A method for constructing tetrasubstituted alkenes by distal C(sp3)-H bond diarylation.

Abstract

This invention provides a method for the diarylation of C(sp3)-H bonds. The method comprises: reacting a pyridine derivative with pinacol iodophenylboronic acid in a catalytic system of Ag2CO3, an amino acid ligand, and a noble metal catalyst. This method can achieve highly efficient diarylation of distal methyl C(sp3)-H bonds with yields of 52-66%, under mild reaction conditions, and with simple operation.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more specifically to a method for constructing tetrasubstituted olefins by diarylation of distal C(sp3)-H bonds. Background Technology

[0002] Tetrasubstituted alkenes possess unique chemical structures and properties, and are widely found in various fields of daily life, such as pharmaceuticals, polymer chemistry, and materials chemistry. Polyaryl-substituted alkenes are particularly important, serving as crucial structural segments for many drug molecules and bioactive molecules. Therefore, constructing these compounds and enriching their structural types has become a research hotspot in this field. Over the past few decades, chemists have developed a series of synthetic methods for constructing polyaryl-substituted alkenes, primarily including: witting olefination reactions of carbonyl compounds with ylidene esters, metal-catalyzed addition reactions of alkynes, and elimination reactions of polysubstituted tertiary alcohols. However, these methods all have some drawbacks. For example, it is difficult to control the stereostructure of the olefin product (Z-type / E-type) in most reactions. Furthermore, the tolerance of functional groups during the reaction process and the construction of relatively complex starting materials (especially polysubstituted tertiary alcohols) limit the application of these methods. Therefore, finding and developing efficient and convenient synthetic methods for constructing polyaryl-substituted alkenes is of great significance.

[0003] In recent years, the development of transition metal-catalyzed CH bond functionalization reactions has provided a powerful tool for the synthesis of organic compounds. These reactions can directly convert CH bonds into various functional groups, significantly improving the efficiency of organic synthesis. In particular, the development of Pd-catalyzed C(sp3)-H bond aromatization reactions has provided a novel and highly efficient method for the synthesis of polyaryl compounds. Therefore, the authors hypothesize that geminilation of the primary C(sp3)-H bond followed by a β-H elimination process might yield 1,1-diaryl-substituted olefins. Summary of the Invention

[0004] In view of the technical problems existing in the prior art, the present invention aims to provide a method for constructing tetrasubstituted olefins by diarylation of the distal C(sp3)-H bond, the method comprising the following steps:

[0005] The pyridine derivatives shown in Formula 1 or Formula 2 are reacted with pinacol iodophenylboronic acid in a catalytic system of Ag2CO3, N-acetyl-Lvaline as shown in Formula 6 and a noble metal catalyst.

[0006]

[0007] R1 includes methyl, substituted or unsubstituted phenyl groups.

[0008] Preferably, the substituents of the phenyl group include hydrogen, deuterium, halogen, ketone, substituted or unsubstituted amino, aldehyde, cyano, substituted or unsubstituted alkyl, or substituted or unsubstituted alkoxy groups.

[0009] Preferably, the substituted phenyl group includes monosubstituted phenyl, meta-disubstituted phenyl, and para-disubstituted phenyl;

[0010] Preferably, the monosubstituted phenyl group includes ortho-monosubstituted benzene, meta-monosubstituted phenyl group, and para-monosubstituted phenyl group;

[0011] The substituents of the ortho-monosubstituted phenyl group include hydrogen, methyl, isopropyl, fluorine, trifluoromethyl, or trifluoromethoxy; the substituents of the meta-monosubstituted phenyl group include methoxy, fluorine, chlorine, or trifluoromethyl; and the substituents of the para-monosubstituted phenyl group include methyl, fluorine, chlorine, or trifluoromethoxy.

[0012] Preferably, the amino acid ligand includes one or more of N-acetyl-L-valine, (tert-butoxycarbonyl)alanine, L-tert-leucine, or glycine.

[0013] Preferably, the molar ratio of the pyridine derivative to pinacol iodophenylboronic acid is 1:1~2.

[0014] Preferably, the iodophenylboronic acid pinacol ester comprises 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborhecyclopentane as shown in Formula 3, 2-(3-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborhecyclopentane as shown in Formula 4, or 2-(4-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborhecyclopentane as shown in Formula 5;

[0015]

[0016] Preferably, R2 includes hydrogen, halogen, ester group, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy or substituted or unsubstituted phenyl;

[0017] Preferably, the pinacol iodophenylboronic acid ester comprises 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane as shown in Formula 3.

[0018] Preferably, the molar ratio of the pyridine derivative to the noble metal catalyst is 1:0.005~0.02.

[0019] Preferably, the noble metal catalyst comprises Pd(OAc)2, and the molar ratio of Pd(OAc)2 to N-acetyl-L-valine ligand is 1:1~2.

[0020] Preferably, the reaction is carried out in an organic solvent, which includes one or more of p-xylene, cyclohexane, petroleum ether, ethyl acetate, dichloromethane, toluene, or diethyl ether.

[0021] Preferably, the organic solvent includes p-xylene.

[0022] Preferably, the reaction temperature is 80~130℃ and the reaction time is 10~20h.

[0023] Preferably, after the reaction is completed, the product is separated by thin-layer chromatography or column chromatography.

[0024] Beneficial effects of this invention:

[0025] This invention provides a method for synthesizing polyaryl alkenes by activating the distal methyl C(sp3)-H bond of pyridine derivatives using N-acetyl-L-valine ligand and palladium catalyst. Utilizing N-acetyl-L-valine assistance and Pd(OAc)2 catalysis, a highly efficient distal methyl C(sp3)-H bond diaryration reaction can be achieved. The pinacol iodophenylboronic acid coupling reagent first undergoes self-elimination to form the intermediate benzynyne. The strong complexing ability of pyridine, with the assistance of the N-acetyl-L-valine ligand, forms a stable and relatively large six-membered metal chelate ring intermediate, into which the benzynyne migrates and inserts. Then, reductive elimination completes the distal methyl C(sp3)-H bond diaryration reaction, synthesizing polyaryl alkenes with yields typically ranging from 52% to 66%. The reaction conditions are mild and the operation is simple. Detailed Implementation

[0026] According to a first aspect of the present invention, a method for constructing tetrasubstituted olefins by distal C(sp3)-H bond diarylation is provided, the method comprising the following steps:

[0027] The pyridine derivatives shown in Formula 1 or Formula 2 are reacted with pinacol iodophenylboronic acid in a catalytic system of Ag2CO3, amino acid ligands and noble metal catalysts.

[0028]

[0029] R1 includes methyl, substituted or unsubstituted phenyl groups.

[0030] In this invention, a highly efficient distal methyl C(sp3)-H bond diaromatization reaction can be achieved by using N-acetyl-L-valine as an aid and Pd(OAc)2 as a catalyst. The pinacol ester coupling reagent of iodophenylboronic acid first undergoes self-elimination to form the intermediate benzyne. The strong complexing ability of pyridine, with the assistance of the N-acetyl-L-valine ligand, forms a stable and larger six-membered metal chelate ring intermediate, in which benzyne migrates and inserts, followed by reduction and elimination, thus realizing the distal methyl C(sp3)-H bond diaromatization reaction. Ag2CO3 acts as a base to abstract protons and promote the reaction, and also participates in the reaction as an oxidant to promote the activation of hydrocarbons. This dual action improves the reaction efficiency.

[0031] In a preferred embodiment of the present invention, the substituents of the phenyl group include hydrogen, deuterium, halogen, ketone, substituted or unsubstituted amino, aldehyde, cyano, substituted or unsubstituted alkyl or substituted or unsubstituted alkoxy groups.

[0032] In a preferred embodiment of the present invention, the substituted phenyl group includes monosubstituted phenyl, meta-disubstituted phenyl, and para-disubstituted phenyl.

[0033] Preferably, the monosubstituted phenyl group includes ortho-monosubstituted benzene, meta-monosubstituted phenyl group, and para-monosubstituted phenyl group;

[0034] The substituents of the ortho-monosubstituted phenyl group include hydrogen, methyl, isopropyl, fluorine, trifluoromethyl, or trifluoromethoxy; the substituents of the meta-monosubstituted phenyl group include methoxy, fluorine, chlorine, or trifluoromethyl; and the substituents of the para-monosubstituted phenyl group include methyl, fluorine, chlorine, or trifluoromethoxy.

[0035] In a preferred embodiment of the present invention, the amino acid ligand includes one or more of N-acetyl-L-valine, (tert-butoxycarbonyl)alanine, L-tert-leucine, or glycine.

[0036] In a preferred embodiment of the present invention, the molar ratio of the pyridine derivative to pinacol iodophenylboronic acid is 1:1~2.

[0037] In this invention, the molar ratio of the pyridine derivative to pinacol iodophenylboronic acid is, for example, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9 or 1:2.0.

[0038] In a preferred embodiment of the present invention, the iodophenylboronic acid pinacol ester comprises 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentane as shown in Formula 3, 2-(3-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentane as shown in Formula 4, or 2-(4-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborhexacyclopentane as shown in Formula 5;

[0039]

[0040] Preferably, R2 includes hydrogen, halogen, ester group, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy or substituted or unsubstituted phenyl;

[0041] Preferably, the pinacol iodophenylboronic acid ester comprises 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane as shown in Formula 3.

[0042] In a preferred embodiment of the present invention, the molar ratio of the pyridine derivative to the noble metal catalyst is 1:0.005~0.02.

[0043] In this invention, the molar ratio of the pyridine derivative to the noble metal catalyst is, for example, 1:0.005, 1:0.006, 1:0.007, 1:0.008, 1:0.009, 1:0.010, 1:0.011, 1:0.012, 1:0.013, 1:0.014, 1:0.015, 1:0.016, 1:0.017, 1:0.018, 1:0.019, or 1:0.020.

[0044] In a preferred embodiment of the present invention, the noble metal catalyst comprises Pd(OAc)2, wherein the molar ratio of Pd(OAc)2 to N-acetyl-L-valine ligand is 1:1~2.

[0045] In this invention, the molar ratio of Pd(OAc)2 to N-acetyl-Lvaline ligand is, for example, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9 or 1:2.0.

[0046] In a preferred embodiment of the present invention, the reaction is carried out in an organic solvent, the organic solvent including one or more of p-xylene, cyclohexane, petroleum ether, ethyl acetate, dichloromethane, toluene, or diethyl ether;

[0047] Preferably, the organic solvent includes p-xylene.

[0048] In a preferred embodiment of the present invention, the reaction temperature is 80~130°C and the reaction time is 10~20h.

[0049] In this invention, the reaction temperature is, for example, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C, 110°C, 115°C, 120°C, 125°C, or 130°C.

[0050] The reaction time is, for example, 10h, 11h, 12h, 13h, 14h, 15h, 16h, 17h, 18h, 19h or 20h.

[0051] In a preferred embodiment of the present invention, after the reaction is completed, the product is separated by thin-layer chromatography or column chromatography.

[0052] In this invention, the developing solvent used in the column chromatography separation is a mixture of petroleum ether and ethyl acetate, with a petroleum ether:ethyl acetate ratio of 25:1.

[0053] In this invention, the values ​​listed in the range of conditions are only preferred values, but are not limited to the listed values. Other unlisted values ​​within the range are also applicable.

[0054] Example 1

[0055] This embodiment provides a method for constructing a tetrasubstituted olefin by diarylation of the distal C(sp3)-H bond, the reaction of which is shown in Formula 7 and the reaction conditions are shown in Table 1.

[0056] The specific steps of the reaction are as follows:

[0057] In a dry reaction tube, 0.15 mmol of 3-methyl-2-(2-phenylpropyl)pyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of palladium catalyst, and 0.015 mmol of amino acid ligand were added sequentially, followed by 1 mL of organic solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product 3-methyl-2-(2,3,3-triphenylallyl)pyridine was obtained by column chromatography (petroleum ether:ethyl acetate = 25:1). The yield was calculated.

[0058] The structure of N-acetyl-L-valine is shown in Formula 6:

[0059]

[0060]

[0061] 1H NMR (800 MHz, CDCl3) δ 8.32 (t, J = 3.4 Hz, 1H), 7.44-7.41 (m, 1H),7.28 (t, J = 7.6 Hz, 2H), 7.22 (t, J = 7.5 Hz, 2H), 7.03 (d, J = 6.9 Hz, 2H), 7.02-6.94 (m, 9H), 6.92 (t, J = 6.3 Hz, 1H), 4.04 (s, 2H), 2.09 (s, 3H). 13 C NMR (201MHz, CDCl3) δ 143.1, 142.9, 141.1, 130.7, 129.9, 129.6, 128.7, 128.4, 128.1,127.3, 127.3, 126.7, 125.9, 125.8, 121.0, 41.5, 19.0.

[0062] Table 1 Screening of reaction conditions

[0063]

[0064] Example 2

[0065] In a dry reaction tube, 0.15 mmol of 3-methyl-2-(2-o-tolyl)propylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by the addition of 1 mL of p-xylene as a solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction was completed, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(3,3-diphenyl-2-(o-tolyl)allyl)-3-methylpyridine, with the chemical structure shown in Formula 8. The overall yield of the diaromatic product was 64%, a white solid.

[0066]

[0067] 1 H NMR (800 MHz, CDCl3) δ 8.32 (d, J = 4.9 Hz, 1H), 7.55 (d, J= 6.7 Hz, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.27 (t, J = 7.4 Hz, 1H), 7.22 (d, J = 6.7 Hz, 1H),7.00-6.96 (m, 2H), 6.93 (dd, J = 15.5, 7.6 Hz, 5H), 6.86 (d, J = 7.1 Hz, 4H), 4.09 (d, J = 14.8 Hz, 1H), 3.89 (d, J = 14.8 Hz, 1H), 2.11 (s, 3H), 1.97 (s, 3H). 13 C NMR (201 MHz, CDCl3) δ 158.1, 146.3, 142.8, 142.6, 141.0, 140.6, 137.1,135.9, 135.7, 131.9, 130.1, 130.1, 130.0, 129.7, 128.0, 127.1, 126.7, 126.3,125.9, 124.4, 121.1, 41.6, 19.5, 18.8.

[0068] Example 3

[0069] In a dry reaction tube, 2-(2-(2-isopropylphenyl)propyl)-3-methylpyridine (0.15 mmol), 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (0.225 mmol), Pd(OAc)₂ (0.015 mmol), N-acetyl-L-valine (0.015 mmol), and Ag₂CO₃ (0.30 mmol) were added sequentially, followed by the addition of 1 mL of p-xylene as a solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-(2-isopropylphenyl)-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 9. The overall yield of the borylated product was 60%, and it was a colorless oil.

[0070]

[0071] 1 H NMR (800 MHz, CDCl3) δ 8.37 (d, J= 4.8 Hz, 1H), 7.62 (d, J = 7.3 Hz, 1H), 7.34 (t, J = 7.7 Hz, 2H), 7.28-7.24 (m, 1H), 7.20 (d, J = 7.6 Hz, 1H), 7.05 (d, J = 7.4 Hz, 1H), 7.03 (d, J = 7.7 Hz, 1H), 6.98-6.91 (m, 9H), 4.09 (d, J = 14.5Hz, 1H), 3.86 (d, J = 14.4 Hz, 1H), 3.19-3.14 (m, 1H), 1.91 (s, 3H), 0.82-0.79(m, 3H), 0.49-0.46 (m, 3H). 13 C NMR (201 MHz, CDCl3)δ 158.2, 146.6, 146.2,143.0, 142.5, 141.0, 139.2, 137.2, 135.6, 132.0, 130.5, 130.5, 130.3, 127.9,127.1, 126.8, 126.7, 125.9, 125.5, 124.2, 121.0, 42.4, 29.1, 25.0, 23.1,19.0.

[0072] Example 4

[0073] In a dry reaction tube, 0.15 mmol of 2-(2-(2-fluorophenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-(2-fluorophenyl)-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 10. The overall yield of the diaromatic product was 66%, and it was a colorless oil.

[0074]

[0075] 1 H NMR (800 MHz, CDCl3) δ 8.32 (d, J = 4.8 Hz, 1H), 7.50 (d, J = 7.2 Hz,1H), 7.33-7.30 (m, 2H), 7.26-7.23 (m, 2H), 7.06-6.98 (m, 6H), 6.93 (m, 3H),6.78 (t, J = 9.2 Hz, 1H), 6.71 (t, J = 7.5 Hz, 1H), 4.05 (s, 2H), 2.09 (s, 3H); 13 CNMR (201 MHz, CDCl3) δ 160.7 (m, J = 245.2 Hz), 157.9, 142.6, 142.1, 132.7,132.7, 131.9, 131.6, 129.7, 129.6, 129.5, 129.4, 128.1, 128.0, 128.0, 127.4,126.9, 126.2, 123.1 (m, J = 4.0 Hz), 121.0, 114.7 (m, J = 22.1 Hz), 40.4, 18.8.

[0076] Example 5

[0077] In a dry reaction tube, 2-(2-(2-trifluorophenyl)propyl)-3-methylpyridine (0.15 mmol), 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (0.225 mmol), Pd(OAc)2 (0.015 mmol), N-acetyl-L-valine (0.015 mmol), and Ag2CO3 (0.30 mmol) were added sequentially, followed by the addition of 1 mL of p-xylene as a solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(3,3-diphenyl-2-(2-(trifluoromethyl)phenyl)allyl)-3-methylpyridine, with the chemical structure shown in Formula 11. The overall yield of the diaromatic product was 64%, and it was a pale yellow oil.

[0078]

[0079] 11H NMR (800 MHz, CDCl3) δ 8.32 (d, J J = 4.8 Hz, 1H), 7.44 (dd, J J = 13.8, 7.7 Hz, 3H), 7.33 (t, J J = 7.5 Hz, 2H), 7.26 - 7.24 (m, 2H), 7.11 (t, J J = 7.7 Hz, 1H), 7.06 (t, J J = 7.6 Hz, 1H), 6.98 (d, J J = 4.4 Hz, 4H), 6.95 (dt, J J = 9.2, 4.5 Hz, 2H), 6.86 (d, J J = 7.8 Hz, 1H), 4.16 (d, J J = 15.0 Hz, 1H), 3.87 (d, J J = 15.0 Hz, 1H), 1.96 (s, 3H). 13 13C NMR (201 MHz, CDCl3) δ 157.8, 142.4, 142.3, 142.0, 139.9, 133.7, 132.2, 130.0, 129.8, 129.6, 128.1, 128.1, 127.2, 126.9, 126.5, 126.1, 126.1, 126.0, 125.3 (m, J J = 273.4 Hz), 123.9, 121.2, 41.6, 18.7.

[0080] Example 6

[0081] In a dry reaction tube, 0.15 mmol of 3-methyl-2-(2-(2-(trifluoromethoxy)phenyl)propylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)2, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag2CO3 were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(3,3-diphenyl-2-(2-(trifluoromethoxy)phenyl)allyl)-3-methylpyridine, with the chemical structure shown in Formula 12. The overall yield of the diaromatic product was 65%, a pale yellow oil.

[0082]

[0083] 1 H NMR (800 MHz, CDCl3) δ 8.32 (d, J = 4.8 Hz, 1H), 7.50 (d, J = 7.2 Hz,1H), 7.33-7.30 (m, 2H), 7.26-7.23 (m, 2H), 7.06-6.98 (m, 6H), 6.93 (m, 3H),6.78 (t, J = 9.2 Hz, 1H), 6.71 (t, J = 7.5 Hz, 1H), 4.05 (s, 2H), 2.09 (s, 3H). 13 CNMR (201 MHz, CDCl3) δ 157.9, 146.7, 143.5, 142.3, 142.2, 137.2, 133.9,133.4, 129.6, 129.6, 128.1, 127.7, 127.3, 126.9, 126.2, 125.0, 121.2, 121.1,120.0, 118.3, 118.1, 40.3, 18.7.

[0084] Example 7

[0085] In a dry reaction tube, 0.15 mmol of 2-(2-(3-methoxyphenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-(3-methoxyphenyl)-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 13. The overall yield of the diaromatic product was 65%, a white solid.

[0086]

[0087] 1 H NMR (800 MHz, CDCl3) δ 8.26 (d, J = 6.6 Hz, 1H), 7.34 (d, J = 7.9 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.14 (q, J = 7.7, 6.9 Hz, 3H), 6.96-6.89 (m, 6H), 6.85-6.82 (m, 2H), 6.59 (d, J = 7.6 Hz, 1H), 6.49 (s, 1H), 6.44 (d, J = 8.1 Hz,1H), 3.94 (s, 2H), 3.43 (s, 3H), 2.01 (s, 3H). 13 C NMR (201 MHz, CDCl3)δ 158.6,158.4, 146.5, 143.6, 143.1, 143.0, 141.1, 137.0, 131.5, 130.6, 129.6, 128.2,128.0, 127.3, 126.7, 125.8, 122.2, 120.9, 115.3, 112.2, 55.0, 41.4, 19.0.

[0088] Example 8

[0089] In a dry reaction tube, 0.15 mmol of 2-(2-(3-fluorophenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-(3-fluorophenyl)-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 14. The overall yield of the diaromatic product was 54%, a white solid.

[0090]

[0091] 1 H NMR (800 MHz, CDCl3) δ 8.34 (d, J = 3.3 Hz, 1H), 7.40 (d, J = 7.4 Hz, 1H), 7.28 (t, J = 7.5 Hz, 1H), 7.26-7.22 (m, 3H), 7.02 (dq, J = 14.0, 7.0 Hz, 4H), 6.97 (d, J = 7.1 Hz, 2H), 6.96-6.93 (m, 2H), 6.83 (d, J = 7.7 Hz, 1H), 6.76 (d, J = 12.5 Hz, 1H), 6.66 (t, J = 9.7 Hz, 1H), 4.00 (s, 2H), 2.09 (s, 3H). 13 C NMR (201 MHz, CDCl3) δ 162.7 (m, J = 245.2 Hz), 158.0, 144.7, 142.8, 142.5, 141.9,137.1, 135.9, 131.5, 130.6, 129.5, 128.7, 128.6, 128.1, 127.4, 126.9, 126.1,125.7, 121.1, 116.7 (m, J = 22.1 Hz), 112.8 (m,J = 22.1 Hz), 41.3, 18.9.

[0092] Example 9

[0093] In a dry reaction tube, 0.15 mmol of 2-(2-(3-chlorophenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-(3-chlorophenyl)-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 15. The overall yield of the diaromatic product was 51%, and it was a white solid.

[0094]

[0095] 1 H NMR (800 MHz, CDCl3) δ 8.34 (d, J = 4.8 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.27 (d, J = 7.5 Hz, 1H), 7.24 (dd, J = 13.4, 5.9 Hz, 2H), 7.07 (s, 1H),7.06-7.00 (m, 4H), 6.97 (d, J = 7.2 Hz, 2H), 6.96-6.93 (m, 2H), 6.91 (d, J = 7.3Hz, 3H), 4.00 (s, 2H), 2.08 (s, 3H). 13 C NMR (201 MHz, CDCl3) δ 157.9, 146.6,144.3, 142.8, 142.4, 142.0, 137.1, 135.8, 133.0, 131.5, 130.6, 129.7, 129.5,128.5, 128.5, 128.1, 127.5, 126.9, 126.1, 126.0, 121.1, 41.2, 18.9.

[0096] Example 10

[0097] In a dry reaction tube, 0.15 mmol of 2-(2-(3-(trifluoromethyl)phenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(3,3-diphenyl-2-(3-(trifluoromethyl)phenyl)allyl)-3-methylpyridine, with the chemical structure shown in Formula 16. The overall yield of the diaromatic product was 63%, a pale yellow oil.

[0098]

[0099] 1 H NMR (800 MHz, CDCl3) δ 8.33 (m, 1H), 7.40 (d, J = 5.2 Hz, 2H), 7.29(d, J = 5.5 Hz, 3H), 7.25 (d, J = 4.9 Hz, 1H), 7.24-7.19 (m, 2H), 7.09 (t, J = 7.8Hz, 1H), 7.05-6.98 (m, 4H), 6.95-6.93 (m, 3H), 4.04 (s, 2H), 2.08 (s, 3H). 13 CNMR (201 MHz, CDCl3) δ 157.8, 146.6, 143.2, 142.6, 142.4, 142.3, 137.1,135.8, 133.4, 131.5, 130.7, 129.7 (m, J = 32.2 Hz), 129.5, 129.2, 128.1, 127.7,127.5, 127.0, 126.8 (m, J = 4.0 Hz), 126.2, 122.6, (m, J = 4.0 Hz), 121.2, 41.1, 18.8.

[0100] Example 11

[0101] In a dry reaction tube, 3-methyl-2-(2-(p-tolyl)propyl)pyridine (0.15 mmol), 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (0.225 mmol), Pd(OAc)₂ (0.015 mmol), N-acetyl-L-valine (0.015 mmol), and Ag₂CO₃ (0.30 mmol) were added sequentially, followed by the addition of 1 mL of p-xylene as a solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(3,3-diphenyl-2-(p-tolyl)allyl)-3-methylpyridine, with the chemical structure shown in Formula 17. The overall yield of the diaromatic product was 52%, a white solid.

[0102]

[0103] 1 H NMR (800 MHz, CDCl3) δ 8.33 (dd, J = 4.9, 1.7 Hz, 1H), 7.42-7.39 (m,2H), 7.27 (t, J = 7.5 Hz, 2H), 7.22 (m, 2H), 7.02 (dd, J = 8.0, 6.5 Hz, 2H),7.00-6.96 (m, 3H), 6.92 (d, J = 7.7 Hz, 3H), 6.80 (d, J = 7.8 Hz, 2H), 4.03 (s, 2H), 2.15 (s, 3H), 2.10 (s, 3H). 13 C NMR (201 MHz, CDCl3) δ 158.4, 143.4,143.1, 140.8, 139.0, 135.3, 131.7, 130.8, 129.7, 129.6, 128.1, 128.0, 127.3,126.6, 125.7, 121.0, 41.5, 21.1, 19.0.

[0104] Example 12

[0105] In a dry reaction tube, 0.15 mmol of 2-(2-(4-fluorophenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-(4-fluorophenyl)-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 18. The overall yield of the diaromatic product was 62%, a pale yellow oil.

[0106]

[0107] 1 H NMR (800 MHz, CDCl3) δ 8.32 (d, J = 4.9 Hz, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.28 (t, J = 7.5 Hz, 2H), 7.23 (q, J = 7.4, 5.9 Hz, 2H), 7.03 (t, J = 7.3 Hz,2H), 7.01-6.96 (m, 4H), 6.94 (dd, J = 14.6, 7.4 Hz, 4H), 6.68 (t, J = 8.6 Hz,1H), 4.00 (s, 2H), 2.08 (s, 3H). 13 C NMR (201 MHz, CDCl3) δ 161.7 (m, J = 245.2Hz), 158.1, 143.0, 142.7, 141.5, 131.4, 131.4, 131.4, 130.7, 129.5, 128.1,127.4, 126.8, 125.9, 114.3 (m, J = 20.1 Hz), 41.5, 18.9.

[0108] Example 13

[0109] In a dry reaction tube, 0.15 mmol of 2-(2-(4-chlorophenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)2, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag2CO3 were added sequentially, followed by the addition of 1 mL of p-xylene as a solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography. The chemical structure of 2-(2-(4-chlorophenyl)-3,3-diphenylallyl)-3-methylpyridine is shown in Formula 19. The overall yield of the diaromatic product was 52%, and it was a pale yellow oil.

[0110]

[0111] 1 H NMR (800 MHz, CDCl3) δ 8.33 (dd, J = 4.9, 1.7 Hz, 1H), 7.40-7.38 (m,1H), 7.28 (t, J = 7.6 Hz, 2H), 7.26-7.21 (m, 2H), 7.03 (m, 4H), 7.00-6.95 (m,6H), 6.93 (dd, J = 7.6, 4.8 Hz, 1H), 4.00 (s, 2H), 2.08 (s, 3H). 13 C NMR (201MHz, CDCl3) δ 158.0, 146.6, 142.9, 142.6, 141.7, 140.9, 137.1, 136.0, 131.6,131.5, 131.2, 130.7, 129.5, 128.1, 127.5, 127.5, 126.9, 126.0, 121.1, 41.3,18.9.

[0112] Example 14

[0113] In a dry reaction tube, 3-methyl-2-(2-(4-(trifluoromethoxy)phenyl)propyl)pyridine (0.15 mmol), 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane (0.225 mmol), Pd(OAc)₂ (0.015 mmol), N-acetyl-L-valine (0.015 mmol), and Ag₂CO₃ (0.30 mmol) were added sequentially, followed by the addition of 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(3,3-diphenyl-2-(4-(trifluoromethoxy)phenyl)allyl)-3-methylpyridine, with the chemical structure shown in Formula 20. The overall yield of the diaromatic product was 55%, and it was a pale yellow oil.

[0114]

[0115] 1 H NMR (800 MHz, CDCl3)δ 8.33 (dd, J = 4.9, 1.7 Hz, 1H), 7.40 -7.37 (m,2H), 7.28 (t, J = 7.6 Hz, 2H), 7.25-7.22 (m, 2H), 7.08-7.05 (m, 2H), 7.04-6.99(m, 3H), 6.95-6.93 (m, 3H), 6.84 (d, J = 8.3 Hz, 2H), 4.01 (s, 2H), 2.08 (s, 3H). 13 C NMR (201 MHz, CDCl3) δ 158.0, 147.2, 146.6, 142.8, 142.5, 141.9,141.1, 137.1, 135.8, 131.5, 131.2, 130.7, 129.5, 128.1, 127.4, 126.9, 126.1,121.1, 119.7, 41.4, 18.9.

[0116] Example 15

[0117] In a dry reaction tube, 0.15 mmol of 2-(2-(2,4-dimethylphenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-(3,5-dimethylphenyl)-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 21. The overall yield of the diaromatic product was 63%, a white solid.

[0118]

[0119] 1 H NMR (800 MHz, CDCl3) δ 8.34 (d, J = 3.3 Hz, 1H), 7.41 (d, J = 7.2 Hz, 1H), 7.28 (t, J = 7.5 Hz, 2H), 7.22 (q, J = 8.1, 6.7 Hz, 2H), 7.05-6.95 (m, 6H), 6.92 (dd, J = 7.5, 4.9 Hz, 1H), 6.63 (s, 2H), 6.60 (s, 1H), 4.01 (s, 2H), 2.09(s, 3H), 2.05 (s, 6H). 13 C NMR (201 MHz, CDCl3) δ 158.5, 146.3, 143.4, 143.0,141.8, 140.6, 137.2, 137.0, 136.4, 131.7, 130.7, 129.7, 128.0, 127.7, 127.5,127.2, 126.6, 125.7, 120.9, 41.5, 21.1, 19.0.

[0120] Example 16

[0121] In a dry reaction tube, 0.15 mmol of 2-(2-(3,5-dimethylphenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-(3,5-dimethylphenyl)-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 22. The overall yield of the diaromatic product was 63%, a white solid.

[0122]

[0123] 1 H NMR (800 MHz, CDCl3) δ 8.35 (d, J = 3.2 Hz, 1H), 7.55 (d, J = 6.8 Hz, 1H), 7.35 (t, J = 7.7 Hz, 2H), 7.28 (t, J = 7.4 Hz, 1H), 7.23 (d, J = 9.3 Hz, 1H),7.02-6.93 (m, 7H), 6.75 (d, J = 8.9 Hz, 2H), 6.68 (s, 1H), 4.09 (d, J = 14.8 Hz, 1H), 3.88 (d, J = 14.8 Hz, 1H), 2.13 (s, 3H), 2.04 (s, 3H), 1.97 (s, 3H). 13 C NMR(201 MHz, CDCl3) δ 158.3, 146.3, 142.9, 142.7, 140.7, 140.4, 137.0, 136.0,133.4, 132.5, 131.8, 130.7, 130.1, 130.0, 129.5, 128.0, 127.0, 127.0, 126.7,125.8, 121.0, 41.7, 29.7, 20.8, 19.1, 18.8.

[0124] Example 17

[0125] In a dry reaction tube, 0.15 mmol of 2-(2-(2-chloro-4-fluorophenyl)propyl)-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-(3-chloro-5-fluorophenyl)-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 23. The overall yield of the diaromatic product was 66%, a pale yellow oil.

[0126]

[0127] 1 H NMR (800 MHz, CDCl3) δ 8.32 (d, J = 4.8 Hz, 1H), 7.45 (d, J = 7.9 Hz, 2H), 7.30 (t, J = 7.8 Hz, 2H), 7.26 (dd, J = 9.9, 3.8 Hz, 2H), 7.06 (d, J = 8.2 Hz, 2H), 7.04 (d, J = 6.0 Hz, 1H), 7.01 (d, J = 8.5 Hz, 2H), 6.94 (dd, J = 7.6, 4.9 Hz, 1H), 6.87 (t, J = 8.1 Hz, 1H), 6.83 (d, J = 9.6 Hz, 1H), 6.71 (d, J = 8.3 Hz, 1H), 4.00 (s, 2H), 2.08 (s, 3H); 13 C NMR (201 MHz, CDCl3) δ 160.4 (m, J= 247.2 Hz),157.8, 146.5, 143.9, 142.3, 141.9, 137.2, 133.6, 133.6, 132.6, 131.7, 130.6,129.7, 129.5, 128.1, 127.5, 127.1, 126.4, 123.6 (m, J = 40.2 Hz), 121.1, 115.6 (m, J = 26.1Hz), 40.2, 18.8.

[0128] Example 18

[0129] In a dry reaction tube, 0.15 mmol of 3-methyl-2-(2-(phenyl-d5)propyl)pyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)2, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag2CO3 were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(3,3-diphenyl-2-(phenyl-d5)allyl)-3-methylpyridine, with the chemical structure shown in Formula 24. The overall yield of the diaromatic product was 58%, a pale yellow oil.

[0130]

[0131] 1 H NMR (800 MHz, CDCl3) δ 8.31 (d, J = 4.7 Hz, 1H), 7.43 (d, J = 6.8 Hz, 2H), 7.30 (d, J = 7.5 Hz, 2H), 7.27-7.21 (m, 3H), 7.02 (d, J = 5.1 Hz, 3H), 6.97(d, J = 8.3 Hz, 3H), 6.92 (dd, J = 7.6, 5.0 Hz, 1H), 4.04 (s, 2H), 2.10 (s, 3H). 13C NMR (201 MHz, CDCl3) δ 158.2, 146.4, 143.1, 142.9, 142.1, 141.1, 137.1,131.7, 130.7, 129.7, 129.6, 129.3, 128.1, 127.9, 127.3, 127.2, 126.7, 125.8,121.0, 41.5, 19.0.

[0132] Example 19

[0133] In a dry reaction tube, 0.15 mmol of 3,5-dimethyl-2-(2-phenylpropyl)pyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 3,5-dimethyl-2-(2,3,3-triphenylallyl)pyridine, with the chemical structure shown in Formula 25. The overall yield of the diaromatic product was 63%, a pale yellow oil.

[0134]

[0135] 1 H NMR (800 MHz, CDCl3) δ 8.16 (s, 1H), 7.45 (d, J = 6.8 Hz, 2H), 7.29(t, J = 7.6 Hz, 2H), 7.23 (t, J = 7.4 Hz, 1H), 7.05 (d, J = 6.7 Hz, 2H), 7.04 (s,1H), 7.03-6.95 (m, 8H), 4.01 (s, 2H), 2.19 (s, 3H), 2.06 (s, 3H). 13C NMR (201MHz, CDCl3) δ 155.1, 146.7, 143.2, 143.0, 142.2, 140.9, 137.9, 137.9, 137.3,130.9, 130.8, 130.1, 129.9, 129.7, 128.0, 127.3, 126.6, 125.8, 125.7, 41.0,18.8, 17.8.

[0136] Example 20

[0137] In a dry reaction tube, 0.15 mmol of 2-isobutyl-3-methylpyridine, 0.225 mmol of 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoboronylcyclopentane, 0.015 mmol of Pd(OAc)₂, 0.015 mmol of N-acetyl-L-valine, and 0.30 mmol of Ag₂CO₃ were added sequentially, followed by 1 mL of p-xylene as solvent. The reaction was carried out at 110 °C for 16 hours. After the reaction, the solvent was removed under reduced pressure, and the product (petroleum ether / ethyl acetate = 25 / 1) was separated by column chromatography to give 2-(2-benzyl-3,3-diphenylallyl)-3-methylpyridine, with the chemical structure shown in Formula 26. The overall yield of the diaromatic product was 65%, a white solid.

[0138]

[0139] 1 H NMR (800 MHz, CDCl3) δ 8.18 (dd, J = 4.9, 1.7 Hz, 1H), 7.28-7.26 (m,2H), 7.21-7.18 (m, 6H), 7.16 (t, J = 7.5 Hz, 2H), 7.13 (t, J = 7.5 Hz, 5H), 7.07(td, J = 7.4, 2.9 Hz, 4H), 7.01 (t, J = 7.4 Hz, 1H), 6.94 (d, J = 7.4 Hz, 1H), 6.72(dd, J = 7.5, 4.8 Hz, 1H), 5.39 (s, 1H), 3.63 (s, 2H), 1.80 (s, 3H). 13C NMR (201MHz, CDCl3) δ 155.6, 145.9, 143.5, 143.3, 143.3, 142.9, 136.1, 136.0, 130.6,129.7, 128.8, 128.7, 128.0, 127.6, 127.6, 126.2, 126.1, 125.8, 120.2, 54.5,36.7, 19.1.

[0140] Comparative Example 1

[0141] The only difference between this comparative example and Example 2 was that N-acetyl-L-valine was replaced with pyroglutamic acid. No diarylized product was obtained.

[0142] Comparative Example 2

[0143] This comparative example did not add any amino acid ligands, and the other conditions were the same as in Example 2. No diarylized product was obtained.

[0144] The applicant declares that the detailed structural features of the present invention are illustrated through the above embodiments, but the present invention is not limited to the above detailed structural features, that is, it does not mean that the present invention must rely on the above detailed structural features to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions for the components selected in the present invention, additions of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0145] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0146] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

[0147] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.

Claims

1. A method for distal C(sp3)-H bond diarylation, characterized in that, The method includes the following steps: The pyridine derivatives shown in Formula 1 or Formula 2 were reacted with 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane in a catalytic system of Ag2CO3, N-acetyl-Lvaline and Pd(OAc)2. R1 includes methyl, substituted or unsubstituted phenyl groups.

2. The method as described in claim 1, characterized in that, The substituents of the phenyl group include hydrogen, deuterium, halogen, ketone, amino, aldehyde, cyano, alkyl, or alkoxy.

3. The method as described in claim 1, characterized in that, The amino acid ligands include one or more of N-acetyl-L-valine, (tert-butoxycarbonyl)alanine, L-tert-leucine, or glycine.

4. The method as described in claim 1, characterized in that, The molar ratio of the pyridine derivative to 2-(2-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane is 1:1~2.

5. The method as described in claim 1, characterized in that, The molar ratio of the pyridine derivative to Pd(OAc)2 is 1:0.005~0.

02.

6. The method as described in claim 1, characterized in that, The molar ratio of Pd(OAc)2 to N-acetyl-Lvaline is 1:1~2.

7. The method as described in claim 1, characterized in that, The reaction is carried out in an organic solvent, including p-xylene.

8. The method as described in claim 1, characterized in that, The reaction temperature is 80~130℃, and the reaction time is 10~20h.

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