Preparation method of visible light catalysis beta-aryl beta-pyridyl alkyl ketone compound

Abstract

The invention discloses a preparation method of a beta-aryl beta-pyridyl alkyl ketone compound, which comprises the following steps: in the presence of a photocatalyst and under the condition of blue light irradiation, reacting a compound shown as a formula (1), a compound shown as a formula (2) and a compound shown as a formula (3) to generate the beta-aryl beta-pyridyl alkyl ketone compound shown as a formula (4), wherein Ar is selected from substituted or unsubstituted aryl, naphthyl and heteroaryl; the compound in the formula (2) is 4-cyanopyridine; the compound of formula (3) is aldehyde; and the photocatalyst is selected from tetrabutyl ammonium decatungstate (TBADT), 9-thioxanthone and a benzophenone type photocatalyst. The preparation method provided by the invention has the advantages of cheap and easily available reaction raw materials, simple reaction operation, wide application range of reaction substrates, easy amplification of reaction, mild reaction conditions and the like, and can realize industrial production and application. # imgabs0 #

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing a delta-aryl delta-pyridyl alkyl ketone compound. Background Art

[0002] In organic synthesis, carbonyl compounds can be reduced to give alcohol compounds, Wittig reaction to give olefins, and reductive amination reaction to give organic amine compounds. Therefore, carbonyl compounds are a very important class of synthons in organic synthesis. At the same time, carbonyl fragments are also widely present in the molecular structure of drugs, such as the lipid regulator fenofibrate, the antipyretic analgesic ketoprofen, and the contraceptive levonorgestrel.

[0003] Heterocyclic rings are a type of structural fragment that is widely found in organic compounds, especially in drug molecules, such as the anticancer drug Ensinco and the anticancer drug Abiraterone. According to statistics, more than 90% of newly approved drugs contain heterocyclic structures, highlighting their important role in medicinal chemistry.

[0004] β-Aryl β-pyridyl alkyl ketone compounds have two important functional groups, carbonyl and heterocyclic. Therefore, they are not only widely used in organic synthesis, but also the core skeleton of drug molecules, such as Gpr116 receptor antagonists, lyase inhibitors, etc.

[0005] Introducing carbonyl and heterocyclic rings at both ends of olefins is a very efficient and simple method to obtain β-aryl β-pyridyl alkyl ketone compounds. In 2024, Chen and Du's research group reported a synthesis method of β-aryl δ-pyridyl alkyl ketones based on a single electron transfer strategy (Zhang, Z.; Wang, J.; Yu, C.; Tan, J.; Du, H.; Chen, N.; Org. Lett. 2024, 26, 4727-4732), and disclosed a metal-free, visible light-driven difunctionalization reaction of acyl DHP derivatives with aromatic olefins and cyanopyridines. The reaction process is shown in the following equation:

[0006]

[0007] However, this technology has obvious defects: first, the reaction can only use aromatic acyl DHP esters as free radical precursors; second, the reaction produces substituted pyridine as a by-product, and the atom economy of the reaction is relatively poor. Summary of the invention

[0008] The present invention provides a method for preparing a β-aryl δ-pyridyl alkyl ketone compound. The present invention realizes for the first time the synthesis of multiple types of β-aryl β-pyridyl alkyl ketone compounds under light-induced conditions by using easily available alkyl aldehydes and aryl aldehydes as free radical precursors.

[0009] The technical solution of the present invention is as follows:

[0010] A method for preparing a β-aryl δ-pyridyl alkyl ketone compound comprises: reacting a compound of formula (1), a compound of formula (2) and a compound of formula (3) in the presence of a photocatalyst and under blue light irradiation to generate a β-aryl β-pyridyl alkyl ketone compound of formula (4):

[0011]

[0012] Wherein, Ar is selected from substituted or unsubstituted aryl, naphthyl, heteroaryl;

[0013] The compound of formula (2) is 4-cyanopyridine;

[0014] The compound of formula (3) is an aldehyde;

[0015] The photocatalyst is selected from tetrabutylammonium decatungstate (TBADT), 9-thioxanthone and benzophenone photocatalysts.

[0016] The compound of formula (3) may be a primary alkyl aldehyde, a secondary alkyl aldehyde, an aromatic aldehyde, or an aldehyde derived from a natural amino acid.

[0017] Preferably, the compound of formula (1) is selected from:

[0018]

[0019]

[0020] The compound of formula (3) is selected from:

[0021]

[0022] Preferably, the photocatalyst is selected from:

[0023]

[0024] Preferably, the wavelength of the blue light is 390-440 nm; more preferably 390 nm or 427 nm.

[0025] Preferably, the reaction is carried out in an organic solvent, and the organic solvent is at least one of acetonitrile, dimethyl sulfoxide, ethyl acetate and acetone.

[0026] Preferably, the molar ratio of the compound of formula (1), the compound of formula (2), the compound of formula (3) and the photocatalyst is 1:1.0-2.5:2.0-5.5:0.01-0.05.

[0027] The reaction temperature is room temperature; preferably, the reaction temperature is 25 to 30°C.

[0028] The β-aryl β-pyridyl alkyl ketone compound prepared by the present invention is a very important organic synthesis intermediate and can be converted into a variety of organic compounds through various chemical reactions.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] (1) The present invention is the first to achieve the synthesis of multiple types of β-aryl β-pyridyl alkyl ketone compounds under photoinduced conditions using simple and readily available aldehydes as free radical precursors.

[0031] (2) The preparation method provided by the present invention can be applied to aromatic olefins, drug-derived olefins, primary alkyl aldehydes, secondary alkyl aldehydes, and aldehydes derived from natural amino acids, and has the advantages of simple and readily available substrates and wide applicability.

[0032] (3) The preparation method of the present invention has the advantages of cheap and readily available reaction raw materials, simple reaction operation, wide application range of reaction substrates, easy reaction scale-up, mild reaction conditions, etc., and can realize industrial production and application. DETAILED DESCRIPTION

[0033] The present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be pointed out that the embodiments described below are intended to facilitate the understanding of the present invention and do not have any limiting effect on the present invention.

[0034] The operation methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturer. Unless otherwise specified, the mol% amount of the photocatalyst in each example is based on Compound 1.

[0035] In the following examples, the photocatalyst is:

[0036]

[0037] Example 1: Effect of PC1 on the reaction

[0038]

[0039] In a glove box, weigh PC1 (2 mol%) and cyanopyridine (0.2 mmol) into a 4 mL sample bottle, add solvent MeCN (1.0 mL), styrene (0.1 mmol), and n-butyraldehyde (0.5 mmol) in sequence, and tighten the PTFE lid. Take the sample bottle out of the glove box, place it under 390 nm blue light, and react at 25 ° C for 30 hours. After the reaction is completed, remove the solvent on a rotary evaporator to obtain a crude product. Use thin layer chromatography or nuclear magnetic resonance to analyze the conversion rate and yield of the reaction. The experimental results obtained are: the nuclear magnetic yield is 82%.

[0040] Example 2: Effect of PC2 on the reaction

[0041] The only difference from Example 1 is that an equimolar amount of PC2 is used to replace PC1, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 5%.

[0042] Example 3: Effect of PC3 on the reaction

[0043] The only difference from Example 1 is that an equimolar amount of PC3 is used to replace PC1, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 10%.

[0044] Example 4: Effect of PC4 on the reaction

[0045] The only difference from Example 1 is that an equimolar amount of PC4 is used to replace PC1, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 12%.

[0046] Example 5: Effect of PC5 on the reaction

[0047] The only difference from Example 1 is that an equimolar amount of PC5 is used to replace PC1, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 8%.

[0048] Example 6: Effect of PC6 on the reaction

[0049] The only difference from Example 1 is that an equimolar amount of PC6 is used to replace PCl, and the rest is the same. The experimental results obtained are: the nuclear magnetic yield is 18%.

[0050] Example 7: Effect of 427nm blue light on the reaction

[0051] The only difference from Example 1 is that the wavelength of the blue light is 427 nm, and the rest are the same. The experimental results obtained are: the nuclear magnetic resonance yield is 60%.

[0052] Example 8: Effect of EA solvent on reaction

[0053] The only difference from Example 1 is that the solvent MeCN is replaced by an equal volume of EA, and the rest is the same. The experimental results obtained are: the NMR yield is 5%.

[0054] Example 9: Effect of DMSO solvent on the reaction

[0055] The only difference from Example 1 is that the solvent MeCN is replaced by an equal volume of DMSO, and the rest is the same. The experimental results obtained are: the NMR yield is 26%.

[0056] Example 10: Effect of Acetone Solvent on Reaction

[0057] The only difference from Example 1 is that the solvent MeCN is replaced by an equal volume of acetone, and the rest is the same. The experimental results obtained are: the nuclear magnetic resonance yield is 82%.

[0058] Example 11: Investigation of olefin and aldehyde reaction substrates

[0059]

[0060] In a glove box, PC1 (2 mol%) and cyanopyridine (0.4 mmol) were weighed into a 4 mL sample bottle, and solvent MeCN (2.0 mL), olefin (0.2 mmol), and aldehyde (1.0 mmol) were added in sequence, and the PTFE lid was screwed tight. The sample bottle was taken out of the glove box, placed under 390 nm blue light, and reacted at 25 ° C for 30 hours. After the reaction was completed, the solvent was removed by rotary evaporation to obtain a crude product. The conversion rate and separation yield of the reaction were analyzed by thin layer chromatography or nuclear magnetic resonance. The experimental results are shown in Table 1.

[0061] Table 1 Investigation of olefin and aldehyde reaction substrates

[0062]

[0063]

[0064]

[0065]

[0066]

[0067] The analytical data of compound 5-41 are as follows:

[0068] Analytical data of β-aryl β-pyridylalkyl ketone 5

[0069] 1 H NMR (600MHz, CDCl3) 68.50-8.46 (m, 2H), 7.29 (t, J=7.6Hz, 2H), 7.24-7.16 (m, 3H), 7.15-7.11 (m, 2H), 4.59 (t , J=7.4Hz, 1H), 3.17-3.13 (m, 2H), 2.32 (dd, J=7.8, 6.7Hz, 2H), 1.52 (h, J=7.4Hz, 2H), 0.82 (t, J=7.4Hz, 3H).

[0070] 13C NMR (151MHz, CDCl3) δ208.20, 153.03, 150.08, 142.39, 128.95, 127.93, 127.13, 123.18, 48.04, 45.59, 45.29, 17.15, 13.71.

[0071] HRMS (ESI) m / z [M+H] + Calculate for C 17 H 20 NO: 254.1540, found: 254.1546.

[0072] Analytical data of β-aryl β-pyridyl alkyl ketone 6

[0073] 1 H NMR (600MHz, CDCl3) δ8.40 (d, J=5.8Hz, 2H), 7.25-7.18 (m, 2H), 7.10-7.05 (m, 2H), 7.05-7.02 (m, 2H), 4.49 (t, J= 7.4Hz, 1H), 3.12-3.01 (m, 2H), 2.25 (t, J=7.3Hz, 2H), 1.45 (h, J=7.4Hz, 2H), 1.20 (s, 9H), 0.73 (t, J=7.4Hz, 3H).

[0074] 13 C NMR (151MHz, CDCl3) 6208.41, 153.22, 149.96, 149.92, 139.21, 127.45, 125.79, 123.21, 48.10, 45.52, 44.80, 34.50, 31.39, 17.10, 13.68.

[0075] HRMS (ESI) m / z [M+H] + Calculate for C 21 H 28 NO: 310.2165, found: 310.2175.

[0076] Analytical data of β-aryl β-pyridylalkyl ketone 7

[0077] 1H NMR (600MHz, CDCl3) 68.52-8.48 (m, 2H), 7.57-7.49 (m, 4H), 7.44-7.38 (m, 2H), 7.35-7.31 (m, 1H), 7.25-7.24 (m, 1H), 7.22-7 .18 (m, 2H), 4.65 (t, J=7.4Hz, 1H), 3.19 (d, J=7.4Hz, 2H), 2.35 (t, J=7.3Hz, 2H), 1.54 (h, J=7.4Hz, 2H), 0.83 (t, J=7.4Hz, 3H).

[0078] 13 C NMR (151MHz, CDCl3) 6208.13, 153.59, 149.67, 141.27, 140.64, 140.16, 128.92 , 128.33, 127.69, 127.51, 127.14, 123.37, 48.02, 45.60, 44.98, 17.19, 13.74.

[0079] HRMS (ESI) m / z [M+H] + Calculate for C 23 H 24 NO: 330.1852, found: 330.1861.

[0080] Analytical data of β-aryl β-pyridyl alkyl ketone 8

[0081] 1 H NMR (600MHz, CDCl3) δ8.51 (s, 2H), 7.18 (d, J=4.7Hz, 2H), 7.13-7.07 (m, 2H), 6.86-6.80 (m, 2H), 4.56 (t, J=7. 4Hz, 1H), 3.77 (s, 3H), 3.12 (d, J=7.4Hz, 2H), 2.35-2.30 (m, 2H), 1.52 (h, J=7.4Hz, 2H), 0.82 (t, J=7.4Hz, 3H).

[0082] 13 C NMR (151MHz, CDCl3) 6208.27, 158.72, 154.43, 149.22, 134.20, 128.92, 123.47, 114.41, 55.41, 48.17, 45.59, 44.58, 17.16, 13.73.

[0083] HRMS (ESI) m / z [M+H] + Calculate for C18 H 22 NO2: 284.1645, found: 284.1653.

[0084] Analytical data of β-aryl β-pyridyl alkyl ketone 9

[0085] 1 H NMR (600MHz, CDCl3) 68.46 (d, J=5.6Hz, 2H), 7.13-7.09 (m, 2H), 6.78 (d, J=8.3Hz, 1H), 6.72 (dd, J=8.3, 2.1Hz, 1H), 6.66 (d, J=2.1Hz, 1H), 4.52 (t, J=7.4Hz, 1H), 3.81 (d, J=9.6Hz, 6H), 3.10 (dd, J=7.4, 1.3Hz, 2H), 2.32 (td, J=7.2, 1.1Hz, 2H), 1.51 (h, J=7.4Hz, 2H), 0.81 (t, J=7.4Hz, 3H).

[0086] 13 C NMR (151MHz, CDCl3) 6208.31, 153.29, 149.98, 149.24, 148.15, 134.87, 123.0 6, 119.66, 111.59, 111.49, 56.02, 55.99, 48.19, 45.56, 44.83, 17.11, 13.69.

[0087] HRMS (ESI) m / z [M+H] + Calculate for C 19 H 24 NO3: 314.1751, found: 314.1761.

[0088] Analytical data of β-aryl β-pyridylalkyl ketone 10

[0089] 1 H NMR (600MHz, CDCl3) 68.53-8.48 (m, 2H), 7.55 (d, J=8.1Hz, 2H), 7.31 (d, J=8.1Hz, 2H), 7.14-7.09 (m, 2H), 4.67 (t, J=7.3Hz, 1H), 3.22-3.12 (m, 2H), 2.35 (td, J=7.2, 2.1Hz, 2H), 1.54 (h, J=7.4Hz, 2H), 0.83 (t, J=7.4Hz, 3H).

[0090] 13C NMR (151MHz, CDCl3) δ207.45, 151.86, 150.16, 146.31, 129.37 (q, J=32.5Hz), 128.22, 1 25.78 (q, J=3.7Hz), 123.98 (q, J=271.9Hz), 122.96, 47.57, 45.40, 44.79, 17.04, 13.56.

[0091] 19 F NMR (565MHz, CDCl3) δ-62.59.

[0092] HRMS (ESI) m / z [M+H] + Calculate for C 18 H 19 F3NO: 322.1413, found: 322.1421.

[0093] Analytical data of β-aryl β-pyridylalkyl ketone 11

[0094] 1 H NMR (600MHz, CDCl3) 68.51-8.46 (m, 2H), 7.18-7.12 (m, 2H), 7.12-7.08 (m, 2H), 7.02-6.94 (m, 2H), 4.59 (t, J=7. 4Hz, 1H), 3.12 (dd, J=7.4, 1.3Hz, 2H), 2.33 (td, J=7.2, 2.6Hz, 2H), 1.52 (h, J=7.4Hz, 2H), 0.82 (t, J=7.4Hz, 3H).

[0095] 13 C NMR (151MHz, CDCl3) 6207.94, 162.64, 161.01, 152.87, 149.81, 138.07, 13 8.05, 129.45, 129.40, 115.83, 115.69, 48.02, 45.53, 44.48, 17.11, 13.65.

[0096] 19 F NMR (565MHz, CDCl3) δ-115.59.

[0097] HRMS (ESI) m / z [M+H] + Calculate for C 17 H 19 FNO: 272.1445, found: 272.1451.

[0098] Analytical data of β-aryl β-pyridylalkyl ketone 12

[0099] 1 H NMR (600MHz, CDCl3) 68.51-8.47 (m, 2H), 7.31-7.24 (m, 2H), 7.15-7.08 (m, 4H), 4.58 (t, J=7.4Hz, 1H), 3.12 (dd, J=7.4, 1.7Hz, 2H), 2.34 (td, J=7.2, 1.8Hz, 2H), 1.53 (h, J=7.4Hz, 2H), 0.83 (t, J=7.4Hz, 3H).

[0100] 13 C NMR (151MHz, CDCl3) 6207.84, 152.52, 150.21, 140.92, 133.02, 129.31, 129.11, 123.07, 47.89, 45.59, 44.57, 17.17, 13.72.

[0101] HRMS (ESI) m / z [M+H] + Calculate for C 17 H 19 ClNO: 288.1150, found: 288.1158.

[0102] Analytical data of β-aryl β-pyridylalkyl ketone 13

[0103] 1 H NMR (600MHz, CDCl3) δ8.51-8.47(m, 2H), 7.44-7.39(m, 2H), 7.13-7.08(m, 2H), 7.08-7.04(m, 2H), 4.56(t, J=7.4Hz, 1H), 3.17-3.07 (m, 2H), 2.33 (td, J=7.2, 1.7Hz, 2H), 1.53 (h, J=7.4Hz, 2H), 0.83 (t, J=7.4Hz, 3H).

[0104] 13 C NMR (151MHz, CDCl3) 6207.81, 152.42, 150.22, 141.45, 132.07, 129.68, 123.08, 121.07, 47.82, 45.58, 44.62, 17.17, 13.73.

[0105] HRMS (ESI) m / z [M+H] + Calculate for C 17 H 19BrNO: 332.0645, found: 332.0641.

[0106] Analytical data of β-aryl β-pyridylalkyl ketone 14

[0107] 1 H NMR (600MHz, CDCl3) 68.50 (s, 2H), 7.20-7.15 (m, 2H), 7.14-7.10 (m, 2H), 7.04-6.98 (m, 2H), 4.59 (t, J=7.3Hz, 1H ), 3.12 (qd, J=17.1, 7.4Hz, 2H), 2.32 (t, J=7.3Hz, 2H), 2.26 (s, 3H), 1.51 (h, J=7.4Hz, 2H), 0.81 (t, J=7.4Hz, 3H).

[0108] 13 C NMR (151MHz, CDCl3) 6207.95, 169.42, 152.69, 149.98, 149.63, 139.88, 128.86, 123.28, 121.95, 48.02, 45.51, 44.58, 21.18, 17.11, 13.66.

[0109] HRMS (ESI) m / z [M+H] + Calculate for C 19 H 22 NO3: 312.1594, found: 312.1603.

[0110] Analytical data of β-aryl β-pyridylalkyl ketone 15

[0111] 1 H NMR (600MHz, CDCl3) 68.43 (d, J=5.0Hz, 2H), 8.27 (s, 1H), 7.42 (d, J=8.3Hz, 2H), 7.15-7.06 (m, 4H), 4.52 (t, J=7. 4Hz, 1H), 3.11 (d, J=7.4Hz, 2H), 2.32 (t, J=7.3Hz, 2H), 2.09 (s, 3H), 1.50 (h, J=7.3Hz, 2H), 0.80 (t, J=7.4Hz, 3H).

[0112] 13C NMR (151MHz, CDCl3) δ208.22, 168.48, 153.06, 150.80, 149.98, 138.15, 137.00, 128.45, 120.37, 47.99, 45.58, 44.71, 24.62, 17.15, 13.72.

[0113] HRMS (ESI) m / z [M+H] + Calculate for C 19 H 23 N2O2: 311.1754, found: 311.1759.

[0114] Analytical data of β-aryl β-pyridylalkyl ketone 16

[0115] 1 H NMR (600MHz, CDCl3) 68.51 (s, 2H), 7.99-7.94 (m, 2H), 7.27 (d, J=9.1Hz, 2H), 7.13 (d, J=5.3Hz, 2H), 4.66 (t, J=7.3Hz , 1H), 3.89 (s, 3H), 3.17 (d, J=7.3Hz, 2H), 2.34 (td, J=7.2, 1.3Hz, 2H), 1.53 (h, J=7.4Hz, 2H), 0.83 (t, J=7.4Hz, 3H).

[0116] 13 C NMR (151MHz, CDCl3) 6207.56, 166.68, 152.18, 150.00, 147.39, 130.16, 129.04, 127.90, 123.08, 52.13, 47.58, 45.44, 45.04, 17.05, 13.59.

[0117] HRMS (ESI) m / z [M+H] + Calculate for C 19 H 22 NO3: 312.1594, found: 312.1602.

[0118] Analytical data of β-aryl β-pyridylalkyl ketone 17

[0119] 1H NMR (600MHz, CDCl3) δ8.51-8.47(m, 2H), 7.81-7.74(m, 3H), 7.67-7.64(m, 1H), 7.51-7.42(m, 2H), 7.29-7.25(m, 1H), 7. 20-7.16 (m, 2H), 4.77 (t, J=7.4Hz, 1H), 3.30-3.20 (m, 2H), 2.39-2.33 (m, 2H), 1.53 (h, J=7.3Hz, 2H), 0.85-0.79 (m, 3H).

[0120] 13 C NMR (151MHz, CDCl3) 6208.15, 152.90, 150.12, 139.79, 133.57, 132.53, 128.78, 127.88 , 127.77, 126.50, 126.32, 126.30, 126.10, 123.31, 47.94, 45.63, 45.32, 17.17, 13.72.

[0121] HRMS (ESI) m / z [M+H] + Calculate for C 21 H 22 NO: 304.1696, found: 304.1702.

[0122] Analytical data of β-aryl β-pyridylalkyl ketone 18

[0123] 1 H NMR (600MHz, CDCl3) 68.54-8.50 (m, 2H), 7.18 (ddd, J=12.5, 4.8, 1.4Hz, 3H), 6.92 (dd, J=5.1, 3.5Hz, 1H), 6.81 (dt, J=3.5, 1.1Hz, 1H), 4.84 ( t, J=7.3Hz, 1H), 3.22 (dd, J=17.1, 7.0Hz, 1H), 3.13 (dd, J=17.1, 7.6Hz, 1H), 2.41-2.28 (m, 2H), 1.54 (h, J=7.3Hz, 2H), 0.84 (t, J=7.4Hz, 3H).

[0124] 13 C NMR (151MHz, CDCl3) δ207.58, 152.57, 150.24, 145.94, 127.03, 124.94, 124.50, 122.98, 49.46, 45.55, 40.85, 17.16, 13.73.

[0125] HRMS (ESI) m / z [M+H] + Calculate for C i5 H 18 NOS: 260.1104, found: 260.1113.

[0126] Analytical data of β-aryl β-pyridylalkyl ketone 19

[0127] 1 H NMR (600MHz, CDCl3) 68.48 (d, J=5.4Hz, 2H), 7.64 (d, J=7.8Hz, 2H), 7.57 (d, J =7.5Hz, 2H), 7.40-7.28 (m, 6H), 7.17 (d, J = 8.4Hz, 2H), 7.12 (d, J = 5.3Hz, 2H) , 7.04 (d, J = 8.4Hz, 2H), 4.60 (t, J = 7.3Hz, 1H), 3.28 (t, J = 7.3Hz, 2H), 3.21-3 .05 (m, 4H), 2.33 (t, J = 7.3Hz, 2H), 1.61-1.46 (m, 2H), 0.82 (t, J = 7.4Hz, 3H).

[0128] 13 C NMR (151MHz, CDCl3) 6207.76, 170.49, 161.31, 152.48, 149.90, 149.41, 145.52, 139.84, 135.10, 132.32, 128.84, 128.7 1, 128.58, 128.48, 128.46, 128.03, 127.80, 126.46, 122.97, 121.75, 47.84, 45.34, 44.38, 31.16, 23.42, 16.94, 13.50.

[0129] HRMS (ESI) m / z [M+H] + Calculate for C 35 H 33 N2O4: 545.2435, found: 545.2427.

[0130] Analytical data of β-aryl β-pyridylalkyl ketone 20

[0131] 1H NMR (600MHz, CDCl3)68.49-8.45(m, 2H), 7.69-7.64(m, 2H), 7.49-7.44(m, 2H ), 7.19-7.14 (m, 2H), 7.03 (d, J = 2.5Hz, 1H), 7.00-6.98 (m, 2H), 6.88 (d, J = 9.0 Hz, 1H), 6.68 (dd, J=9.0, 2.6Hz, 1H), 4.59 (t, J=7.3Hz, 1H), 3.88 (s, 2H), 3.82 (s, 3H), 3.18-3 .06 (m, 2H), 2.43 (s, 3H), 2.32 (t, J = 7.3Hz, 2H), 1.52 (h, J = 7.3Hz, 2H), 0.82 (t, J = 7.4Hz, 3H).

[0132] 13 C NMR (151MHz, CDCl3) 6207.80, 169.20, 168.31, 156.15, 152.58, 149.96, 149.56, 139.96, 139.40, 136.24, 133.83, 131.20, 130.88, 1 30.47, 129.17, 128.79, 123.02, 121.71, 115.01, 111.90, 111.78, 101.30, 55.76, 47.89, 45.43, 44.44, 30.57, 17.02, 13.58, 13.38.

[0133] HRMS (ESI) m / z [M+H] + Calculate for C 36 H 34 ClN2O5: 609.2151, found: 609.2152.

[0134] Analytical data of β-aryl β-pyridylalkyl ketone 21

[0135] 1H NMR (600MHz, CDCl3) 68.50 (d, J=5.3Hz, 2H), 8.00 (d, J=8.2Hz, 2H), 7.27 (s, 2H), 7.11 (d, J=5.2Hz, 2H), 4.6 7(t, J=7.4Hz, 1H), 4.66-4.60 (m, 2H), 4.42 (d, J=2.6Hz, 1H), 4.32 (dd, J=11.8, 4.0Hz, 1H), 4.25 (dd, J=7.9, 1.7Hz, 1H), 3.95 (dd, J=13.0, 1.9Hz, 1H), 3.79 (d, J=13.0Hz, 1H), 3.17 (d, J=7.3Hz, 2H), 2.34 (td, J=7.2, 1. 6Hz, 2H), 1.63 (m, 2H), 1.44 (s, 3H), 1.36 (s, 3H), 1.34 (s, 3H), 1.26 (q, J=5.2Hz, 3H), 0.83 (t, J=7.4Hz, 3H).

[0136] 13 C NMR (151MHz, CDCl3) 6207.67, 165.71, 152.13, 150.26, 150.00, 147.79, 130.48, 128.91, 128.07, 123.15, 109.34, 108. 98, 101.80, 70.97, 70.74, 70.28, 65.65, 61.52, 47.71, 45.59, 45.16, 26.68, 26.02, 25.72, 24.19, 17.18, 14.35, 13.72.

[0137] HRMS (ESI) m / z [M+H] + Calculate for C 30 H 38 NO8: 540.2592, found: 540.2589.

[0138] Analytical data of β-aryl β-pyridylalkyl ketone 22

[0139] 1H NMR (600MHz, CDCl3) δ8.48 (d, J=5.3Hz, 2H), 7.29 (t, J=7.6Hz, 2H), 7.23-7.17 (m, 3H), 7.13 (d, J=5.8Hz, 2H), 4.59 (t, J=7 .4Hz, 1H), 3.15 (d, J=7.4Hz, 2H), 2.34 (t, J=7.4Hz, 2H), 1.48 (p, J=7.3Hz, 2H), 1.29-1.18 (m, 12H), 0.87 (d, J=7.2Hz, 3H).

[0140] 13 C NMR (151MHz, CDCl3) δ208.12, 152.83, 149.85, 142.20, 128.73, 127.72, 126.89, 122 .97, 47.76, 45.08, 43.46, 31.74, 29.27, 29.23, 29.13, 28.98, 23.48, 22.55, 13.99.

[0141] HRMS (ESI) m / z [M+H] + Calculate for C 23 H 32 NO: 338.2479, found: 338.2478.

[0142] Analytical data of β-aryl β-pyridyl alkyl ketone 23

[0143] 1 H NMR (600MHz, CDCl3) δ8.48-8.44(m, 2H), 7.29-7.26(m, 2H), 7.21-7.17(m, 3H), 7.1 4-7.12 (m, 2H), 4.57 (t, J=7.3Hz, 1H), 3.18-3.08 (m, 2H), 2.24 (s, 2H), 0.91 (s, 9H).

[0144] 13 C NMR (151MHz, CDCl3) 6207.66, 152.98, 149.76, 142.23, 128.71, 127.78, 126.88, 123.08, 55.53, 50.03, 45.06, 30.98, 29.53.

[0145] HRMS (ESI) m / z [M+H] + Calculate for C 19 H 24 NO: 282.1853, found: 282.1851.

[0146] Analytical data of β-aryl β-pyridylalkyl ketone 24

[0147] 1 H NMR (600MHz, CDCl3) δ8.45 (d, J=5.1Hz, 2H), 7.27 (t, J=7.5Hz, 2H), 7.23 (t, J=7.5Hz, 2H), 7.21-7.13 (m, 4H), 7.07 (d, J=6.2Hz, 4H), 4.57 (t, J=7.4Hz, 1H), 3.12 (d, J=7.4Hz, 2H), 2.81 (t, J=6.9Hz, 2H), 2.67 (td, J=7.5, 4.2Hz, 2H).

[0148] 13 C NMR (151MHz, CDCl3) δ206.86, 152.65, 149.60, 141.90, 140.47, 128.63, 128 .29, 128.04, 127.55, 126.81, 125.95, 122.86, 47.90, 44.89, 44.58, 29.25.

[0149] HRMS (ESI) m / z [M+H] + Calculate for C 22 H 22 NO: 315.1696, found: 316.1694.

[0150] Analytical data of β-aryl β-pyridyl alkyl ketone 25

[0151] 1 H NMR (600MHz, CDCl3) 68.47 (d, J=5.1Hz, 2H), 7.43 (d, J=7.8Hz, 1H), 7.34 (dd, J=14.2, 6.4Hz, 2H), 7.31-7.19 (m, 4H), 7.15 (d, J=7.5Hz, 2H), 7.10 (d, J=5.1Hz, 2H), 4.58 (t, J=7.4Hz, 1H), 3.15 (d, J=7.5Hz, 2H), 2.86 (t, J=7.4Hz, 2H), 2.76-2.63 (m, 2H).

[0152] 13C NMR (151MHz, CDCl3) δ206.37, 152.77, 149.88, 141.84, 141.61, 131.75, 130.74 (q, J=32.0Hz), 128.88, 128.85, 127.68 , 127.09, 124.93 (dd, J=7.2, 3.2Hz), 124.09 (q, J=272.4Hz), 123.03 (q, J=4.5Hz), 122.97, 48.04, 45.18, 44.48, 28.99.

[0153] 19 F NMR (565MHz, CDCl3) δ-62.54.

[0154] HRMS (ESI) m / z [M+H] + Calculate for C 23 H 21 F3NO: 384.1570, found: 384.1574.

[0155] Analytical data of β-aryl β-pyridylalkyl ketone 26

[0156] 1 H NMR (600MHz, CDCl3) δ8.50-8.46 (m, 2H), 7.29 (t, J=7.6Hz, 2H), 7.27-7.11 (m, 5H), 4.58 (t, J=7.4Hz, 1H), 4.10 (q, J=7 .1Hz, 2H), 3.16 (d, J=7.4Hz, 2H), 2.42-2.26 (m, 2H), 2.26-2.21 (m, 2H), 1.52 (h, J=3.4Hz, 4H), 1.23 (t, J=7.1Hz, 3H).

[0157] 13 C NMR (151MHz, CDCl3) 6207.49, 173.16, 152.69, 149.77, 142.00, 128.69, 127. 63, 126.88, 122.89, 60.13, 47.67, 45.00, 42.90, 33.79, 24.09, 22.70, 14.07.

[0158] HRMS (ESI) m / z [M+H] + Calculate for C 21 H 26 NO3: 340.1907, found: 340.1904.

[0159] Analytical data of β-aryl β-pyridylalkyl ketone 27

[0160] 1 H NMR (600MHz, CDCl3) 68.49-8.45 (m, 2H), 7.32-7.11 (m, 7H), 4.57 (t, J=7.5Hz, 1H), 3.43 (dt , J=6.3, 3.6Hz, 2H), 3.15 (d, J=7.5Hz, 2H), 2.37 (td, J=6.7, 4.3Hz, 2H), 1.65-1.59 (m, 4H).

[0161] 13 C NMR (151MHz, CDCl3) δ207.59, 152.89, 150.03, 142.16, 128.98, 127.88, 127.19, 123.13, 47.90, 45.30, 44.63, 42.59, 31.74, 20.82.

[0162] HRMS (ESI) m / z [M+H] + Calculate for C 18 H 21 ClNO: 302.1310, found: 302.1309.

[0163] Analytical data of β-aryl β-pyridyl alkyl ketone 28

[0164] 1 H NMR (600MHz, CDCl3) 68.49-8.45 (m, 2H), 7.36-6.96 (m, 7H), 4.58 (t, J=7.4Hz, 1H), 3.19 (d, J=7.4Hz, 2H), 2.66-2.60 (m, 4H), 2.03 (s, 3H).

[0165] 13 C NMR (151MHz, CDCl3) δ205.89, 152.34, 149.55, 141.66, 128.52, 127.40, 126.72, 122.67, 47.83, 44.74, 42.77, 27.34, 15.38.

[0166] HRMS (ESI) m / z [M+H] + Calculate for C 17 H 20 NOS: 286.1260, found: 286.1259.

[0167] Analytical data of β-aryl β-pyridyl alkyl ketone 29

[0168] 1 H NMR (600MHz, CDCl3) δ8.48-8.44(m, 2H), 7.31-7.23(m, 2H), 7.23-7.15(m, 3H), 7.14-7.10(m, 2H), 4.59( t, J=7.3Hz, 1H), 3.83 (t, J=6.3Hz, 2H), 3.29-3.17 (m, 2H), 2.61-2.48 (m, 2H), 0.84 (s, 9H), 0.01 (s, 6H).

[0169] 13 C NMR (151MHz, CDCl3) 6206.64, 152.70, 149.62, 142.11, 128.55, 127.55, 126.69, 122.84, 58.42, 48.73, 45.96, 44.58, 25.57, 17.93, -5.76.

[0170] HRMS (ESI) m / z [M+H] + Calculate for C 22 H 32 NO2Si: 370.2197, found: 370.2197.

[0171] Analytical data of β-aryl β-pyridyl alkyl ketone 30

[0172] 1 H NMR (600MHz, CDCl3) δ8.49-8.46 (m, 2H), 7.29 (t, J=7.6Hz, 2H), 7.22-7.18 (m, 3H), 7.15-7.13 (m, 2H), 4.60 (t, J=7.4Hz, 1 H), 3.18 (p, J=8.5Hz, 1H), 3.09 (dd, J=7.4, 1.5Hz, 2H), 2.13-2.01 (m, 4H), 1.91 (m, J=11.3, 8.8Hz, 1H), 1.77-1.68 (m, 1H).

[0173] 13 C NMR (151MHz, CDCl3) δ208.57, 152.90, 149.80, 142.25, 128.69, 127.68, 126.86, 122.96, 45.66, 45.21, 44.87, 23.88, 17.49.

[0174] HRMS (ESI) m / z [M+H] + Calculate for C18 H 20 NO: 266.1540, found: 266.1538.

[0175] Analytical data of β-aryl β-pyridyl alkyl ketone 31

[0176] 1 H NMR (600MHz, CDCl3) δ8.47 (d, J=5.5Hz, 2H), 7.28 (t, J=7.6Hz, 2H), 7.22-7.17 (m, 3H), 7.15-7.12 (m, 2H), 4.61 (t, J=7.3Hz, 1H), 3.25-3.15 (m, 2H), 2.79 (tt, J=8.8, 6.8Hz, 1H), 1.77-1.68 (m, 2H), 1.63-1.46 (m, 5H), 1.25 (s, 1H).

[0177] 13 C NMR (151MHz, CDCl3) δ209.99, 153.02, 149.84, 142.38, 128.72, 127.76, 126.88, 123.04, 51.81, 47.05, 45.02, 29.62, 28.52, 28.49, 25.79.

[0178] HRMS(ESI)m / z[M+H]+calcd for C 19 H 22 NO: 280.1696, found: 280.1693.

[0179] Analytical data of β-aryl β-pyridyl alkyl ketone 32

[0180] 1 H NMR (600MHz, CDCl3) 68.47 (d, J=5.5Hz, 2H), 7.28 (q, J=6.8, 6.1Hz, 2H), 7.22-7.17 (m, 3H), 7.14-7.11 (m, 2H), 4.60 (t, J=7.3Hz , 1H), 3.25-3.14 (m, 2H), 2.27 (dt, J=11.8, 4.2Hz, 1H), 1.75-1.70 (m, 4H), 1.63 (dq, J=12.6, 3.3, 2.8Hz, 1H), 1.28-1.11 (m, 5H).

[0181] 13C NMR (151MHz, CDCl3) δ210.91, 153.13, 149.89, 142.47, 128.78, 127.84, 126.93, 123.11, 51.23, 45.95, 44.91, 28.19, 28.15, 25.74, 25.55, 25.53.

[0182] HRMS (ESI) m / z [M+H] + Calculate for C 20 H 24 NO: 294.1853, found: 294.1853

[0183] Analytical data of β-aryl β-pyridyl alkyl ketone 33

[0184] 1 H NMR (600MHz, CDCl3) δ8.49 (s, 2H), 7.33-7.26 (m, 2H), 7.25-7.16 (m, 3H), 7.14 (d, J=4.8Hz, 2H), 4.62 (t, J=7.3Hz, 1H), 3.93 (dd, J=14. 1, 7.3Hz, 2H), 3.36 (dddd, J=11.4, 8.6, 5.9, 2.9Hz, 2H), 3.21 (d, J=7.3Hz, 2H), 2.47 (dddd, J=15.0, 11.0, 3.8Hz, 1H), 1.70-1.44 (m, 4H).

[0185] 13 C NMR (151MHz, CDCl3) 6208.83, 152.76, 149.88, 142.11, 128.78, 127.71, 127.00, 122.96, 66.99, 47.93, 45.57, 44.84, 27.70.

[0186] HRMS (ESI) m / z [M+H] + Calculate for C 19 H 22 NO2: 296.1645, found: 296.1651.

[0187] Analytical data of β-aryl β-pyridyl alkyl ketone 34

[0188] 1H NMR (600MHz, CDCl3) 68.50-8.46 (m, 2H), 7.96-7.92 (m, 2H), 7.59-7.54 (m, 1H), 7.45 (t, J=7.8Hz, 2H), 7.30 (t, J=7.6Hz, 2H), 7.27-7.20 (m, 3H), 7.20-7.17 (m, 2H), 4.81 (t, J=7.2Hz, 1H), 3.81-3.68 (m, 2H).

[0189] 13 C NMR (151MHz, CDCl3) δ197.22, 153.02, 149.92, 142.50, 136.76, 133.40, 128.88, 128.74, 128.04, 127.89, 127.01, 123.21, 45.28, 43.90.

[0190] HRMS (ESI) m / z [M+H] + Calculate for C 20 H 18 NO: 288.1383, found: 288.1381.

[0191] Analytical data of β-aryl β-pyridyl alkyl ketone 35

[0192] 1 H NMR (600MHz, CDCl3) 68.51-8.47 (m, 2H), 7.89-7.85 (m, 2H), 7.45-7.41 (m, 2H), 7.30 (dd, J=8.4, 6.9Hz, 2H), 7.23 (d, J=7.5Hz, 3H), 7.19-7.15 (m, 2H), 4.79 (t, J=7.2Hz, 1H), 3.76-3.64 (m, 2H).

[0193] 13 C NMR (151MHz, CDCl3) δ196.00, 152.71, 150.01, 142.27, 139.92, 135.01, 129.43, 129.05, 128.89, 127.82, 127.08, 123.09, 45.25, 43.84.

[0194] HRMS (ESI) m / z [M+H] + Calculate for C 20 H 24 NO: 322.0993, found: 322.1003.

[0195] Analytical data of β-aryl β-pyridyl alkyl ketone 36

[0196] 1 H NMR (600MHz, CDCl3) 68.52-8.45 (m, 3H), 8.01-7.93 (m, 2H), 7.91-7.85 (m, 2H), 7.59 (dddd, J=29.7, 8.2, 6 .9, 1.3Hz, 2H), 7.34-7.27 (m, 4H), 7.25-7.21 (m, 3H), 4.88 (t, J=7.2Hz, 1H), 3.88 (dq, J=17.3, 7.2Hz, 2H).

[0197] 13 C NMR (151MHz, CDCl3) δ197.11, 152.94, 150.00, 142.54, 135.71, 134.08, 132.48, 129.71, 129. 55, 128.87, 128.67, 128.63, 127.92, 127.82, 127.01, 126.93, 123.71, 123.19, 45.39, 43.97.

[0198] HRMS (ESI) m / z [M+H] + Calculate for C 24 H 20 NO: 338.1540, found: 338.1537.

[0199] Analytical data of β-aryl β-pyridylalkyl ketone 37

[0200] 1 H NMR (600MHz, CDCl3) δ8.48 (d, J=5.1Hz, 2H), 7.53 (s, 1H), 7.30 (t, J=7.7Hz, 2H), 7.24 (d, J =8.5Hz, 4H), 7.18 (d, J = 5.1Hz, 2H), 4.78 (t, J = 7.4Hz, 1H), 3.68-3.55 (m, 2H), 2.28 (s, 3H).

[0201] 13 C NMR (151MHz, CDCl3) 6189.93, 152.71, 149.97, 143.42, 142.27, 138.98, 133.90, 129.86, 128.83, 127.87, 127.02, 123.15, 45.36, 44.44, 15.52.

[0202] HRMS (ESI) m / z [M+H]+ Calculate for C 19 H 18 NOS: 308.1104, found: 308.1103.

[0203] Analytical data of β-aryl β-pyridyl alkyl ketone 38

[0204] 1 H NMR (600MHz, CDCl3) 68.57 (s, 2H), 7.50-7.33 (m, 8H), 7.30 (t, J=7.3Hz, 1H), 7.25 (s, 1H), 7.20 (d, J=4.8Hz, 2H), 5.28 (s, 1H), 5.15 (s, 2H), 4.64 (t, J=7.3Hz, 1H), 3.44 (d, J=5.7Hz, 2H), 3.24 (d, J=7.3Hz, 2H), 2.77-2.54 (m, 2H).

[0205] 13 C NMR (151MHz, CDCl3) δ207.24, 156.20, 152.42, 149.92, 141.76, 136.41, 128.83, 12 8.44, 128.06, 127.98, 127.62, 127.07, 122.85, 66.57, 47.96, 45.09, 43.07, 35.43.

[0206] HRMS (ES I) m / z [M+H] + cal cd for C 24 H 25 N203: 389.1860, found: 389.1864.

[0207] Analytical data of β-aryl β-pyridyl alkyl ketone 39

[0208] 1H NMR (600MHz, CDCl3) 68.50-8.46 (m, 2H), 7.29 (td, J=7.6, 1.7Hz, 2H), 7.24-7.19 (m, 1H ), 7.19-7.15 (m, 2H), 7.13-7.09 (m, 2H), 5.36 (t, J = 8.4Hz, 1H), 4.56 (td, J = 7.6, 4.1Hz , 1H), 4.31 (dt, J=8.6, 4.4Hz, 1H), 3.27-3.10 (m, 2H), 3.02 (ddd, J=21.5, 17.9, 4.5Hz, 1H), 2.90 (ddd, J=22.1, 17.9, 4.3Hz, 1H), 1.41 (d, J=2.3Hz, 9H), 1.31 (d, J=3.6Hz, 9H).

[0209] 13 C NMR (151MHz, CDCl3) δ205.88, 170.01, 155.52, 152.49, 149.97, 141.90, 128.87, 127.67, 127.08, 122.93, 82.14, 50.03, 47.80, 45.20, 44.87, 28.29, 27.71, 0.99.

[0210] HRMS (ESI) m / z [M+H] + Calculate for C 26 H 35 N2O5: 455.2541, found: 455.2538.

[0211] Analytical data of β-aryl β-pyridyl alkyl ketone 40

[0212] 1 H NMR (600MHz, CDCl3) δ8.51-8.46 (m, 2H), 7.29 (dd, J=8.4, 7.0Hz, 2H), 7.24-7.20 (m, 1H), 7.20-7.17 (m, 2H), 7.13 (dd, J=4.7, 1.7Hz, 2H), 4.58 (t, J=7.4Hz, 1H), 3.99 (m, 2 H), 3.14 (dd, J=7.5, 3.7Hz, 2H), 2.63 (s, 2H), 2.27 (d, J=6.7Hz, 2H), 1.88 (dtq, J=11. 0, 6.9, 3.6Hz, 1H), 1.43 (d, J=1.0Hz, 9H), 0.97 (d, J=12.8Hz, 2H), 0.91-0.81 (m, 2H).

[0213] 13C NMR (151MHz, CDCl3) δ207.07, 154.92, 152.85, 150.14, 142.17, 129.01, 127. 94, 127.25, 123.13, 79.50, 50.24, 48.64, 45.36, 31.94, 31.75, 29.84, 28.59.

[0214] HRMS (ESI) m / z [M+H] + Calculate for C 25 H 33 N2O3: 409.2486, found: 409.2483.

[0215] Analytical data of β-aryl β-pyridylalkyl ketone 41

[0216] 1 H NMR (600MHz, CDCl3) δ8.58 (s, 2H), 7.30 (t, J=7.6Hz, 2H), 7.25-7.19 (m, 5H), 7.06 (d, J=2.2Hz, 2H), 6.65 (t, J =2.3Hz, 1H), 4.78 (t, J = 7.2Hz, 1H), 3.81 (s, 6H), 3.73 (dd, J = 17.5, 7.9Hz, 1H), 3.66 (dd, J = 17.4, 6.6Hz, 1H).

[0217] 13 C NMR (151MHz, CDCl3) 6197.03, 161.13, 152.92, 149.95, 142.58, 138.80, 129.01, 128.01, 127.15, 106.06, 105.68, 55.77, 45.54, 44.12.

[0218] HRMS (ESI) m / z [M+H] + Calculate for C 22 H 22 NO3: 348.1594, found: 348.1595.

[0219] The embodiments described above provide a detailed description of the technical solutions and beneficial effects of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, supplements and equivalent substitutions made within the scope of the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a β-aryl β-pyridyl alkyl ketone compound, characterized in that: include: In the presence of a photocatalyst and under the irradiation of blue light, the compound of formula (1), the compound of formula (2) and the compound of formula (3) react to generate a β-aryl β-pyridyl alkyl ketone compound of formula (4): Wherein, Ar is selected from substituted or unsubstituted aryl, naphthyl, heteroaryl; The compound of formula (2) is 4-cyanopyridine; The compound of formula (3) is an aldehyde; The photocatalyst is selected from tetrabutylammonium decatungstate (TBADT), 9-thioxanthone and benzophenone photocatalysts.

2. The preparation method according to claim 1, characterized in that: The compound of formula (3) may be a primary alkyl aldehyde, a secondary alkyl aldehyde, an aromatic aldehyde, or an aldehyde derived from a natural amino acid.

3. The preparation method according to claim 1, characterized in that: The compound of formula (1) is selected from:

4. The preparation method according to claim 1, characterized in that: The compound of formula (3) is selected from:

5. The preparation method according to claim 1, characterized in that: The catalyst is selected from:

6. The preparation method according to claim 1, characterized in that: The wavelength of the blue light is 390-440nm.

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