CN110452169B - Method for constructing tetrahydroisoquinoline compounds - Google Patents

Abstract

The present application discloses a compound having the structural formula shown in formula I. And the preparation method of the compound, the method utilizes amino-directed phenethylamine ortho-position C(sp ² )-H bond alkenylation cyclization reaction, thereby obtaining a method for efficiently synthesizing tetrahydroisoquinoline compounds.

Description

A kind of method of constructing tetrahydroisoquinoline compounds

technical field

The present application relates to a compound and a preparation method thereof, in particular to a method for the alkenylation and cyclization of an amino-directed phenethylamine ortho-position C(sp ² )-H bond.

Background technique

Phenethylamine is a kind of very important structural motif, which exists in some biologically active molecules, such as the authorized drugs Amphetamine, Baclofen, Methylphenidate, etc. The modification of the structure of phenethylamine can be used for the later derivatization of drugs. Or the synthesis of new drugs provides a certain basis, so it is of great significance. The modification of phenethylamine by C–H activation strategy is a fast and efficient method, and many reports have been reported. These methods have enriched the diversity of phenethylamine derivatization, but in general, these methods all require the assistance of an external guiding group, and they all need to introduce a guiding group on phenethylamine first, and then remove the guiding group at last, which greatly increases the Significantly reduces the atom economy and step economy of the synthesis.

In fact, the amino group itself is an ortho-directing group, but due to the strong coordination ability of the amino group, it will form a catalytically inactive metal complex with metal catalysts [M(RNH ₂ ) ₂ X ₂ ] (Vicente, J.; Saura-Llamas, I.; Palin, MG; Jones, PG; Ramírez de Arellano, MC Organometallics 1997, 16, 826), leading to poisoning of metal catalysts and reduced catalyst activity (Ryabov, ADChew. Rev. 1990, 90, 403; Vicente, J.; Saura -Llamas, I.; Palin, MG; Jones, PG; Ramírez de Arellano, MC Organometallics 1997, 16, 826; Font, H.; Font-Bardia, M.; Gomez, K.; , I.; Martinez, M. Dalton Trans 2014, 43, 13525.). In addition, there is another reason that simple amines, that is, amines with H in the ortho-position of the amine group, can be converted into imines or ketones and aldehydes by oxidation. At present, there are three main methods to overcome the above limitations: 1) Electronic effect: introducing electron withdrawing groups (such as acyl, sulfonyl, etc.) on the nitrogen atom to reduce the electron cloud density on the nitrogen atom, thereby reducing the coordination ability of the nitrogen atom , and at the same time can be used as a good guiding group. Among them, the transition metal catalyzed activation of aliphatic amine C–H bond assisted by static directing groups is the most widely developed. However, this method has inherent drawbacks, that is, firstly, the fatty amine substrate needs to be covalently bonded to the guiding group, and finally the guiding group needs to be removed to obtain the target product, which reduces the economical step of the reaction. 2) Steric hindrance effect: aliphatic amines with large sterically hindered groups in the ortho-position of nitrogen atoms are used as reaction substrates. In 2017, Garcia et al. realized the alkenyl cyclization of the ortho-C(sp ² )–H bond of phenethylamine with a quaternary carbon in the α-position of the para-amino group under the catalysis of palladium (Mancinelli, A.; Alamillo, C.; Albert, J.; Ariza, X.; Etxabe, H.; Farras, J.; Garcia, J.; Granell, J. Organometallics 2017, 36, 911-919). Due to the existence of large steric hindrance groups, it is difficult to form non-catalytically active diamine-metal complexes. In addition, because the α-position of the amino group is a quaternary carbon, the amino group cannot be oxidized, preventing the oxidation side reaction, but at the same time, it also greatly The scope of application of the substrate is limited; 3) Acid regulation: adding acid to the reaction system makes the amine and acid form a salt, greatly reducing the concentration of free amine in the reaction system, thereby inhibiting the formation of diamine-metal complexes; At the same time, the protonation of the amino group can also reduce the side reaction of the amino group being oxidized.

In summary, the amino-directed phenethylamine ortho-C(sp ² )–H bond alkenyl cyclization was realized by directly using the unprotected amine group (NH ₂ ) as the directing group through the activation of carbon-hydrogen bonds. There is only one report on the reaction to synthesize tetrahydroisoquinoline compounds, but its applicability is very limited, for example, the substrate is limited to amines without α-H. Therefore, how to obtain the substrate is not limited to the alkenyl cyclization reaction of phenethylamine without α-H, so as to obtain the practical synthesis of tetrahydroisoquinoline compounds using the CH bond activation reaction is a problem that needs to be solved.

SUMMARY OF THE INVENTION

According to one aspect of the present application, a compound is provided.

The compound has the structural formula shown in formula I:

选自芳香族化合物中芳香环上相邻的两个碳原子各失去一个氢所形成的基团；in,

It is selected from the group formed by the loss of one hydrogen on each of the adjacent two carbon atoms on the aromatic ring in the aromatic compound;

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₇ are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, and non-hydrocarbyl.

Optionally, R ₁ , R ₂ , and R ₃ are independently selected from hydrogen, C1-C20 alkyl, and non-hydrocarbyl-substituted C1-C20 alkyl;

R ₄ and R ₅ are independently selected from hydrogen, C1-C20 alkyl group, and ester group;

R ₇ is selected from -COOR ₈ and -PO(OR ₁₀ ) ₂ , wherein R ₈ and R ₁₀ are independently selected from C1-C5 alkyl groups.

Optionally, at least one of R ₄ and R ₅ is H.

Optionally, R ₄ and R ₅ are H at the same time.

Optionally, the compound has the structural formula shown in formula I-1:

Optionally, R ₆₁ , R ₆₂ , R ₆₃ , R ₆₄ are independently selected from hydrogen, halogen, halogen-substituted C1-C5 alkyl, ester-substituted C1-C5 alkenyl, C1-C5 alkoxy group; the ester group in the "C1-C5 alkenyl substituted by an ester group" is -COOR ₈ , wherein R ₈ is a C1-C5 alkyl group;

R ₁ is selected from hydrogen, C1-C5 alkyl;

R ₂ and R ₃ are independently selected from hydrogen and ester group-substituted C1-C5 alkyl groups; the ester group in the "ester group-substituted C1-C5 alkyl group" is -COOR ₉ , wherein R ₉ is C1 ~C5 alkyl;

R ₄ , R ₅ are independently selected from hydrogen, ester group;

R ₇ is selected from -COOR ₈ and -PO(OR ₁₀ ) ₂ , wherein R ₈ and R ₁₀ are independently selected from C1-C5 alkyl groups.

_{R7 can} be selected from formate or phosphonate. In the case of an ester group, it is -COOR ₈ , wherein R ₈ is a C1-C5 alkyl group. When it is a phosphonate, it is -PO(OR ₁₀ ) ₂ , wherein R ₁₀ is a C1-C5 alkyl group. Optionally, the structural formula of the compound shown in formula I is selected from the following compounds:

According to another aspect of the present application, a preparation method of a compound is provided. The present application develops an amino-directed phenethylamine ortho-position C(sp ² )-H bond alkenylation cyclization reaction, thereby obtaining an efficient method for synthesizing tetrahydroisoquinoline compounds. Specifically, under the action of the decisive bis-trifluoromethylsulfonimide acid, the phenethylamine itself is used as NH ₂ as a guide group, and the palladium-catalyzed phenethylamine ortho-C ( sp ² )-H-bond alkenyl cyclization reaction. A wide range of substrates is available, and phenethylamine with or without substituents at the α position can be applied to the reaction system, including amino acid esters, so that the method can be used to synthesize non-natural amino acid derivatives. In addition, this method is also applicable to secondary phenethylamine substrates. This method enables scale-up reactions. It is worth mentioning that the hydrochloride salt of baclofen, a drug molecule protected by an ester group, can also react, and the corresponding product can be obtained in good yield. This method has a good synthetic application prospect in the synthesis of tetrahydroisoquinoline compounds with pharmaceutical active intermediates.

The preparation method of the compound comprises the following steps:

Compound II and compound III are reacted in a reaction system containing a catalyst to generate the compound shown in formula I;

The structural formula of compound II is shown in formula II-1, formula II-2 or formula II-3;

The structural formula of compound III is shown in formula III;

选自芳香族化合物中芳香环上相邻的两个碳原子各失去一个氢所形成的基团；in,

It is selected from the group formed by the loss of one hydrogen on each of the adjacent two carbon atoms on the aromatic ring in the aromatic compound;

R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₇ are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, and non-hydrocarbyl.

Optionally, R ₁ , R ₂ , and R ₃ are independently selected from hydrogen, C1-C20 alkyl, and non-hydrocarbyl-substituted C1-C20 alkyl;

R ₄ and R ₅ are independently selected from hydrogen, C1-C20 alkyl group, and ester group;

R ₇ is selected from -COOR ₈ and -PO(OR ₁₀ ) ₂ , wherein R ₈ and R ₁₀ are independently selected from C1-C5 alkyl groups.

_{R7 can} be selected from formate or phosphonate. When formate, it is -COOR ₈ , wherein R ₈ is a C1-C5 alkyl group. When it is a phosphonate, it is -PO(OR ₁₀ ) ₂ , wherein R ₁₀ is a C1-C5 alkyl group.

Optionally, R ₄ and R ₅ are independently selected from hydrogen, a C1-C20 alkyl group, an ester group, and at least one of R ₄ and R ₅ is H.

Optionally, R ₄ and R ₅ are H at the same time.

选自苯环上相邻的两个碳原子各失去一个氢所形成的基团。Optionally,

It is selected from the group formed by the loss of one hydrogen from each of the two adjacent carbon atoms on the benzene ring.

为

其中R₆₁、R₆₂、R₆₃、R₆₄独立地选自氢、卤素、卤素取代的C1～C5的烷基、酯基取代的C1～C5的烯烃基、C1～C5的烷氧基；所述“酯基取代的C1～C5的烯基”中的酯基为-COOR₈，其中R₈为C1～C5的烷基。Optionally,

for

wherein R ₆₁ , R ₆₂ , R ₆₃ , and R ₆₄ are independently selected from hydrogen, halogen, halogen-substituted C1-C5 alkyl, ester-substituted C1-C5 alkenyl, and C1-C5 alkoxy; The ester group in the "C1-C5 alkenyl substituted by an ester group" is -COOR ₈ , wherein R ₈ is a C1-C5 alkyl group.

Optionally, compound II is selected from the following compounds:

Compound III is selected from the following compounds:

Optionally, the catalyst includes a compound containing palladium element, a compound containing silver element, an organic acid, and a ligand.

Optionally, the compound containing palladium element is selected from at least one of palladium acetate, palladium trifluoroacetate and bis(acetonitrile) palladium chloride;

The compound containing silver element is selected from at least one of silver carbonate, silver acetate, silver oxide, silver trifluoroacetate, silver tetrafluoroborate, silver pivalate, silver tungstate and silver fluoride;

The organic acid is selected from pentafluorobenzoic acid, trifluoroacetic acid, 3-trifluoromethylbenzoic acid, trifluoromethanesulfonic acid, 3,5-bis-trifluoromethylbenzoic acid, 1-adamantanecarboxylic acid, acetic acid, At least one of bis-trifluoromethanesulfonimide acid;

The ligand is selected from at least one of amino acid ligands, phosphine ligands, pyridine ligands, acid ligands, and carbene ligands.

Optionally, the ligand is selected from at least one of N-acetyl-L-phenylalanine, N-acetyl-L-alanine, N-acetyl-β-alanine, 2-hydroxypyridine .

Optionally, the molar ratio of compound II to the compound containing palladium element is 1:0.8-1.2;

The molar ratio of compound II to the compound containing silver element is 1:2～3;

The molar ratio of compound II to organic acid is 1:0.8～1.2;

The molar ratio of compound II to ligand is 1:1.8-2.2.

Optionally, the catalyst is palladium acetate, silver acetate, 2-hydroxypyridine, bis-trifluoromethanesulfonimide acid;

The mole number of palladium acetate is 10% of the mole number of compound II;

The mole number of silver acetate is twice the equivalent of the mole number of compound II;

The moles of 2-hydroxypyridine are 20% of the moles of compound II;

The number of moles of bis-trifluoromethanesulfonimide acid is equivalent to the number of moles of compound II.

Optionally, the molar ratio of compound II and compound III is 1:1.2-2.

Optionally, the reaction system also includes a solvent;

The solvent is selected from N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, hexafluoroisopropanol, dichloroethane, mixed solution of hexafluoroisopropanol and dichloroethane , at least one of dichloromethane, methanol, tert-amyl alcohol, and toluene.

Optionally, the reaction system also includes a solvent;

The solvent is hexafluoroisopropanol and dichloroethane in a volume ratio of 1:4 to 1:9.

Optionally, the reaction temperature is 50°C to 120°C, and the reaction time is 10 hours to 25 hours.

Optionally, the reaction temperature is 80°C to 90°C, and the reaction time is 12 hours to 24 hours.

According to another aspect of the present application, the application of the method in the preparation of tetrahydroisoquinoline compounds is provided.

In this application, trifluoromethanesulfonic acid is abbreviated as HOTf; acetate is abbreviated as OAc; bis-trifluoromethanesulfonimide acid is abbreviated as Tf ₂ NH; hexafluoroisopropanol is abbreviated as HFIP; dichloromethane is abbreviated as DCM .

In this application, C1-C5, C1-C20, etc. all refer to the number of carbon atoms contained in the group.

In this application, the term "hydrocarbyl" refers to a group formed by the loss of any hydrogen atom on the molecule of hydrocarbon compounds; the hydrocarbon compounds include alkane compounds, alkene compounds, alkyne compounds and aromatic compounds, such as toluene lost The p-tolyl group formed by the hydrogen atom in the para position of the methyl group on the benzene ring, or the benzyl group formed by the loss of any hydrogen atom on the methyl group from toluene, etc.

In this application, the term "alkyl" refers to a group formed by the loss of any hydrogen atom on the molecule of an alkane compound.

In this application, the term "aryl" refers to a group formed by the loss of a hydrogen atom on the aromatic ring on the molecule of an aromatic compound; for example, p-toluene formed by the loss of a hydrogen atom in the para position of the methyl group on the benzene ring. base.

In this application, the term "halogen" refers to at least one of fluorine, chlorine, bromine, and iodine.

In this application, the term "non-hydrocarbon substituent" refers to a group formed by the loss of any hydrogen atom from a compound containing other elements other than H and C (such as halogen, S, O, P, N, etc.), For example, alkoxy, halogen, nitro, cyano, ester, carboxyl, hydroxyl, carbonyl, phosphate and the like.

In this application, -Me is -CH ₃ .

In the present application, -Et is -CH ₂ CH ₃ .

In the present application, -n-Bu is -CH ₂ CH ₂ CH ₂ CH ₃ .

In this application, -t-Bu is tert-butyl.

The beneficial effects that this application can produce include:

1) The preparation method of the compound provided by this application uses the amino group of phenethylamine itself as a guiding group to guide, and selectively activates the ortho-position C(sp ² )-H, so that the phenethylamine is directly modified without Requires additional static directing groups, which have better atom economy and step economy.

2) The preparation method of the compound provided by the application has a wide range of applicable substrates, and the phenethylamine with a substituent or without a substituent in the α position can be applied to the reaction system, including amino acid ester, so that the reaction can be used to synthesize. Unnatural amino acid derivatives with wide applicability.

3) The preparation method of the compound provided by the present application can carry out an enlarged reaction, and the amount of the palladium catalyst can be reduced to 2 mol% to 1 mol%.

4) The preparation method of the compound provided in this application is also applicable to secondary phenethylamine.

5) In the preparation method of the compound provided in this application, the hydrochloride of the ester group-protected drug molecule baclofen can also react, and the corresponding product can be obtained in a good yield.

6) The preparation method of the compound provided in this application has a good application prospect in the construction of tetrahydroisoquinoline.

Detailed ways

The present application will be described in detail below with reference to the examples, but the present application is not limited to these examples.

Unless otherwise specified, the raw materials and catalysts in the examples of the present application are purchased through commercial channels.

The analytical method in the embodiment of the application is as follows:

Proton ¹ H-NMR was performed on Bruker's 400AVANCE III spectrometer (Spectrometer), 400MHz, CDCl ₃ and JEOL's (JEOL) ECZ600S spectrometer (Spectrometer), 600MHz, CDCl ₃ , respectively measured;

¹³ C-NMR was 400 MHz, CDCl ₃ and 600 MHz, CDCl ₃ respectively; high-resolution mass spectrometer: Bruker Impact II UHR-TOF mass spectrometry.

The yield of the target product is calculated by the following formula: Yield %=(the mass of the target product actually obtained ÷ the theoretically obtained mass of the target product)×100%.

Example 1

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and o-methylphenethylamine of formula 1-2 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product samples were denoted 1-3, a total of 40.6 mg, and a yield of 87%.

The detection data of product samples 1-3 are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ 7.09-7.01 (m, 2H), 6.96 (d, J=7.6Hz, 1H), 4.46 (dd, J=10.0, 3.2Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.23 (dt, J=12.4, 6.0Hz, 1H), 3.06 (dt, J=12.4, 6.0Hz, 1H), 2.85 (dd, J=16.0, 3.6Hz, 1H), ¹³ C NMR (151MHz, CDCl ₃ ) δ 172.5, 137.6, 136.9, 134.1, 127.9, 125.5, 123.8, 60.7, 53.1, 41.4, 40.39, 27.3, 19.5, 14.3. HRMSCalcd for C ₁₄ H ₂₀ NO ₂ [M+H] ⁺ 234.1489, found 234.1489.

Example 2

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and phenethylamine (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were recorded as 2-3 and 2-4, respectively. The total of 2-3 was 21.5 mg with a yield of 49%, and the total of 2-4 was 16.5 mg with a yield of 26%.

The detection data of product samples 2-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.15-7.08 (m, 4H), 4.46 (dd, J=10.0, 3.2 Hz, 1H), 4.18 (q, J=7.2 Hz, 2H), 3.20 (td, J=12.4, 6.0Hz, 1H), 3.02 (ddd, J=12.4, 7.2, 5.2Hz, 1H), 2.90–2.70 (m, 4H), 2.29 (s, 1H), 1.26 (t, J=7.2Hz) , 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.5, 137.7, 135.6, 129.6, 126.4, 126.0, 60.7, 52.8, 41.4, 40.7, 29.9, 14.3.

The detection data of product samples 2-4 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.94 (d, J=15.6 Hz, 1H), 7.43 (d, J=7.2 Hz, 1H), 7.21-7.13 (m, 2H), 6.34 (d, J= 15.6Hz, 1H), 4.49 (dd, J=9.2, 3.6Hz, 1H), 4.27 (q, J=7.2Hz, 2H), 4.18 (q, J=7.2Hz, 2H), 3.36 (td, J= 12.4, 6.0Hz, 1H), 3.07 (td, J=12.8, 6.0Hz, 1H), 2.93–2.74 (m, 4H), 2.18 (s, 1H), 1.34 (t, J=7.2Hz, 3H), 1.27 (t, J=7.2 Hz, 3H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 172.2, 166.9, 141.7, 138.3, 134.8, 134.0, 127.9, 126.0, 124.9, 120.2, 60.7, 60.6, 52.9, 41.1, 40.1 ,27.0,14.4,14.2.HRMS Calcd for C ₁₈ H ₂₄ NO ₄ [M+H] ⁺ 318.1700,found318.1700.

Example 3

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and o-methoxyphenethylamine of formula 3-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated 3-3, a total of 36.4 mg, and a yield of 73%.

The detection data of product samples 3-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.13 (t, J=8.0 Hz, 1H), 6.71 (t, J=8.4 Hz, 2H), 4.45 (dd, J=9.6, 3.2 Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.82 (s, 3H), 3.20 (dt, J=12.4, 6.0Hz, 1H), 3.01 (dt, J=12.4, 6.0Hz, 1H), 2.86 (dd, J=16.0, 3.2Hz, 1H), 2.75 (dd, J=16.0, 10.0Hz, 1H), 2.68 (t, J=6.0Hz, 2H), 2.32 (s, 1H), 1.27 (t, J=7.2 Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.5, 157.3, 138.8, 126.3, 124.5, 118.1, 107.6, 60.7, 55.4, 52.7, 41.2, 40.1, 23.7, 14.3.

Example 4

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and o-fluorophenethylamine of formula 4-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 4-3, a total of 32.3 mg, and a yield of 68%.

The detection data of product samples 4-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.12 (dd, J=13.6, 7.6 Hz, 1H), 6.90-6.86 (m, 2H), 4.45 (dd, J=9.6, 3.2 Hz, 1H), 4.18 ( q, J=7.2Hz, 2H), 3.22 (dt, J=12.0, 6.4Hz, 1H), 3.02 (dt, J=12.4, 6.0Hz, 1H), 2.85 (dd, J=16.4, 3.6Hz, 1H) ), 2.78–2.72(m, 3H), 2.22(s, 1H), 1.27(t, J=7.2Hz, 3H). ¹³ C NMR(151MHz, CDCl ₃ )δ172.2,160.8(d, J=244.5Hz) ,140.0(d,J=5.1Hz),126.7(d,J=8.6Hz),123.3(d,J=18.6Hz),121.3(d,J=2.9Hz),112.7(d,J=21.7Hz) ,60.8,52.5,41.1,39.8,22.7(d,J=3.6Hz),14.3.HRMS Calcd for C ₁₃ H ₁₇ FNO ₂ [M+H] ⁺ 238.1238,found 238.1238.

Example 5

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and o-chlorophenethylamine (0.2 mmol) represented by formula 5-1. The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated 5-3, a total of 40.5 mg, and a yield of 80%.

The detection data of product sample 5-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.24 (d, J=7.6 Hz, 1H), 7.10 (t, J=7.6 Hz, 1H), 7.02 (d, J=7.6 Hz, 1H), 4.45 (dd , J=9.6, 3.6Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.23 (dt, J=12.4, 6.0Hz, 1H), 3.05 (dt, J=12.4, 6.0Hz, 1H) , 2.85–2.72(m, 4H), 2.08(s, 1H), 1.27(t, J=7.2Hz, 3H). ¹³ C NMR(151MHz, CDCl ₃ )δ172.2,140.1,134.9,133.7,127.3,126.7, 124.5, 60.8, 52.8, 41.1, 40.1, 27.7, 14.30. HRMS Calcd for C ₁₃ H ₁₇ ClNO ₂ [M+H] ⁺ 254.0942, found254.0942.

Example 6

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2equiv) and o-bromophenethylamine represented by formula 6-1 (0.2mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 6-3, a total of 51.7 mg, and a yield of 87%.

The detection data of product sample 6-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.43 (d, J=7.2 Hz, 1H), 7.08-7.01 (m, 2H), 4.45 (dd, J=9.2, 4.0 Hz, 1H), 4.18 (q, J＝7.2Hz, 2H), 3.23(dt, J＝12.4, 6.0Hz, 1H), 3.05(dt, J＝12.4, 6.0Hz, 1H), 2.85–2.72(m, 4H), 2.25(s, 1H) ), 1.27 (t, J=7.2Hz, 3H). ¹³ C NMR (101MHz, CDCl ₃ )δ172.1, 140.3, 135.1, 130.5, 127.1, 126.0, 125.1, 60.7, 52.9, 41.0, 40.2, 30.5, 14.2.HRMSCalcd for C ₁₃ H ₁₇ BrNO ₂ [M+H] ⁺ 298.0437, found 298.0438.

Example 7

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and o-trifluoromethylphenethylamine of formula 7-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 7-3, a total of 41.4 mg, and a yield of 72%.

The detection data of product sample 7-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.51 (d, J=7.2 Hz, 1H), 7.29 (d, J=7.2 Hz, 1H), 7.24 (t, J=7.6 Hz, 1H), 4.54 (dd , J=8.0, 4.8Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.25–3.19 (m, 1H), 3.07–3.01 (m, 1H), 3.00–2.96 (m, 2H), 2.85-2.76(m, 2H), 2.48(s, 1H), 1.26(t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ ) δ 172.0, 139.2, 134.5, 130.0, 129.1(q, J = 29.4Hz), 125.7, 124.5 (q, J = 274.4 Hz), 124.4 (q, J = 5.8 Hz), 60.8, 53.0, 41.4, 39.8, 26.4, 14.3. HRMSCalcd for C ₁₄ H ₁₇ F ₃ NO ₂ [ M+H] ⁺ 288.1206, found 288.1207.

Example 8

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (100.1 mg, 0.6 mmol, 3 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (32.6 μL, 0.3 mmol, 1.5 equiv) and m-methylphenethylamine of formula 8-1 (0.2 mmol). The system was reacted at 90°C for 24h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated 8-3, a total of 28.9 mg, and a yield of 62%.

The detection data of product sample 8-3 are as follows:

¹ H NMR (600MHz, CDCl ₃ ) δ 6.98-6.94 (m, 2H), 6.91 (s, 1H), 4.43 (dd, J=9.6, 2.4Hz, 1H), 4.16 (q, J=7.2Hz, 2H), 3.19 (dt, J=12.6, 5.4Hz, 1H), 3.00 (ddd, J=12.6, 7.8, 4.8Hz, 1H), 2.84 (dd, J=16.2, 3.6Hz, 1H), 2.81–2.79 (m, 1H), 2.74–2.69 (m, 2H), 2.50 (s, 1H), 2.28 (s, 3H), 1.25 (t, J=7.2Hz, 3H). ¹³ C NMR (151 MHz, CDCl ₃ ) δ172.5,136.0,135.3,134.4,130.1,126.9,125.9,60.7,52.6,41.3,40.8,29.7,21.0,14.3.HRMS Calcd for C ₁₄ H ₂₀ NO ₂ [M+H] ⁺ 234.1489,found 234.1490.

Example 9

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and m-trifluoromethylphenethylamine of formula 9-1 (0.2 mmol). The system was reacted at 90°C for 24h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. A sample of the obtained product was designated as 9-3. A total of 39 mg of 9-3 was obtained, and the yield was 68%.

The detection data of product sample 9-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.40-7.36 (m, 2H), 7.21 (d, J=8.0 Hz, 1H), 4.50 (d, J=7.6 Hz, 1H), 4.18 (q, J= 7.2Hz, 2H), 3.23 (dt, J=12.0, 5.6Hz, 1H), 3.04 (ddd, J=12.4, 7.2, 5.2Hz, 1H), 2.97–2.73 (m, 4H), 2.23 (s, 1H) ), 1.27 (t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.0, 141.5, 136.4, 128.7 (q, J=32.5Hz), 126.5, 126.0 (t, J=272.6Hz) ,124.2(q,J=272.0Hz),122.8(d,J=3.6Hz),60.9,52.7,41.0,40.4,29.8,14.3.HRMS Calcd forC ₁₄ H ₁₇ F ₃ NO ₂ [M+H] ⁺ 288.1206 ,found 288.1206.

Example 10

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (100.1 mg, 0.6 mmol, 3 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (32.6 μL, 0.3 mmol, 1.5 equiv) and p-methylphenethylamine of formula 10-1 (0.2 mmol). The system was reacted at 90 °C for 24 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were recorded as 10-3 and 10-4, respectively. The total of 10-3 was 15.4 mg with a yield of 33%, and the total of 10-4 was 33.1 mg with a yield of 50%.

The detection data of product sample 10-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 6.98 (q, J=8.0 Hz, 2H), 6.91 (s, 1H), 4.45 (dd, J=9.6, 2.8 Hz, 1H), 4.18 (q, J= 7.2Hz, 2H), 3.20 (td, J=12.4, 5.6Hz, 1H), 3.02 (ddd, J=12.4, 7.2, 5.2Hz, 1H), 2.88 (dd, J=16.0, 3.2Hz, 1H), 2.84–2.69(m, 3H), 2.55(s, 1H), 2.30(s, 3H), 1.27(t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.5, 137.2, 135.5, 132.3,129.4,127.4,126.5,60.7,52.7,41.3,40.8,29.3,21.2,14.3.HRMS Calcd for C ₁₄ H ₂₀ NO ₂ [M+H] ⁺ 234.1489,found 234.1490.

The detection data of product sample 10-4 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.91 (d, J=15.6 Hz, 1H), 7.26 (s, 1H), 6.96 (s, 1H), 6.34 (d, J=15.6 Hz, 1H), 4.46 (dd, J=9.2, 3.2Hz, 1H), 4.26 (q, J=7.2Hz, 2H), 4.19 (q, J=7.2Hz, 2H), 3.24 (td, J=12.8, 6.4Hz, 1H) ,3.05(td,J=12.4,6.4Hz,1H),2.91–2.74(m,4H),2.31(s,3H),2.09(s,1H),1.34(t,J=7.2Hz,3H), 1.27 (t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ ) δ 172.3, 167.1, 141.8, 138.1, 135.5, 133.8, 131.9, 128.7, 125.7, 120.0, 60.8, 60.6, 52.9, 41.2, 40.21 , 26.71, 21.2, 14.4, 14.3. HRMS Calcd for C ₁₉ H ₂₆ NO ₄ [M+H] ⁺ 332.1856, found 332.1854.

Example 11

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (100.1 mg, 0.6 mmol, 3 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (32.6 μL, 0.3 mmol, 1.5 equiv) and p-methoxyphenethylamine of formula 11-1 (0.2 mmol). The system was reacted at 90°C for 24h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were recorded as 11-3 and 11-4, respectively. The total of 11-3 was 21.4 mg with a yield of 43%, and the total of 11-4 was 26.4 mg with a yield of 38%.

The detection data of product sample 11-3 are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ 7.02 (d, J=8.4Hz, 1H), 6.73 (dd, J=8.4, 2.4Hz, 1H), 6.63 (d, J=2.4Hz, 1H), 4.43 (dd, J=9.6, 3.2Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.77 (s, 3H), 3.19 (td, J=12.8, 5.6Hz, 1H), 3.00 (ddd, J=12.4,7.2,5.2Hz,1H),2.85(dd,J=16.0,3.6Hz,1H),2.81–2.64(m,3H),2.28(s,1H),1.27(t,J=7.2Hz , 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.4, 157.8, 138.6, 130.4, 127.5, 112.6, 111.1, 60.7, 55.4, 53.0, 41.4, 40.9, 29.0, 14.3.

The detection data of product sample 11-4 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.91 (d, J=15.6 Hz, 1H), 6.97 (d, J=2.4 Hz, 1H), 6.70 (d, J=2.0 Hz, 1H), 6.33 (d , J＝15.6Hz, 1H), 4.46(dd, J＝8.8, 4.0Hz, 1H), 4.27(q, J＝7.2Hz, 2H), 4.19(q, J＝7.2Hz, 2H), 3.80(s ,3H),3.24(td,J＝12.0,5.6Hz,1H),3.04(td,J＝12.4,6.0Hz,1H),2.89–2.75(m,4H),2.31(s,1H),1.34( t, J=7.2Hz, 3H), 1.27 (t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ ) δ 168.5, 163.2, 153.9, 138.0, 135.9, 131.3, 123.6, 116.7, 110.1, 106.5 ,57.2,57.0,51.7,49.5,37.5,36.6,22.8,10.7,10.6.HRMS Calcd for C ₁₉ H ₂₆ NO ₅ [M+H] ⁺ 348.1805,found 348.1805.

Example 12

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (100.1 mg, 0.6 mmol, 3 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (32.6 μL, 0.3 mmol, 1.5 equiv) and p-fluorophenethylamine of formula 12-1 (0.2 mmol). The system was reacted at 90°C for 24h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were recorded as 12-3 and 12-4, respectively. The total yield of 12-3 was 19 mg with a yield of 40%, and the yield of 12-4 was 17.4 mg with a yield of 26%.

The detection data of product sample 12-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.06 (dd, J=8.0, 6.0 Hz, 1H), 6.86 (td, J=8.4, 2.4 Hz, 1H), 6.80 (dd, J=10.0, 2.4 Hz, 1H), 4.43 (dd, J=9.2, 2.8Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.20 (td, J=11.2, 5.6Hz, 1H), 3.01 (ddd, J=12.4 , 7.2, 4.8Hz, 1H), 2.86-2.69(m, 4H), 2.27(s, 1H), 1.27(t, J=7.2Hz, 3H). ¹³ C NMR(101MHz, CDCl ₃ )δ172.1,161.0( d, J＝244.5Hz), 139.2 (d, J＝6.4Hz), 130.9 (d, J＝3.0Hz), 130.8 (d, J＝7.8Hz), 113.6 (d, J＝2.1Hz), 112.3 ( d, J＝2.2Hz), 60.8, 52.7, 41.0, 40.8, 29.0, 14.2. HRMS Calcd for C ₁₃ H ₁₇ FNO ₂ [M+H] ⁺ 238.1238, found 238.1238.

The detection data of product sample 12-4 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.88 (d, J=16.0 Hz, 1H), 7.13 (dd, J=9.6, 2.4 Hz, 1H), 6.86 (dd, J=9.6, 2.4 Hz, 1H) ,6.32(d,J＝15.6Hz,1H),4.46(dd,J＝8.4,4.4Hz,1H),4.27(q,J＝7.2Hz,2H),4.19(q,J＝7.2Hz,2H) ,3.26(dt,J＝12.4,6.0Hz,1H),3.05(dt,J＝12.4,6.0Hz,1H),2.86–2.75(m,4H),2.39(s,1H),1.34(t,J =7.2Hz, 3H), 1.27(t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ ) δ 171.9, 166.6, 160.9 (d, J=244.8Hz), 140.5 (d, J=2.0Hz) ), 140.4(d, J＝6.2Hz), 135.9(d, J＝7.4Hz), 130.5(d, J＝2.7Hz), 121.4, 114.4(d, J＝21.7Hz), 111.7(d, J＝ 22.2Hz), 61.0, 60.8, 53.0, 40.8, 40.3, 26.6, 14.4, 14.3. HRMSCalcd for C ₁₈ H ₂₃ FNO ₄ [M+H] ⁺ 336.1606, found 336.1608.

Example 13

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and p-bromophenethylamine of formula 13-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. A sample of the obtained product was designated as 13-3. A total of 30.9 mg of 13-3 was obtained, and the yield was 52%.

The detection data of product sample 13-3 are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ 7.27-7.24 (m, 2H), 6.98 (d, J=8.4Hz, 1H), 4.43 (dd, J=9.6, 3.2Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.20 (td, J=12.4, 5.6Hz, 1H), 3.01 (ddd, J=12.4, 7.2, 5.2Hz, 1H), 2.85 (dd, J=16.0, 3.6Hz, 1H) _The ^_ ,119.5,60.9,52.5,41.1,40.5,29.2,14.3.HRMS Calcd for C ₁₃ H ₁₇ BrNO ₂ [M+H] ⁺ 298.0437,found298.0435.

Example 14

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and p-trifluoromethylphenethylamine of formula 14-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were recorded as 14-3 and 14-4, respectively. The total of 14-3 was 38.5 mg with a yield of 67%, and the total of 14-4 was 10.0 mg with a yield of 13%.

The detection data of product sample 14-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.39 (d, J=8.0 Hz, 1H), 7.35 (s, 1H), 7.22 (d, J=8.4 Hz, 1H), 4.50 (dd, J=9.6, 2.8Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.24 (td, J=12.4, 6.0Hz, 1H), 3.05 (ddd, J=12.4, 7.2, 5.2Hz, 1H), 2.95– 2.75(m, 4H), 2.48(s, 1H), 1.27(t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ ) δ 172.0, 139.7, 138.2, 130.1, 128.4 (q, J=32.3 Hz), 124.2(q, J＝272.25Hz), 123.2, 122.8, 60.9, 52.7, 41.0, 40.4, 29.8, 14.3. HRMS Calcd for C ₁₄ H ₁₇ F ₃ NO ₂ [M+H] ⁺ 288.1206, found 288.1204.

The detection data of product sample 14-4 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.90 (d, J=16.0 Hz, 1H), 7.65 (s, 1H), 7.39 (s, 1H), 6.41 (d, J=15.6 Hz, 1H), 4.56 (dd, J=8.4, 4.0Hz, 1H), 4.28 (q, J=7.2Hz, 2H), 4.19 (q, J=7.2Hz, 2H), 3.31 (td, J=12.8, 5.6Hz, 1H) ¹³ C NMR (151MHz, CDCl ₃ ) δ 171.7, 166.5, 140.3, 139.0, 138.5, 135.0, 128.7 (q, J=32.5 Hz), 125.7 (q, J=272.40 Hz), 124.1 (d, J=3.47 Hz), 122.2 ,121.7(d,J＝3.3Hz),61.1,60.9,52.9,40.8,39.9,27.1,14.4,14.2.HRMSCalcd for C ₁₉ H ₂₃ F ₃ NO ₄ [M+H] ⁺ 386.1574,found 386.1575.

Example 15

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and 2,3-dimethylphenethylamine of formula 15-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 15-3, a total of 36.6 mg, and a yield of 74%.

The detection data of product sample 15-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 6.98 (d, J=8.0 Hz, 1H), 6.87 (d, J=8.0 Hz, 1H), 4.45 (dd, J=9.6, 2.4 Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.23 (dt, J=12.4, 6.0Hz, 1H), 3.04 (dt, J=12.4, 6.0Hz, 1H), 2.85 (dd, J=16.0, 3.2Hz, 1H), 2.76–2.66(m, 3H), 2.34(s, 1H), 2.26(s, 3H), 2.13(s, 3H), 1.27(t, J=7.2Hz, 3H). ¹³ C NMR(151MHz) , CDCl ₃ )δ172.6,135.2,135.1,134.6,133.8,127.4,123.3,60.7,53.1,41.4,40.7,27.8,20.5,14.8,14.3.HRMS Calcdfor C ₁₅ H ₂₂ NO ₂ [M+H] ⁺ 248.1645, found 248.1645.

Example 16

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and 2,4-dichlorophenethylamine of formula 16-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 16-3, a total of 40.2 mg, and a yield of 70%. The detection data of product sample 16-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.25 (d, J=2.0 Hz, 1H), 7.03 (d, J=1.2 Hz, 1H), 4.40 (dd, J=8.8, 4.0 Hz, 1H), 4.18 (q, J=7.2Hz, 2H), 3.21 (dt, J=12.0, 6.0Hz, 1H), 3.03 (dt, J=12.4, 6.0Hz, 1H), 2.83–2.72 (m, 4H), 2.25 ( s, 1H), 1.27 (t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ171.7, 141.3, 135.4, 132.3, 131.6, 127.0, 124.6, 60.8, 52.7, 40.8, 39.9, 27.2, 14.2. HRMS Calcd for C ₁₃ H ₁₆ Cl ₂ NO ₂ [M+H] ⁺ 288.0553, found 288.0553.

Example 17

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (100.1 mg, 0.6 mmol, 3 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (2.6 μL, 0.3 mmol, 1.5 equiv) and N-methylphenethylamine (0.2 mmol). The system was reacted at 90°C for 24h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were recorded as 17-3 and 17-4, respectively. The total of 17-3 was 20.5 mg with a yield of 44%, and the total of 17-4 was 33.1 mg with a yield of 50%.

The detection data of product sample 17-3 are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ 7.22-7.00 (m, 4H), 4.28-4.05 (m, 3H), 3.12 (ddd, J=12.8, 9.6, 4.8Hz, 1H), 3.01-2.89 (m ,1H),2.85–2.78(m,2H),2.67(dt,J＝16.0,4.0Hz,1H),2.60(dd,J＝15.2,5.2Hz,1H),2.49(s,3H),1.25( t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.3, 137.2, 134.1, 129.1, 127.4, 126.5, 126.1, 60.6, 60.0, 46.3, 42.3, 41.0, 25.1, 14.27. HRMS Calcd for C ₁₄ H ₂₀ NO ₂ [M+H] ⁺ 234.1489, found 234.1489.

The detection data of product sample 17-4 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.95 (d, J=16.0 Hz, 1H), 7.44 (d, J=7.2 Hz, 1H), 7.22-7.07 (m, 2H), 6.35 (d, J= 16.0Hz, 1H), 4.27 (q, J=7.3Hz, 2H), 4.17 (qd, J=7.2, 2.0Hz, 3H), 3.21–3.07 (m, 1H), 3.03–2.92 (m, 1H), 2.91–2.70(m, 3H), 2.59(dd, J=15.2, 5.6Hz, 1H), 2.47(s, 3H), 1.34(t, J=7.2Hz, 3H), 1.25(t, J=7.2Hz) , 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.2,167.0,141.6,138.0,133.5,129.4,126.2,125.0,120.1,60.7,60.1,45.7,42.2,40.6,22.6,14.4,14.3.HRMS Calcd for C ₁₉ H ₂₆ NO ₄ [M+H] ⁺ 332.1856, found 332.1856.

Example 18

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and N-methyl-o-methylphenethylamine of formula 18-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 18-3, a total of 41.5 mg, and a yield of 84%. The detection data of product sample 18-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.06 (t, J=7.2 Hz, 1H), 7.02 (d, J=6.4 Hz, 1H), 6.94 (d, J=7.6 Hz, 1H), 4.29-4.05 (m, 3H), 3.14 (ddd, J=13.2, 10.0, 5.2Hz, 1H), 2.91–2.70 (m, 3H), 2.58 (dd, J=15.2, 5.2Hz, 1H), 2.52–2.48 (m , 1H), 2.46(s, 3H), 2.22(s, 3H), 1.25(t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.4, 137.0, 136.5, 132.6, 127.9, 125.7 ,125.2,60.5,60.2,45.8,42.1,40.9,22.5,19.3,14.3.HRMS Calcd for C ₁₅ H ₂₂ NO ₂ [M+H] ⁺ 248.1645,found 248.1645.

Example 19

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (32.6 μL, 0.3 mmol, 1.5 equiv) and N-methyl-o-methoxyphenethylamine of formula 19-1 (0.2 mmol). The system was reacted at 90°C for 24h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 19-3, a total of 27.4 mg, and a yield of 52%.

The detection data of product sample 19-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.12 (t, J=8.0 Hz, 1H), 6.70 (t, J=8.0 Hz, 2H), 4.21-4.14 (m, 3H), 3.82 (s, 3H) ¹³ C NMR (101MHz, CDCl ₃ )δ172.2,156.9,138.1,126.3,122.9,119.5,107.5,60.5,59.6,55.3,45.3,42.0,40.7,18.8,14.2.HRMS Calcd for C ₁₅ H ₂₂ NO ₃ [M+H] ⁺ 264.1594, found 264.1595.

Example 20

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and N-methyl-o-bromophenethylamine of formula 20-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 20-3, a total of 34.8 mg, and a yield of 56%.

The detection data of product sample 20-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.43 (d, J=7.6 Hz, 1H), 7.08–7.01 (m, 2H), 4.19–4.14 (m, 3H), 3.16–3.09 (m, 1H), 2.94–2.79 (m, 3H), 2.70–2.63 (m, 1H), 2.56 (dd, J=11.2, 5.6Hz, 1H), 2.46 (s, 3H), 1.25 (t, J=7.2Hz, 3H) . ¹³ C NMR (151MHz, CDCl ₃ ) δ 172.0, 139.7, 133.7, 130.7, 127.4, 126.6, 125.6, 60.7, 59.9, 45.6, 42.0, 40.6, 25.7, 14.3. HRMS Calcd for C ₁₄ H ₁₉ BrNO ₂ [M+H ] ⁺ 312.0594, found 312.0594.

Example 21

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (100.1 mg, 0.6 mmol, 3 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (2.6 μL, 0.3 mmol, 1.5 equiv) and N-methyl-p-methylphenethylamine of formula 21-1 (0.2 mmol). The system was reacted at 90°C for 24h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were respectively recorded as 21-3 and 21-4. The total amount of 21-3 was 33.6 mg with a yield of 68%, and the total of 21-4 was 10.4 mg with a yield of 15%.

The detection data of product sample 21-3 are as follows:

¹ H NMR (400MHz, CDCl ₃ )δ6.99-6.94(m,2H),6.90(m,1H),4.24-4.13(m,2H),4.13-4.08(m,1H),3.20-3.02(m ,1H),2.95–2.85(m,1H),2.82–2.75(s,2H),2.61(t,J=5.2Hz,1H),2.57(t,J=5.2Hz,1H),2.46(s, 3H), 2.28(s, 3H), 1.26(t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.4, 137.1, 135.5, 131.1, 128.9, 127.9, 127.4, 60.5, 60.0, 46.3 ,42.3,41.2,24.5,21.2,14.3.HRMS Calcd for C ₁₅ H ₂₂ NO ₂ [M+H] ⁺ 248.1645,found 248.1646.

The detection data of product sample 21-4 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.92 (d, J=16.0 Hz, 1H), 7.27 (s, 1H), 6.95 (s, 1H), 6.34 (d, J=16.0 Hz, 1H), 4.26 (q, J=7.2Hz, 2H), 4.21–4.13 (m, 3H), 3.18–3.08 (m, 1H), 3.03–2.65 (m, 4H), 2.58 (dd, J=15.2, 5.2Hz, 1H ), 2.30(s, 3H), 1.34(t, J=7.2Hz, 3H), 1.26(t, J=7.1Hz, 3H). ¹³ C NMR(151MHz, CDCl ₃ )δ172.2,167.1,141.7,137.7, 135.7,133.3,130.5,130.1,125.8,119.8,60.7,60.6,60.1,45.7,42.1,40.8,22.0,21.1,14.4,14.3.HRMSCalcd for C ₂₀ H ₂₈ NO ₄ [M+H] ⁺ 346.2013,found 346.2 .

Example 22

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and N-methyl-p-methoxyphenethylamine of formula 22-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were recorded as 22-3 and 22-4, respectively. The total amount of 22-3 was 28.9 mg with a yield of 55%, and the total of 22-4 was 9.4 mg with a yield of 13%.

The detection data of product sample 22-3 are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ 7.00 (d, J=8.4Hz, 1H), 6.73 (dd, J=8.4, 2.4Hz, 1H), 6.63 (d, J=2.4Hz, 1H), 4.22 –4.15(m,2H),4.12(dd,J=7.6,5.2Hz,1H),3.76(s,3H),3.10(ddd,J=12.8,9.6,4.8Hz,1H),2.91–2.76(m , 3H), 2.63–2.53(m, 2H), 2.47(s, 3H), 1.26(t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.3, 157.8, 138.3, 130.0, 126.1 ,113.0,112.0,60.6,60.1,55.3,46.3,42.2,41.1,24.0,14.3.HRMS Calcd for C ₁₅ H ₂₂ NO ₃ [M+H] ⁺ 264.1594,found 264.1595.

The detection data of product sample 22-4 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.92 (d, J=16.0 Hz, 1H), 6.98 (d, J=2.4 Hz, 1H), 6.71 (d, J=2.0 Hz, 1H), 6.33 (d , J=16.0Hz, 1H), 4.27 (q, J=7.2Hz, 2H), 4.23–4.11 (m, 3H), 3.79 (s, 3H), 3.19–3.08 (m, 1H), 2.96–2.79 ( m,3H),2.72–2.64(m,1H),2.59(dd,J=15.6,5.6Hz,1H),2.46(s,3H),1.34(t,J=7.2Hz,3H),1.26(t , J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.1, 167.0, 157.7, 141.5, 134.6, 125.8, 120.2, 114.8, 110.6, 60.7, 60.3, 55.4, 45.7, 42.0, 40.8, 31.0, 21.7, 14.4, 14.3. HRMS Calcd for C ₂₀ H ₂₈ NO ₅ [M+H] ⁺ 362.1962, found362.1963.

Example 23

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and N-methyl-p-fluorophenethylamine of formula 23-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were recorded as 23-3 and 23-4, respectively. The total of 23-3 was 27.1 mg with a yield of 54%, and the total of 23-4 was 5.6 mg with a yield of 8%.

The detection data of product sample 23-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.04 (dd, J=7.2, 8.4 Hz, 1H), 6.90-6.76 (m, 2H), 4.25-4.06 (m, 3H), 3.14-3.02 (m, 1H) ), 2.96–2.74 (m, 3H), 2.67–2.54 (m, 2H), 2.47 (s, 3H), 1.25 (t, J=7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172. 0,161.1(d,J＝244.2Hz),139.1(d,J＝6.0Hz),130.4(d,J＝7.7Hz),129.6,113.8(d,J＝7.1Hz),113.6(d,J＝7.1Hz ),60.7,59.9,46.3,42.2,40.7,24.4,14.3.HRMS Calcd for C ₁₄ H ₁₉ FNO ₂ [M+H] ⁺ 252.1394,found252.1394.

The detection data of product sample 23-4 are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ 7.89 (d, J=15.6Hz, 1H), 7.13 (dd, J=9.2, 2.4Hz, 1H), 6.88 (dd, J=8.8, 2.4Hz, 1H) ,6.33(d,J=16.0Hz,1H),4.27(q,J=7.2Hz,2H),4.22-4.14(m,3H),3.17-3.09(m,1H),2.96-2.82(m,3H) ), 2.74–2.68(m, 1H), 2.59(dd, J=15.2, 5.6Hz, 1H), 2.47(s, 3H), 1.34(t, J=7.2Hz, 3H), 1.26(t, J= 7.2Hz, 4H). ¹³ C NMR (151MHz, CDCl ₃ )δ171.8, 166.7, 161.0 (d, J=245.1 Hz), 140.4, 140.1, 135.5 (d, J=7.3 Hz), 129.1, 121.3, 115.8 (d HRMS Calcd for C ₁₉ H ₂₅ FNO ₄ [M+H] ⁺ 350.1762, found350.1763.

Example 24

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (32.6 μL, 0.3 mmol, 1.5 equiv) and N-methyl-2,4-dichlorophenethylamine of formula 24-1 (0.2 mmol). The system was reacted at 90°C for 24h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 24-3, a total of 31.3 mg, and a yield of 52%. The detection data of product sample 24-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.26 (d, J=2.0 Hz, 1H), 7.04 (d, J=1.6 Hz, 1H), 4.30-4.04 (m, 3H), 3.13-3.06 (m, 1H), 2.95–2.72 (m, 3H), 2.63 (ddd, J=17.6, 5.2, 2.8Hz, 1H), 2.55 (dd, J=15.2, 5.6Hz, 1H), 2.44 (s, 3H), 1.26 (t, J=7.2Hz, 3H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 171.6, 140.7, 135.0, 131.8, 130.8, 127.1, 125.9, 60.7, 59.6, 45.0, 41.8, 40.2, 22.3, 14.2. HRMS Calcd for C ₁₄ H ₁₈ Cl ₂ NO ₂ [M+H] ⁺ 302.0709, found 302.0709.

Example 25

Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (100.2 mg, 0.6 mmol, 3 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol) were added to a dry 38 mL sealed tube under air. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (26.1 μL, 0.24 mmol, 1.2 equiv) and phenethylamine hydrochloride of formula 25-1 (55.3 mg, 0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 25-3. 25-3 _cis totaled 44.1 mg with a 65% yield, and 25-3 _trans totaled 23.1 mg with a 34% yield.

The detection data of the product sample 25-3 _cis are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ 7.18-7.16 (m, 1H), 7.14 (s, 1H), 7.12-7.11 (m, 1H), 4.48 (dd, J=8.6, 3.4Hz, 1H), 4.22–4.10 (m, 4H), 3.63 (s, 1H), 3.29 (m, 1H), 3.20 (qd, J=12.7, 3.8Hz, 2H), 3.01 (dd, J=16.6, 3.5Hz, 1H) , 2.87 (ddd, J=32.9, 16.4, 8.8Hz, 2H), 2.62 (dd, J=16.2, 4.6Hz, 1H), 1.26 (t, J=7.1Hz, 6H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.3,171.9,138.0,136.3,132.5,130.4,127.4,125.8,61.1,60.8,52.7,45.4,40.4,39.8,34.0,14.3,14.2.HRMS Calcd for C ₁₇ H ₂₃ ClNO ₄ [M+H] ⁺ 340.1310,found340.1311.

The detection data of the product sample 25-3 _trans are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.16 (dd, J=8.3, 2.1 Hz, 1H), 7.11 (d, J=8.3 Hz, 1H), 7.08 (s, 1H), 4.48 (dd, J= 9.9, 3.5Hz, 1H), 4.26–4.08 (m, 4H), 3.26 (m, 2H), 2.98–2.89 (m, 1H), 2.84 (dd, J=16.1, 9.9Hz, 1H), 2.78–2.64 (m, 2H), 2.58 (dd, J=15.9, 4.3Hz, 1H), 2.37–2.18 (s, br, 1H), 1.26 (dt, J=9.9, 7.1Hz, 6H). ¹³ C NMR (151MHz) , CDCl ₃ )δ172.4,171.9,139.1,136.3,132.2,130.2,127.3,126.5,60.9,60.7,52.3,43.0,40.5,40.1,34.1,14.3,14.3.HRMS Calcd for C ₁₇ H ₂₃ ClNO ₄ [M+ H] ⁺ 340.1310,found340.1311.

Example 26

Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (100.2 mg, 0.6 mmol, 3 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol) were added to a dry 38 mL sealed tube under air. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added to the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), ethyl acrylate (32.6 μL, 0.3 mmol, 1.5 equiv) and phenethylamine of formula 26-1 (33.2 μL, 0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product samples were denoted as 26-3 and 26-4, respectively. 26-3 _trans totaled 22.2 mg with a yield of 40%, and 26-3 _cis totaled 11.6 mg with a yield of 21%. 18.8 mg of 26-4 in 25% yield.

The detection data of the product sample 26-3 _trans are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.20-7.05 (m, 4H), 4.67 (t, J=6.9 Hz, 1H), 4.20 (q, J=7.2 Hz, 2H), 3.92 (dd, J= 8.9, 4.8Hz, 1H), 3.75 (s, 3H), 3.12 (dd, J=16.2, 4.8Hz, 1H), 2.99 (dd, J=16.1, 8.8Hz, 1H), 2.77–2.71 (m, 2H ), 2.48(s, br, 1H), 1.29(t, J=7.1Hz, 3H). ¹³ CNMR(151MHz, CDCl ₃ )δ173.7,172.0,136.7,133.2,129.4,126.8,126.5,126.5,60.8,52.3 ,51.6,51.4,41.8,31.8,14.3.HRMS Calcd for C ₁₅ H ₁₉ NNaO ₄ [M+Na] ⁺ 300.1206,found300.1206.

The detection data of the product sample 26-3 _cis are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ 7.20-7.11 (m, 4H), 4.58-4.49 (m, 1H), 4.18 (q, J=7.2Hz, 2H), 3.79 (s, 3H), 3.75 ( dd, J=10.6, 4.5Hz, 1H), 3.12–2.95 (m, 3H), 2.72 (dd, J=16.6, 9.3Hz, 1H), 1.26 (t, J=7.1Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ173.1,172.3,136.6,134.3,129.5,126.7,126.6,125.1,60.9,55.6,53.2,52.4,41.4,32.9,14.3.HRMS Calcd forC ₁₅ H ₁₉ NNaO ₄ [M+Na] ⁺ 300.1206, found 300.1206.

The detection data of product sample 26-4 are as follows:

¹ H NMR (600 MHz, CDCl ₃ ) δ 7.94 (d, J=15.8 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.23 (t, J=7.7 Hz, 1H), 7.18 (d ,J=7.8Hz,1H),6.36(d,J=15.8Hz,1H),4.55(d,J=9.1Hz,1H),4.28(q,J=7.2Hz,2H),4.18(q,J =7.1Hz,2H),3.82(s,3H),3.72(dd,J=11.4,3.7Hz,1H),3.23(dd,J=16.1,3.8Hz,1H),3.05(dd,J=16.7, 3.1Hz, 1H), 2.95(dd, J＝16.2, 11.3Hz, 1H), 2.72(dd, J＝16.7, 9.2Hz, 1H), 1.86–1.52(s, br, 1H), 1.35(t, J = 7.1Hz, 3H), 1.26 (t, J = 7.1Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ ) δ 172.9, 172.1, 166.9, 141.5, 137.5, 134.2, 133.7, 126.9, 126.6, 125.1, 120.8, 60.9, 60.8, 55.4, 53.4, 52.5, 41.6, 30.3, 14.4, 14.3. HRMSCalcd for C ₂₀ H ₂₅ NNaO ₆ [M+Na] ⁺ 398.1574, found 398.1571.

Example 27

Under air, into a dry 120 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 2 mol%), AgOAc (334 mg, 2 mmol, 2 equiv.), 2-hydroxypyridine (9.5 mg, 0.1 mmol, 10 mol. %), then Tf ₂ NH (281 mg, 1.0 mmol, 1.0 equiv) was added in the glove box, and finally DCM (6.4 mL), HFIP (1.6 mL), ethyl acrylate (131 μL, 1.2 mmol, 1.2 equiv) and o-methylphenethylamine of formula 27-1 (141 μL, 1.0 mmol). The system was reacted at 90°C for 24h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product samples were designated as 1-3, a total of 207.5 mg, and a yield of 89%.

Example 28

Under air, into a dry 120 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 1 mol%), AgOAc (668 mg, 4 mmol, 4 equiv.), 2-hydroxypyridine (9.5 mg, 0.1 mmol, 5 mol. %), then Tf ₂ NH (562 mg, 2.0 mmol, 1.0 equiv) was added in the glove box, and finally DCM (8 mL), HFIP (2 mL), ethyl acrylate (262 μL, 2.4 mmol, 1.2 equiv) and formula 28 were added in sequence - o-methylphenethylamine of 1 (282 μL, 2.0 mmol). The system was reacted at 90°C for 48h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product samples were designated as 1-3, a total of 284.0 mg, and a yield of 61%.

Example 29

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), methyl acrylate (21.7 μL, 0.24 mmol, 1.2 equiv) and o-methylphenethylamine of formula 29-1 (0.2 mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product sample was designated as 29-3, and the NMR yield was 81% (internal standard: dibromomethane 0.2 mmol, 14 μL).

Example 30

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added in the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), n-butyl acrylate (34.6 μL, 0.24 mmol) were added in sequence , 1.2equiv) and o-methylphenethylamine of formula 30-1 (0.2mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The resulting product sample was designated as 30-3, a total of 44.4 mg, and a yield of 85%.

The detection data of product sample 30-3 are as follows:

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.06 (t, J=7.2, 7.2 Hz, 1H), 7.01 (d, J=7.2 Hz, 1H), 6.94 (d, J=7.2 Hz, 1H), 4.46 (dd, J=9.6, 3.6Hz, 1H), 4.11 (t, J=6.6Hz, 2H), 3.27–3.23 (m, 1H), 3.08–3.04 (m, 1H), 2.87–2.84 (m, 1H) ), 2.79–2.75 (m, 1H), 2.71–2.60 (m, 4H), 2.21 (s, 3H), 1.62–1.57 (m, 2H), 1.38–1.32 (m, 2H), 0.91 (t, J =7.2Hz, 3H). ¹³ C NMR (151MHz, CDCl ₃ )δ172.5, 137.2, 136.8, 133.8, 127.9, 125.5, 123.6, 64.6, 53.0, 41.1, 40.4, 30.7, 27.0, 19.4, 19.2, 13.7. HRMS Calcd for C ₁₄ H ₂₀ NO ₂ [M+H] ⁺ 234.1489, found 234.1489.

Example 31

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added to the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), tert-butyl acrylate (34.8 μL, 0.24 mmol) were added in sequence , 1.2equiv) and o-methylphenethylamine of formula 31-1 (0.2mmol). The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product sample was designated as 31-3, and the NMR yield was 20% (internal standard: dibromomethane 0.2 mmol, 14 μL).

Example 32

Under air, into a dry 38 mL sealed tube was added Pd(OAc) ₂ (4.5 mg, 0.02 mmol, 10 mol%), AgOAc (66.8 mg, 0.4 mmol, 2 equiv.), 2-hydroxypyridine (3.8 mg, 0.04 mmol. , 20 mol%), then Tf ₂ NH (56.2 mg, 0.2 mmol, 1.0 equiv) was added to the glove box, and finally DCM (1.6 mL), HFIP (0.4 mL), diethyl vinylphosphonate (36.9 μL) were added sequentially , 0.24mmol, 1.2equiv) and o-methylphenethylamine (0.2mmol) shown in formula 32-2. The system was reacted at 90 °C for 12 h, then cooled to room temperature, the solvent and remaining ethyl acrylate were evaporated under reduced pressure, and then dichloromethane and saturated sodium carbonate were added to the residue for extraction, the organic layer was collected, and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated under reduced pressure, and the residue was separated by silica gel column chromatography (petroleum ether/ethyl acetate/triethylamine=11/1/0.4 as eluent) to obtain the product. The obtained product sample was designated as 32-3, and the NMR yield was 6% (internal standard: dibromomethane 0.2 mmol, 14 μL).

The above are only a few embodiments of the present application, and are not intended to limit the present application in any form. Although the present application is disclosed as above with preferred embodiments, it is not intended to limit the present application. Without departing from the scope of the technical solutions of the present application, any changes or modifications made by using the technical contents disclosed above are equivalent to equivalent implementation cases and fall within the scope of the technical solutions.

Claims (13)

1. a preparation method of a compound, is characterized in that, comprises the following steps: Compound II and compound III are reacted in a reaction system containing a catalyst to generate the compound shown in formula I; The structural formula of compound II is shown in formula II-1, formula II-2 or formula II-3; The structural formula of compound III is shown in formula III;

The compound has the structural formula shown in formula I-1:

R ₆₁ , R ₆₂ , R ₆₃ , and R ₆₄ are independently selected from hydrogen, halogen, halogen-substituted C1-C5 alkyl group, ester-substituted C1-C5 alkenyl group, and C1-C5 alkoxy group; the The ester group in "C1-C5 alkenyl substituted by ester group" is -COOR ₈ , wherein R ₈ is a C1-C5 alkyl group; R ₁ is selected from hydrogen, C1-C5 alkyl; R ₂ and R ₃ are independently selected from hydrogen and ester group-substituted C1-C5 alkyl groups; the ester group in the "ester group-substituted C1-C5 alkyl group" is -COOR ₉ , wherein R ₉ is C1 ~C5 alkyl; R ₇ is selected from -COOR ₈ , -PO(OR ₁₀ ) ₂ , wherein R ₈ and R ₁₀ are independently selected from C1-C5 alkyl groups; R ₄ and R ₅ are independently selected from hydrogen, C1-C20 alkyl and at least one of R ₄ and R ₅ is H; in,

for

wherein R ₆₁ , R ₆₂ , R ₆₃ , and R ₆₄ are independently selected from hydrogen, halogen, halogen-substituted C1-C5 alkyl, ester-substituted C1-C5 alkenyl, and C1-C5 alkoxy; The ester group in the "C1-C5 alkenyl substituted by an ester group" is -COOR ₈ , wherein R ₈ is a C1-C5 alkyl group; The catalyst includes a compound containing palladium element, a compound containing silver element, an organic acid, and a ligand; The compound containing palladium element is selected from at least one of palladium acetate, palladium trifluoroacetate and bis(acetonitrile) palladium chloride; The compound containing silver element is selected from at least one of silver carbonate, silver acetate, silver oxide, silver trifluoroacetate, silver tetrafluoroborate, silver pivalate, silver tungstate and silver fluoride; The organic acid is selected from pentafluorobenzoic acid, trifluoroacetic acid, 3-trifluoromethylbenzoic acid, trifluoromethanesulfonic acid, 3,5-bis-trifluoromethylbenzoic acid, 1-adamantanecarboxylic acid, acetic acid, at least one of bis-trifluoromethanesulfonimide; The ligand is selected from at least one of amino acid ligands, phosphine ligands, pyridine ligands, acid ligands, and carbene ligands. 2. the preparation method of compound according to claim 1 is characterized in that, the structural formula of compound shown in formula I is selected from following compound:

3. The method according to claim 1, wherein Compound II is selected from the following compounds:

Compound III is selected from the following compounds:

4. the preparation method of compound according to claim 1, is characterized in that, The ligand is selected from at least one of N-acetyl-L-phenylalanine, N-acetyl-L-alanine, N-acetyl-β-alanine, and 2-hydroxypyridine. 5. The preparation method of the compound according to claim 1, wherein the molar ratio of compound II to the compound containing palladium element is 1:0.8～1.2; The molar ratio of compound II to the compound containing silver element is 1:2～3; The molar ratio of compound II to organic acid is 1:0.8～1.2; The molar ratio of compound II to ligand is 1:1.8-2.2. 6. the preparation method of compound according to claim 1 is characterized in that, described catalyst is palladium acetate, silver acetate, 2-hydroxypyridine, bis-trifluoromethanesulfonimide; The mole number of palladium acetate is 10% of the mole number of compound II; The mole number of silver acetate is twice the equivalent of the mole number of compound II; The moles of 2-hydroxypyridine are 20% of the moles of compound II; The number of moles of bistrifluoromethanesulfonimide is equivalent to the number of moles of compound II. 7 . The preparation method of the compound according to claim 1 , wherein the molar ratio of compound II and compound III is 1:1.2-2. 8 . 8. The preparation method of compound according to claim 1, is characterized in that, also comprises solvent in described reaction system; The solvent is selected from N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, hexafluoroisopropanol, dichloroethane, mixed solution of hexafluoroisopropanol and dichloroethane , at least one of dichloromethane, methanol, tert-amyl alcohol, and toluene. 9. The preparation method of compound according to claim 1, is characterized in that, also comprises solvent in described reaction system; The solvent is hexafluoroisopropanol and dichloroethane in a volume ratio of 1:4 to 1:9. 10 . The preparation method of the compound according to claim 1 , wherein the temperature of the reaction is 50° C. to 120° C., and the time of the reaction is 10 hours to 25 hours. 11 . 11 . The preparation method of the compound according to claim 1 , wherein the reaction temperature is 80° C.˜90° C., and the reaction time is 12 hours˜24 hours. 12 . 12. A method for preparing a compound, comprising the steps of: compound II and compound III react in a reaction system containing a catalyst to generate the compound shown in formula I; Compound II is

Compound III is

Compound I is

and / or

Under air, 0.02 mmol Pd(OAc) ₂ , 0.6 mmol AgOAc, 0.04 mmol 2-hydroxypyridine were added to a dry 38 mL sealed tube, then 0.2 mmol Tf ₂ NH was added to the glove box, and 1.6 mL DCM was added in sequence. 0.4 mL of HFIP, 0.3 mmol of ethyl acrylate and 0.2 mmol of phenethylamine, the system was reacted at 90° C. for 12 h, and then cooled to room temperature. 13. The application of the method of any one of claims 1 to 12 in the preparation of tetrahydroisoquinoline compounds.