0.45 mmol, 129.7 mg), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was petroleum ether:dichloromethane:methanol = 15:15:1. The product was a pale yellow solid, 62.3 mg, yield 75%. mp 81.5-82.8℃. 1 H NMR (400MHz, CDCl3): δ8.77(d,J=8.4Hz,1H),7.77-7.69(m,2H),7.60-7.53(m,2H),7.47-7.42(m,2H),7.32-7 .29(m,2H),7.24-7.21(m,3H),6.81(dt,J1=16.4,J2=6.8Hz,1H),2.88(t,J=7.2Hz,2H),2.70(q,J=7.6Hz,2H). 13C NMR (100MHz, CDCl3): δ143.8,141,6,141.1,139.4,130.3,128.8,128.4,128.3,127.9,127.7,126.0,124.9,122.3,1 19.9,119.0,35.3,35.1.IR(neat):2923,1637,1561,1510,1453,1344,1230,1077,989,969,826,772,746,731,700cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 19 H 18 NO276.1383; Found 276.1378.

[0289] Example 31 Compound (4a)

[0290]

[0291] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2O (0.45 mmol, 103.7 mg), and 1A (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 1:1 as the eluent. The product was a pale yellow solid, 61.5 mg, in yield (83%). The mp values ​​were 72.3–73.4 °C. 1 H NMR (400MHz, CDCl3): δ8.77(d,J=8.8Hz,1H),7.79(d,J=8.4Hz,1H),7.73(t,J=8.0Hz,1H),7.63(d,J=8.8Hz,1H),7.57(t,J=8.0Hz,1H),7.50(d,J=8 .8Hz,1H),7.40(d,J=16.0Hz,1H),6.84(dt,J1=16.4,J2=7.2Hz,1H),3.62 (t,J=6.4Hz,2H),2.55(q,J=7.2Hz,2H),2.04(dt,J1=14.0,J2=6.8Hz,2H). 13C NMR (100MHz, CDCl3): δ143.4,141.6,138.3,130.3,128.8,128.0,127.8,124.9,123.0,119.9,119.2,44.1 ,31.5,30.7.IR(neat):2921,1637,1559,1427,1352,1283,1243,1201,1087,975,967,873,802,751,730cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 14 H 15 NOCl 248.0837; Found 248.0838.

[0292] Example 32 Compound (4b)

[0293]

[0294] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2p (0.45 mmol, 89.1 mg), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 1:1 as the eluent. The product was a pale yellow liquid, 45.3 mg, in yield (70%). The mp values ​​were 64.6–65.3 °C. 1 H NMR (400MHz, CDCl3): δ8.73(d,J=8.4Hz,1H),8.54(d,J=12.4Hz,1H),7.76-7.70(m,2H),7.56(d,J=8.8Hz,1H),7 .52(t,J=8.0Hz,1H),7.23(d,J=8.8Hz,1H),6.38(d,J=12.4Hz,1H),4.10(q,J=6.8Hz,2H),1.40(t,J=6.8Hz,3H). 13C NMR (100MHz, CDCl3): δ157.7,142.8,141.8,130.2,127.7,127.4,127.0,125.3,120.5,119.1,100.2,67 .2,14.8.IR(neat):2974,1627,1612,1562,1346,1315,1213,1173,1023,926,801,770,746,731,665cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 13 H 14 NO2 216.1019; Found 216.1018.

[0295] Example 33 Compound (4c)

[0296]

[0297] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2q (0.45 mmol, 94.6 mg), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 2:1 as the eluent. The product was a pale yellow solid, 46.9 mg, with a yield of 69%. 1 H NMR (400MHz, CDCl3): δ8.77(d,J=8.8Hz,1H),7.77(d,J=8.0Hz,1H),7.71(t,J=8.0Hz,1H),7.60(q,J=8.8Hz,1H),7.55(t,J=7.6Hz,1H),7.51(d,J=8.8 Hz,1H),7.39(d,J=16.0Hz,1H),6.80(dt,J1=16.4,J2=6.8Hz,1H),2.39(q, J=7.6Hz,2H),1.57-1.50(m,2H),1.45-1.36(m,2H),0.94(t,J=7.6Hz,3H). 13C NMR (100MHz, CDCl3): δ143.9,141.6,140.8,130.2,128.8,127.74,127.72,124.8,121.7,119.9,119.0,33.3 ,30.8,22.2,13.8.IR(neat):2956,2922,2854,1637,1561,1512,1354,1240,1204,1081,970,841,774,727cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 15 H 18 NO 228.1383; Found 228.1379.

[0298] Example 34 Compound (4d)

[0299]

[0300] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2r (0.45 mmol, 87.3 mg), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was petroleum ether:dichloromethane:methanol = 15:15:1. The product was a white solid, 47.7 mg, yield 75%. mp 147.5-148.8℃. 1 H NMR (400MHz, CDCl3): δ8.76(d,J=8.8Hz,1H),7.76-7.69(m,2H),7.58-7.52(m,2H),7.42(d,J=8.4Hz,1H) ,7.37(s,1H),6.44(dd,J1=15.8,J2=9.2Hz,1H),1.81-1.73(m,1H),1.00-0.95(m,2H),0.70-0.66(m,2H). 13CNMR (100MHz, CDCl3): δ145.6,143.5,141.6,130.2,128.4,127.7,127.6,124.8,119.8,119.1,119.0, 15.9,8.6.IR(neat):3000,1633,1560,1507,1348,1302,1242,975,962,928,890,829,781,729,667cm - 1 .HRMS(ESI)m / z:[M+H] + Calcd for C 14 H 14 NO 212.1070; Found 212.1065.

[0301] Example 35 Compound (4e)

[0302]

[0303] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2s (0.45 mmol, 94.6 mg), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was petroleum ether:dichloromethane:methanol = 15:15:1. The product was a pale yellow liquid, 49.5 mg, yield 73%. mp 81.7-83.0℃. 1 H NMR (400MHz, CDCl3): δ8.77(d,J=8.8Hz,1H),7.78(d,J=8.0Hz,1H),7.72(t,J=7.6Hz,1H),7.62(d ,J=9.2Hz,1H),7.56(t,J=8.4Hz,2H),7.37(d,J=16.8Hz,1H),6.79(d,J=16.8Hz,1H),1.21(s,9H). 13C NMR (100MHz, CDCl3): δ150.8,144.4,141.6,130.3,128.7,127.8,127.7,124.9,119.9,119.0,117.2,3 4.5,29.1.IR(neat):2958,1634,1560,1511,1458,1352,1269,1253,1237,1131,1082,976,810,749cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 15 H 18 NO 228.1383; Found 228.1382.

[0304] Example 36 Compound (4f)

[0305]

[0306] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2t (0.45 mmol, 196.4 mg), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was exposed to air and stirred for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 2:1 as the eluent. The product was a pale yellow liquid, 50.6 mg, with a yield of 37%. 1 H NMR (400MHz, CDCl3): δ8.77(d,J=8.4Hz,1H),7.78(d,J=8.0Hz,1H),7.73(d,J=7.2Hz,1H),7.69(d,J=6.8Hz,1H),7.56(t,J=7.6Hz,1H) ,7.46(d,J=8.8Hz,2H),7.42-7.36(m,6H),6.80(dt,J1=16.8,J1=6.8Hz,1H),3.87(t,J=6.4Hz,2H),2.65(q,J=6.8Hz,2H),1.07(s,9H). 13C NMR (100MHz, CDCl3): δ143.8,141.7,137.1,135.5,133.7,130.3,129.6,128.9,128.0,127.8,127.7,124.9,123.4,120.0,1 19.1,63.2,37.0,29.1,26.8,19.2.IR(neat):2929,2856,1560,1471,1427,1354,1239,1108,972,822,801,732,700,687cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 29 H 32 NO2Si 454.2197; Found 454.2187.

[0307] Example 37 Compound (4g)

[0308]

[0309] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2u (0.45 mmol, 140.5 mg), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 16 h. Then, the cap was opened, and the system was stirred in air for 1 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography. The eluent was petroleum ether:dichloromethane:methanol = 15:15:1. The product was a pale yellow liquid, 73.3 mg, with a yield of 74%. 1 H NMR (400MHz, CDCl3): δ8.83(d,J=8.8Hz,1H),7.84(d,J=8.4Hz,1H),7.79(t,J=7.6Hz,1H),7.68(d,J=8.8Hz,1H),7.63(t,J=7.2Hz,1H),7.58(d, J=8.8Hz,1H),7.51(d,J=16.4Hz,1H),6.89(dt,J1=16.4,J1=7.2Hz,1H),3.88(t,J=6.4Hz,2H),2.68(q,J=6.8Hz,2H),0.98(s,9H),0.15(s,6H). 13C NMR (100MHz, CDCl3): δ143.7,141.6,137.0,130.2,128.8,127.9,127.8,124.9,123.3,119.9,118.9,62.3,37 .1,25.8,18.2.IR(neat):2952,2927,2855,1560,1354,1343,1243,1186,1137,1084,961,832,802,770,732cm -1 .HRMS(ESI)m / z:[M] + Calcd for C 19 H 28 NO2Si 330.1884; Found 330.1876.

[0310] Example 38 Compound (4h)

[0311]

[0312] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2 m⁻¹ (0.45 mmol, 140.5 mg), and 1 h⁻¹ (0.3 mmol, 87.2 mg). After capping, the mixture was removed from the glove box and allowed to react at room temperature for 24 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 2:1 as the eluent. The product was a pale yellow liquid, 22.8 mg, with a yield of 21%. 1 H NMR (400MHz, CDCl3): δ8.03(d,J=9.2Hz,1H),7.44(s,1H),7.36-7.35(m,5H),7.30-7.26(m,1H),7.20(dd,J=9.2,2.4Hz,1H),6. 82(dt,J1=15.6,J2=6.8Hz,1H),6.67(d,J=16.0Hz,1H),4.56(s,2H),3.94(s,3H),3.67(t,J=6.8Hz,2H),2.65(q,J=6.4Hz,2H). 13C NMR (100MHz, CDCl3): δ161.4,156.4,150.6,142.4,138.2,134.7,131.7,128.4,127.7,127.6,125.0,120.3,119.9,116.8,107.4, 73.0,69.2,55.6,33.4.IR(neat):2854,1617,1581,1504,1447,1366,1256,1218,1167,1121,1094,1029,966,849,820,735,697cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 21 H 21 NO2Cl 354.1255; Found 354.1256.

[0313] Example 39 Compound (4i)

[0314]

[0315] In a nitrogen-filled glove box, CuCl2 (0.02 mmol, 2.7 mg), Xantphos (0.02 mmol, 11.6 mg), and KO were added sequentially to a 4 mL sample vial. t Bu (0.2 mmol, 22.4 mg), THF (1.0 mL), 2 m⁻¹ (0.3 mmol, 86.5 mg), and 1 f (0.2 mmol, 31.8 mg). After capping, the mixture was removed from the glove box and allowed to react at room temperature for 16 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 30:1 as the eluent. The product was a colorless liquid, 46.8 mg, with a yield of 77%. 1 H NMR (400MHz, CDCl3): δ8.01(d,J=8.8Hz,1H),7.57(d,J=8.4Hz,1H),7.50(d,J=6.8Hz,1H),7.46(d,J=8.4Hz,1H),7.38-7.32(m,5H),7.30-7. 26(m,1H),6.90(dt,J1=15.6,J2=6.8Hz,1H),6.79(d,J=16.0Hz,1H),4.57(s,2H),3.67(t,J=6.8Hz,2H),2.81(s,3H),2.65(q,J=6.4Hz,2H). 13C NMR (100MHz, CDCl3): δ154.8,147.0,138.3,137.0,136.3,133.04,133.01,129.5,128.4,127.7,127.6,127.0,125.6,1 25.3,118.6,72.9,69.4,33.4,17.8.IR(neat):2854,1597,1564,1501,1362,1206,1094,1028,968,828,761,734,696cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 21 H 22 NO 304.1696; Found 304.1698.

[0316] Example 40 Compound (4j)

[0317]

[0318] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2 m-1 (0.45 mmol, 129.7 mg), and 1 i (0.3 mmol, 58.6 mg). After capping, the mixture was removed from the glove box and allowed to react at room temperature for 24 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:ethyl acetate = 10:1 as the eluent. The product was a colorless liquid, 35.0 mg, yield 34%. mp 54.2–55.3 °C. 1 H NMR (400MHz, CDCl3): δ9.36(d,J=8.0Hz,1H),8.04(d,J=8.0Hz,1H),7.86(d,J =8.0Hz,1H),7.73-7.64(m,3H),7.61(d,J=8.4Hz,1H),7.51(d,J=8.0Hz,1H), 7.39-7.33(m,4H),7.30-7.26(m,1H),7.05(dt,J1=16.0,J2=7.2Hz,1H),6.84 (d,J=15.6Hz,1H),4.58(s,2H),3.70(t,J=6.8Hz,2H),2.69(q,J=6.8Hz,2H). 13C NMR (100MHz, CDCl3): δ154.5,146.0,138.3,136.0,133.8,132.6,131.5,128.4,128.0,127.70,127.66,127.6,126.9,126.7,125.1, 125.0,124.5,119.6,73.0,69.4,33.4.IR(neat):2858,1593,1479,1451,1368,1117,1097,1073,960,837,799,749,733,725,695cm -1 .HRMS(ESI)m / z:[M+H] + Calcd for C 24 H 22 NO 340.1696; Found 340.1701.

[0319] Example 41 Compound (4k)

[0320]

[0321] In a nitrogen-filled glove box, CuTc (0.02 mmol, 3.8 mg), DPEphos (0.04 mmol, 21.5 mg), and KO were added sequentially to a 4 mL sample vial. t Bu (0.2 mmol, 22.4 mg), THF (1.0 mL), 2v (0.26 mmol, 59.8 mg), and 1a (0.2 mmol, 29.0 mg). After capping, the mixture was removed from the glove box and reacted at room temperature for 10 h. Then, the cap was opened, and the system was stirred in air for 0.5 h. The reaction solution was filtered through a short silica gel column, washed with EA, concentrated, and then subjected to silica gel column chromatography with petroleum ether:dichloromethane:methanol = 15:15:1 as the eluent. The product was a pale yellow solid, 34.8 mg, with a yield of 70%. 1 HNMR (400MHz, CDCl3): δ8.79(d,J=8.8Hz,1H),8.10(d,J=16.4Hz,1H),7.77(d,J=8.0Hz,1H),7.73 (t,J=7.6Hz,1H),7.66-7.63(m,4H),7.61-7.55(m,2H),7.39(t,J=7.2Hz,2H),7.35-7.32(m,1H). 13C NMR (100MHz, CDCl3): δ143.8,141.8,136.4,136.2,130.4,129.1,128.82,128.76,128.0,127.8,127.5,124.8,119.9,119.5,119.0.

[0322] Comparative Example 1:

[0323]

[0324] In a nitrogen-filled glove box, CuBr (4.3 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 1a (43.5 mg, 0.3 mmol), and 2a-1 (54.4 mg, 0.45 mmol). After capping, the mixture was removed from the glove box and allowed to react at room temperature for 24 h. TLC showed that the starting material remained, the reaction system was disordered, and the target compound was not detected.

[0325] Comparative Example 2:

[0326]

[0327] In a nitrogen-filled glove box, CuCl2 (4.0 mg, 0.03 mmol), Xantphos (17.4 mg, 0.03 mmol), and KO were added sequentially to a 4 mL sample vial. t Bu (33.7 mg, 0.3 mmol), THF (1.5 mL), 2m-2 (92.7 mg, 0.45 mmol), and 1a (0.3 mmol, 43.5 mg). After capping, the mixture was removed from the glove box and allowed to react at room temperature for 16 h. When the temperature was raised to 80 °C, a large amount of the starting material remained, and the target compound was not detected.

[0328] Comparative Example 3:

[0329]

[0330] Cu(acac)₂ (7.8 mg, 0.03 mmol) and KO were added sequentially to the sample vial. t Bu (101 mg, 0.9 mmol), toluene (5 mL), 1a (43.5 mg, 0.3 mmol), and 2a (122.4 mg, 0.6 mmol) were reacted at 110 °C for 2 h. The reaction revealed the formation of a quinoline oxynitride dimer, but no target product was observed.

[0331] Quinoline N + -O - Optimization of arylation / alkenylation reaction conditions for similar compounds (3a and 3t-1)

[0332] In a nitrogen-filled glove box, copper catalyst, ligand, base, solvent, aryl or alkenyl borate ester, and quinoline N2 are added sequentially to a 4 mL sample vial. + -O - Compound. After capping, remove from the glove box and allow to react at room temperature. Then, open the cap and add 1,4-benzoquinone to the system, continuing stirring at room temperature for 1.5 h (3a) or stirring in air for 1 h (3t-1). Filter the reaction solution through a short silica gel column, wash with EA, concentrate, vacuum dry, and dissolve in a deuterated reagent. After dissolution, add 0.2 mmol of dibromomethane as an internal standard to determine the NMR yield.

[0333]

[0334] Scale: 0.2 mmol

[0335]

[0336] [b]1.0equiv DMAP was added.[c]1.0equiv MTBD was added.[d]Determinedby 1 H NMR analysis of the crude mixture using CH2Br2as internal standard

[0337]

[0338]

[0339] a NMR yield, dibromomethane (1.0 equiv., 34.8 mg) in CDCl3 as the internal standard.

[0340] b 1.3 equiv 2 was used. c 1.1equiv 2 was used. d 10 mol% Xantphos was used.

Claims

1. A method for preparing a C2-position arylated or alkenylated quinoline compound, characterized in that, It is either method one or method two. Method 1 includes the following steps: In a solvent, in the presence of a copper complex and a base, quinoline N as shown in Formula II is... + -O - The compounds undergo a cross-coupling reaction as shown in Formula III-1 with the alkenyl borate esters to generate the corresponding C2-alkenylated quinoline compounds as shown in Formula I-1A, or are further oxidized with an oxidizing agent to generate the corresponding C2-alkenylated quinoline N as shown in Formula I-1B. + -O - Compounds of this type are sufficient; ； Method 2 includes the following steps: In a solvent, in the presence of a copper complex and a base, quinoline N as shown in Formula II is... + -O - The compounds undergo cross-coupling reactions as shown below with arylated or heteroarylated borosilicate esters as represented by Formula III-2 to generate the corresponding C2-arylated quinoline compounds as represented by Formula I-2A, or further undergo oxidation reactions with oxidants to generate the corresponding C2-arylated quinoline N as represented by Formula I-2B. + -O - Compounds of this type are sufficient; ； The copper complex is a mixture of copper salt catalyst and phosphine ligand or a complex formed by the two. The alkali is an alkali metal tertiary alkoxide; The copper salt catalyst is a monovalent copper salt or a divalent copper salt; The phosphine ligands are 2-(di-1-adamantanephosphine)dimethylaminobenzene, 1,1'-bis(diphenylphosphine)ferrocene, 9,9-dimethyl-4,5-bisdiphenylphosphineoxane, or bis(2-diphenylphosphine) ether. The solvent is one or more of aromatic solvents and ether solvents; The oxidant is 1,4-benzoquinone or O2, wherein the O2 is air or oxygen; R is a borate ester group; Ar is an unsubstituted or substituted aryl group, or an unsubstituted or substituted heteroaryl group; the substituted aryl group and the substituted heteroaryl group are substituents independently selected from halogens, OH, CN, C1-C6 straight-chain or branched alkyl groups, and C1-C6 straight-chain or branched alkoxy groups. n is selected from any integer between 0 and [M-1], where M represents the quinoline N shown in Equation II. + -O - The maximum number of substitutions on a class of compounds; m is selected from any integer between 0 and [M-1], where M represents the maximum number of substitutions on Ar; R 1 R 2 and R 3 The group is hydrogen, halogen, -C(=O)-O-, or a group formed by linking one or more substituents selected from the following: C1-C6 straight-chain or branched alkyl, C1-C6 straight-chain or branched alkoxy, C2-C4 straight-chain or branched alkenyl, C2-C4 straight-chain or branched alkynyl, C1-C4 straight-chain or branched heteroalkyl, 3-15 membered cycloalkyl, 3-6 membered heterocycloalkyl, aryl, and heteroaryl; when the group is formed by linking multiple substituents, the substituents may be the same or different; the substituents may optionally be surrounded by one or more R... 1-1 replace; The Ar and R mentioned 1 R 2 and R 3 In this context, the aryl group is independently C6-C. 10 Aryl; The Ar and R mentioned 1 R 2 and R 3 In this context, the heteroaryl group is a 5-10 member heteroaryl group, containing 1, 2, 3 or 4 heteroatoms or heteroatomic groups selected from N, O, S, S(=O), or S(=O)2; R 1-1 It is independently a halogen, haloalkyl, or ether group.

2. The preparation method according to claim 1, characterized in that, It satisfies one or more of the following conditions: (1) The cross-coupling reaction is carried out under the protection of an inert gas, wherein the inert protective gas is one or more of nitrogen, helium, argon or neon; (2) The alkali metal tertiary alkoxide is KO t Bu, NaO t Bu or LiO t Bu; (3) The quinoline N as shown in Formula II + -O - The molar ratio of the compound to the base is 1:0.5-1:5; (4) The copper salt catalyst is one or more of CuCl, CuCl2, CuBr, Cu(acac)2, Cu(OTf)2, Cu(OAc)2, Cu(MeCN)4PF6 and CuTc; (5) The quinoline N as shown in Formula II + -O - The molar ratio of the compound to the copper salt catalyst is 1:0.01-1:1; (6) The molar ratio of the copper salt catalyst to the phosphine ligand is 1:0.5-1:10; (7) The quinoline N as shown in Formula II + -O - The molar ratio of the class of compounds to arylated, heteroarylated, or alkenylated borate esters as shown in Formula III-2 or Formula III-1 is 1:0.1-1:10; (8) The aromatic solvent is one or more of benzene, toluene, and xylene; (9) The ether solvent is one or more of diethyl ether, 1,4-dioxane and tetrahydrofuran; (10) The molar volume ratio of the arylated, heteroarylated or alkenyl borate ester compound as shown in Formula III-2 to the solvent is 0.01-1 mmol / mL; (11) The reaction temperature of the cross-coupling reaction is 0°C. o C-100 o C; (12) The reaction temperature of the oxidation reaction is 0. o C-100 o C; (13) Arylated quinoline N at the C2 position as shown in Formula I-2B + -O - In this class of compounds, the oxidant is 1,4-benzoquinone; the quinoline N + -O - The molar ratio of the compound to the oxidant is 1:1.8-1:3; In the C2-position alkenylated quinoline N as shown in Formula I-1B + -O - In this type of compound, the oxidizing agent is air; (14) In the borate ester compounds, the borate ester group is Bpin or Bneop.

3. The preparation method according to claim 2, characterized in that, One or more of the following conditions must be met: (1) The alkali mentioned is KO t Bu; (2) The quinoline N as shown in Formula II + -O - The molar ratio of the compound to the base is 1:0.8 to 1:1.5; (3) The copper salt catalyst is one or more of CuCl, CuCl2, CuBr, CuTc, Cu(acac)2, Cu(OTf)2 and Cu(MeCN)4PF6; (4) The quinoline N as shown in Formula II + -O - The molar ratio of the compound to the copper salt catalyst is 1:0.02-1:0.50; (5) The molar ratio of the copper salt catalyst to the phosphine ligand is 1:0.5-1:5; (6) The quinoline N as shown in Formula II + -O - The molar ratio of the class of compounds to arylated, heteroarylated, or alkenylated borate esters as shown in Formula III-2 or Formula III-1 is 1:0.5-1:2.0; (7) The solvent is one or more of toluene, tetrahydrofuran and 1,4-dioxane; (8) The molar volume ratio of the arylated, heteroarylated or alkenyl borate ester compound as shown in Formula III-2 to the solvent is 0.1-0.5 mmol / mL; (9) The reaction temperature of the cross-coupling reaction is 0°C. o C-50 o C; (10) The reaction temperature of the oxidation reaction is 0°C. o C-50 o C; (11) The C2-arylated quinoline N as shown in Formula I-2B + -O - The molar ratio of the compound to the oxidant is 1:

2.

4. The preparation method according to claim 3, characterized in that, One or more of the following conditions must be met: (1) The quinoline N as shown in Formula II + -O - The molar ratio of the compound to the base is 1:1; (2) The copper salt catalyst is CuCl2, CuBr or CuTc; (3) The quinoline N as shown in Formula II + -O - The molar ratio of the compound to the copper salt catalyst is 1:0.05-1:0.12; (4) The molar ratio of the copper salt catalyst to the phosphine ligand is 1:1, 1:1.2 or 1:2; (5) The quinoline N as shown in Formula II + -O - The molar ratio of the class of compounds to arylated, heteroarylated, or alkenylated borate esters as shown in Formula III-2 or Formula III-1 is 1:1 to 1:1.

6. (6) The solvent is tetrahydrofuran; (7) The molar volume ratio of the arylated, heteroarylated or alkenyl borate ester compound as shown in Formula III-2 to the solvent is 0.2 mmol / mL; (8) The reaction temperature of the cross-coupling reaction is room temperature; (9) The reaction temperature of the oxidation reaction is room temperature.

5. The preparation method according to claim 4, characterized in that, One or more of the following conditions must be met: (1) The quinoline N as shown in Formula II + -O - The molar ratio of the compound to the arylated, heteroarylated, or alkenylated borate esters as shown in Formula III-2 is 1:1.3 or 1:1.

5. (2) The reaction temperature of the cross-coupling reaction is 25°C. o C; (3) The reaction temperature of the oxidation reaction is 25°C. o C.

6. The preparation method according to claim 1, characterized in that, It meets the following conditions: n is 0, 1, or 2; m is 0, 1, or 2.

7. The preparation method according to claim 1, characterized in that, It satisfies one or more of the following conditions: (1) The R mentioned above 1 R 2 and R 3 In this context, the alkyl group is independently a C1-C4 straight-chain or branched alkyl group; (2) The R mentioned above 1 R 2 and R 3 In this context, the alkoxy group is independently a C1-C4 straight-chain or branched alkoxy group; (3) The R mentioned above 1 R 2 and R 3 In this context, the cycloalkyl group is independently a 3-6 membered cycloalkyl group; (4) The Ar and R mentioned above 1 R 2 and R 3 In this context, the aryl group is independently phenyl or naphthyl; (5) The Ar and R mentioned above 1 R 2 and R 3 In this context, the heteroaryl group is furanyl, pyrroleyl, thiophenyl, thiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, or indoleyl.

8. The preparation method according to claim 7, characterized in that, It satisfies the following conditions: the Ar and R mentioned above 1 R 2 and R 3 In this context, the heteroaryl group is either furanyl or indoleyl.

9. The preparation method according to claim 8, characterized in that, It satisfies the following conditions: the Ar and R mentioned above 1 R 2 and R 3 In the above, the heteroaryl group is or .

10. The preparation method according to claim 1, characterized in that, It satisfies one or more of the following conditions: (1) R 1 They may be the same or different, each independently selected from hydrogen, halogen, C1-C4 straight-chain or branched alkyl, C1-C4 straight-chain or branched alkoxy, and C6-C 10 aryl; or any two adjacent R 1 Together with the carbon atom attached to it, they form a 6-10 membered aromatic ring; (2) R 2 Whether identical or different, they are each independently selected from C1-C6 straight-chain or branched alkyl groups, 3-6 membered cycloalkyl groups, -(C1-C4)alkylene-(R a ), C1-C6 straight-chain or branched alkoxy groups and C6-C 10 Aryl; R a for , C6-C 10 Aryl or halogen-substituted C1-C6 straight-chain or branched alkyl groups; R 2-1 R 2-2 and R 2-3 Independently C1-C6 straight-chain or branched alkyl or C6-C 10 Aryl; (3) R 3 They may be the same or different, each independently selected from hydrogen, halogen, C1-C6 straight-chain or branched alkyl, C1-C6 straight-chain or branched alkoxy, and -C(=O)-OR. b ; R b Selected from 3-15 membered cycloalkyl groups or containing one or more R groups b-1 Substituted 3-15 membered cycloalkyl groups; R b-1 It is a C1-C6 straight-chain or branched alkyl group.

11. The preparation method according to claim 10, characterized in that, It satisfies the following condition: when Ar is a substituted aryl group or a substituted heteroaryl group, the substituent is a C1-C6 straight-chain or branched alkyl group.

12. The preparation method according to claim 10, characterized in that, It satisfies one or more of the following conditions: (1) When Ar is a substituted aryl group and a substituted heteroaryl group, and the substituent is a halogen, the halogen is fluorine, chlorine, bromine or iodine; (2) When Ar is a substituted aryl group and a substituted heteroaryl group, and the substituent is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is a C1-C4 straight-chain or branched alkyl group. (3) When Ar is a substituted aryl group and a substituted heteroaryl group, and the substituent is a C1-C6 straight-chain or branched alkoxy group, the C1-C6 straight-chain or branched alkoxy group is methoxy, ethoxy, propoxy or isopropoxy. (4) When R 1 When the halogen is halogen, the halogen is fluorine, chlorine, bromine or iodine; (5) When R 1 When the alkyl group is a C1-C4 straight-chain or branched alkyl group, the C1-C4 straight-chain or branched alkyl group is a C1-C3 straight-chain or branched alkyl group. (6) When R 1 When the alkoxy group is a straight-chain or branched alkoxy group of C1-C4, the straight-chain or branched alkoxy group of C1-C4 is a straight-chain or branched alkoxy group of C1-C3. (7) When R 1 For C6-C 10 In the aryl case, the C6-C 10 The aryl group is a benzene ring or a naphthalene ring; (8) When any two adjacent R 1 When the carbon atom attached to it forms a 6-10 membered aromatic ring, the 6-10 membered aromatic ring is a benzene ring or a naphthalene ring; (9) When R 2 When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl, ethyl, propyl, isopropyl, or... n Bu or t Bu; (10) When R 2 When the alkyl group is a 3-6 membered cycloalkyl group, the 3-6 membered cycloalkyl group is cyclopropyl, cyclobutyl, or cyclopentyl; (11) When R 2 -(C1-C4)alkylene-(R a When ), the -(C1-C4) alkylene group is independently -CH2-, -CH2CH2-, -CH(CH3)-, -CH(CH3)CH2- or -C(CH3)2-; (12) When R 2-1 R 2-2 and R 2-3 When independently a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl, ethyl, propyl or tert-butyl; (13) When R 2-1 R 2-2 and R 2-3 Independently for C 6-10 When aryl, the C 6-10 The aryl group is phenyl or naphthyl; (14) When R a For C6-C 10 When the aryl group is present, the C6-C 10 The aryl group is phenyl or naphthyl; (15) When R a When the halogen is a halogen-substituted C1-C6 straight-chain or branched alkyl group, the halogen is fluorine, chlorine or bromine; (16) When R a When the C1-C6 straight-chain or branched alkyl group is halogen-substituted, the C1-C6 straight-chain or branched alkyl group is methyl, ethyl or propyl; (17) When R 2 When the alkoxy group is a straight-chain or branched alkoxy group of C1-C6, the straight-chain or branched alkoxy group of C1-C6 is a straight-chain or branched alkoxy group of C1-C3. (18) When R 2 For C6-C 10 In the aryl case, the C6-C 10 The aryl group is a benzene ring or a naphthalene ring; (19) When R 3 When the halogen is halogen, the halogen is fluorine, chlorine, bromine or iodine; (20) When R 3 When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is a C1-C4 straight-chain or branched alkyl group. (21) When R 3 When the alkoxy group is a straight-chain or branched alkoxy group of C1-C6, the straight-chain or branched alkoxy group of C1-C6 is a straight-chain or branched alkoxy group of C1-C3. (22) When R b When the 3-15 membered cycloalkyl group is a 6-12 membered cycloalkyl group; (23) When R b-1 When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is a C1-C4 straight-chain or branched alkyl group.

13. The preparation method according to claim 12, characterized in that, It satisfies one or more of the following conditions: (1) When Ar is a substituted aryl group and a substituted heteroaryl group, and the substituent is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl, ethyl, propyl, isopropyl or tert-butyl. (2) When R 1 When the halogen is halogen, the halogen is chlorine or bromine; (3) When R 1 When the alkyl group is a C1-C4 straight-chain or branched alkyl group, the C1-C4 straight-chain or branched alkyl group is methyl, ethyl, propyl or isopropyl; (4) When R 1 When the alkoxy group is a straight-chain or branched alkoxy group of C1-C4, the straight-chain or branched alkoxy group of C1-C4 is methoxy, ethoxy, propoxy, or isopropoxy. (5) When R 1 For C6-C 10 In the aryl case, the C6-C 10 The aryl group is a benzene ring; (6) When any two adjacent R 1 When the carbon atom attached to it forms a 6-10 membered aromatic ring, the 6-10 membered aromatic ring is a benzene ring; (7) When R 2 When it is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is... n Bu or t Bu; (8) When R 2 When it is a 3-6 membered cycloalkyl group, the 3-6 membered cycloalkyl group is cyclopropyl; (9) When R 2 -(C1-C4)alkylene-(R a When ), the -(C1-C4) alkylene group is -CH2CH2-; (10) When R 2-1 R 2-2 and R 2-3 When independently a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl or tert-butyl; (11) When R 2-1 R 2-2 and R 2-3 Independently for C 6-10 When aryl, the C 6-10 The aryl group is phenyl; (12) When R a For C6-C 10 When the aryl group is present, the C6-C 10 The aryl group is phenyl; (13) When R a When the halogen is a halogen-substituted C1-C6 straight-chain or branched alkyl group, the halogen is chlorine; (14) When R a When the C1-C6 straight-chain or branched alkyl group is halogen-substituted, the C1-C6 straight-chain or branched alkyl group is methyl; (15) When R 2 When the alkoxy group is a straight-chain or branched alkoxy group of C1-C6, the straight-chain or branched alkoxy group of C1-C6 is methoxy, ethoxy, propoxy, or isopropoxy. (16) When R 2 For C6-C 10 In the aryl case, the C6-C 10 The aryl group is a benzene ring; (17) When R 3 When the halogen is halogen, the halogen is fluorine, chlorine, or bromine; (18) When R 3 When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl, ethyl, propyl, isopropyl or tert-butyl; (19) When R 3 When the alkoxy group is a straight-chain or branched alkoxy group of C1-C6, the straight-chain or branched alkoxy group of C1-C6 is methoxy, ethoxy, propoxy, or isopropoxy. (20) When R b When it is a 3-15 membered cycloalkyl group, the 3-15 membered cycloalkyl group is or ; (21) When R b-1 When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl, ethyl, propyl, isopropyl, or tert-butyl.

14. The preparation method according to claim 13, characterized in that, It satisfies one or more of the following conditions: (1) When Ar is a substituted aryl group and a substituted heteroaryl group, and the substituent is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is a methyl group. (2) When R 1 When the alkyl group is a C1-C4 straight-chain or branched alkyl group, the C1-C4 straight-chain or branched alkyl group is methyl; (3) When R 1 When the C1-C4 straight-chain or branched alkoxy group is a C1-C4 straight-chain or branched alkoxy group, the C1-C4 straight-chain or branched alkoxy group is a methoxy group. (4) When R 2 When the C1-C6 straight-chain or branched alkoxy group is a C1-C6 straight-chain or branched alkoxy group, the C1-C6 straight-chain or branched alkoxy group is an ethoxy group. (5) When R 3 When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl or tert-butyl; (6) When R 3 When the C1-C6 straight-chain or branched alkoxy group is a C1-C6 straight-chain or branched alkoxy group, the C1-C6 straight-chain or branched alkoxy group is a methoxy group. (7) When R b-1 When the alkyl group is a C1-C6 straight-chain or branched alkyl group, the C1-C6 straight-chain or branched alkyl group is methyl.

15. The preparation method according to claim 12, characterized in that, It satisfies one or more of the following conditions: (1) When n is 1, R 1 It can be hydrogen, bromine, chlorine, methyl, phenyl, or methoxy; (2) R 2 for- n Bu, cyclopropyl, - t Bu、 , -CH2CH2Ph, -CH2CH2CH2Cl, , -OCH2CH3 or phenyl; (3) When m is 1, R 3 It is hydrogen, fluorine, chlorine, bromine, methyl, tert-butyl, methoxy, or .

16. The preparation method according to claim 15, characterized in that, It meets the following conditions: When n is 1, R 1 It can be methyl or bromine.

17. The preparation method according to claim 1, characterized in that, It satisfies one or more of the following conditions: (1) The quinoline N as shown in Formula II + -O - The class of compounds has any of the following structures: ； (2) The alkenyl borate ester compound shown in Formula III-1 has any of the following structures: ； (3) The arylated or heteroarylated borate esters shown in Formula III-2 have any of the following structures: 。 18. The preparation method according to claim 1, characterized in that, It satisfies one or more of the following conditions: (1) The C2-alkenylated quinoline compound as shown in Formula I-1A has any of the following structures: ； (2) The C2-alkenylated quinoline N as shown in Formula I-1B + -O - The class of compounds has any of the following structures: ； (3) The C2-arylated quinoline compound shown in Formula I-2A has the following structure: ； (4) The C2-arylated quinoline N as shown in Formula I-2B + -O - The class of compounds has any of the following structures: 。

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