A process for the preparation of a tetralone compound

Abstract

The application provides a novel preparation method of tetrahydronaphthone compounds, and comprises the following steps: 1,6-alkynyl compounds are reacted with water under the synergistic catalysis of a transition metal and an amine nucleophile to generate tetrahydronaphthone compounds. The above synthesis method is simple and fast in preparation process, the catalyst is low in price, and the substrate has wide applicability, and therefore, the method is expected to be used for industrial production.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic chemical synthesis, and particularly relates to a preparation method of tetrahydronaphthone compounds. BACKGROUND

[0002] The existing preparation methods of tetrahydronaphthone compounds in the literature are as follows.

[0003] Method one (Synthesis. 2016, 48, 2050-2056):

[0004]

[0005] Method two (Korean J. Chem. Eng. 2017, 34, 701-705):

[0006]

[0007] Method three (Org. Biomol. Chem., 2023, 21, 910-924):

[0008]

[0009] Method four (The Journal of Organic Chemistry 2024, 89, 13575-13584):

[0010]

[0011] In the above-mentioned preparation methods of tetrahydronaphthone compounds, method one has narrow applicability to substrates; the chromium catalyst used in method two is a toxic heavy metal; method three requires multi-step synthesis, and has poor step economy and atom economy; method four consumes 3 equivalents of hydrazone reagent, releases gas during the conversion process, and has explosion hazards during scale-up, which is not conducive to safe production. SUMMARY

[0012] In order to overcome the shortcomings and deficiencies of the prior art, the present application aims to provide a preparation method of tetrahydronaphthone compounds. In this preparation method, the raw materials are cheap and easy to obtain, and the product synthesis method is simple and efficient.

[0013] The present application is realized by the following technical solutions:

[0014]

[0015] The preparation method of tetrahydronaphthone compounds of the present application comprises the following steps:

[0016] Under nitrogen protection, a 1,6-enyne compound is dissolved in a solvent, a transition metal catalyst and a nucleophilic catalyst are added, and then an organic acid additive and water are added. After the reaction, the tetralone compound is separated and purified to obtain the tetralone compound.

[0017] Where R 1 Selected from hydrogen atom, C1~C 12 One of alkyl, aryl, and heteroaryl; wherein R 1 Any one or more hydrogen atoms of the upper aromatic ring may be replaced by a substituent;

[0018] R 2 Selected from C1~C 12 One of alkyl, aryl, and heteroaryl; wherein R 1 Any one or more hydrogen atoms of the upper aromatic ring may be replaced by a substituent;

[0019] R 3 Selected from hydrogen atom, halogen, C1~C 12 Alkyl or heteroaromatic ring;

[0020] R 4 Selected from hydrogen atom or C1~C 12 alkyl.

[0021] Substituent Definitions and General Terms:

[0022] The term "aryl" as used herein refers to a monocyclic or bicyclic carbon ring system containing 6-10 ring atoms, wherein at least one ring system is aromatic. Examples of aryl groups include phenyl and naphthyl. The alkyl groups may independently be unsubstituted or substituted with one or more substituents described herein.

[0023] The term "alkyl" used in the present invention refers to a group containing 1 to 12 carbon atoms. The alkyl group can be linear or branched, and independently unsubstituted or substituted with one or more substituents described in the present invention.

[0024] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0025] The transition metal catalyst is one of Cu(OAc)2·H2O, Cu(OAc)2·H2O, Cu(OAc)2, CuSO4·5H2O, AgOTf, CuSO4, CuCl2, CuO, CuCl, CuBr, and CuI, preferably Cu(OAc)2·H2O.

[0026] The molar ratio of the transition metal catalyst to the 1,6-enyne compound is 0.01 to 1:1, preferably 0.1 to 0.2:1.

[0027] The nucleophilic catalyst is selected from C1 to C12 one of alkylamine, aniline, piperidine, triethylamine, preferably alkylamine, more preferably n-butylamine.

[0028] The molar ratio of the nucleophile to the 1,6-alkynyl compound is 0.01-1:1, preferably 0.2:1.

[0029] The organic acid additive is selected from C1-C 12 one of alkyl carboxylic acid, phosphoric acid, preferably acetic acid.

[0030] The molar ratio of the organic acid reagent to the 1,6-alkynyl compound is 0.01-10:1, preferably 10:1.

[0031] The molar ratio of the water to the 1,6-alkynyl compound is 1-100:1, preferably 20:1.

[0032] The solvent is selected from one of 1,1-dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, trifluorotoluene, 1,4-dioxane, acetonitrile, toluene, chlorobenzene, xylene, preferably 1,2-dichloroethane.

[0033] The ratio of the solvent to the 1,6-alkynyl compound is 1-40 mL:1 mmol, preferably 20 mL:1 mmol.

[0034] The condition is 25-120℃ for 2h-48h, preferably 80℃ for 4h.

[0035] The 1,6-alkynyl compound can be prepared according to known literatures (for example, Angew. Chem. Int. Ed. 2011, 50, 8968).

[0036]

[0037] Tetralone skeleton is a basic component of organic synthesis, and these structures are widely present in natural products, drugs, bioactive substances, such as CYP27A1 inhibitor, Sertraline, 10-norparvulenone, etc. The present application provides a simple and efficient method for constructing tetralone skeleton.

[0038] The following bioactive molecules contain tetralone skeleton, which illustrates the potential application value of the method.

[0039]

[0040] The tetralone compound prepared by the present application is exemplified as follows:

[0041]

[0042] The present application has the following advantages and effects compared with the prior art:

[0043] The preparation process of the present application is simple and fast. The tetrahydronaphthone compound can be efficiently synthesized through a simple one-step process. The operation is simple. The raw materials are easy to prepare. The catalyst used is in small amount and cheap and easy to obtain. The prepared tetrahydronaphthone compound has strong substrate compatibility and simple purification. BRIEF DESCRIPTION OF DRAWINGS

[0044] Figure 1 The technical scheme of the present application. The catalyst in the figure is equivalent to transition metal catalysis + nucleophilic catalyst; 1,6-alkyne is equivalent to A, tetrahydronaphthone is equivalent to B. DETAILED DESCRIPTION

[0045] The present application will be further described below in combination with specific examples, but the examples do not limit the present application in any form. Unless otherwise specified, the reagents, methods and equipment used in the present application are conventional reagents, methods and equipment in the technical field, which can be directly purchased or synthesized by known literature methods.

[0046] Example 1

[0047]

[0048] A dry Schlenk tube with a stir bar was taken, Cu(OAc)2·H2O (8 mg, 20% mmol) was added, replaced with nitrogen for three times, then 1a (61.6 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) were added, stirred at 80℃ for 4h, the reaction was complete, the solvent was removed by rotary evaporation, and the product 2a (58 mg, 89%) was obtained by purification with flash column chromatography (eluent petroleum ether: ethyl acetate volume ratio 10:1), white solid, melting point: 152-153℃, 1 H NMR (400 MHz, CDCl3) δ 8.21 (dd, J = 6.9, 2.4 Hz, 1H), 7.57-7.51 (m, 2H), 7.48-7.38 (m, 3H), 7.27 (s, 1H), 7.25-7.08 (m, 7H), 5.30 (d, J = 4.6 Hz, 1H), 3.96 (dt, J = 14.6, 4.4 Hz, 1H), 3.80 (dd, J = 17.2, 14.5 Hz, 1H), 2.83 (dd, J = 17.1, 4.2 Hz, 1H); 13C NMR (101 MHz, CDC13) δ 199.6, 197.8, 141.5, 140.2, 137.6, 133.6, 133.1, 132.9, 128.8, 128.5, 128.4, 128.2, 128.12, 128.10, 127.6, 51.6, 44.2, 38.6; HRMS (ESI) Calcd for C23H18O2Na (M+Na)+ 349.1199, found 349.1205.

[0049] Example 2

[0050]

[0051] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1b (65.2 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 80 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2b (60 mg, 87%) was obtained as a white solid, m.p. 132-133 °C, after purification by flash column chromatography (eluent petroleum ether: ethyl acetate 10:1, v / v). 1 H NMR (400 MHz, CDC13) δ 8.20 (dd, J = 6.7, 2.7 Hz, 1H), 7.63 - 7.53 (m, 2H), 7.50 - 7.39 (m, 3H), 7.29 (t, J = 7.8 Hz, 2H), 7.21 - 7.08 (m, 3H), 6.94 - 6.78 (m, 2H), 5.28 (d, J = 4.7 Hz, 1H), 3.94 (dt, J = 14.5, 4.5 Hz, 1H), 3.76 (dd, J = 17.2, 14.5 Hz, 1H), 2.81 (dd, J = 17.2, 4.3 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 199.4, 197.4, 162.0 (d, 1 J C-F = 247.5 Hz), 141.2, 137.4, 136.0 (d, 4 J C-F = 3.0 Hz), 133.6, 133.3, 132.8, 129.2, 129.1, 128.5 (d, 3 J C-F = 3.0 Hz), 128.2, 128.1, 115.6 (d, 2 J C-F= 22.2 Hz), 51.4, 43.4, 38.8; 19 F NMR (376 MHz, CDC13) δ -114.77; HRMS (ESI) Calcd for C 23 H 17 02FNa (M + Na) + 367.1105, found 367.1115.

[0052] Example 3

[0053]

[0054] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1c (68.6 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was added. The reaction mixture was stirred at 100 °C for 4 h. The solvent was removed and the product 2c (48 mg, 67%) was obtained as a yellow solid, m.p. 161-162 °C, after purification by flash column chromatography (eluent petroleum ether: ethyl acetate 10:1, v / v). 1 H NMR (400 MHz, CDC13) δ 8.20 (dd, 1H), 7.59 (d, J = 7.1 Hz, 2H), 7.51 - 7.40 (m, 3H), 7.31 (t, J = 7.8 Hz, 2H), 7.18 - 7.09 (m, 5H), 5.28 (d, J = 4.8 Hz, 1H), 3.93 (dt, J = 14.5, 4.4 Hz, 1H), 3.77 (dd, 1H), 2.80 (dd, J = 17.1, 4.2 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 199.3, 197.3, 141.1, 138.7, 137.4, 133.6, 133.4, 133.3, 132.8, 128.92, 128.85, 128.6, 128.5, 128.2, 51.1, 43.5, 38.7; HRMS (ESI) Calcd for C 23 H 17 02NaCl (M + Na) + 383.0809, found 383.0814.

[0055] Example 4

[0056]

[0057] A dry Schlenk tube with stir bar was charged with Cu(OAc)2H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1d (77.4 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 80 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2d (61 mg, 76%) was obtained as a white solid, m.p. 155-156 °C, 1 H NMR (400 MHz, CDC13) δ 8.20 (dd, J = 7.3, 2.0 Hz, 1H), 7.64 - 7.55 (m, 2H), 7.51 - 7.40 (m, 3H), 7.35 - 7.26 (m, 4H), 7.15 - 7.04 (m, 3H), 5.28 (d, J = 4.6 Hz, 1H), 3.91 (dt, J = 14.5, 4.4 Hz, 1H), 3.77 (dd, J = 17.1, 14.4 Hz, 1H), 2.80 (dd, J = 17.1, 4.2 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 199.3, 197.3, 141.1, 139.3, 137.4, 133.6, 133.4, 132.8, 131.8, 129.3, 128.6, 128.5, 128.20, 128.17, 121.4, 51.1, 43.6, 38.6; HRMS (ESI) Calcd for C 23 H 17 O2NaBr (M + Na) + 427.0304, found 427.0312.

[0058] Example 5

[0059]

[0060] A dry Schlenk tube with stir bar was charged with Cu(OAc)2H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1e (66.6 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 100 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2e (30 mg, 43%) was obtained as a red-brown solid, m.p. > 300 °C, 1H NMR (400 MHz, CDC13) δ 8.21 (dd, J = 7.0, 2.3 Hz, 1H), 7.59 (d, J = 7.0 Hz, 2H), 7.52 - 7.42 (m, 5H), 7.32 (dd, J = 14.5, 8.0 Hz, 4H), 7.13 (dd, J = 6.6, 2.1 Hz, 1H), 5.30 (d, J = 4.6 Hz, 1H), 4.01 (dt, J = 14.4, 4.5 Hz, 1H), 3.81 (dd, J = 17.1, 14.3 Hz, 1H), 2.83 (dd, J = 17.1, 4.3 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 198.8, 196.6, 145.5, 140.6, 137.1, 133.8, 133.7, 132.7, 132.5, 128.7, 128.5, 128.39, 128.37, 128.3, 128.2, 118.4, 111.4, 50.5, 44.0, 38.2; HRMS (ESI) Calcd for C 24 H 17 NO2Na (M + Na) + 374.1151, found 374.1153.

[0061] Example 6

[0062]

[0063] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1f (64.4 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was added. The reaction mixture was stirred at 100 °C for 4 h. The solvent was removed by rotary evaporation. The residue was purified by flash column chromatography (eluent: petroleum ether: ethyl acetate, 10:1, by volume) to give the product 2f (42 mg, 62%) as a white solid, m.p. 163-164 °C, 1H NMR (400 MHz, CDC13) δ 8.23 - 8.17 (m, 1H), 7.55 (d, J = 7.3 Hz, 2H), 7.46 - 7.40 (m, 3H), 7.26 (t, 2H), 7.10 (d, J = 8.1 Hz, 3H), 6.98 (d, J = 8.1 Hz, 2H), 5.28 (d, J = 4.5 Hz, 1H), 3.92 (dt, J = 14.5, 4.3 Hz, 1H), 3.78 (dd, 1H), 2.81 (dd, J = 17.1, 4.1 Hz, 1H), 2.21 (s, 3H); 13 CNMR (101 MHz, CDC13) δ 199.8, 198.0, 141.5, 137.7, 137.2, 137.1, 133.5, 133.0, 132.9, 129.3, 128.6, 128.3, 128.2, 128.1, 128.0, 127.4, 51.7, 43.9, 38.8, 21.0; HRMS (ESI) Calcd for C 24 H 20 O2Na(M+Na) + 363.1356, found 363.1364.

[0064] Example 7

[0065]

[0066] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1 g (67.2 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 100 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2 g (45 mg, 64%) was obtained as a brown solid, melting point: 149-151 °C, after purification by flash column chromatography (eluent: petroleum ether: ethyl acetate, 10:1, v / v). 1H NMR (400 MHz, CDC13) δ 8.20 (dd, J = 7.1 Hz, 1H), 7.57 (d, J = 7.4 Hz, 2H), 7.47 - 7.39 (m, 3H), 7.28 (s, 1H), 7.24 - 7.09 (m, 2H), 6.74 (d, J = 27.2 Hz, 3H), 5.27 (d, J = 4.7 Hz, 1H), 3.86 (dt, J = 14.6, 4.4 Hz, 1H), 3.70 (dd, J = 17.1, 14.7 Hz, 1H), 2.80 (dd, J = 17.2, 4.2 Hz, 1H), 2.13 (s, 6H); 13 C NMR (101 MHz, CDC13) δ 199.6, 198.0, 141.7, 139.9, 138.2, 137.8, 133.5, 133.1, 132.9, 128.9, 128.4, 128.2, 128.1, 128.04, 128.01, 125.4, 51.7, 44.2, 38.7, 21.2; HRMS (ESI) Calcd for C 25 H 22 O2Na (M + Na) + 377.1512, found 377.1517.

[0067] Example 8

[0068]

[0069] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1h (71.6 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL), stirred at 100 °C for 4 h, the reaction was completed, the solvent was removed, and the product 2h (39 mg, 52%) was obtained by purification with flash column chromatography (eluent petroleum ether: ethyl acetate = 10:1), yellow solid, melting point: 143-144 °C, 1H NMR (400 MHz, CDC13) δ 8.25 (dd, J = 15.8, 8.2 Hz, 2H), 7.86 (d, J = 8.2 Hz, 1H), 7.67 (t, J = 7.7 Hz, 1H), 7.60 - 7.44 (m, 4H), 7.25 - 7.21 (m, 1H), 7.20 - 7.08 (m, 5H), 6.96 (t, J = 7.5 Hz, 2H), 5.56 (d, J = 4.7 Hz, 1H), 4.82 (dt, J = 14.5, 4.5 Hz, 1H), 3.96 (dd, J = 16.9, 14.5 Hz, 1H), 2.90 (dd, J = 17.0, 3.9 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 199.1, 198.0, 141.7, 137.2, 135.2, 134.0, 133.6, 133.2, 132.9, 131.2, 129.5, 128.4, 128.2, 128.1, 128.00, 127.96, 127.9, 126.9, 125.7, 125.3, 124.2, 122.1, 49.7, 38.7, 38.6.

[0070] Example 9

[0071]

[0072] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1i (71.6 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL), stirred at 80 °C for 4 h, the reaction was completed, the solvent was removed, and the product 2i (44 mg, 59%) was obtained as a white solid by purification with flash column chromatography (eluent: petroleum ether: ethyl acetate = 10: 1). 1 H NMR (400 MHz, CDC13) δ 8.25 (dd, J = 15.8, 8.2 Hz, 2H), 7.86 (d, J = 8.2 Hz, 1H), 7.67 (t, J = 7.7 Hz, 1H), 7.60 - 7.44 (m, 4H), 7.25 - 7.21 (m, 1H), 7.20 - 7.08 (m, 5H), 6.96 (t, J = 7.5 Hz, 2H), 5.56 (d, J = 4.7 Hz, 1H), 4.82 (dt, J = 14.5, 4.5 Hz, 1H), 3.96 (dd, J = 16.9, 14.5 Hz, 1H), 2.90 (dd, J = 17.0, 3.9 Hz, 1H); 13CNMR (101 MHz, CDC13) δ 199.7, 197.7, 141.5, 137.6, 137.5, 133.6, 133.3, 133.00, 132.94, 132.6, 128.5, 128.4, 128.3, 128.2, 128.1, 127.8, 127.5, 126.3, 126.2, 125.9, 125.8, 115.1, 51.4, 44.3, 38.9.

[0073] Example 10

[0074]

[0075] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1j (59.6 mg, 0.2 mmol), n-butylamine (29.2 mg, 0.4 mmol), acetic acid (0.24 mL, 2 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) were added. The reaction mixture was stirred at 80 °C for 4 h. The reaction was complete. The solvent was removed by rotary evaporation. The product 2j (62 mg, 99%, cis:trans = 50:50) was obtained as a brown oil after purification by flash column chromatography (eluent: petroleum ether: ethyl acetate, 10:1, v / v), 1H NMR (400 MHz, CDC13) for mixture: δ 8.18 (dd, J = 7.6, 1.4 Hz, 1H), 8.12 (dd, 1H), 8.10 (s, 1H), 8.08 (s, 1H), 7.80 (s, 1H), 7.78 (s, 1H), 7.64 (t, J = 7.4 Hz, 1H), 7.56 (t, 1H), 7.54 - 7.52 (m, 1H), 7.52 - 7.48 (m, 1H), 7.48 - 7.41 (m, 3H), 7.40 - 7.34 (m, 3H), 7.27 (s, 1H), 7.17 (s, 1H), 7.15 (d, 1H), 7.06 (d, J = 7.6 Hz, 1H), 6.16 (dd, J = 3.3, 1.9 Hz, 1H), 6.09 (dd, J = 3.3, 1.9 Hz, 1H), 5.99 (d, J = 3.2 Hz, 1H), 5.97 (d, J = 3.3 Hz, 1H), 5.52 (d, J = 4.7 Hz, 1H), 5.45 (d, J = 5.3 Hz, 1H), 4.03 (dd, J = 5.1 Hz, 1H), 3.98 (dd, J = 10.9, 5.4 Hz, 1H), 3.49 (dd, J = 17.8, 14.2 Hz, 1H), 3.11 (dd, J = 17.2, 5.0 Hz, 1H), 2.97 (dd, J = 17.2, 6.6 Hz, 1H), 2.87 (dd, J = 17.8, 4.8 Hz, 1H); 13 C NMR (101 MHz, CDC13) for mixture: δ 199.8, 198.8, 196.7, 195.8, 154.3, 153.6, 141.9, 141.6, 140.6, 139.9, 137.0, 136.4, 134.0, 133.8, 133.6, 133.2, 133.1, 132.7, 129.1, 129.0, 128.8, 128.5, 128.40, 128.36, 128.2, 128.0, 127.9, 127.3, 110.4, 106.8, 106.4, 50.4, 48.8, 39.4, 37.6, 37.3, 37.1; HRMS (ESI) Calcd for C 21 H 16 O3Na (M + Na) + 339.0992, found 339.1000.

[0076] Example 11

[0077]

[0078] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1k (66.8 mg, 0.2 mmol), n-butylamine (29.2 mg, 0.4 mmol), acetic acid (0.24 mL, 2 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was added. The reaction mixture was stirred at 100 °C for 4 h. The solvent was removed, and the product 2k (62 mg, 88%, cis:trans = 40:60) was obtained as a brown oil after purification by flash column chromatography (eluent: petroleum ether: ethyl acetate, 10:1, v / v), 1 H NMR (400 MHz, CDC13) for cis-isomer: δ 8.18 - 8.16 (m, 1H), 8.05 - 8.03 (m, 2H), 7.66 - 7.62 (m, 1H), 7.55 - 7.53 (m, 1H), 7.51 - 7.47 (m, 3H), 7.25 - 7.21 (m, 4H), 7.18 - 7.13 (m, 2H), 6.53 (d, J = 15.7 Hz, 1H), 6.00 (dd, J = 15.7, 8.4 Hz, 1H), 5.27 (d, J = 4.8 Hz, 1H), 3.52 - 3.46 (m, 1H), 3.28 (dd, J = 17.6, 13.1 Hz, 1H), 2.73 - 2.69 (m, 1H); 13 C NMR (101 MHz, CDC13) for cis-isomer: δ 2199.3, 197.1, 141.0, 137.6, 136.5, 133.6, 133.5, 133.1, 132.9, 129.6, 128.9, 128.5, 128.4, 128.0, 127.9, 127.7, 126.3, 50.0, 42.3, 39.7; 1 H NMR (400 MHz, CDC13) for trans-isomer: δ 8.16 - 8.13 (m, 1H), 8.03 - 8.00 (m, 2H), 7.62 - 7.56 (m, 1H), 7.53 - 7.51 (m, 1H), 7.46 - 7.37 (m, 3H), 7.21 - 7.18 (m, 4H), 7.11 - 7.06 (m, 2H), 6.44 (d, J = 15.8 Hz, 1H), 6.14 (dd, J = 15.8, 7.8 Hz, 1H), 5.02 (d, J = 6.2 Hz, 1H), 3.58 - 3.52 (m, 1H), 3.03 (dd, J = 17.0, 4.6 Hz, 1H), 2.77 - 2.73 (m, 1H); 13C NMR (101 MHz, CDC13) for trans-isomer: δ 200.2, 196.2, 140.5, 136.9, 136.4, 134.1, 133.7, 132.0, 131.8, 129.5, 129.1, 128.9, 128.8, 128.5, 127.9, 127.8, 127.4, 126.3, 52.5, 41.7, 41.6; HRMS (ESI) Calcd for C 25 H 20 02Na (M + Na) + 375.1356, found 375.1363.

[0079] Example 12

[0080]

[0081] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1l (64.4 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 100 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2l (58 mg, 86%) was obtained as a white solid, m.p. 166-167 °C, after purification by flash column chromatography (eluent petroleum ether: ethyl acetate 10: 1, v / v). 1 H NMR (400 MHz, CDC13) δ 8.20 (dd, J = 6.5, 2.9 Hz, 1H), 7.49 - 7.38 (m, 4H), 7.25 - 7.15 (m, 4H), 7.15 - 7.08 (m, 2H), 7.05 (d, J = 8.0 Hz, 2H), 5.26 (d, J = 4.6 Hz, 1H), 3.94 (dt, J = 14.5, 4.3 Hz, 1H), 3.82 (dd, J = 16.9, 14.5 Hz, 1H), 2.83 (dd, J = 16.9, 3.9 Hz, 1H), 2.32 (s, 3H); 13 C NMR (101 MHz, CDC13) δ 199.1, 197.9, 144.0, 141.7, 140.3, 135.1, 133.5, 132.9, 129.1, 128.70, 128.68, 128.12, 128.08, 128.0, 127.6, 127.5, 51.3, 44.3, 38.7, 21.6; HRMS (ESI) Calcd for C 24 H 20O2Na (M+Na) + 363.1356, found 363.1364.

[0082] Example 13

[0083]

[0084] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2.H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1 m (64.4 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 80 °C for 4 h. The reaction was complete. The solvent was removed by rotary evaporation. The product 2m (51 mg, 75%) was obtained as a white solid after purification by flash column chromatography (eluent: petroleum ether: ethyl acetate, 10:1, v / v), m.p. 119-120 °C, 1 H NMR (400 MHz, CDC13) δ 8.21 (dd, J = 7.3, 2.0 Hz, 1H), 7.47 - 7.39 (m, 2H), 7.33 (d, J = 7.8 Hz, 1H), 7.29 (s, 1H), 7.25 - 7.16 (m, 5H), 7.16 - 7.07 (m, 3H), 5.27 (d, J = 4.6 Hz, 1H), 3.95 (dt, J = 14.6, 4.4 Hz, 1H), 3.79 (dd, J = 17.1, 14.6 Hz, 1H), 2.83 (dd, J = 17.3, 4.2 Hz, 1H), 2.25 (s, 3H); 13 C NMR (101 MHz, CDC13) δ 199.7, 197.9, 141.6, 140.3, 138.1, 137.6, 133.8, 133.5, 132.9, 129.1, 128.7, 128.2, 128.14, 128.08, 128.0, 127.6, 127.5, 125.7, 51.8, 44.3, 38.6, 21.2; HRMS (ESI) Calcd for C 24 H 20 O2Na (M+Na) + 363.1356, found 363.1364.

[0085] Example 14

[0086]

[0087] A dry Schlenk tube with stir bar was charged with Cu(OAc)2H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1n (67.6 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 100 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2n (35 mg, 49%) was obtained as a white solid by flash column chromatography (eluent petroleum ether: ethyl acetate, 10:1, v / v), m.p. 167-168 °C, 1 H NMR (400 MHz, CDC13) δ 8.20 (dd, J = 7.1, 2.2 Hz, 1H), 7.60 - 7.50 (m, 2H), 7.47 - 7.37 (m, 2H), 7.25 - 7.15 (m, 4H), 7.15 - 7.08 (m, 2H), 6.73 (d, J = 9.0 Hz, 2H), 5.23 (d, J = 4.6 Hz, 1H), 3.93 (dt, J = 14.5, 4.3 Hz, 1H), 3.89 - 3.73 (m, 4H), 2.81 (dd, J = 16.9, 4.0 Hz, 1H); 13 CNMR (101 MHz, CDC13) δ 197.9, 197.7, 163.5, 141.8, 140.4, 133.4, 133.0, 130.9, 130.6, 128.7, 128.1, 128.0, 127.6, 127.5, 113.6, 55.4, 51.2, 44.3, 38.8; HRMS (ESI) Calcd for C 24 H 20 O3Na (M + Na) + 379.1305, found 379.1313.

[0088] Example 15

[0089]

[0090] A dry Schlenk tube with stir bar was charged with Cu(OAc)2H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1o (65.2 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 100 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2o (47 mg, 69%) was obtained as a white solid by flash column chromatography (eluent petroleum ether: ethyl acetate, 10:1, v / v), m.p. 185-186 °C,1 H NMR (400 MHz, CDC13) δ 8.21 (dd, J = 7.4, 2.0 Hz, 1H), 7.60 - 7.52 (m, 2H), 7.49 - 7.41 (m, 2H), 7.23 - 7.06 (m, 6H), 6.95 - 6.86 (m, 2H), 5.24 (d, J = 4.8 Hz, 1H), 3.96 (dt, J = 14.5, 4.5 Hz, 1H), 3.74 (dd, J = 17.3, 14.6 Hz, 1H), 2.83 (dd, J = 17.3, 4.3 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 197.9, 197.6, 165.6 (d, 1 J C-F = 256.5 Hz), 141.3, 140.1, 134.0 (d, 4 J C-F = 3.0 Hz), 133.6, 133.0, 131.2 (d, 3 J C-F = 9.1 Hz), 128.8, 128.2, 128.14, 128.05, 127.7, 127.5, 115.5 (d, 2 J C-F = 22.2 Hz), 51.7, 44.2, 38.5; 19 F NMR (376 MHz, CDC13) δ -104.74; HRMS (ESI) Calcd for C 23 H 17 O2FNa (M + Na) + 367.1105, found 367.1115.

[0091] Example 16

[0092]

[0093] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1p (68.6 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 80 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2p (59 mg, 82%) was obtained as a white solid, m.p. 165-166 °C, after purification by flash column chromatography (eluent petroleum ether: ethyl acetate 10:1, v / v). 1H NMR (400 MHz, CDC13) δ 8.20 (dd, J = 6.5, 2.8 Hz, 1H), 7.50 - 7.33 (m, 6H), 7.24 - 7.12 (m, 5H), 7.12 - 7.03 (m, 1H), 5.21 (d, J = 4.7 Hz, 1H), 3.95 (dt, J = 14.5, 4.5 Hz, 1H), 3.74 (dd, J = 17.3, 14.5 Hz, 1H), 2.83 (dd, J = 17.3, 4.3 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 198.4, 197.5, 141.2, 140.0, 139.7, 135.9, 133.6, 132.9, 129.8, 128.8, 128.7, 128.22, 128.17, 128.0, 127.7, 127.5, 51.8, 44.2, 38.5; HRMS (ESI) Calcd for C 23 H 17 02NaCl (M+Na) + 383.0809, found 383.0814.

[0094] Example 17

[0095]

[0096] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1q (77.4 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 80 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2q (65 mg, 80%) was obtained as a white solid, m.p. 164-165 °C, after purification by flash column chromatography (eluent petroleum ether: ethyl acetate 10: 1, v / v). 1 H NMR (400 MHz, CDC13) δ 8.20 (dd, J = 6.5, 2.8 Hz, 1H), 7.50 - 7.33 (m, 6H), 7.24 - 7.12 (m, 5H), 7.12 - 7.03 (m, 1H), 5.21 (d, J = 4.7 Hz, 1H), 3.95 (dt, J = 14.5, 4.5 Hz, 1H), 3.74 (dd, J = 17.3, 14.5 Hz, 1H), 2.83 (dd, J = 17.3, 4.3 Hz, 1H); 13C NMR (101 MHz, CDC13) δ 198.6, 197.5, 141.1, 140.0, 136.3, 133.6, 132.9, 131.7, 129.9, 128.9, 128.5, 128.23, 128.17, 128.1, 127.7, 127.5, 51.8, 44.2, 38.5; HRMS (ESI) Calcd for C 23 H 17 O2NaBr (M + Na) + 427.0304, found 427.0312.

[0097] Example 18

[0098]

[0099] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1r (75.2 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was added. The reaction mixture was stirred at 80 °C for 4 h. The solvent was removed and the product 2r (55 mg, 70%) was obtained as a white solid after purification by flash column chromatography (eluent: petroleum ether: ethyl acetate, 10:1, v / v), m.p. 110-111 °C, 1 H NMR (400 MHz, CDC13) δ 8.22 (dd, 1H), 7.59 (d, J = 8.2 Hz, 2H), 7.55 - 7.40 (m, 4H), 7.23 - 7.04 (m, 6H), 5.27 (d, J = 4.7 Hz, 1H), 3.99 (dt, J = 14.5, 4.5 Hz, 1H), 3.73 (dd, J = 17.4, 14.5 Hz, 1H), 2.86 (dd, J = 17.2, 4.2 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 199.0, 197.4, 140.8, 140.3, 139.8, 134.3, 134.0, 133.7, 132.9, 128.9, 128.7, 128.4, 128.2, 128.1, 127.8, 127.5, 125.4 (q, 4JC-F = 4.0 Hz), 52.3, 44.2, 38.3; 19 F NMR (376 MHz, CDC13) δ -62.99; HRMS (ESI) Calcd for C 24 H 17 O2NaF3 (M + Na)+ 417.1073, found 417.1080.

[0100] Example 19

[0101]

[0102] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1s (61.8 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was added. The mixture was stirred at 80 °C for 4 h. The reaction was complete. The solvent was removed by rotary evaporation. The product 2s (28 mg, 43%) was obtained as a white solid after purification by flash column chromatography (eluent: petroleum ether: ethyl acetate, 2:1, v / v), m.p. 181-182 °C, 1 H NMR (400 MHz, CDC13) δ 8.68 (d, J = 43.6 Hz, 2H), 8.22 (dd, J = 6.9, 2.4 Hz, 1H), 7.81 (dt, J = 8.0, 1.9 Hz, 1H), 7.51 - 7.43 (m, 2H), 7.26 - 7.08 (m, 7H), 5.26 (d, J = 4.8 Hz, 1H), 4.00 (dt, J = 14.5, 4.5 Hz, 1H), 3.70 (dd, J = 17.4, 14.6 Hz, 1H), 2.86 (dd, J = 17.3, 4.0 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 198.6, 197.3, 153.3, 149.7, 140.6, 139.7, 135.6, 133.7, 133.0, 129.0, 128.4, 128.2, 128.1, 127.9, 127.4, 123.3, 52.4, 44.1, 38.3; HRMS (ESI) Calcd for C 22 H 18 NO2(M-H) - 328.1332, found 328.1339.

[0103] Example 20

[0104]

[0105] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1t (62.8 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 80 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2t (37 mg, 56%) was obtained as a white solid, mp: 177-178 °C, 1 H NMR (400 MHz, CDC13) δ 8.20 (dd, J = 7.6, 1.6 Hz, 1H), 7.58 (d, J = 1.7 Hz, 1H), 7.50 - 7.41 (m, 2H), 7.26 - 7.10 (m, 8H), 5.01 (d, J = 4.6 Hz, 1H), 3.93 (dt, J = 14.6, 4.4 Hz, 1H), 3.74 (dd, J = 17.2, 14.6 Hz, 1H), 2.82 (dd, J = 17.3, 4.2 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 197.7, 193.0, 143.0, 141.3, 140.3, 133.6, 133.2, 132.9, 128.7, 128.19, 128.15, 128.0, 127.6, 127.5, 127.0, 126.2, 54.2, 44.3, 38.6; HRMS (ESI) Calcd for C 21 H 16 O2NaS (M + Na) + 355.0763, found 355.0772.

[0106] Example 21

[0107]

[0108] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1t (62.8 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was stirred at 80 °C for 4 h. The reaction was complete, the solvent was removed, and the product 2t (37 mg, 56%) was obtained as a white solid, mp: 177-178 °C, 1H NMR (400 MHz, CDC13) for cis-isomer: δ 8.16 (d, J = 7.9 Hz, 1H), 7.55 - 7.52 (m, 1H), 7.45 - 7.41 (m, 2H), 7.34 - 7.29 (m, 4H), 7.19 - 7.16 (m, 1H), 4.38 (d, J = 4.7 Hz, 1H), 3.84 - 3.76 (m, 2H), 3.09 - 2.96 (m, 2H), 2.39 (ddd, J = 17.8, 8.2, 6.4 Hz, 2H), 1.50 - 1.43 (m, 2H), 1.23 - 1.17 (m, 5H), 0.87 - 0.84 (m, 3H); 13 C NMR (101 MHz, CDC13) for cis-isomer: δ 209.4, 197.6, 140.9, 140.3, 133.6, 132.4, 129.0, 128.1, 128.0, 127.9, 127.7, 127.5, 57.6, 46.0, 43.2, 38.0, 31.4, 28.4, 22.7, 22.4, 14.0; 1 H NMR (400 MHz, CDC13) for trans-isomer: δ 8.13 (d, J = 7.8 Hz, 1H), 7.52 - 7.47 (m, 1H), 7.41 - 7.35 (m, 2H), 7.29 - 7.27 (m, 1H), 7.25 - 7.19 (m, 3H), 7.06 (d, J = 7.7 Hz, 1H), 4.35 (d, J = 8.7 Hz, 1H), 3.78 - 3.71 (m, 1H), 3.65 (dd, J = 17.0, 14.5 Hz, 1H), 2.98 - 2.72 (m, 2H), 2.33 - 2.13 (m, 2H), 1.75 (ddd, J = 17.9, 8.4, 6.2 Hz, 1H), 1.43 - 1.30 (m, 2H), 1.14 - 1.06 (m, 4H), 0.84 - 0.78 (m, 3H); 13 C NMR (101 MHz, CDC13) for trans-isomer: δ 209.4, 197.6, 140.9, 140.3, 133.6, 132.4, 129.0, 128.1, 128.0, 127.9, 127.7, 127.5, 57.6, 46.0, 43.2, 38.0, 31.4, 28.4, 22.7, 22.4, 14.0; HRMS (ESI) Calcd for C 23 H 26 O2Na(M+Na) + 357.1825, found 357.1832.

[0109] Example 22

[0110]

[0111] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1v (65.2 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL), stirred at 80 °C for 4 h, the reaction was complete, the solvent was removed, and the product 2v (42 mg, 61%) was obtained as a brown solid, m.p. 173-174 °C, after purification by flash column chromatography (eluent petroleum ether: ethyl acetate 10:1, v / v). 1 H NMR (400 MHz, CDC13) δ 8.24 (dd, J = 8.8, 6.0 Hz, 1H), 7.57 - 7.49 (m, 2H), 7.44 (t, J = 7.4 Hz, 1H), 7.28 (s, 1H), 7.24 (s, 1H), 7.23 - 7.06 (m, 6H), 6.79 (dd, J = 8.8, 2.5 Hz, 1H), 5.26 (d, J = 4.7 Hz, 1H), 3.95 (dt, J = 14.5, 4.5 Hz, 1H), 3.75 (dd, J = 17.3, 14.5 Hz, 1H), 2.82 (dd, J = 17.4, 4.4 Hz, 1H); 13 C NMR (101 MHz, CDC13) δ 198.9, 196.3, 165.5 (d, 1 J C-F = 256.5 Hz), 144.2 (d, 3 J C-F = 9.1 Hz), 139.7, 137.3, 133.3, 131.1 (d, 3 J C-F = 10.1 Hz), 129.7 (d, 4 J C-F = 3.0 Hz), 128.8, 128.5, 128.4, 127.7, 127.5, 115.6 (d, 2 J C-F = 22.2 Hz), 114.7 (d, 2 J C-F = 22.2 Hz), 51.6, 44.2, 38.4; 19 F NMR (376 MHz, CDC13) δ -104.29; HRMS (ESI) Calcd for C23 H 17 O2FNa(M+Na) + 367.1105, found 367.1115.

[0112] Example 23

[0113]

[0114] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), after three times of nitrogen replacement, 1w (64.4 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL) was added. The mixture was stirred at 80 °C for 4 h. The reaction was complete. The solvent was removed by rotary evaporation. The product 2w (54 mg, 80%) was obtained as a white solid after purification by flash column chromatography (eluent: petroleum ether: ethyl acetate, 10:1, v / v), m.p. 140-141 °C, 1 H NMR (400 MHz, CDC13) δ 8.10 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 7.8 Hz, 2H), 7.45 - 7.26 (m, 2H), 7.25 - 7.13 (m, 6H), 7.13 - 7.06 (m, 1H), 6.89 (s, 1H), 5.25 (d, J = 4.7 Hz, 1H), 3.93 (dt, J = 14.5, 4.5 Hz, 1H), 3.75 (dd, J = 17.2, 14.5 Hz, 1H), 2.79 (dd, J = 17.2, 4.2 Hz, 1H), 2.30 (s, 3H); 13 C NMR (101 MHz, CDC13) δ 199.6, 197.6, 144.5, 141.6, 140.2, 137.6, 133.0, 130.7, 129.1, 128.7, 128.6, 128.5, 128.3, 128.2, 127.6, 127.5, 51.5, 44.4, 38.6, 21.7; HRMS (ESI) Calcd for C 24 H 20 O2Na(M+Na) + 363.1356, found 363.1364.

[0115] Example 24

[0116]

[0117] A dry Schlenk tube with a stir bar was charged with Cu(OAc)2-H2O (8 mg, 20% mmol), 1x (36.8 mg, 0.2 mmol), n-butylamine (2.9 mg, 20% mmol), acetic acid (0.12 mL, 1 mmol), water (36 mg, 2 mmol) and 1,2-dichloroethane (4 mL). After three nitrogen purges, the mixture was stirred at 80 °C for 4 h. The reaction was complete and the solvent was removed. The product 2x (33 mg, 45%, cis:trans = 50:50) was obtained as a white oily liquid after purification by flash column chromatography (eluent petroleum ether: ethyl acetate 10:1), 1 H NMR (400 MHz, CDC13) for mixture: δ 8.14 (s, 1H), 8.12 (s, 1H), 8.10-8.05 (m, 2H), 8.05-8.00 (m, 2H), 7.68-7.64 (m, 1H), 7.64-7.61 (m, 1H), 7.58-7.50 (m, 4H), 7.49-7.42 (m, 2H), 7.42-7.35 (m, 2H), 7.13-7.09 (m, 1H), 7.04 (dd, J = 7.6, 1.3 Hz, 1H), 5.12-5.08 (m, 1H), 5.08-5.05 (m, 1H), 2.81 (ddd, J = 12.1, 6.7, 5.0 Hz, 1H), 2.78-2.69 (m, 1H), 2.46 (ddd, J = 13.8, 5.0, 3.1 Hz, 1H), 2.41-2.32 (m, 2H), 2.26 (td, J = 13.4, 11.8 Hz, 1H), 1.31 (d, J = 6.7 Hz, 3H), 1.20 (d, J = 6.8 Hz, 3H); 13 C NMR (101 MHz, CDC13) for mixture: δ 201.3, 199.8, 199.7, 199.2, 142.3, 141.1, 136.7, 135.9, 133.73, 133.67, 133.5, 133.3, 133.2, 132.7, 129.03, 129.01, 128.98, 128.9, 128.7, 128.3, 127.9, 127.83, 127.77, 127.5, 47.7, 45.9, 42.0, 37.7, 35.7, 34.4, 15.42, 15.35; HRMS (ESI) Calcd for C 18 H 16 O2Na (M + Na) + 287.1043, found 287.1051.

[0118] The above embodiments are the preferred embodiments of the present application, but the embodiments of the present application are not limited to the above embodiments, and any changes, modifications, substitutions, combinations, simplifications, etc. made without departing from the spirit and principles of the present application should be equivalent replacement manners and should be included in the protection scope of the present application.

Claims

1. A process for the preparation of a tetrahydronaphthalenone compound, characterized by, The reaction formula is as follows: wherein: R is one of aryl, heteroaryl; wherein R 1 is one of aryl, heteroaryl; wherein R 1 any one or more hydrogen atoms of the aromatic ring can be substituted by a substituent; R 2 is C1-C 12 one of alkyl, aryl, heteroaryl; R 3 is a hydrogen atom, halogen, C1-C4alkyl; or 12 alkyl; R 4 is a hydrogen atom; The preparation method of the tetrahydronaphthone compound comprises the following steps: Under nitrogen protection, the 1,6-alkynyl compound is dissolved in a solvent, a catalyst Cu(OAc)2.H2O and a nucleophilic reagent n-butylamine are added, then acetic acid and water are added, and after reaction, the tetrahydronaphthone compound is separated and purified.

2. The method of claim 1, wherein: The solvent is selected from one of 1,1-dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, trifluorotoluene, 1,4-dioxane, acetonitrile, toluene, chlorobenzene and xylene.

3. The method of claim 1, wherein: Reaction is carried out at 25-150 DEG C for 0.5-48 hours to obtain the tetrahydronaphthone compound.

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