Synthesis method of dialkyl selenide compound

Abstract

The invention provides a synthesis method of a dialkyl selenide compound, which comprises the following step: by taking olefin and sodium selenide as raw materials and acid as an additive, reacting in an organic solvent under the protection of inert gas to obtain the dialkyl selenide compound. Compared with a traditional process, the method has the advantages of cheap and easily available raw materials, mild conditions, simple operation, high atom economy, excellent chemical selectivity, good functional group compatibility, wide substrate universality and the like, and is suitable for industrial production of the dialkyl selenide compounds, especially complex organic selenium compounds containing multiple functional groups.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis and relates to a method for synthesizing a dialkyl selenide compound. Background Art

[0002] Selenium is an important nutritional trace element and is closely related to health (Biomolecules 2023, 13, 799; Molecules 2024, 29, 136.). Studies have shown that organic selenium compounds have a wide range of uses, especially in the field of medicine, and have important biological functions such as anti-tumor, anti-inflammatory, anti-viral, and anti-aging. Among them, dialkyl selenoethers are a very important class of organic selenium compounds (New J. Chem. 2023, 47, 9959–9988; Pharmaceutics. 2023, 15, 104.). Not only that, in organisms, glutathione peroxidase is an important selenoprotein with many important functions such as anti-oxidation and protecting cells from damage. Among them, the dialkyl selenoether structural unit of the enzyme plays an important role (Int. J. Mol. Sci. 2023, 24, 10109; Front. Pharmacol. 2023, 14, 1147414.). In addition, dialkyl selenoethers are also a novel class of organic catalysts and ligands with high catalytic activity and are widely used in organic synthesis. Therefore, the development of new synthetic methods and new structural types of dialkyl selenoether compounds is of great research significance.

[0003] At present, there are many methods for synthesizing diaryl selenide compounds, but the methods for synthesizing dialkyl selenide compounds are very limited and have many problems. For example, Zhang et al. first used bromocarbon to react with magnesium to prepare Grignard reagent RMgBr, then reacted with elemental selenium to obtain RSeMgBr, and finally reacted with olefins or halogenated hydrocarbons under copper catalysis to obtain dialkyl selenide. The disadvantages of this method are that it has many steps, harsh conditions, poor functional group compatibility, the use of metal catalysts, and complex operations (Tetrahedron Letters, 2012, 53, 5688–5690; ARKIVOC, 2012, 8, 146-156.). Lee, Krief and others reported that dialkyl selenide was obtained by nucleophilic substitution reaction using halogenated hydrocarbons as raw materials. This method has the disadvantages of difficult raw materials, strong base conditions, limited substrate range, and inapplicability to substrates with complex functional groups, and can only obtain straight-chain selenide compounds (Molecules, 2022, 27, 5224; Synlett, 2004, 10, 1751–1754.). Therefore, it is of great research value and practical significance to develop a method for synthesizing dialkyl selenide compounds that is efficient, mild, has good chemical selectivity, good functional group compatibility, and rich and diverse structural types. Summary of the invention

[0004] In order to solve the problems existing in the prior art, the present invention aims to provide a method for synthesizing dialkyl selenide compounds with high efficiency, mild conditions, good functional group compatibility and chemical selectivity, and wide applicability. The method has mild conditions, a wide substrate range, and simple operation, which is conducive to the industrial preparation of selenide compounds.

[0005] The present invention is achieved through the following technical solutions:

[0006] A method for synthesizing a dialkyl selenide compound comprises: using olefin and sodium selenide as raw materials, using acid as an additive, and carrying out a reaction in an organic solvent under the protection of an inert gas to obtain the dialkyl selenide compound.

[0007] Preferably, the olefin is one or both of the compounds of formula (1) and formula (2), and the structural formula of the dialkyl selenide compound is shown in formula (3):

[0008]

[0009] Wherein, R1 and R3 are each independently selected from alkyl, substituted alkyl, aryl, substituted aryl, heterocyclic aryl, or R1 and R2 are connected to form a cycloalkyl or substituted cycloalkyl; R2 and R4 are each independently selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclic aryl, or R3 and R4 are connected to form a cycloalkyl or substituted cycloalkyl; R1 and R3 are the same or different, and R2 and R4 are the same or different.

[0010] Furthermore, when the compound of formula (1) and the compound of formula (2) are both monosubstituted aromatic olefins, the reaction is carried out under the protection of an inert gas with or without light protection.

[0011] Furthermore, the molar ratio of the acid, sodium selenide and olefin is (2-3.5):(2-3):1.

[0012] Furthermore, the organic solvent is one or more of tetrahydrofuran, ethanol and methanol.

[0013] Furthermore, the reaction temperature is room temperature and the reaction time is 10-40h.

[0014] Furthermore, when both the compound of formula (1) and the compound of formula (2) are aliphatic olefins, or at least one of the compound of formula (1) and the compound of formula (2) is a disubstituted aromatic olefin, the reaction is carried out under inert gas protection and heating conditions, the heating temperature is 100-120° C., and the reaction time is 16-24 hours.

[0015] Furthermore, the molar ratio of the acid, sodium selenide and olefin is (1.5-3.5):(1-2.5):1.

[0016] Furthermore, the organic solvent is one or more of 1,4-dioxane, ethanol, isopropanol, water, tetrahydrofuran and toluene.

[0017] Preferably, the acid is acetic acid, formic acid, benzoic acid, trifluoroacetic acid or hydrochloric acid.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] The present invention uses easily available olefins as raw materials, odorless sodium selenide as a selenization reagent, and cheap and easily available organic weak acids as additives, and realizes the synthesis of dialkyl selenide compounds with a separation yield of up to 92%. Compared with the traditional process, the present invention has the advantages of cheap and easily available raw materials, mild conditions, simple operation, high atom economy, excellent chemical selectivity, good functional group compatibility, and wide substrate universality, and is suitable for the industrial production of dialkyl selenide compounds, especially complex organic selenium compounds containing multiple functional groups.

[0020] Furthermore, the present invention can not only efficiently synthesize symmetrical dialkyl selenoethers, but also synthesize asymmetrical dialkyl selenoethers with a moderate yield.

[0021] Furthermore, the substrate scope of the present invention is wide, and is applicable not only to simple aromatic and aliphatic olefins, but also to complex aromatic and aliphatic olefins derived from drug molecules and natural products. DETAILED DESCRIPTION

[0022] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention, all of which belong to the scope of the present invention.

[0023] It should be noted that the process equipment or devices not specifically specified in the following embodiments are all conventional equipment or devices in the art.

[0024] It should be noted that the terms "include" and "have" and any variations thereof are intended to cover non-exclusive inclusions. For example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices. Moreover, unless otherwise specified, the numbering of each method step is only a convenient tool for identifying each method step, and is not intended to limit the order of arrangement of each method step or to define the scope of the present invention. Changes or adjustments in their relative relationships should also be regarded as the scope of the present invention without substantially changing the technical content.

[0025] The synthesis method of the dialkyl selenoether compound of the present invention comprises: using olefin and sodium selenide as raw materials, using acid as additive, and reacting in an organic solvent under the protection of an inert gas to obtain the dialkyl selenoether compound. The acid is preferably acetic acid, formic acid, benzoic acid, trifluoroacetic acid or hydrochloric acid, and more preferably acetic acid.

[0026] Specifically, the reaction formula of the present invention is as follows:

[0027]

[0028] Wherein, R1 and R3 are each independently selected from alkyl, substituted alkyl, aryl, substituted aryl, heterocyclic aryl, or R1 and R2 are connected to form a cycloalkyl or substituted cycloalkyl; R2 and R4 are each independently selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclic aryl, or R3 and R4 are connected to form a cycloalkyl or substituted cycloalkyl; R1 and R3 are the same or different, and R2 and R4 are the same or different.

[0029] The substituents in the substituted alkyl group mainly refer to drug molecules or natural products, such as ibuprofen, naproxen, bezafibrate, probenecid, camphoric acid, fenbufen, ketoprofen, indomethacin, and chlorambucil; the substituents in the substituted aryl group are methyl, pyrazolyl, amide, hydroxymethyl, methylthio, halogen, ester, etc.; the substituents in the substituted cycloalkyl group are ester groups.

[0030] In some preferred embodiments of the present invention, the olefin is 4-allylanisole, 4-phenyl-1-butene, 1-heptene, dibenzyl oct-4-enedioate, dimethyl 3-cyclopentene-1,1-dicarboxylate, cycloheptene, 1-(4-vinylphenyl)-1H-pyrazole, 4-acetylaminostyrene, 4-hydroxymethylstyrene, 4-methylthiostyrene, 4-fluorostyrene, 4-bromostyrene, 4-vinyl-methylbenzoate, 3-vinylthiophene, 4-vinylferrocene, β- -methylstyrene, 4-methylstyrene, 4-methoxystyrene, naphthylethylene, pent-4-en-1-yl 2-(4-isobutylphenyl)propionate, pent-4-en-1-yl (S)-2-(6-methoxynaphthalen-2-yl)propionate, pent-4-en-1-yl 2-(4-(2-(4-chlorobenzamido)ethyl)phenoxy)-2-methylpropionate, pent-4-en-1-yl 4-(N,N-dipropylsulfamoyl)benzoate, pent-4-en-1-yl (1S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate, pent-4-en-1-yl 4-((1,1'-biphenyl)-4-yl)-4-oxobutyrate, pent-4-en-1-yl 2-(3-benzoylphenyl) propionate, pent-4-en-1-yl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl) acetate, 4-vinylphenyl (S)-2 -(6-methoxynaphthalen-2-yl) propionate, 4-vinylbenzyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl) acetate, 4-vinylbenzyl 4-(4-(bis(2-chloroethyl)amino)phenyl)butyrate, 4-vinylbenzyl 4-((1,1'-biphenyl)-4-yl)-4-oxobutyrate and 4-vinylbenzyl (S)-2-(6-methoxynaphthalen-2-yl) propionate or two thereof.

[0031] When both the compound of formula (1) and the compound of formula (2) are monosubstituted aromatic olefins, the synthesis method is specifically as follows: sodium selenide, acid, and olefin are added to an organic solvent, and reacted under the protection of an inert gas and light-proof (or not light-proof) conditions to obtain a dialkyl selenide ether compound. At this time, in the reaction, the molar ratio of the acid, sodium selenide, and olefin is preferably (2-3.5): (2-3): 1, the organic solvent is one or more of tetrahydrofuran, ethanol, and methanol, preferably tetrahydrofuran, the reaction temperature is room temperature, and the reaction time is preferably 10-40 hours.

[0032] When the compound of formula (1) and the compound of formula (2) are both aliphatic olefins, or at least one of the compound of formula (1) and the compound of formula (2) is a disubstituted aromatic olefin, the synthesis method is specifically: sodium selenide, acid, and olefin are added to an organic solvent, and heated to react under inert gas protection conditions to obtain a dialkyl selenide ether compound. At this time, the heating temperature is preferably 100-120°C, and the reaction time is preferably 16-24h; the preferred molar ratio of acid, sodium selenide and olefin is (1.5-3.5): (1-2.5): 1; the organic solvent is one or more of 1,4-dioxane, ethanol, isopropanol, water, tetrahydrofuran and toluene, preferably 1,4-dioxane. The monosubstituted aromatic olefin described in the present invention refers to an aromatic olefin having one hydrogen substituted on the double bond. The disubstituted aromatic olefin refers to an aromatic olefin having two hydrogen substituted on the double bond.

[0033] In the synthesis method of the present invention, the amount of the organic solvent used is 0.2M.

[0034] Example 1

[0035]

[0036] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane, 29μL (0.5mmol, 2.5equiv) of acetic acid and 34μL (0.2mmol, 1.0equiv) of 4-allyl anisole in sequence, and react at 120°C for 24h. After the reaction, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 34.4mg of pure product by preparative thin layer chromatography, with a yield of 91%.

[0037] 1 H NMR (400MHz, CDCl3) δ7.10–7.03(m,4H),6.86–6.80(m,4H),3.80(s,6H),3.14–3 .03(m,2H),3.01–2.89(m,2H),2.76–2.67(m,2H),1.34(dd,J=16.0,6.8Hz,6H); 13 C NMR (100MHz, CDCl3) δ158.24,132.34,132.26,130.21,129.51,113.78,113.76,55.37,44.25,44.10,35.50,22.06,21.90; HRMS (LCMS-ESI) m / z Calcd.for C 20 H 26 NaO2Se[M+Na]+ 401.0990,found:401.1008.

[0038] Example 2

[0039]

[0040] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane, 29μL (0.5mmol, 2.5equiv) of acetic acid and 31μL (0.2mmol, 1.0equiv) of 4-phenyl-1-butene, and stir at 120°C for 24h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 32mg of pure product by preparative thin layer chromatography, with a yield of 92%.

[0041] 1 H NMR (400MHz, CDCl3) δ7.23–7.17(m,4H),7.14–7.08(m,6H),2.92(ddd,J=13.6,6.8 ,2.9Hz,2H),2.67(t,J=7.8Hz,4H),1.95–1.73(m,4H),1.40(dd,J=6.9,4.7Hz,6H); 13 CNMR(100MHz, CDCl3)δ142.00,128.56,128.50,125.96,40.16,34.16,34.04,33.89,33.81,23.17,23.08; HRMS(LCMS-ESI)m / zCalcd.for C 20 H 27 Se[M+H] + 347.1272, found:347.1243.

[0042] Example 3

[0043]

[0044] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane, 29μL (0.5mmol, 2.5equiv) of acetic acid and 29μL (0.2mmol, 1.0equiv) of 1-heptene in sequence, and stir at 120°C for 24h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 19.6mg of pure product by preparative column chromatography, with a yield of 70%.

[0045] 1 H NMR (400MHz, CDCl3) δ3.04–2.93(m,2H),1.69–1.59(m,2H),1.58–1.50(m,2H),1.46–1.36(m,9H),1.35–1.23(m,9H),0.88(dd,J=8.5,5.3Hz,6H); 13 C NMR (100MHz, CDCl3) δ38.55,38.43,34.40,34.25,31.83,27.65,27.55,23.04,22.93,22.72,22.71,14.18; HRMS (LCMS-ESI) m / z Calcd.for C 14 H 31 Se[M+H] + 279.1585, found:279.1582.

[0046] Example 4

[0047]

[0048] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane, 29μL (0.5mmol, 2.5equiv) of acetic acid and 67μL (0.2mmol, 1.0equiv) of dibenzyl oct-4-enedioate in sequence, and stir at 120°C for 24h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 36.8mg of pure product by preparative thin layer chromatography, with a yield of 47%.

[0049] 1 H NMR (400MHz, CDCl3) δ7.41–7.27(m,20H),5.10(d,J=2.3Hz,8H),2.95–2.70(m,2H),2.56–2.44(m,4 H),2.39–2.27(m,4H),2.04–1.91(m,2H),1.91–1.81(m,2H),1.81–1.67(m,4H),1.64–1.56(m,4H); 13C NMR (100MHz, CDCl3) δ173.19,173.15,173.13,172.93,136.13,136.10,136. 07,136.04,128.68,128.43,128.38,128.35,66.45,66.41,66.35,66.31,45 .36,40.76,40.74,35.80,35.65,35.48,35.46,34.02,33.91,32.47,32.37, 32.28,31.03,30.98,30.95,30.91,23.22,23.05,23.01; HRMS(LCMS-ESI)m / z Calcd.forC 44 H 50 NaO8Se[M+Na] + 809.2563, found:809.2559.

[0050] Example 5

[0051]

[0052] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide and 38mg (0.2mmol, 1.0equiv) of dimethyl 3-cyclopentene-1,1-dicarboxylate, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane and 29μL (0.5mmol, 2.5equiv) of acetic acid in sequence, and stir at 120°C for 24h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 21.5mg of pure product by column chromatography, with a yield of 48%.

[0053] 1 H NMR (400MHz, CDCl3) δ3.72 (s, 12H), 3.36–3.25 (m, 2H), 2.78 (dd, J = 13.7, 7.2 Hz,2H),2.46(dt,J=13.0,6.2Hz,2H),2.11–2.23(m,6H),1.82–1.68(m,2H); 13 C NMR(100MHz, CDCl3)δ172.74,172.26,60.07,52.99,52.95,42.88,42.83,36.11,35.98,34.60,34.48,33.97; HRMS(LCMS-ESI)m / z Calcd.for C 18 H 26 NaO8Se[M+Na] +473.0685,found:473.0689.

[0054] Example 6

[0055]

[0056] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane, 29μL (0.5mmol, 2.5equiv) of acetic acid and 24μL (0.2mmol, 1.0equiv) of cycloheptene in sequence, and stir at 120°C for 24h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 16.4mg of pure product by column chromatography, with a yield of 60%.

[0057] 1 H NMR (400MHz, CDCl3) δ3.13–3.02(m,2H),2.12–1.98(m,4H),1.76–1.63(m,8H),1.75–1.64(m,7H),152–1.41(m,5H); 13 C NMR (100MHz, CDCl3) δ40.05, 36.37, 28.30, 27.03; HRMS (LCMS-ESI) m / z Calcd.for C 14 H 26 KSe[M+K] + 313.0831, found:313.0847.

[0058] Example 7

[0059]

[0060] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid and 26μL (0.2mmol, 1.0equiv) of 4-methylstyrene in sequence, and stir at room temperature in the dark for 23h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate by preparative thin layer chromatography to obtain 26.1mg of pure product with a yield of 82%.

[0061] 1H NMR(400MHz, CDCl3) δ7.21–7.06(m,8H),3.94(dd,J=14.1,7.0Hz,1H),3.86(q,J =7.2Hz,1H),2.33(d,J=8.1Hz,6H),1.69(d,J=7.1Hz,3H),1.58(d,J=7.2Hz,3H); 13 C NMR(100MHz, CDCl3)δ142.17,141.40,136.45,129.21,127.45,127.26,38.52,38.22,23.29,22.99,21.23; HRMS(LCMS-ESI)m / z Calcd.for C 18 H 22 NaSe[M+Na] + 341.0779,found:341.0775.

[0062] Example 8

[0063]

[0064] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide and 34mg (0.2mmol, 1.0equiv) of 1-(4-vinylphenyl)-1H-pyrazole. Under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran and 34μL (0.6mmol, 3.0equiv) of acetic acid in sequence. Stir for 22h at room temperature in the dark. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 33.4mg of pure product by preparative thin layer chromatography with a yield of 79%.

[0065] 1 H NMR (400MHz, CDCl3) δ7.91(d,J=2.4Hz,2H),7.87(d,J=2.4Hz,2H),7.73(d,J=1.7Hz,2H),7.71(d,J=1.7Hz,2H),7.64–7.60(m,4H),7.60–7.55(m,4H) ,7.37–7.31(m,8H),6.48–6.46(m,2H),6.46–6.43(m,2H),4.03(q,J=7.1H z,2H),3.89(q,J=7.2Hz,2H),1.72(d,J=7.1Hz,6H),1.60(d,J=7.2Hz,6H); 13C NMR (100MHz, CDCl3) δ143.26,142.57,141.13,141.11,138.92,138.87,128.65,128.40,1 26.79,119.29,119.28,107.68,107.66,38.17,38.04,23.12,22.90; HRMS(LCMS-ESI)m / z Calcd.for C 22 H 23 N4Se[M+H] + 423.1082, found:423.1076.

[0066] Example 9

[0067]

[0068] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide and 33mg (0.2mmol, 1.0equiv) of 4-acetylaminostyrene, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran and 34μL (0.6mmol, 3.0equiv) of acetic acid in sequence, and stir at room temperature in the dark for 40h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 36.8mg of pure product by preparative thin layer chromatography, with a yield of 91%.

[0069] 1 H NMR (400MHz, CDCl3) δ7.44(s,1H),7.38(d,J=8.4Hz,5H),7.29–7.25(m,4H),7.17(d,J=8.4Hz,4H),7.10(d,J=8.4Hz,4H ),3.96(q,J=7.1Hz,2H),3.84(q,J=7.2Hz,2H),2.17(s,6H),2.16(s,6H),1.63(d,J=7.2Hz,6H),1.55(d,J=7.2Hz,6H); 13 C NMR (100MHz, CDCl3) δ142.54,141.91,136.60,136.53,135.10,129.72,128.88,128.61,124. 89,124.72,38.51,38.34,23.26,23.15,19.98,19.94,19.56; HRMS(LCMS-ESI)m / zCalcd.for C 20 H 24 N2NaO2Se[M+Na] +427.0895,found:427.0888.

[0070] Example 10

[0071]

[0072] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid and 26μL (0.2mmol, 1.0equiv) of 4-hydroxymethylstyrene in sequence, and stir at room temperature in the dark for 22h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 25.3mg of pure product by preparative thin layer chromatography, with a yield of 72%.

[0073] 1 H NMR (400MHz, CDCl3) δ7.29–7.23(m,4H),7.18(s,4H),4.65(s,2H),4.61(s,2H),4.00(q,J=7 .1Hz,1H),3.89(q,J=7.2Hz,1H),2.02(s,2H),1.66(d,J=7.1Hz,3H),1.58(d,J=7.2Hz,3H); 13 C NMR(100MHz, CDCl3)δ144.50,143.80,139.42,139.26,127.75,127.55,127.26,127.22,65.18,65.14,38.64,38.37,23.15; HRMS(LCMS-ESI)m / zCalcd.for C 18 H 22 NaO2Se[M+Na] + 373.0677,found:373.0681.

[0074] Embodiment 11

[0075]

[0076] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid, and 30μL (0.2mmol, 1.0equiv) of 4-methylthiostyrene in sequence, and stir at room temperature in the dark for 40h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 33.6mg of pure product by preparative thin layer chromatography, with a yield of 88%.

[0077] 1 H NMR (400MHz, CDCl3) δ7.21–7.13(m,8H),3.95(q,J=7.1Hz,1H),3.83(q,J=7.2H z,1H),2.49(s,3H),2.47(s,3H),1.67(d,J=7.1Hz,3H),1.57(d,J=7.2Hz,3H); 13 CNMR(100MHz, CDCl3)δ142.01,141.29,136.66,128.10,127.86,126.76,38.31,38.16,23.13,22.89,16.07; HRMS(LCMS-ESI)m / z Calcd.for C 18 H 22 NaS2Se[M+Na] + 405.0220,found:405.0215.

[0078] Example 12

[0079]

[0080] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid and 25μL (0.2mmol, 1.0equiv) of 4-fluorostyrene in sequence, and stir at room temperature in the dark for 22h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate by preparative thin layer chromatography to obtain 24.9mg of pure product with a yield of 76%.

[0081] 1H NMR(400MHz, CDCl3)δ7.21(ddd,J=8.6,5.4,3.1Hz,8H),7.01–6.92(m,8H),3.94(q ,J=7.1Hz,2H),3.83(q,J=7.2Hz,2H),1.67(d,J=7.1Hz,6H),1.56(d,J=7.1Hz,6H); 13 C NMR (100MHz, CDCl3) δ162.86,160.42,140.67,140.63,140.07,140.04,129.11,129.03,128. 88,128.80,115.46,115.43,115.24,115.22,38.01,37.83,23.37,23.11; HRMS(LCMS-ESI)m / z Calcd.for C 16 H 16 F2NaSe[M+Na] + 349.0277,found:347.0239.

[0082] Embodiment 13

[0083]

[0084] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid and 28μL (0.2mmol, 1.0equiv) of 4-bromostyrene in sequence, and stir at room temperature in the dark for 23h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 38.2mg of pure product by preparative thin layer chromatography, with a yield of 85%.

[0085] 1 H NMR (400MHz, CDCl3) δ7.43–7.35(m,8H),7.14–7.07(m,8H),3.92(q,J=7.1Hz,2H),3.77(q,J=7.2Hz,2H),1.65(d,J=7.1Hz,6H),1.54(d,J=7.2Hz,6H); 13 C NMR (100MHz, CDCl3) δ143.98,143.29,131.64,129.34,129.08,120.55,120.54,38.09,37.98,23.06,22.83; HRMS (LCMS-ESI) m / z Calcd.for C 16H 17 Br2Se[M+H] + 446.8857,found:446.8857.

[0086] Embodiment 14

[0087]

[0088] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid and 32μL (0.2mmol, 1.0equiv) of 4-vinyl-benzoic acid methyl ester in sequence, and stir at room temperature in the dark for 40h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 35.2mg of pure product by preparative thin layer chromatography, with a yield of 87%.

[0089] 1 H NMR (400MHz, CDCl3) δ8.00–7.87(m,8H),7.32–7.24(m,8H),3.99(dd,J=14.1,7.1Hz,2H) ,3.93–3.88(m,12H),3.83(q,J=7.1Hz,2H),1.68(d,J=7.1Hz,6H),1.56(d,J=7.2Hz,6H); 13 C NMR (100MHz, CDCl3) δ166.92,166.89,150.16,149.44,129.94,129.92,129.79,128.83, 128.75,127.62,127.37,52.20,52.18,38.43,38.31,22.75,22.53; HRMS(LCMS-ESI)m / z Calcd.for C 20 H 22 NaO4Se[M+Na] + 429.0576,found:429.0575.

[0090] Embodiment 15

[0091]

[0092] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid and 21μL (0.2mmol, 1.0equiv) of 3-vinylthiophene in sequence, and stir at room temperature in the dark for 22h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 18.1mg of pure product by preparative thin layer chromatography, with a yield of 60%.

[0093] 1 H NMR (400MHz, CDCl3) δ7.21–7.16(m,4H),7.01(dd,J=5.0,1.2Hz,2H),6.96(dd,J=5.0,1.2Hz,2H ),6.94–6.90(m,4H),3.99(dq,J=21.3,7.1Hz,4H),1.63(d,J=7.1Hz,6H),1.56(d,J=7.1Hz,6H); 13 C NMR(100MHz, CDCl3)δ145.79,145.32,127.39,127.31,125.94,125.87,120.34,120.25,33.53,33.33,23.05,22.90; HRMS(LCMS-ESI)m / zCalcd.for C 12 H 15 S2Se[M+H] + 302.9775,found:302.9777.

[0094] Example 16

[0095]

[0096] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide and 43mg (0.2mmol, 1.0equiv) of 4-vinylferrocene, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran and 34μL (0.6mmol, 3.0equiv) of acetic acid in sequence, and stir at room temperature in the dark for 22h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate by preparative thin layer chromatography to obtain 46.6mg of pure product with a yield of 92%.

[0097] 1H NMR (400MHz, CDCl3) δ4.25–4.08 (m, 36H), 3.93 (dq, J = 24.1, 7.0Hz, 4H), 1.78 (d, J = 7.0Hz, 12H); 13 C NMR (100MHz, CDCl3) δ92.99,92.77,68.71,68.69,67.75,67.71,67.69,67.66,6 7.57,66.19,66.10,33.54,33.29,22.98,22.72; HRMS(LCMS-ESI)m / zCalcd.for C 24 H 26 Fe2Se[M] + 505.9893,found:505.9901.

[0098] Embodiment 17

[0099]

[0100] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane, 29μL (0.5mmol, 2.5equiv) of acetic acid and 28μL (0.2mmol, 1.0equiv) of β-methylstyrene in sequence, and stir at 120°C for 24h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 24.2mg of pure product by preparative thin layer chromatography, with a yield of 76%.

[0101] 1 H NMR (400MHz, CDCl3) δ7.25–7.07(m,20H),3.58(t,J=7.6Hz,2H),3.44(t,J=7.6Hz,2H),1 .92(p,J=7.3Hz,4H),1.77(p,J=7.3Hz,4H),0.75(t,J=7.3Hz,6H),0.68(t,J=7.3Hz,6H); 13 C NMR(100MHz, CDCl3)δ143.77,142.98,128.48,128.37,128.00,126.79,126.78,46.29,30.21,30.11,13.25,13.10; HRMS(LCMS-ESI)m / z Calcd.for C 18 H 22 NaSe[M+Na] + 341.0779,found:341.0764.

[0102] Embodiment 18

[0103]

[0104] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid, 14μL (0.1mmol, 0.5equiv) of 4-methylstyrene, and 14μL (0.1mmol, 0.5equiv) of 4-methoxystyrene in sequence, and stir at room temperature in the dark for 22h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate by preparative thin layer chromatography to obtain 14.9mg of pure product with a yield of 44%.

[0105] 1 H NMR (400MHz, CDCl3) δ7.24–7.14(m,8H),7.09(dd,J=10.5,8.2Hz,4H),6.87–6.79(m,4H),3.98–3.91(m,2H),3.90–3.82(m,2H),3.81(s ,3H),3.79(s,3H),2.34(s,3H),2.32(s,3H),1.69(d,J=1.3Hz,3H),1.68(d,J=1.3Hz,3H),1.59(d,J=2.1Hz,3H),1.57(d,J=2.1Hz,3H); 13 C NMR (100MHz, CDCl3) δ158.42,158.41,142.18,141.45,137.25,136.54,136.44,129.22,129.19,128.61,128.43,127.45,127. 25,113.88,113.84,55.41,55.40,38.54,38.27,38.23,37.94,23.40,23.31,23.11,23.02,21.22,21.21; HRMS(LCMS-ESI)m / z Calcd.for C 18 H 22 NaOSe[M+Na] + 357.0728, found:357.0749.

[0106] Embodiment 19

[0107]

[0108] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide and 17mg (0.1mmol, 0.5equiv) of 1-(4-vinylphenyl)-1H-pyrazole. Under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid and 16μL (0.1mmol, 0.5equiv) of naphthalene vinyl in sequence. Stir for 22h at room temperature in the dark. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 20mg of pure product by preparative thin layer chromatography with a yield of 49%.

[0109] 1 H NMR(400MHz, CDCl3) δ7.84(d,J=2.4Hz,1H),7.77–7.62(m,9H),7.57–7.50(m,3H),7.45(d,J=8 .4Hz,4H),7.42–7.33(m,5H),7.26(d,J=8.5Hz,2H),7.21(d,J=8.6Hz,2H),7.18(s,1H),6.38( dt,J=12.7,2.0Hz,2H),4.11(q,J=7.1Hz,1H),3.94(dq,J=14.2,7.1Hz,2H),3.76(q,J=7.2Hz, 1H), 1.71 (d, J = 7.1Hz, 3H), 1.64 (d, J = 7.1Hz, 3H), 1.60 (d, J = 7.2Hz, 3H), 1.50 (d, J = 7.2Hz, 3H); 13 C NMR (100MHz, CDCl3) δ143.51,142.70,142.13,141.55,141.16,141.10,138.93,138. 84,133.32,133.26,132.71,132.63,128.75,128.54,128.46,128.43,127.80,127.73 ,126.83,126.79,126.32,126.26,126.03,125.84,125.81,125.45,119.29,119.23,1 07.68,107.61,39.18,39.14,38.21,38.04,23.20,22.95,22.84; HRMS(LCMS-ESI)m / z Calcd.for C 23 H 23 N2Se[M+H] + 407.1021, found:407.1011.

[0110] Embodiment 20

[0111]

[0112] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane, 29μL (0.5mmol, 2.5equiv) of acetic acid and 55mg (0.2mmol, 1.0equiv) of pent-4-en-1-yl 2-(4-isobutylphenyl) propionate, and stir at 120°C for 24h. After the reaction is completed, dilute and filter with ethyl acetate, distill under reduced pressure to remove the solvent, and use column chromatography to obtain 44mg of pure product with a yield of 69%.

[0113] 1 H NMR (400MHz, CDCl3) δ7.20(d,J=8.0Hz,4H),7.09(d,J=8.0Hz,4H),4.13–4.00(m,4H),3.68(q,J=7.1Hz,2H),2.88(dt,J=13.2,6.6Hz,2H),2.44(d,J= 7.2Hz,4H),1.84(dp,J=13.5,6.8Hz,2H),1.73–1.65(m,4H),1.61–1.51(m ,4H),1.48(d,J=7.2Hz,6H),1.35(d,J=6.8Hz,6H),0.89(d,J=6.6Hz,12H); 13 CNMR (100MHz, CDCl3) δ174.87,140.60,137.92,129.42,127.26,64.49,64.46,64.42,64.39,45.31,45.28,45.16,34.56,34 .48,34.43,33.94,33.89,33.86,30.30,26.98,26.94,23.14,23.06,23.03,22.53,18.62,18.60,18.57; HRMS(LCMS-ESI)m / z Calcd.for C 36 H 54 NaO4Se[M+Na] + 653.3080, found:653.3085.

[0114] Embodiment 21

[0115]

[0116] In a 10mL Schlenk reaction tube, 50mg (0.4mmol, 2.0equiv) of sodium selenide and 60mg (0.2mmol, 1.0equiv) of pent-4-en-1-yl (S)-2-(6-methoxynaphthalen-2-yl) propionate were added, and under N2 conditions, 1.0mL of ultra-dry 1,4-dioxane and 29μL (0.5mmol, 2.5equiv) of acetic acid were added in sequence, and stirred at 120°C for 24h. After the reaction was completed, the mixture was diluted and filtered with ethyl acetate, and the solvent was removed by distillation under reduced pressure. 58.4mg of the pure product was separated by preparative thin layer chromatography with a yield of 86%.

[0117] 1 H NMR (400MHz, CDCl3) δ7.72–7.64(m,6H),7.40(d,J=8.5Hz,2H),7.16–7.08(m,4H),4.10–4.03(m,4H),3.90(d,J=2.0Hz,6H) ,3.84(q,J=7.1Hz,2H),2.84–2.70(m,2H),1.71–1.60(m,4H),1.57(d,J=7.2Hz,6H),1.55–1.41(m,4H),1.30–1.24(m,6H); 13 C NMR (100MHz, CDCl3) δ174.76,157.73,135.85,133.78,129.37,129.02,127.23,126.34,126.02,126.01,119.07,105.68,64.57,64.52,64 .50,55.39,45.61,34.52,34.49,34.46,34.41,33.87,33.77,26.97,26.94,26.90,23.03,22.94,22.93,18.61,18.59; HRMS(LCMS-ESI)m / z Calcd.for C 38 H 46 NaO6Se[M+Na] + 701.2352, found:701.2345.

[0118] Embodiment 22

[0119]

[0120] In a 10mL Schlenk reaction tube, 50mg (0.4mmol, 2.0equiv) of sodium selenide and 86mg (0.2mmol, 1.0equiv) of pent-4-en-1-yl 2-(4-(2-(4-chlorobenzamido)ethyl)phenoxy)-2-methylpropanoate were added. Under N2 conditions, 1.0mL of ultra-dry 1,4-dioxane and 29μL (0.5mmol, 2.5equiv) of acetic acid were added in sequence, and stirred at 120°C for 24h. After the reaction was completed, the mixture was diluted and filtered with ethyl acetate, and the solvent was distilled off under reduced pressure. The pure product (79.3mg) was separated by preparative thin layer chromatography with a yield of 84%.

[0121] 1 H NMR (400MHz, CDCl3) δ7.61(d,J=8.5Hz,4H),7.33(d,J=8.5Hz,4H),7.05(d,J=8.4Hz,4H),6.76(d,J=8.3Hz,4H),6.41(d,J=4.2Hz,2H),4. 13(dt,J=6.2,4.9Hz,4H),3.60(dd,J=13.0,6.9Hz,4H),2.90–2.79(m,6H),1.79–1.67(m,4H),1.62–1.46(m,16H),1.34(d,J=6.9Hz,6H); 13 C NMR (100MHz, CDCl3) δ174.41,166.51,154.17,137.64,133.08,132.48,132.45,129.57,128.82,128.42,119.36,119.33,79.1 7,65.25,65.23,41.40,34.82,34.52,34.40,33.87,26.90,26.86,25.52,25.45,23.16,23.05; HRMS(LCMS-ESI)m / zCalcd.for C 48 H 58 Cl2N2NaO8Se[M+Na] + 963.2628, found:963.2612.

[0122] Embodiment 23

[0123]

[0124] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane, 29μL (0.5mmol, 2.5equiv) of acetic acid and 71mg (0.2mmol, 1.0equiv) of pent-4-en-1-yl 4-(N,N-dipropylaminosulfonyl)benzoate, and stir at 120°C for 24h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by distillation under reduced pressure, and separate 49.9mg of pure product by preparative thin layer chromatography, with a yield of 63%.

[0125] 1 H NMR (400MHz, CDCl3) δ8.14(d,J=8.4Hz,4H),7.87(d,J=8.4Hz,4H),4.36(t,J=6.5Hz,4H),3.17–2.98(m,10H),1. 97–1.88(m,4H),1.81–1.70(m,4H),1.54(dd,J=15.1,7.5Hz,8H),1.48(d,J=6.9Hz,6H),0.86(t,J=7.4Hz,12H); 13 C NMR (100MHz, CDCl3) δ165.37,144.40,133.70,130.31,127.14,65.46,50.05,34.78, 34.66,34.06,34.05,27.14,27.11,23.24,23.16,22.06,11.28; HRMS(LCMS-ESI)m / z Calcd.for C 36 H 56 N2NaO8S2Se[M+Na] + 811.2536, found:811.2546.

[0126] Embodiment 24

[0127]

[0128] In a 10mL Schlenk reaction tube, 50mg (0.4mmol, 2.0equiv) of sodium selenide and 48mg (0.2mmol, 1.0equiv) of pent-4-en-1-yl (1S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate were added, and under N2 conditions, 1.0mL of ultra-dry 1,4-dioxane and 29μL (0.5mmol, 2.5equiv) of acetic acid were added in sequence, and stirred at 120°C for 24h. After the reaction was completed, the mixture was diluted and filtered with ethyl acetate, and the solvent was removed by distillation under reduced pressure. 37.3mg of the pure product was separated by column chromatography with a yield of 60%.

[0129] 1 H NMR (400MHz, CDCl3) δ4.22(t,J=6.4Hz,4H),3.03–2.92(m,2H),2.47–2.35(m,2H),2.01(ddd,J=13.6,9.3,4.5Hz,2H),1.91(ddd ,J=13.2,10.8,4.6Hz,2H),1.86–1.77(m,4H),1.71–1.61(m,6H),1.43(d,J=6.9Hz,6H),1.09(s,6H),1.04(s,6H),0.94(s,6H); 13 C NMR (100MHz, CDCl3) δ178.23,167.61,91.21,65.43,54.87,54.22,34.58,34.51,34.50,33.95,33.93,33.8 9,30.77,29.04,27.02,26.97,26.95,26.93,23.20,23.18,23.10,16.90,16.88,9.81; HRMS(LCMS-ESI)m / z Calcd.for C 30 H 46 NaO8Se[M+Na] + 637.2250,found:637.2245.

[0130] Embodiment 25

[0131]

[0132] In a 10mL Schlenk reaction tube, 50mg (0.4mmol, 2.0equiv) of sodium selenide and 65mg (0.2mmol, 1.0equiv) of pent-4-en-1-yl 4-((1,1'-biphenyl)-4-yl)-4-oxobutyrate were added. Under N2 conditions, 1.0mL of ultra-dry 1,4-dioxane and 29μL (0.5mmol, 2.5equiv) of acetic acid were added in sequence, and stirred at 120°C for 24h. After the reaction, the mixture was diluted and filtered with ethyl acetate, and the solvent was removed by distillation under reduced pressure. 52.3mg of the pure product was obtained by preparative thin layer chromatography with a yield of 72%.

[0133] 1 H NMR (400MHz, CDCl3) δ8.05(d,J=7.6Hz,4H),7.68(d,J=7.8Hz,4H),7.62(d,J=7.9Hz,4H),7.47(t,J=7.5Hz,4H),7.40(dd,J=8.3,6.3Hz,2H),4 .16–4.09(m,4H),3.34(t,J=6.6Hz,4H),3.04–2.95(m,2H),2.78(t,J=6 .6Hz,4H),1.84–1.73(m,4H),1.73–1.62(m,4H),1.44(d,J=6.9Hz,6H); 13 C NMR (100MHz, CDCl3) δ197.75,173.04,145.95,139.93,135.36,129.06,128.73,128.34,127.36,64.5 5,64.54,34.68,34.61,34.02,33.98,33.50,28.39,27.06,27.00,23.15,23.07; HRMS(LCMS-ESI)m / z Calcd.for C 42 H 46 NaO6Se[M+Na] + 749.2352, found:749.2361.

[0134] Embodiment 26

[0135]

[0136] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide, and under N2 conditions, add 1.0mL of ultra-dry 1,4-dioxane, 29μL (0.5mmol, 2.5equiv) of acetic acid and 65mg (0.2mmol, 1.0equiv) of pent-4-en-1-yl 2-(3-benzoylphenyl) propionate, and stir at 120°C for 24h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by distillation under reduced pressure, and separate 64.1mg of pure product by preparative thin layer chromatography, with a yield of 88%.

[0137] 1 H NMR (400MHz, CDCl3) δ7.81–7.76(m,4H),7.75(s,2H),7.66(dd,J=7.6,1.1Hz,2H),7.61–7.55(m,2H),7.53(d,J=7.7Hz,2H),7.50–7.39(m,6H ),4.06(dd,J=8.1,4.5Hz,4H),3.78(q,J=7.2Hz,2H),2.93–2.81(m,2H),1.75–1.65(m,4H),1.60–1.47(m,10H),1.35(dd,J=6.8,1.3Hz,6H); 13 C NMR (100MHz, CDCl3) δ196.53,174.15,141.03,141.02,137.98,137.59,132.60,131.61,130.16,129.30,129.28,129.12,128.62,128.4 1,64.77,64.75,64.73,64.70,45.52,34.54,34.44,34.41,33.89,33.84,33.82,26.95,26.93,23.15,23.04,18.54; HRMS(LCMS-ESI)m / z Calcd.for C 42 H 46 NaO6Se[M+Na] + 749.2352, found:749.2348.

[0138] Embodiment 27

[0139]

[0140] In a 10mL Schlenk reaction tube, 50mg (0.4mmol, 2.0equiv) of sodium selenide and 85mg (0.2mmol, 1.0equiv) of pent-4-en-1-yl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl) acetate were added. Under N2 conditions, 1.0mL of ultra-dry 1,4-dioxane and 29μL (0.5mmol, 2.5equiv) of acetic acid were added in sequence, and stirred at 120°C for 24h. After the reaction was completed, the mixture was diluted and filtered with ethyl acetate, and the solvent was distilled off under reduced pressure. 40.4mg of the pure product was separated by preparative thin layer chromatography with a yield of 43%.

[0141] 1 H NMR (400MHz, CDCl3) δ7.68–7.63(m,4H),7.46(d,J=8.1Hz,4H),6.96(d,J=2.5Hz,2H),6.86(dd,J=9.0,1.4Hz,2H),6.69–6.63(m,2H),4.14–4 .06(m,4H),3.83(d,J=1.1Hz,6H),3.65(s,4H),2.94–2.84(m,2H),2.3 8(s,6H),1.80–1.67(m,4H),1.62–1.52(m,4H),1.36(d,J=6.9Hz,6H); 13 C NMR (100MHz, CDCl3) δ171.00,168.39,156.15,139.37,136.02,134.02,131.30,130.92,130.77,129.24,115.07,112.74,111.72, 111.70,101.48,101.46,64.88,64.84,55.83,34.68,34.53,33.93,30.50,27.10,27.05,23.20,23.09,13.50; HRMS(LCMS-ESI)m / z Calcd.for C 48 H 50 C l2 N2NaO8Se[M+Na] + 955.2002, found:955.1990.

[0142] Embodiment 28

[0143]

[0144] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide and 67mg (0.2mmol, 1.0equiv) of 4-vinylphenyl (S)-2-(6-methoxynaphthalen-2-yl) propionate, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran and 34μL (0.6mmol, 3.0equiv) of acetic acid in sequence, and stir at room temperature in the dark for 22h. After the reaction is completed, dilute and filter with ethyl acetate, remove the solvent by vacuum distillation, and separate 65.3mg of pure product by preparative thin layer chromatography, with a yield of 87%.

[0145] 1 H NMR (400MHz, CDCl3) δ7.80–7.70(m,12H),7.54–7.46(m,4H),7.21–7.12(m,15H),6.93–6.85(m,8H),4.08(p,J=7.0Hz,4H) ,3.98–3.86(m,14H),3.75(qd,J=7.1,3.0Hz,2H),1.72–1.66(m,12H),1.62(dd,J=7.1,0.7Hz,6H),1.50(d,J=7.2Hz,6H); 13 CNMR(100MHz, CDCl3)δ173.30,173.23,157.86,149.51,142.45,142.43,141.77,135.25,133.93,129.43,129.09,128.50,12 8.24,127.48,126.23,121.37,121.31,119.22,105.72,55.42,45.67,38.07,37.81,23.19,22.93,18.63; HRMS(LCMS-ESI)m / z Calcd.forC 44 H 42 NaO6Se[M+Na] + 769.2039,found:769.2056.

[0146] Embodiment 29

[0147]

[0148] In a 10mL Schlenk reaction tube, add 50mg (0.4mmol, 2.0equiv) of sodium selenide and 95mg (0.2mmol, 1.0equiv) of 4-vinylbenzyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl) acetate, and under N2 conditions, add 1.0mL of ultra-dry tetrahydrofuran and 34μL (0.6mmol, 3.0equiv) of acetic acid in sequence, and stir at room temperature in the dark for 22h. After the reaction is completed, dilute and filter with ethyl acetate, distill under reduced pressure to remove the solvent, and separate by preparative thin layer chromatography to obtain 92.9mg of pure product with a yield of 90%.

[0149] 1 H NMR (400MHz, CDCl3) δ7.67–7.61(m,8H),7.49–7.42(m,8H),7.23(t,J=10.0Hz,19H),6.9 4(dd,J=6.1,2.5Hz,4H),6.87(dd,J=9.0,1.4Hz,4H),6.66(dt,J=9.0,2.3Hz,4H),5.11(d ,J=10.1Hz,8H),3.96(q,J=7.0Hz,2H),3.86(q,J=7.1Hz,2H),3.76(d,J=4.9Hz,12H),3. 71(d,J=6.0Hz,8H),2.37(d,J=5.1Hz,12H),1.68(d,J=7.1Hz,6H),1.57(d,J=7.1Hz,6H); 13 C NMR (100MHz, CDCl3) δ170.77,170.74,168.34,156.12,145.14,144.48,13 9.33,136.04,136.03,134.35,134.33,133.97,131.26,130.87,130.67,12 9.20,128.37,127.69,127.50,115.05,112.57,111.88,101.32,66.60,66 .58,55.73,38.37,38.13,30.49,23.04,22.81,13.49; HRMS(LCMS-ESI)m / z Calcd.for C 56 H 50 C l2 N2NaO8Se[M+Na] + 1051.2002, found:1051.2004.

[0150] Embodiment 30

[0151]

[0152] In a 10mL Schlenk reaction tube, 50mg (0.4mmol, 2.0equiv) of sodium selenide was added. Under N2 conditions, 1.0mL of ultra-dry tetrahydrofuran, 34μL (0.6mmol, 3.0equiv) of acetic acid and 85mg (0.2mmol, 1.0equiv) of 4-vinylbenzyl 4-(4-(bis(2-chloroethyl)amino)phenyl)butyrate were added in sequence. The mixture was stirred at room temperature and protected from light for 22h. After the reaction, the mixture was diluted and filtered with ethyl acetate, and the solvent was removed by distillation under reduced pressure. The pure product (78.3mg) was separated by preparative thin layer chromatography with a yield of 85%.

[0153] 1 H NMR (400MHz, CDCl3) δ7.27(d,J=1.6Hz,8H),7.25(s,8H),7.05(dd,J=8.8,2.7Hz,8H),6 .63(dd,J=8.6,1.5Hz,8H),5.09(s,4H),5.07(s,4H),3.97(q,J=7.1Hz,2H),3.87(q,J= 7.2Hz,2H),3.73–3.66(m,16H),3.65–3.57(m,16H),2.56(td,J=7.7,3.1Hz,8H),2.37( td,J=7.5,5.2Hz,8H),1.99–1.87(m,8H),1.69(d,J=7.1Hz,6H),1.57(d,J=7.2Hz,6H); 13 C NMR (100MHz, CDCl3) δ173.48,173.45,145.12,144.40,144.32,134.65,134.63,130.74,129.80,128.48,127.72,127. 53,112.35,65.97,65.94,53.73,40.57,38.39,38.14,34.05,33.72,33.71,26.85,23.07,22.82; HRMS(LCMS-ESI)m / z Calcd.forC 46 H 57 C l4 N2O4Se[M+H] + 921.2232, found:921.2216.

[0154] Embodiment 31

[0155]

[0156] In a 10mL Schlenk reaction tube, 50mg (0.4mmol, 2.0equiv) of sodium selenide, 36mg (0.1mmol, 0.5equiv) of 4-vinylbenzyl 4-((1,1'-biphenyl)-4-yl)-4-oxobutanoate and 33mg (0.1mmol, 0.5equiv) of 4-vinylbenzyl (S)-2-(6-methoxynaphthalen-2-yl) propionate were added, and 1.0mL of ultra-dry tetrahydrofuran and 34μL (0.6mmol, 3.0equiv) of acetic acid were added in sequence under N2 conditions, and stirred at room temperature in the dark for 22h. After the reaction was completed, the mixture was diluted and filtered with ethyl acetate, and the solvent was removed by distillation under reduced pressure. 28.7mg of the pure product was obtained by preparative thin layer chromatography with a yield of 36%.

[0157] 1 H NMR(400MHz, CDCl3)δ8.01–7.93(m,2H),7.64–7.50(m,7H),7.39(dd,J=10.2,4.7Hz,2H),7.35–7.29(m,2H),7.23–7.01(m,10H),5 .12–4.93(m,4H),3.90–3.71(m,6H),3.28(q,J=6.7Hz,2H),2.77(q,J=6.8Hz,2H),1.59(dd,J=7.1,1.9Hz,3H),1.54–1.45(m,6H); 13 C NMR (100MHz, CDCl3) δ197.74,174.62,174.60,172.95,172.92,157.76,146.05,146.03,145.16,145.00,14 4.45,144.28,139.97,135.68,135.37,134.61,134.51,133.82,129.41,129.09,129.04,128.77,128.51,1 28.49,128.39,128.22,127.76,127.68,127.56,127.48,127.40,127.26,126.40,126.11,119.11,119.10, 105.71,55.43,45.59,38.42,38.20,33.52,28.47,23.10,23.09,22.87,22.84,18.71; HRMS(LCMS-ESI)m / z Calcd.forC 48 H 46 NaO6Se[M+Na] + 821.2352, found:821.2378.

[0158] The raw materials used in the present invention are cheap and readily available, the reaction operation is simple and practical, the conditions are mild, the yield and purity of the obtained product are high, and the technical difficulties of the complicated steps and complex raw materials in the synthesis method existing in the prior art are solved, which is a breakthrough in the existing synthesis technology and has high application value. The present invention is suitable for the synthesis of dialkyl selenide compounds.

[0159] The above contents are only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any modification, equivalent substitution and improvement made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. A method for synthesizing a dialkyl selenide compound, characterized in that: include: Olefin and sodium selenide are used as raw materials, acid is used as an additive, and a reaction is carried out in an organic solvent under the protection of an inert gas to obtain a dialkyl selenide compound.

2. The method for synthesizing dialkyl selenide compounds according to claim 1, characterized in that: The olefin is one or both of the compound of formula (1) and the compound of formula (2), and the structural formula of the dialkyl selenide compound is shown in formula (3): Wherein, R1 and R3 are each independently selected from alkyl, substituted alkyl, aryl, substituted aryl, heterocyclic aryl, or R1 and R2 are connected to form a cycloalkyl or substituted cycloalkyl; R2 and R4 are each independently selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclic aryl, or R3 and R4 are connected to form a cycloalkyl or substituted cycloalkyl; R1 and R3 are the same or different, and R2 and R4 are the same or different.

3. The method for synthesizing dialkyl selenide compounds according to claim 2, characterized in that: When the compound of formula (1) and the compound of formula (2) are both monosubstituted aromatic olefins, the reaction is carried out under the protection of an inert gas and in the absence of light or in the presence of light.

4. The method for synthesizing dialkyl selenide compounds according to claim 3, characterized in that: The molar ratio of the acid, sodium selenide and olefin is (2-3.5):(2-3):

1.

5. The method for synthesizing dialkyl selenide compounds according to claim 3, characterized in that: The organic solvent is one or more of tetrahydrofuran, ethanol and methanol.

6. The method for synthesizing dialkyl selenide compounds according to claim 3, characterized in that: The reaction temperature is room temperature and the reaction time is 10-40h.

7. The method for synthesizing dialkyl selenide compounds according to claim 2, characterized in that: When the compound of formula (1) and the compound of formula (2) are both aliphatic olefins, or at least one of the compound of formula (1) and the compound of formula (2) is a disubstituted aromatic olefin, the reaction is carried out under inert gas protection and heating conditions, the heating temperature is 100-120° C., and the reaction time is 16-24 hours.

8. The method for synthesizing dialkyl selenide compounds according to claim 7, characterized in that: The molar ratio of the acid, sodium selenide and olefin is (1.5-3.5):(1-2.5):

1.

9. The method for synthesizing dialkyl selenide compounds according to claim 7, characterized in that: The organic solvent is one or more of 1,4-dioxane, ethanol, isopropanol, water, tetrahydrofuran and toluene.

10. The method for synthesizing dialkyl selenide compounds according to claim 1, characterized in that: The acid is acetic acid, formic acid, benzoic acid, trifluoroacetic acid or hydrochloric acid.

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