An allyl-substituted biaryl compound and its preparation method

Abstract

This invention provides an allyl-substituted biaryl compound and its preparation method. The method utilizes 1-arylisoquinoline or substituted pyridine as a substrate and allyl acetate as an allylation reagent. The nitrogen atom directs C-H activation, followed by the interaction between the carbon-metal bond and the allyl metal to complete the C-H activation / allylation reaction. This process is mild and simple; it can be carried out efficiently with low catalyst loading, and has advantages such as readily available raw materials, mild reaction conditions, high atom economy, and a wide range of applicable substrates.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to an allyl-substituted biaryl compound, its preparation method, and its application. Background Technology

[0002] Allyl-modified aromatic and heterocyclic compounds, as an important class of structural units, have shown broad application prospects in various fields such as medicinal chemistry, fragrance industry, and functional materials due to their unique chemical properties. Of particular note is the significant lipophilic property conferred by the benzyl group, which not only effectively enhances the drug-like properties of these compounds in the biopharmaceutical field, but also provides key structural support for the molecular design of novel agrochemicals.

[0003] Traditional coupling methods still face two key challenges: firstly, the substrate requires pre-activation (e.g., introducing halogen / metal functional groups), leading to cumbersome synthetic steps and poor atom economy; secondly, the chemical instability of key intermediates (especially heteroaryl metal reagents) severely hinders their industrial application. These technical bottlenecks have prompted researchers to dedicate themselves to developing more efficient, greener, and more universally applicable novel C-allylation methods. Summary of the Invention

[0004] The present invention aims to solve at least one of the technical problems existing in the prior art, and innovatively provides a new synthetic strategy for allyl-substituted biaryl compounds.

[0005] Therefore, in a first aspect, this invention provides a method for preparing allyl-substituted biaryl compounds by rhodium-catalyzed CH bond activation / allylation. This method utilizes 1-arylisoquinoline or substituted pyridine as a substrate and allyl acetate as an allylation reagent. The activation of CH is promoted by the directing effect of the nitrogen atom, followed by the interaction between the carbon-metal bond and the allyl metal to complete the CH activation / allylation reaction. This process is mild and simple; it can be carried out efficiently with low catalyst loading, and has advantages such as readily available raw materials, mild reaction conditions, high atom economy, and a wide range of applicable substrates.

[0006] In a second aspect, the present invention provides an allyl-substituted biaryl compound prepared by the above method.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] The method for preparing an allyl-substituted biaryl compound provided in the first aspect of the present invention includes the following steps: under a protective gas atmosphere, in a polar organic solvent, in the presence of a rhodium catalyst, a halogen reagent, a metal oxidant and an additive, compound 1 and compound 2 are subjected to the CH activation / allylation reaction as shown below to obtain compound of general formula 3.

[0009]

[0010] The structural formula of compound 3 is shown in any one of formulas I to III:

[0011]

[0012] In a preferred embodiment of the present invention, the molar ratio of compound 1 to compound 2 is 1:(1-3).

[0013] In a preferred embodiment of the present invention, the polar organic solvent is selected from at least one of methanol, tert-amyl alcohol, acetonitrile, N,N-dimethylformamide, dichloromethane, dichloroethane, tetrahydrofuran, o-xylene, or n-hexane;

[0014] The metal oxidant is selected from at least one of copper acetate, silver acetate, silver carbonate, silver nitrate, silver oxide, or cuprous oxide.

[0015] The additive is selected from at least one of cesium carbonate, sodium carbonate, silver carbonate, lithium carbonate, cesium fluoride, or sodium acetate.

[0016] The volume molar ratio of the solvent to compound 1 is (0.05-0.2) mmol / mL.

[0017] In a preferred embodiment of the present invention, during the reaction, the rhodium catalyst is a dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2); the catalyst dosage is 3.0-5.0 mol%, preferably 5 mol%;

[0018] The halogenating agent used in the reaction is AgSbF6, with an amount of 10-30 mol%, preferably 20 mol%.

[0019] The reaction temperature is 40-100 ℃, and the reaction time is 20-24 h.

[0020] Furthermore, the reaction is carried out under a protective gas atmosphere; the reaction temperature is preferably 80 °C; the solvent is preferably methanol (MeOH); the halogenating agent is silver hexafluoroantimonate (AgSbF6); the oxidant is preferably silver acetate (AgOAc); the additive is preferably cesium fluoride (CsF); the molar ratio of compound 1 to compound 2 is preferably 1:3; the volume molar ratio of solvent to compound 1 is preferably 0.1 mmol / mL; and the reaction time is preferably 22 h. The raw materials used in the preparation of this invention are simple, readily available, environmentally friendly, and inexpensive; the reaction conditions are mild, the operation is simple, and the yield is high; the post-reaction processing is convenient and suitable for industrial production.

[0021] In addition, after the reaction is completed, the product separation and purification steps are included, such as filtration, concentration, and column chromatography. For example, after the reaction is completed, the product is cooled to room temperature, quenched with water, extracted three times with dichloromethane, the organic phases are combined, washed with saturated brine, dried over anhydrous Na2SO4, filtered through silica gel, the liquid is collected, concentrated by vacuum distillation to remove the organic solvent, and then separated by column chromatography.

[0022] According to a second aspect of the present invention, an allyl-substituted biaryl compound (compound 3) prepared according to the above method is provided, the specific structure of which is shown in any one of formulas I to IV above:

[0023]

[0024] Preferably, R1 is independently selected from H, halogen, C 1-12 Alkyl, C 1-12 Alkoxy, substituted or unsubstituted phenyl;

[0025] R2 is independently selected from H, halogen, C 1-12 Alkyl, C 1-12 Alkoxy, C 2-12 Straight-chain alkanes containing unsaturated bonds;

[0026] R3 is independently selected from H and C. 1-12 alkyl;

[0027] Furthermore, in R1, the C mentioned 1-12 Alkyl group is C 1-3 alkyl groups; the C 1-12 The alkoxy group is C 1-3 The alkoxy group; the substituted or unsubstituted phenyl group is a phenyl group;

[0028] When R1 is a halogen, the halogen is fluorine or chlorine;

[0029] In R2, C 1-12 Alkyl group is C 1-3 alkyl groups; the C 1-12 The alkoxy group is C1-3 The alkoxy group; the C 2-12 Straight-chain alkanes containing unsaturated bonds have allyl substituents;

[0030] When R2 is a halogen, the halogen is bromine or chlorine;

[0031] In R3, the C mentioned 1-12 The alkyl group is C 1-3 Alkyl groups.

[0032] According to a preferred embodiment of the present invention, the allyl-substituted biaryl compound is selected from at least one of the following allyl-substituted biaryl compounds:

[0033]

[0034] Compared with the prior art, the present invention has the following technical effects:

[0035] The present invention directly constructs an allyl-substituted biaryl compound in one step from the starting material 1-arylisoquinoline or substituted pyridine (compound 1) and allyl acetate (compound 2) under the conditions of a rhodium catalyst, a halogenating agent, an oxidant, an additive, and a solvent. The starting materials of the present invention are simple, readily available, environmentally friendly, and inexpensive; the reaction conditions are mild, the operation is simple, and the yield is high; gram-scale preparation can be achieved while maintaining a high yield; no pre-functionalization step is required, significantly reducing costs; the post-reaction processing is simple and suitable for industrial production. Detailed Implementation

[0036] Definitions and general terms

[0037] As used in this article, "substituted or unsubstituted" means that a group may or may not be further substituted by one or more groups selected from the following: C 1-10 alkyl, C 1-10 alkoxy, nitro, halogen, hydroxyl, cyano, carboxyl, C 2-5 ester group, C 1-10 alkyl halogenates.

[0038] “C 1-10 "alkyl" indicates an alkyl group with a total number of carbon atoms of 1-10, including C10 and C20. 1-10 straight-chain alkyl, C 1-10 Branched alkyl groups and C 3-10The cycloalkyl group can be, for example, a straight-chain alkyl group with a total number of carbon atoms of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; a branched-chain alkyl group with a total number of carbon atoms of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; or a cycloalkyl group with a total number of carbon atoms of 3, 4, 5, 6, 7, 8, 9, or 10, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, methylcyclopropyl, ethylcyclopropyl, cyclopentyl, methylcyclopentyl, cyclohexyl, etc. "C 1-6 "alkyl" has a similar interpretation, except that the number of carbon atoms is different.

[0039] “C 1-10 "alkoxy group" refers to an alkoxy group with a total number of carbon atoms of 1-10, including C. 1-10 straight-chain alkoxy, C 1-10 Branched alkoxy groups and C 2-10 The cycloalkoxy group can be, for example, a straight-chain alkoxy group with a total number of carbon atoms of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; a branched-chain alkoxy group with a total number of carbon atoms of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; or a cycloalkoxy group with a total number of carbon atoms of 2, 3, 4, 5, 6, 7, 8, 9, or 10, such as methoxy, ethoxy, n-propoxy, isopropoxy, etc. "C 1-6 The "alkoxy group" has a similar explanation, except that the number of carbon atoms is different.

[0040] "Substituted or unsubstituted phenyl" means that at least one H in the phenyl group is optionally substituted by the corresponding group defined herein.

[0041] C 2-12 "A straight-chain alkane containing unsaturated bonds" refers to a straight-chain or branched hydrocarbon group having one or more double or triple bonds, and the total number of carbon atoms in the alkenyl group is 2-12, and the double bonds in the group can be in any position.

[0042] "Halogen" includes any one or more of fluorine, chlorine, bromine, and iodine.

[0043] Unless otherwise specified, the term "about" in this invention actually means that the error is allowed to be within ±1%, for example, about 100 is actually 100 ± 1% × 100.

[0044] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention.

[0045] The following are specific embodiments of the present invention, and the technical solutions of the present invention will be further described in conjunction with the embodiments, but the present invention is not limited to these embodiments.

[0046] Unless otherwise specified, the reagents, methods and equipment used in this invention are all conventional reagents, methods and equipment in this technical field.

[0047] The yield calculation method of this invention is as follows: Yield = Product mass / (Product molecular weight * Amount of material fed).

[0048] Example 1

[0049] The allyl-substituted biaryl compound provided in Example 1 has the chemical name 1-(2-allylnaphth-1-yl)isoquinoline, and its structural formula and preparation method are as follows:

[0050]

[0051] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-naphthylisoquinoline (1a, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 10 / 1, R f = 0.35), the purified product weighed 44.3 mg, and was a light yellow oily substance with a yield of 75%. The product characterization data are as follows:

[0052] 1H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 6.0 Hz, 1H), 7.98 (d, J = 8.4Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.80 (d, J = 6.0Hz, 1H), 7.72-7.69 (m, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.45-7.42 (m, 2H), 7.41-7.38 (m, 1H), 7.28-7.25 (m, 1H), 7.02 (d, J = 8.4 Hz, 1H), 5.85-5.78 (m,1H), 4.91-4.89 (m, 1H), 4.87-4.84 (m, 1H), 3.23-3.15 (m, 2H). 13 C NMR (151MHz, CDCl3) δ 160.1, 142.5, 136.7, 136.3, 136.2, 134.6, 132.9, 132.2, 130.4,128.7, 127.9, 127.5, 127.5, 127.4, 126.9, 126.3, 125.9, 125.3, 120.2, 115.9,38.2. HRMS (ESI): exact mass calculated for: C 22 H 17 N [M+H] + : 296.1434, found296.1459.

[0053] Example 2

[0054] Example 2 provides an allyl-substituted biaryl compound, chemically named 1-(2-allyl-4-methylnaphth-1-yl)isoquinoline, with the following structural formula and preparation method:

[0055]

[0056] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-(4-methylnaphth-1-yl)isoquinoline (1b, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 10 / 1, R f = 0.38), the purified product weighed 44.5 mg, and was a light yellow oily substance with a yield of 72%. The product characterization data are as follows:

[0057] 1 H NMR (600 MHz, CDCl3) δ 8.73 (d, J = 5.4 Hz, 1H), 8.05 (dt, J = 8.4,0.6 Hz, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.76 (dd, J = 6.0, 1.2 Hz, 1H), 7.68-7.65 (m, 1H), 7.46-7.42 (m, 2H), 7.38 (s, 1H), 7.37-7.35 (m, 1H), 7.25-7.22(m, 1H), 7.0 (dt, J = 8.4, 0.6 Hz, 1H), 5.82-5.75 (m, 1H), 4.88-4.86 (m, 1H), 4.85-4.81 (m, 1H), 3.16-3.08 (m, 2H), 2.79 (s, 3H). 13C NMR (150 MHz, CDCl3) δ160.4, 142.6, 136.9, 136.2, 135.9, 135.0, 133.1, 133.0, 131.5, 130.3, 128.9,128.3, 127.6, 127.3, 126.9, 126.6, 125.9, 125.1, 124.1, 120.1, 115.8, 38.2,19.6. HRMS (ESI): exact mass calculated for: C 23 H 19 N [M+H] + : 310.1590, found310.1608.

[0058] Example 3

[0059] Example 3 provides an allyl-substituted biaryl compound, chemically named 1-(2-allyl-4-methoxynaphth-1-yl)isoquinoline, with the following structural formula and preparation method:

[0060]

[0061] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-(4-methoxynaphth-1-yl)isoquinoline (1c, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 5 / 1, R f = 0.30), the purified product weighed 49.4 mg, was a light yellow oil, and the yield was 76%. The product characterization data are as follows:

[0062] 1H NMR (600 MHz, CDCl3) δ 8.72 (d, J = 5.4 Hz, 1H), 8.31 (d, J = 8.4Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 6.0 Hz, 1H), 7.68-7.65 (m,1H), 7.45 (dd, J = 6.4, 1.2 Hz, 1H), 7.41-7.35 (m, 2H), 7.25-7.22 (m, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.85 (s, 1H), 5.83-5.76 (m, 1H), 4.90-4.84 (m, 2H),4.09 (s, 3H), 3.15–3.12 (m, 2H). 13 C NMR (150 MHz, CDCl3) δ 160.4, 155.8,142.6, 136.9, 136.7, 136.3, 134.0, 130.3, 129.2, 127.7, 127.3, 126.9, 126.8,125.7, 124.6, 124.5, 121.9, 120.1, 116.0, 105.4, 55.7, 38.7. HRMS (ESI):exact mass calculated for: C 23 H 19 NO [M+H] + : 326.1539, found 326.1569.

[0063] Example 4

[0064] Example 4 provides an allyl-substituted biaryl compound, chemically named 1-(2-allyl-4-phenylnaphth-1-yl)isoquinoline, with the following structural formula and preparation method:

[0065]

[0066] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-(4-phenylnaphth-1-yl)isoquinoline (1d, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 10 / 1, R f = 0.44), the purified product weighed 52.0 mg, and was a light yellow oily substance with a yield of 70%. The product characterization data are as follows:

[0067] 1 H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 5.4 Hz, 1H), 7.98 (d, J = 8.4Hz, 1H), 7.94 (d, J = 9.0 Hz, 1H), 7.83 (d, J = 5.4 Hz, 1H), 7.73 (t, J = 7.8Hz, 1H), 7.59-7.58 (m, 2H), 7.54 (q, J = 8.4 Hz, 3H), 7.48 (s, 1H), 7.47-7.43(m, 2H), 7.37-7.34 (m, 1H), 7.25-7.23 (m, 1H), 7.03 (d, J = 8.4 Hz, 1H),5.83-5.76 (m, 1H), 4.86-4.79 (m, 2H), 3.24-3.15 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 160.2, 142.8, 142.7, 141.0, 140.8, 136.6, 136.3, 135.8, 134.4,133.3, 130.6, 130.4, 130.2, 128.8, 128.6, 128.3, 127.5, 127.4, 127.4, 127.3,127.0, 126.3, 126.1, 125.4, 120.2, 116.1, 38.2. HRMS (ESI): exact masscalculated for: C 28 H 21 N [M+H] + : 372.1747, found 372.1783.

[0068] Example 5

[0069] Example 5 provides an allyl-substituted biaryl compound, chemically named 1-(2-allyl-4-fluoronaphth-1-yl)isoquinoline, with the following structural formula and preparation method:

[0070]

[0071] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-(4-fluoronaphth-1-yl)isoquinoline (1e, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 10 / 1, R f = 0.37), the purified product weighed 52.0 mg, and was a light yellow oily substance with a yield of 83%. The product characterization data are as follows:

[0072] 1 H NMR (600 MHz, CDCl3) δ 8.73 (dd, J = 5.4, 1.2 Hz, 1H), 8.16 (d, J =8.4 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 5.4 Hz, 1H), 7.70-7.68(m, 1H), 7.47 (ddd, J = 8.4, 6.6, 1.2 Hz, 1H), 7.41-7.38 (m, 2H), 7.30-7.27(m, 1H), 7.23 (d, J = 10.8 Hz, 1H), 6.99 (dd, J = 8.4, 1.2 Hz, 1H ), 5.80-5.73 (m, 1H), 4.93-4.91 (m, 1H), 4.88-4.84 (m, 1H), 3.17-3.07 (m, 2H). 13 CNMR (150 MHz, CDCl3) δ 159.4, 158.9 (d, J = 253.7 Hz), 142.6, 137.1 (d, J =7.6 Hz), 136.3, 136.1, 134.4 (d, J = 4.5 Hz), 130.8, 130.5, 128.9, 127.5,127.3, 127.3, 127.0, 125.9 (d, J = 3.0 Hz), 125.6 (d, J = 1.5 Hz), 122.6 (d,J = 16.6 Hz), 120.5 (d, J = 4.5 Hz), 120.4, 116.6, 110.8 (d, J = 19.6 Hz), 38.1. 19 F NMR (377 MHz, CDCl3) δ -122.9. HRMS (ESI): exact mass calculated for:C 22 H 16 FN [M+H] + : 314.1340, found 314.1365.

[0073] Example 6

[0074] Example 6 provides an allyl-substituted biaryl compound, chemically named 1-(2-allyl-4-chloronaphth-1-yl)isoquinoline, with the following structural formula and preparation method:

[0075]

[0076] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-(4-chloronaphth-1-yl)isoquinoline (1f, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 10 / 1, R f = 0.36), the purified product weighed 50.0 mg, and was a light yellow oily substance with a yield of 76%. The product characterization data are as follows:

[0077] 1 H NMR (600 MHz, CDCl3) δ 8.73 (d, J = 6.0 Hz, 1H), 8.34 (d, J = 9.0Hz, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 6.0 Hz, 1H), 7.70-7.67 (m,1H), 7.66 (s, 1H), 7.54-7.51 (m, 1H), 7.39-7.38 (m, 2H), 7.30-7.28 (m, 1H),7.02 (d, J = 8.4 Hz, 1H), 5.80-5.73 (m, 1H), 4.93-4.91 (m, 1H), 4.88-4.84 (m, 1H), 3.16–3.07 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 159.2, 142.7, 136.8, 136.3,136.0, 134.2, 134.1, 132.5, 130.5, 129.6, 128.7, 127.6, 127.6, 127.2, 127.1,127.0, 126.4, 124.5, 120.4, 116.7, 37.9. HRMS (ESI): exact mass calculatedfor: C 22 H 16 ClN [M+H] + : 330.1044, found 330.1365.

[0078] Example 7

[0079] Example 7 provides an allyl-substituted biaryl compound, chemically named 1-(2-allyl-6-methylphenyl)isoquinoline, with the following structural formula and preparation method:

[0080]

[0081] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-(o-tolyl)isoquinoline (1 g, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 10 / 1, R f = 0.42), the purified product weighed 27.0 mg, was a light yellow oil, and the yield was 52%. The product characterization data are as follows:

[0082] 1H NMR (600 MHz, CDCl3) δ 8.64 (d, J = 6.0 Hz, 1H), 7.89 (d, J = 8.4Hz, 1H), 7.69-7.67 (m, 2H), 7.52-7.50 (m, 1H), 7.47-7.45 (m, 1H), 7.33 (t, J= 7.8 Hz, 1H), 7.20 (t, J = 7.8 Hz, 2H), 5.73-5.66 (m, 1H), 4.80-4.77 (m,1H), 4.71-4.67 (m, 1H), 2.99-2.91 (m, 2H), 1.90 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 161.0, 142.5, 138.6, 138.1, 137.0, 136.6, 136.3, 130.2, 128.4, 128.0, 127.9, 127.4, 127.0, 126.7, 119.8, 115.5, 37.9, 19.9. HRMS (ESI):exact mass calculated for: C 19 H 17 N [M+H] + : 260.1434, found 260.1462.

[0083] Example 8

[0084] Example 8 provides an allyl-substituted biaryl compound, chemically named 1-(2-allyl-6-methoxyphenyl)isoquinoline, with the following structural formula and preparation method:

[0085]

[0086] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-(2-methoxyphenyl)isoquinoline (1h, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 5 / 1, R f = 0.38), the purified product weighed 39.1 mg, and was a light yellow oily substance with a yield of 71%. The product characterization data are as follows:

[0087] 1 H NMR (600 MHz, CDCl3) δ 8.64 (d, J = 6.0 Hz, 1H), 7.86 (d, J = 7.8Hz, 1H), 7.67-7.64 (m, 2H), 7.56 (dd, J = 8.4, 1.2 Hz, 1H), 7.46-7.43 (m,1H), 7.40 (t, J = 7.8 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 6.91 (d, J = 8.4 Hz,1H), 5.71-5.64 (m, 1H), 4.78-4.76 (m, 1H), 4.72-4.69 (m, 1H), 3.62 (s, 3H), 3.03-2.96 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 158.6, 157.6, 142.4, 140.5,136.8, 136.1, 130.0, 129.5, 128.5, 127.7, 127.3, 127.0, 126.8, 121.8, 119.9,115.6, 108.9, 55.8, 37.5. HRMS (ESI): exact mass calculated for: C 19 H 17 NO [M+H] + : 276.1383, found 276.1401.

[0088] Example 9

[0089] Example 9 provides an allyl-substituted biaryl compound, chemically named 1-(2-allyl-6-bromophenyl)isoquinoline, with the following structural formula and preparation method:

[0090]

[0091] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-(2-bromophenyl)isoquinoline (1i, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 10 / 1, R f = 0.39), the purified product weighed 26.5 mg, was a light yellow oil, and the yield was 41%. The product characterization data are as follows:

[0092] 1H NMR (600 MHz, CDCl3) δ 8.57 (dd, J = 9.0, 5.4 Hz, 1H), 7.83 (d, J =7.8 Hz, 1H), 7.66-7.61 (m, 2H), 7.52 (dd, J = 7.8, 1.2 Hz, 1H), 7.46-7.41 (m,2H), 7.27 (d, J = 7.8 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 5.63-5.57 (m, 1H), 4.77-4.70 (m, 1H), 4.67-4.59 (m, 1H), 2.99-2.84 (m, 2H). 13 C NMR (150 MHz, CDCl3) δ 159.8, 142.2, 141.5, 136.8, 136.3, 136.1, 130.6, 130.4, 129.9,128.4, 127.6, 127.3, 127.1, 126.8, 120.6, 116.4, 115.7, 38.3. HRMS (ESI):exact mass calculated for: C 18 H 14 BrN [M+H] + : 324.0382, found 324.0404.

[0093] Example 10

[0094] Example 10 provides an allyl-substituted biaryl compound, chemically named 1-(2,6-diallyl-4-methoxyphenyl)isoquinoline, with the following structural formula and preparation method:

[0095]

[0096] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 1-(4-methoxyphenyl)isoquinoline (1k, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 10 / 1, R f = 0.45), the purified product weighed 31.0 mg, was a light yellow oil, and the yield was 49%. The product characterization data are as follows:

[0097] 1 H NMR (600 MHz, CDCl3) δ 8.62 (d, J = 6.0 Hz, 1H), 7.87 (d, J = 7.8Hz, 1H), 7.69-7.66 (m, 2H), 7.55 (d, J = 8.4 Hz, 1H), 7.48-7.45 (m, 1H), 6.79(s, 2H), 5.71-5.65 (m, 2H), 4.81-4.79 (m, 2H), 4.72-4.69 (m, 2H), 3.87 (s,3H), 2.97-2.88 (m, 4H). 13 C NMR (150 MHz, CDCl3) δ 160.5, 159.8, 142.1, 140.4,136.7, 136.7, 136.3, 130.4, 128.7, 127.3, 126.9, 120.0, 115.9, 115.9, 112.7,112.7, 55.3, 38.1, 38.1. HRMS (ESI): exact mass calculated for: C 22 H 21NO [M+H] + : 316.1696, found 316.1722.

[0098] Example 11

[0099] Example 11 provides an allyl-substituted biaryl compound, chemically named 2-(2-allylnaphth-1-yl)-3-methylpyridine, with the following structural formula and preparation method:

[0100]

[0101] Dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2) (CAS No.: 12354-85-7) (5 mol%, CAS: 12354-85-7), silver hexafluoroantimonate (20 mol%, CAS: 26042-64-8), silver acetate (2.0 equiv, CAS: 563-63-3), cesium fluoride (25 mol%, CAS: 13400-13-0), 3-methyl-2-(naphth-1-yl)pyridine (1j, 0.2 mmol), and allyl acetate (2a, 0.6 mmol, CAS: 591-87-7) were added to a 10 mL sealed tube equipped with a magnetic stirrer, and methanol (2.0 mL, CAS: 67-56-1) was added as a solvent. The mixture was stirred at 80 °C for 22 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated brine, dried over anhydrous Na₂SO₄, concentrated under reduced pressure, and purified by silica gel column chromatography. The eluent was a mixture of petroleum ether (CAS No.: 8032-32-4) and ethyl acetate (CAS No.: 141-78-6) (PE / EA = 10 / 1, R f = 0.44), the purified product weighed 40.9 mg, was a light yellow oil, and the yield was 79%. The product characterization data are as follows:

[0102] 1H NMR (600 MHz, CDCl3) δ 8.64 (dd, J = 4.8, 1.8 Hz, 1H), 7.86 (dd, J= 9.0, 3.0 Hz, 2H), 7.65 (dd, J = 7.8, 1.8 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H),7.43-7.40 (m, 1H), 7.34-7.31 (m, 1H), δ 7.29 (dd, J = 7.8, 4.8 Hz, 1H), 7.12(d, J = 8.4 Hz, 1H), 5.92-5.85 (m, 1H), 4.99-4.96 (m, 1H), 4.94-4.90 (m, 1H), 3.24 (d, J = 6.0 Hz, 2H), 1.97 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 157.9,147.3, 137.6, 136.7, 136.1, 135.1, 133.2, 132.4, 132.0, 128.2, 128.0, 127.7,126.3, 125.2, 125.2, 122.5, 115.8, 37.9, 18.8. HRMS (ESI): exact masscalculated for: C 19 H 17 N [M+H] + : 260.1434, found 260.1460.

[0103] The undescribed parts of this invention are the same as or implemented using existing technology. The applicant declares that this invention is illustrated through the above specific embodiments, but the invention is not limited to the above detailed methods, i.e., it does not mean that the invention must rely on the above detailed methods to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials for the product of this invention, additions of auxiliary components, and selection of specific methods all fall within the protection and disclosure scope of this invention.

Claims

1. An allyl-substituted biaryl compound, characterized in that, Its structural formula is that of the compound shown in formula I, II or III: ， R1 is independently selected from H, halogens, and C. 1-12 Alkyl, C 1-12 Alkoxy, substituted or unsubstituted phenyl; R2 is independently selected from H, halogen, C 1-12 Alkyl, C 1-12 Alkoxy, C 2-12 Straight-chain alkanes containing unsaturated bonds; R3 is independently selected from H and C. 1-12 alkyl.

2. The isoquinolone compound according to claim 1, characterized in that: in, In R1, the C 1-12 Alkyl group is C 1-3 alkyl groups; the C 1-12 The alkoxy group is C 1-3 The alkoxy group; the substituted or unsubstituted phenyl group is selected from phenyl groups; When R1 is a halogen, the halogen is fluorine or chlorine; In R2, C 1-12 Alkyl group is C 1-3 alkyl groups; the C 1-12 The alkoxy group is C 1-3 The alkoxy group; the C 2-12 Straight-chain alkanes containing unsaturated bonds have allyl substituents; When R2 is a halogen, the halogen is bromine or chlorine; In R3, the C mentioned 1-12 The alkyl group is C 1-3 Alkyl groups.

3. The allyl-substituted biaryl compound according to claim 1 or 2, characterized in that, The allyl-substituted biaryl compound is selected from at least one of the following formulas:

4. The method for preparing the allyl-substituted biaryl compound according to claim 1 or 2, characterized in that, Includes the following steps: Under a protective gas atmosphere, in a polar organic solvent, and in the presence of a rhodium catalyst, a halogenated reagent, a metal oxidant, and additives, compound 1 and compound 2 undergo the CH activation / allylation reaction shown below to obtain compound 3, which is an allyl-substituted biaryl compound. The reaction formula is as follows: ， The molar ratio of compound 1 to compound 2 is 1:1-3; The volume molar ratio of the polar organic solvent to compound 1 is 0.05-0.2 mmol / mL; The amount of rhodium catalyst used is 3.0-5.0 mol%; The amount of the halogenating reagent used is 10-30 mol%; The reaction temperature is 40-100℃, and the reaction time is 20-24h.

5. The preparation method according to claim 4, characterized in that, The protective gas is selected from argon; Compound 1 is selected from 1-arylisoquinoline or substituted pyridine; The polar organic solvent is selected from at least one of methanol, tert-amyl alcohol, acetonitrile, N,N-dimethylformamide, dichloromethane, dichloroethane, tetrahydrofuran, o-xylene, or n-hexane; The metal oxidant is selected from at least one of copper acetate, silver acetate, silver carbonate, silver nitrate, silver oxide, or cuprous oxide. The additive is selected from at least one of cesium carbonate, sodium carbonate, silver carbonate, lithium carbonate, cesium fluoride, or sodium acetate.

6. The preparation method according to claim 4, characterized in that, The rhodium catalyst is a dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([Cp*RhCl2]2), used in an amount of 5.0 mol%; The halogenating agent used in the reaction was AgSbF6, and the amount used was 20 mol.

7. The preparation method according to claim 4, characterized in that, in The reaction was carried out under a protective gas atmosphere; the reaction temperature was 80 °C; the solvent was methanol; the halogenating agent was silver hexafluoroantimonate (AgSbF6); the oxidizing agent was silver acetate (AgOAc); and the additive was cesium fluoride (CsF). The molar ratio of compound 1 to compound 2 is 1:3, the preferred volume molar ratio of solvent to compound 1 is 0.1 mmol / mL, and the reaction time is 22 h.

8. The preparation method according to claim 4, characterized in that, The process also includes the separation and purification of the product: after the reaction is completed, the product is cooled to room temperature, quenched with water, extracted three times with dichloromethane, and the organic phases are combined; then it is washed with saturated brine, dried with anhydrous Na2SO4, filtered with silica gel, the liquid is collected, concentrated by vacuum distillation to remove the organic solvent, and then separated by column chromatography.

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