Palladium-catalyzed N-monoallylamine derivative synthesis method

Abstract

The invention relates to the field of chemical synthesis, in particular to a palladium-catalyzed N-monoallylamine derivative synthesis method. According to the invention, (heterocyclic) aryl primary amine and secondary amine are used as allyl receptors, so that the use of highly toxic allylamine, allyl alcohol and halogenated allyl compounds with environmental pollution risks can be avoided, and diallylamine as an allyl source is not reported yet. The preparation method provided by the invention only needs a small amount of palladium catalyst, is simple and safe to operate, easily available in raw materials, few in reaction steps, mild in reaction conditions, wide in substrate expansion range and high in compound functional group tolerance, and the product yield can reach 97% or above. The high-efficiency synthesis method provided by the invention can generate monoallyl substituted secondary amine and tertiary amine derivatives with high chemical selectivity, not only can gram-grade monoallyl amine derivatives, but also can be smoothly applied to derivatization reaction of drugs on the market.

Description

Technical Field

[0001] The invention relates to the field of chemical synthesis, and in particular to a palladium-catalyzed synthesis method of N-monoallylamine derivatives. Background Art

[0002] Allylamine is an important organic compound. As a versatile intermediate or precursor, it is widely used in the synthesis of natural products, medicines, pesticides, materials and dyes. Over the years, chemists have developed a variety of substrates and catalytic systems for the synthesis of N-monoallylamine compounds. Currently, there are several synthetic methods for obtaining N-allylamine derivatives:

[0003] 1) Using primary amine and allyl alcohol as raw materials, under the catalysis of metal (Org. Lett. 2010, 12, 2726-2729; Tetrahedron Lett. 2010, 51, 1982-1984; Chem. Lett. 1995, 1121-1122; Synthesis 1999,1747–1752; Tetrahedron Lett.2000,41,7097-7100; J.Am.Chem.Soc.2002,124,10968-10969;Chem.Commun.2003,234-235;Org. Lett.2004,6,4085-4088;Org.Lett.2004,6,425-427;J.Organomet.Chem.2005,690,2531-2535;Org.Biomol.Chem.2011,9,2548-2554 ;J.Catal.2020,382,141-149;Chem.Lett.1986,293-294;Org.Lett.2007,9,3371-3374;Chem.Eur.J.2008,14,10047-10057;J.Am.Chem.Soc.2009,131,14317-14328;Angew.Chem.Int.Ed.2017,56,4950-4954.) The hydroxyl group of the allyl alcohol leaves and forms an allyl cation intermediate with the metal, and then the corresponding allylamine derivative is formed under the nucleophilic attack of the amine;

[0004] 2) With leaving groups (acetoxy (Adv.Synth.Catal.2005,347,1198-1202; Tetrahedron 2006,62,3752-3760; J.Org.Chem.2009,74,3982-3985; TetrahedronLett.1988,29,2251-2254; Eur.J.Inorg.Chem.2009,1796-1805), halogen (Org.Lett.2007,9,2661-2664; Eur.J.Org.Chem.2007,2007,1369-1377; TetrahedronLett.2014,55,2711-2714; ChemCatChem 2015, 7, 1813-1817.) Allyl derivatives substituted with trimethylsilyl (Tetrahedron Lett. 1988, 29, 4949-4952) are used as raw materials, and allyl cations are also generated under the catalysis of transition metals, which continue to react with primary or secondary amines to obtain the corresponding N-allyl analogs;

[0005] 3) Using azide as the amino source, the halogen of the brominated allyl compound is removed under the action of indium (Synthetic Commun. 2002, 32, 2771-2777.), and the target compound can be obtained by continuing the reaction;

[0006] 4) Using propargylamine compounds as raw materials, directly reducing them to obtain the target product (J.Org.Chem.2001,66,5624-5626; Adv.Synth.Catal.2006,348,305-308);

[0007] 5) Using allylamine and aldehyde raw materials, the imine is generated and then reduced in situ by borane in a "one-pot" method to obtain N-allylamine derivatives (Tetrahedron 2004, 60, 7899-7906.);

[0008] 6) Allylamine compounds are synthesized by direct substitution reaction of allylamine with aryl halide (Org. Lett. 2003, 5, 793-796; Org. Lett. 2003, 5, 2453-2455.) or arylboronic acid (J. Org. Chem. 2006, 71, 9522-9524; Green Chem. 2018, 20, 4891-4900; Angew. Chem. Int. Ed. 2007, 46, 8291-8294.).

[0009] Although the above-mentioned methods provide a variety of methods for the preparation of N-monoallylamine compounds, the above methods also have obvious disadvantages: 1) the allyl alcohol and allylamine used are highly toxic substances; 2) the halides produced by allyl halides are not environmentally friendly; 3) the atom economy of the reaction using allyl compounds with leaving groups is not high enough; 4) it is not possible to selectively synthesize monoallyl or N,N-diallyl substituted amine compounds. At present, there is no report on allylamine as an allyl group. Therefore, it is very necessary to develop a palladium catalytic system with diallylamine or triallylamine as the source of allylamine groups to synthesize N-monoallylamine derivatives with high atom economy and high selectivity. Summary of the invention

[0010] The main purpose of the present invention is to provide a palladium-catalyzed synthesis method of N-monoallylamine derivatives. The technical solution adopted by the present invention is as follows:

[0011] A method for synthesizing an N-monoallylamine derivative, wherein the structural formula of the N-monoallylamine derivative is shown in I

[0012]

[0013] Wherein: R is any one of C1-C6 alkyl, C1-C6 perfluoroalkyl, C6-C12 aryl, benzyl, and C2-C10 heterocyclic group;

[0014] R' is any one of hydrogen, C1-C6 alkyl, C1-C6 perfluoroalkyl, C6-C12 aryl, benzyl, and C2-C10 heterocyclic group;

[0015] The synthesis method is shown below:

[0016]

[0017] In the formula, the preparation steps of compound I are:

[0018] S1, placing a palladium metal precursor and a ligand in an organic solvent and stirring them in a closed magnetic manner;

[0019] S2, continue to stir in a closed manner after adding additives;

[0020] S3, continue to add compound II and stir in a sealed manner;

[0021] S4, after adding compound III, the reaction system is replaced with nitrogen and the temperature is raised and stirred until compound II is completely consumed;

[0022] S5. Concentrate the reaction solution and then use silica gel column chromatography to obtain compound I.

[0023] Furthermore, the molar ratio of compound II to compound III is II:III=1.0:0.6-3.0.

[0024] Furthermore, in the compound III, R" is any one of hydrogen, allyl, methyl, and trimethylsilyl.

[0025] Furthermore, the palladium metal precursor is any one of palladium halide, palladium sulfate, palladium nitrate, palladium perchlorate, palladium acetate, palladium trifluoroacetate, palladium trifluoromethanesulfonate, palladium tetrafluoroborate, palladium hexafluorophosphate, palladium hexafluoroantimonate, a complex of palladium metal salt and acetonitrile, a complex of palladium metal salt and 1,10-phenanthroline compound or a zero-valent palladium complex.

[0026] Further, the ligands include 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 4,4'-di-tert-butyl-2,2'-bipyridine, 1,1'-bis(diphenylphosphino)ferrocene, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, bis(2-diphenylphosphinophenyl)ether, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino) ) propane, bis(diphenylphosphinobutane), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl, 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl, 1,1'-bis(dicyclohexylphosphino)-ferrocene, triphenylphosphine, 1,1'-bis(di-tert-butylphosphino)-ferrocene, one or more of which are selected and mixed as ligands.

[0027] Furthermore, the additive is any one of copper trifluoromethanesulfonate, cuprous trifluoromethanesulfonate, silver trifluoromethanesulfonate, scandium trifluoromethanesulfonate, indium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, bismuth trifluoromethanesulfonate, iron trifluoromethanesulfonate, magnesium trifluoromethanesulfonate, and calcium trifluoromethanesulfonate.

[0028] Furthermore, the ratio of the amount of the palladium metal precursor, the ligand, and the additive to the amount of the compound represented by formula I-1 is 0.0005:1-0.1:1.

[0029] Furthermore, the organic solvent includes any one or more combinations of benzene, xylene, chlorobenzene, carbon tetrachloride, ethylene glycol dimethyl ether, ethyl acetate, acetonitrile, ethyl chloride, ethylene dichloride, 1,4-dioxane, 1,2-dichloropropane, N-methylpyrrolidone, NN-dimethylpropylene urea, dimethylformamide or dimethylacetamide.

[0030] Furthermore, the eluent used in the column chromatography is a mixture of petroleum ether and ethyl acetate, and the volume ratio V petroleum ether:V ethyl acetate = 100:1 to 1:2.

[0031] The beneficial effects of the present invention are as follows: (1) The present invention provides a method for synthesizing N-monoallylamine derivatives, which can avoid the use of highly toxic allylamine, allyl alcohol and halogenated allyl compounds with environmental pollution risks, while diallylamine or triallylamine as the source of allyl groups has not been reported.

[0032] (2) The preparation method of the present invention requires only a small amount of palladium catalyst, is simple and safe to operate, has readily available raw materials, has few reaction steps, mild reaction conditions, a wide range of substrate expansion, and high tolerance for compound functional groups, and the product yield can reach more than 97%.

[0033] (3) The efficient and green synthesis method of the present invention can generate monoallyl-substituted secondary amine derivatives with high selectivity, which can not only prepare such compounds on a gram scale, but also be applied to the derivatization of marketed drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is the NMR spectrum (hydrogen spectrum) of the product Ⅰ-2 obtained in the example of the present invention;

[0035] Figure 2 This is the NMR spectrum (carbon spectrum) of the product Ⅰ-2 obtained in the example of the present invention;

[0036] Figure 3 This is the NMR spectrum (hydrogen spectrum) of the product Ⅰ-3 obtained in the example of the present invention;

[0037] Figure 4 This is the NMR spectrum (carbon spectrum) of the product Ⅰ-3 obtained in the example of the present invention;

[0038] Figure 5 This is the NMR spectrum (hydrogen spectrum) of the product Ⅰ-4 obtained in Example of the present invention;

[0039] Figure 6 This is the NMR spectrum (carbon spectrum) of the product Ⅰ-4 obtained in the example of the present invention. DETAILED DESCRIPTION

[0040] The technical solution of the present invention is further described below with reference to the accompanying drawings and through specific embodiments:

[0041] The following are the best examples of the compounds prepared by the present invention. In all the following examples, the nuclear magnetic spectrum detection was obtained by a Bruker 500 instrument in CDCl3. The δ value is the internal standard relative value (CHCl3 calibration δ7.261H NMR and 77.1613CNMR. The high resolution mass spectrum (HRMS) was obtained by a 4G quadrupole time-of-flight (QTof) mass spectrometer.

[0042] Example 1

[0043] The reaction formula of Example 1, the specific structures of the compounds II-1, III-1 and the product I-1 used are as follows. Experiments show that the preferred palladium metal precursor of the present invention is palladium acetate (Pd(OAc)2), the preferred ligand is 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene (Xantphos), the preferred additive is zinc trifluoromethanesulfonate (Zn(OTf)2), the preferred organic solvent is 1,4-dioxane, the preferred temperature is 70 degrees, the maximum yield of the reaction product is 96%, the best raw material molar ratio is compound II: compound III = 1:1, wherein compound II should be an equivalent value, and the optimal reaction concentration is 0.125M.

[0044]

[0045] The specific experimental steps are: take a dry 10mL reaction tube, put in a magnetic stirrer, add 2.2mgPd(OAc)2 (2mol% palladium element) and 6.9mg ligand Xantphos (2.4mol%) dissolved in 4mL of 1,4-dioxane solution, stir for 20min at room temperature, and the solution turns reddish brown. Add 7.3mg zinc trifluoromethanesulfonate (4mol%) to the mixture and continue to stir for 10min, then add 46.5mg aniline (0.5mmol) and stir for 5min. Then add 48.5mg diallylamine (0.5mmol) and replace the reaction system with nitrogen atmosphere, heat to 70 degrees and stir the reaction, and monitor by thin layer chromatography (TLC) until the aniline raw material is completely consumed (about 24h). After the reaction is completed, the reaction mixture is rotary evaporated under reduced pressure of a water pump to remove the organic solvent. The residue was purified by column chromatography on 200-300 mesh silica gel with an eluent (volume ratio V petroleum ether: V ethyl acetate = 100:1-20:1) to obtain the compound Ⅰ-1, which was identified by NMR (hydrogen spectrum, carbon spectrum).

[0046] N-allylaniline (64mg, Yield=96%, Rf=0.50 (PE / EA=20:1)) was isolated as colorless oil.1H NMR (500MHz, CDCl3) δ7.23–7.19(m,2H),6.72(t,J=7.3Hz,1H),6.64(d,J=7.7Hz,2H),6.03–5.94(m,1H), 5.29(dq,J=17.2,1.5Hz,1H),5.17(dq,J=10.3,1.6Hz,1H),3.84(s,1H),3.78(dt,J=5.4,1.5Hz,2H); 13C NMR (125MHz, CDCl3) δ148.12,135.53,129.32,117.63,116.35,113.08,46.65.

[0047] Example 2

[0048] The reaction formula of Example 2, the specific structures of the compounds II-1, III-1 and the product I-1 used are as follows. Experiments show that the preferred palladium metal precursor of the present invention is palladium acetate (Pd(OAc)2), the preferred ligand is 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene (Xantphos), the preferred additive is zinc trifluoromethanesulfonate (Zn(OTf)2), the preferred organic solvent is 1,4-dioxane, the preferred temperature is 70 degrees, the maximum yield of the reaction product is 96%, the best raw material molar ratio is compound II: compound III = 1:1, wherein compound II should be an equivalent value, and the optimal reaction concentration is 0.125M.

[0049]

[0050] The specific experimental steps are: take a dry 10mL reaction tube, put in a magnetic stirrer, add 2.2mgPd(OAc)2 (2mol% palladium element) and 6.9mg ligand Xantphos (2.4mol%) dissolved in 4mL of 1,4-dioxane solution, stir at room temperature for 20min, and the solution turns reddish brown. Add 7.3mg zinc trifluoromethanesulfonate (4mol%) to the mixture and continue to stir for 10min, then add 72mg 2-aminoquinoline (0.5mmol) and stir for 5min. Then add 48.5mg diallylamine (0.5mmol) and replace the reaction system with nitrogen atmosphere, heat to 70 degrees and stir the reaction, and monitor by thin layer chromatography (TLC) until the aniline raw material is completely consumed (about 24h). After the reaction is completed, the reaction mixture is rotary evaporated under reduced pressure of a water pump to remove the organic solvent. The residue was purified by column chromatography on 200-300 mesh silica gel with an eluent (volume ratio V petroleum ether: V ethyl acetate = 10:1 to 1:1) to obtain the compound Ⅰ-2, which was identified by NMR (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0051] N-allylquinolin-2-amine (60mg, Yield=65%, Rf=0.50 (PE / EA=2:1)) wasisolated as a yellow oil.1H NMR(500MHz, CDCl3)δ7.82(d,J=8.9Hz,1H),7.71–7.66(m,1H),7.59(dd,J=7.9,1.2Hz,1H),7.55–7.51(m,1H),7.24–7.19(m,1H),6.64(d, 13C NMR(125MHz, CDCl3)δ156.85,148.03,137.57,135.28,129.71,127.56,126.22,123.59,122.25,116.34,111.28,44.35.HRMS(ESI)m / z:[M+H]+Calcd for C12H13N2185.1073; found 185.1073.

[0052] Example 3

[0053] The reaction formula of Example 3, the structures of the specifically used compounds II-1, III-1 and the product I-1 are as follows. Experiments show that the preferred palladium metal precursor of the present invention is palladium acetate (Pd(OAc)2), the preferred ligand is 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene (Xantphos), the preferred additive is zinc trifluoromethanesulfonate (Zn(OTf)2), the preferred organic solvent is 1,4-dioxane, the preferred temperature is 70 degrees, the maximum yield of the reaction product is 96%, the best raw material molar ratio is compound II: compound III = 1:1, wherein compound II should be an equivalent value, and the optimal reaction concentration is 0.125M.

[0054]

[0055] The specific experimental steps are: take a dry 10mL reaction tube, put in a magnetic stirrer, add 2.2mg Pd(OAc)2 (2mol% palladium element) and 6.9mg ligand Xantphos (2.4mol%) dissolved in 4mL of 1,4-dioxane solution, stir for 20min at room temperature, and the solution turns reddish brown. Add 7.3mg zinc trifluoromethanesulfonate (4mol%) to the mixture and continue to stir for 10min, then add 54mg N-methyl-2-aminopyridine (0.5mmol) and stir for 5min. Then add 48.5mg diallylamine (0.5mmol) and replace the reaction system with nitrogen atmosphere, heat to 70 degrees and stir the reaction, and monitor by thin layer chromatography (TLC) until the aniline raw material is completely consumed (about 24h). After the reaction is completed, the reaction mixture is rotary evaporated under reduced pressure of a water pump to remove the organic solvent. The residue was purified by column chromatography on 200-300 mesh silica gel with an eluent (volume ratio V petroleum ether: V ethyl acetate = 20:1-5:1) to obtain compound Ⅰ-3, which was identified by NMR (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0056] N-allyl-N-methylpyridin-2-amine (45mg, Yield=61%, Rf=0.50 (PE / EA=10:1)) was isolated as a transparent oil.1H NMR(500MHz, CDCl3) δ8.15(ddd,J=4.9,1.9,0.8Hz,1H),7.44–7.40(m,1H),6.52(ddd,J=7.0,5.0,0.7Hz,1H),6.48(dt,J=8.5 13C NMR(125MHz, CDCl3)δ158.69,147.99,137.27,133.83,116.02,111.69,105.91,52.40,35.92.HRMS(ESI)m / z:[M+H]+Calcd forC9H13N2149.1073; found 149.1072.

[0057] Example 4

[0058] The reaction formula of Example 4, the specific structures of the compounds II-1, III-1 and the product I-1 used are as follows. Experiments show that the preferred palladium metal precursor of the present invention is palladium acetate (Pd(OAc)2), the preferred ligand is 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene (Xantphos), the preferred additive is zinc trifluoromethanesulfonate (Zn(OTf)2), the preferred organic solvent is 1,4-dioxane, the preferred temperature is 70 degrees, the maximum yield of the reaction product is 96%, the best raw material molar ratio is compound II: compound III = 1:1, wherein compound II should be an equivalent value, and the optimal reaction concentration is 0.125M.

[0059]

[0060] The specific experimental steps are: take a dry 10mL reaction tube, put in a magnetic stirrer, add 2.2mg Pd(OAc)2 (2mol% palladium element) and 6.9mg ligand Xantphos (2.4mol%) dissolved in 4mL of 1,4-dioxane solution, stir for 20min at room temperature, and the solution turns reddish brown. Add 7.3mg zinc trifluoromethanesulfonate (4mol%) to the mixture and continue to stir for 10min, then add 124.5mg of the marketed drug sulfapyridine (Sulfapyridine, 0.5mmol) and stir for 5min. Then add 48.5mg diallylamine (0.5mmol) and replace the reaction system with a nitrogen atmosphere, heat to 70 degrees and stir the reaction, and monitor by thin layer chromatography (TLC) until the aniline raw material is completely consumed (about 24h). After the reaction is completed, the reaction mixture is rotary evaporated under reduced pressure of a water pump to remove the organic solvent. The residue was purified by column chromatography on 200-300 mesh silica gel with an eluent (volume ratio V petroleum ether: V ethyl acetate = 10:1-2:1) to obtain compound Ⅰ-4, which was identified by NMR (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0061] 4-(allylamino)-N-(pyridin-2-yl)benzenesulfonamide (92mg, Yield=63%, Rf=0.30 (PE / EA=2:1)) was isolated as a white solid; mp 152–153℃.1H NMR(400MHz, CDCl3)δ8.38(dd,J=5.6,1.4Hz,1H),7.69–7.64(m,2H),7.64–7.59(m,1H),7.38(dt,J=8.7 ,1.0Hz,1H),6.84–6.80(m,1H),6.57–6.50(m,2H),5.93–5.82(m,1H),5.25(dq,J=17.2,1.6Hz,1H),5.1 8(dq,J=10.3,1.4Hz,1H),3.78(dt,J=5.3,1.6Hz,2H); 13CNMR(100MHz,CDCl3)δ154.00,151.32,143.57 ,140.84,134.12,129.04,128.03,117.11,115.71,113.98,112.04,45.93.HRMS(ESI)m / z:[M+H]+Calcd for C14H16N3O2S290.0958; found 290.0956.

[0062] Compound I-1

[0063]

[0064] N-allylaniline (64 mg, Yield=96%, Rf=0.50 (PE / EA=20:1)) was isolated as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.23–7.19 (m, 2H), 6.72 (t, J=7.3 Hz, 1H), 6.64 (d, J=7.7 Hz, 2H), 6.03–5.94 (m, 1H), 5.29 (dq, J=17.2, 1.5 Hz, 1H), 5.17 (dq, J=10.3, 1.6 Hz, 1H), 3.84 (s, 1H), 3.78 (dt, J=5.4, 1.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 148.12, 135.53, 129.32, 117.63, 116.35, 113.08, 46.65.

[0065] Compound I-2

[0066]

[0067] N-allylquinolin-2-amine (60 mg, Yield=65%, Rf=0.50 (PE / EA=2:1)) was isolated as a yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.82 (d, J=8.9 Hz, 1H), 7.71–7.66 (m, 1H), 7.59 (dd, J=7.9, 1.2 Hz, 1H), 7.55–7.51 (m, 1H), 7.24–7.19 (m, 1H), 6.64 (d, J=8.9 Hz, 1H), 6.07–5.96 (m, 1H), 5.31 (dq, J=17.2, 1.6 Hz, 1H), 5.18 (dq, J=10.3, 1.5 Hz, 1H), 4.89 (s, 1H), 4.15 (tt, J=5.8, 1.4 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 156.85, 148.03, 137.57, 135.28, 129.71, 127.56, 126.22, 123.59, 122.25, 116.34, 111.28, 44.35. HRMS(ESI) m / z: [M+H]+ Calcd for C12H13N2 185.1073; found 185.1073.

[0068] Compound I-3

[0069]

[0070] N-allyl-N-methylpyridin-2-amine (45 mg, Yield=61%, Rf=0.50 (PE / EA=10:1)) was isolated as a transparent oil. 1H NMR (500 MHz, CDCl3) δ 8.15 (ddd, J=4.9, 1.9, 0.8 Hz, 1H), 7.44–7.40 (m, 1H), 6.52 (ddd, J=7.0, 5.0, 0.7 Hz, 1H), 6.48 (dt, J=8.5, 0.9 Hz, 1H), 5.88–5.80 (m, 1H), 5.15–5.14 (m, 1H), 5.12 (dq, J=6.1, 1.6 Hz, 1H), 4.14 (dt, J=5.1, 1.6 Hz, 2H), 3.03 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 158.69, 147.99, 137.27, 133.83, 116.02, 111.69, 105.91, 52.40, 35.92. HRMS (ESI) m / z: [M+H]+ Calcd for C9H13N2 149.1073; found 149.1072.

[0071] Compound I-4

[0072]

[0073] 4-(allylamino)-N-(pyridin-2-yl)benzenesulfonamide (92 mg, Yield = 63%, Rf = 0.30 (PE / EA = 2:1)) was isolated as a white solid; mp 152–153 °C. 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, J = 5.6, 1.4 Hz, 1H), 7.69–7.64 (m, 2H), 7.64–7.59 (m, 1H), 7.38 (dt, J = 8.7, 1.0 Hz, 1H), 6.84–6.80 (m, 1H), 6.57–6.50 (m, 2H), 5.93–5.82 (m, 1H), 5.25 (dq, J = 17.2, 1.6 Hz, 1H), 5.18 (dq, J = 10.3, 1.4 Hz, 1H), 3.78 (dt, J = 5.3, 1.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 154.00, 151.32, 143.57, 140.84, 134.12, 129.04, 128.03, 117.11, 115.71, 113.98, 112.04, 45.93. HRMS (ESI) m / z: [M+H]+ Calcd for C14H16N3O2S 290.0958; found 290.0956.

[0074] Compound I-5

[0075]

[0076] N-allyl-4-fluoroaniline (71 mg, Yield = 94%, Rf = 0.50 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 6.92–6.86 (m, 2H), 6.58–6.54 (m, 2H), 5.99–5.90 (m, 1H), 5.28 (dq, J = 17.1, 1.6 Hz, 1H), 5.18 (dq, J = 10.2, 1.4 Hz, 1H), 3.74 (dt, J = 5.4, 1.5 Hz, 2H), 3.68 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 155.99 (d, J = 233.5 Hz), 144.49 (d, J = 1.7 Hz), 135.45, 116.49, 115.74 (d, J = 22.2 Hz), 113.91 (d, J = 7.4 Hz), 47.29; 19F NMR (471 MHz, CDCl3) δ –128.03.

[0077] Compound I-6

[0078]

[0079] N-allyl-4-chloroaniline (77 mg, Yield = 92%, Rf = 0.50 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.17–7.10 (m, 2H), 6.57–6.52 (m, 2H), 5.99–5.88 (m, 1H), 5.29 (dq, J = 17.2, 1.7 Hz, 1H), 5.19 (dq, J = 10.2, 1.5 Hz, 1H), 3.75 (dt, J = 5.4, 1.7 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 146.69, 135.06, 129.10, 122.07, 116.52, 114.11, 46.63.

[0080] Compound I-7

[0081]

[0082] N-allyl-4-bromoaniline(94mg, Yield=89%, Rf=0.50(PE / EA=20:1)) was isolated as a colorless oil. 1H NMR(400MHz, CDCl3)δ7.29–7.21(m, 2H), 6.52–6.46(m, 2H), 5.99–5.85(m, 1H), 5.27(dq, J=17.2, 1.6Hz, 1H), 5.18(dq, J=10.3, 1.5Hz, 1H), 3.74(dt, J=5.4, 1.7Hz, 2H); 13C NMR(100MHz, CDCl3)δ147.09, 134.97, 131.95, 116.54, 114.60, 109.07, 46.51.

[0083] Compound I-8

[0084]

[0085] N-allyl-4-(trifluoromethyl)aniline(96mg, Yield=95%, Rf=0.50(PE / EA=20:1)) was isolated as a colorless oil. 1H NMR(500MHz, CDCl3)δ7.40(d, J=8.5Hz, 2H), 6.61(d, J=8.5Hz, 2H), 5.97–5.88(m, 1H), 5.29(dq, J=17.2, 1.7Hz, 1H), 5.20(dq, J=10.3, 1.5Hz, 1H), 4.15(s, 1H), 3.83–3.80(m, 2H); 13C NMR(125MHz, CDCl3)δ150.57, 134.55, 125.11(q, J=268.6Hz), 126.70(q, J=3.8Hz), 119.03(q, J=32.4Hz), 116.82, 112.13, 46.09; 19F NMR(471MHz, CDCl3)δ–60.99.

[0086] Compound I-9

[0087]

[0088] N-allyl-4-nitroaniline(82mg,Yield=92%,Rf=0.50(PE / EA=20:1))was isolated as a colorless oil.1H NMR(400MHz,CDCl3)δ8.09–8.02(m,2H),6.56–6.52(m,2H),5.96–5.83(m,1H),5.27(dq,J=17.2,1.7Hz,1H),5.21(dq,J=10.3,1.5Hz,1H),4.85(s,1H),3.89–3.85(m,2H);13C NMR(100MHz,CDCl3)δ153.39,138.08,133.45,126.43,117.30,111.37,45.80.

[0089] Compound I-10

[0090]

[0091] N-allyl-4-(trifluoromethoxy)aniline(99mg,Yield=91%,Rf=0.60(PE / EA=20:1))was isolated as a colorless oil.1H NMR(500MHz,CDCl3)δ7.04(d,J=8.7Hz,2H),6.59–6.56(m,2H),5.98–5.89(m,1H),5.29(dq,J=17.2,1.7Hz,1H),5.19(dq,J=10.3,1.5Hz,1H),3.87(s,1H),3.76(d,J=4.2Hz,2H);13C NMR(125MHz,CDCl3)δ146.93,140.61(q,J=2.2Hz),135.05,122.51,120.85(q,J=253.6Hz),116.65,113.25,46.76;19F NMR(471MHz,CDCl3)δ–58.48.

[0092] Compound I-11

[0093]

[0094] N-allyl-4-methylaniline (69 mg, Yield = 94%, Rf = 0.60 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.14–7.08 (m, 1H), 6.58 (d, J = 7.5 Hz, 1H), 6.51–6.45 (m, 2H), 6.06–5.93 (m, 1H), 5.32 (dq, J = 17.1, 1.7 Hz, 1H), 5.20 (dq, J = 10.2, 1.5 Hz, 1H), 3.80 (dt, J = 5.4, 1.7 Hz, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 145.94, 135.84, 129.83, 126.87, 116.19, 113.32, 47.07, 20.49.

[0095] Compound I-12

[0096]

[0097] N-allyl-4-isopropylaniline (85 mg, Yield = 97%, Rf = 0.60 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.10–7.07 (m, 2H), 6.63–6.60 (m, 2H), 6.05–5.94 (m, 1H), 5.32 (dq, J = 17.2, 1.6 Hz, 1H), 5.19 (dq, J = 10.3, 1.4 Hz, 1H), 3.78 (dt, J = 5.4, 1.6 Hz, 2H), 3.70 (s, 1H), 2.88–2.80 (m, 1H), 1.25 (s, 3H), 1.24 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 146.21, 138.16, 135.87, 127.17, 116.21, 113.15, 47.03, 33.27, 24.37.

[0098] Compound I-13

[0099]

[0100] N-allyl-4-butylaniline (88 mg, Yield = 93%, Rf = 0.70 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.03–7.00 (m, 2H), 6.60–6.57 (m, 2H), 6.03–5.93 (m, 1H), 5.30 (dq, J = 17.2, 1.7 Hz, 1H), 5.17 (dq, J = 10.2, 1.5 Hz, 1H), 3.77 (dt, J = 5.4, 1.7 Hz, 2H), 3.67 (s, 1H), 2.52 (t, J = 7.6 Hz, 2H), 1.59–1.53 (m, 2H), 1.40–1.31 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 146.08, 135.84, 132.15, 129.20, 116.23, 113.17, 47.04, 34.84, 34.14, 22.48, 14.14. HRMS (ESI) m / z: [M+H]+ Calcd for C13H20N 190.1590; found 190.1588.

[0101] Compound I-14

[0102]

[0103] N-allyl-4-methoxyaniline (73 mg, Yield = 90%, Rf = 0.60 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 6.83–6.78 (m, 2H), 6.64–6.59 (m, 2H), 6.05–5.91 (m, 1H), 5.29 (dq, J = 17.2, 1.7 Hz, 1H), 5.17 (dq, J = 10.2, 1.5 Hz, 1H), 3.76 (s, 2H), 3.76–3.72 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 152.27, 142.38, 135.90, 116.18, 114.94, 114.40, 55.85, 47.61.

[0104] Compound I-15

[0105]

[0106] N-allyl-4-phenoxyaniline (98 mg, Yield = 87%, Rf = 0.50 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.36–7.30 (m, 2H), 7.06 (t, J = 7.3 Hz, 1H), 7.02–6.95 (m, 4H), 6.68–6.64 (m, 2H), 6.07–5.95 (m, 1H), 5.35 (dq, J = 17.2, 1.7 Hz, 1H), 5.24 (dq, J = 10.3, 1.6 Hz, 1H), 3.80 (dt, J = 5.4, 1.7 Hz, 2H), 3.62 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 159.13, 147.70, 144.76, 135.50, 129.56, 121.98, 121.25, 117.13, 116.37, 113.99, 47.09.

[0107] Compound I-16

[0108]

[0109] N-allyl-3-chloroaniline (75 mg, Yield = 90%, Rf = 0.50 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.07 (t, J = 8.0 Hz, 1H), 6.69–6.65 (m, 1H), 6.59 (t, J = 2.1 Hz, 1H), 6.50–6.47 (m, 1H), 5.97–5.89 (m, 1H), 5.28 (dq, J = 17.2, 1.5 Hz, 1H), 5.19 (dq, J = 10.2, 1.5 Hz, 1H), 3.88 (s, 1H), 3.76 (d, J = 4.7 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 149.27, 135.09, 134.86, 130.26, 117.42, 116.68, 112.64, 111.39, 46.39.

[0110] Compound I-17

[0111]

[0112] N-allyl-2-chloroaniline(68mg,Yield=81%,Rf=0.60(PE / EA=20:1))was isolated as a colorless oil.1H NMR(400MHz,CDCl3)δ7.28(dd,J=7.7,1.3Hz,1H),7.18–7.11(m,1H),6.70–6.63(m,2H),6.03–5.92(m,1H),5.32(dq,J=17.2,1.7Hz,1H),5.22(dq,J=10.4,1.6Hz,1H),4.49(s,1H),3.86(s,2H);13C NMR(100MHz,CDCl3)δ143.90,134.85,129.20,127.84,119.24,117.41,116.52,111.60,46.18.

[0113] Compound I-18

[0114]

[0115] N-allyl-3,5-dichloroaniline(89mg,Yield=88%,Rf=0.50(PE / EA=20:1))was isolated as a colorless oil.1H NMR(400MHz,CDCl3)δ6.67(t,J=1.7Hz,1H),6.46(d,J=1.7Hz,2H),5.95–5.83(m,1H),5.27(dq,J=17.1,1.7Hz,1H),5.21(dq,J=10.3,1.5Hz,1H),3.98(s,1H),3.73(t,J=5.0Hz,2H);13C NMR(100MHz,CDCl3)δ149.69,135.47,134.17,117.14,116.94,111.11,46.14.HRMS(ESI)m / z:[M+H]+Calcd for C9H10Cl2N202.0185;found 202.0185.

[0116] Compound I-19

[0117]

[0118] N-allyl-3-methylaniline (61 mg, Yield = 83%, Rf = 0.60 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.15–7.07 (m, 1H), 6.58 (d, J = 7.5 Hz, 1H), 6.53–6.45 (m, 2H), 6.06–5.93 (m, 1H), 5.32 (dq, J = 17.2, 1.7 Hz, 1H), 5.20 (dq, J = 10.3, 1.6 Hz, 1H), 3.80 (dt, J = 5.4, 1.7 Hz, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 148.20, 139.05, 135.66, 129.18, 118.57, 116.21, 113.87, 110.24, 46.68, 21.73.

[0119] Compound I-20

[0120]

[0121] N-allyl-2-methylaniline (53 mg, Yield = 72%, Rf = 0.70 (PE / EA = 20:1)) was isolated as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.18–7.14 (m, 1H), 7.10 (d, J = 7.4 Hz, 1H), 6.71 (td, J = 7.4, 1.0 Hz, 1H), 6.65 (d, J = 8.1 Hz, 1H), 6.09–5.98 (m, 1H), 5.33 (dq, J = 17.2, 1.6 Hz, 1H), 5.22 (dq, J = 10.3, 1.5 Hz, 1H), 3.86 (dt, J = 5.3, 1.5 Hz, 2H), 3.65 (s, 1H), 2.19 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 146.03, 135.65, 130.17, 127.20, 122.07, 117.19, 116.33, 110.10, 46.59, 17.60.

[0122] Compound I-21

[0123]

[0124] N-allyl-3,5-dimethylaniline(57mg, Yield=71%, Rf=0.50(PE / EA=20:1)) was isolated as a colorless oil. 1H NMR(400MHz, CDCl3)δ6.41(s, 1H), 6.29(s, 2H), 6.03–5.93(m, 1H), 5.30(dq, J=17.2, 1.7Hz, 1H), 5.18(dq, J=10.3, 1.6Hz, 1H), 3.77(dt, J=5.4, 1.7Hz, 2H), 3.68(s, 1H), 2.26(s, 6H); 13C NMR(100MHz, CDCl3)δ148.31, 138.98, 135.80, 119.71, 116.16, 111.10, 46.77, 21.62.

[0125] Compound I-22

[0126]

[0127] N-allylnaphthalen-1-amine(82mg, Yield=89%, Rf=0.50(PE / EA=20:1)) was isolated as a colorless oil. 1H NMR(400MHz, CDCl3)δ7.89–7.84(m, 2H), 7.55–7.47(m, 2H), 7.43(t, J=9.7Hz, 1H), 7.35–7.31(m, 1H), 6.68(d, J=7.5Hz, 1H), 6.19–6.08(m, 1H), 5.44(dq, J=17.2, 1.7Hz, 1H), 5.30(dq, J=10.3, 1.6Hz, 1H), 4.51(s, 1H), 3.99(dt, J=5.5, 1.7Hz, 2H); 13C NMR(100MHz, CDCl3)δ143.19, 135.21, 134.38, 128.78, 126.66, 125.79, 124.80, 123.54, 119.95, 117.64, 116.71, 104.84, 46.81.

[0128] Compound I-23

[0129]

[0130] N-allyl-N-methylaniline (40 mg, Yield = 54%, Rf = 0.70 (PE / EA = 20:1)) was isolated as a yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.27–7.22 (m, 2H), 6.77–6.75 (m, 1H), 6.75–6.69 (m, 2H), 5.91–5.83 (m, 1H), 5.21–5.18 (m, 1H), 5.18–5.15 (m, 1H), 3.94 (dt, J = 5.0, 1.6 Hz, 2H), 2.96 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 149.60, 133.92, 129.22, 116.51, 116.26, 112.55, 55.38, 38.11.

[0131] Compound I-24

[0132]

[0133] N-allyl-N-phenylaniline (10 mg, Yield = 10%, Rf = 0.80 (PE / EA = 20:1)) was isolated as a yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.27–7.23 (m, 4H), 7.09–6.98 (m, 4H), 6.94 (t, J = 7.3 Hz, 2H), 5.98–5.90 (m, 1H), 5.27 (dq, J = 17.2, 1.8 Hz, 1H), 5.17 (dq, J = 10.4, 1.7 Hz, 1H), 4.36 (dt, J = 4.7, 1.9 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 147.96, 134.38, 129.32, 121.36, 120.83, 116.52, 54.87.

[0134] Compound I-25

[0135]

[0136] N1-allyl-N1-isopropyl-N4-phenylbenzene-1,4-diamine (35 mg, Yield = 26%, Rf = 0.40 (PE / EA = 20:1)) was isolated as a transparent oil. 1H NMR (500 MHz, CDCl3) δ 7.15 (t, J = 7.9 Hz, 2H), 7.03 (d, J = 8.6 Hz, 2H), 6.74–6.65 (m, 3H), 6.59 (d, J = 8.5 Hz, 2H), 6.00–5.90 (m, 1H), 5.27 (dq, J = 17.2, 1.8 Hz, 1H), 5.16 (dq, J = 10.3, 1.7 Hz, 1H), 4.26 (d, J = 4.5 Hz, 2H), 3.65–3.59 (m, 1H), 3.44 (s, 1H), 1.24 (s, 3H), 1.23 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 149.23, 145.13, 137.29, 134.70, 128.90, 128.41, 117.02, 116.20, 114.33, 114.13, 55.30, 44.61, 23.22. HRMS (ESI) m / z: [M+H]+ Calcd for C18H23N2 267.1856; found 267.1859.

[0137] Compound I-26

[0138]

[0139] Ethyl 4-(allylamino)benzoate (66 mg, Yield = 64%, Rf = 0.30 (PE / EA = 20:1)) was isolated as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.70–7.65 (m, 2H), 6.74 (t, J = 5.8 Hz, 1H), 6.60–6.56 (m, 2H), 5.93–5.81 (m, 1H), 5.21 (dq, J = 17.2, 1.8 Hz, 1H), 5.12 (dq, J = 10.3, 1.6 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 3.77–3.73 (m, 2H), 1.26 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 165.90, 152.70, 135.25, 130.89, 116.15, 115.68, 111.13, 59.55, 44.62, 14.40.

[0140] Compound I-27

[0141]

[0142] 4-(allylamino)benzoic acid (64mg, Yield=72%, Rf=0.50 (PE / EA=2:1)) was isolated as a white solid; mp145–146℃.1H NMR(500MHz,DMSO-d6)δ12.00(s,1H),7.68–7.62(m,2H),6.65(t,J=5.8Hz,1H),6.59–6.54(m,1H),5.92– 5.83(m,1H),5.21(dq,J=17.2,1.8Hz,1H),5.11(dq,J=10.3,1.6Hz,1H),3.74(tt,J=5.3,1.8Hz,2H); 13C NMR(125MHz,DMSO-d6)δ167.54,152.47,135.37,131.09,117.01,115.64,111.04,44.67.HRMS(ESI)m / z:[M+H]+Calcd for C10H12NO2 178.0863; found 178.0862.

[0143] Compound I-28

[0144]

[0145] (1r,4r)-4-((2-(allylamino)-3,5-dibromobenzyl)amino)cyclohexan-1-ol(52mg, Yield = 25%, Rf = 0.50(PE / EA = 1:1)) was isolated as a transparent oil. 1H NMR(400MHz, CDCl3)δ7.45(d, J = 2.2Hz, 1H), 7.03(d, J = 2.2Hz, 1H), 5.83–5.69(m, 1H), 5.41(s, 2H), 5.14–5.08(m, 2H), 3.61(s, 2H), 3.57–3.49(m, 1H), 3.03(d, J = 6.5Hz, 2H), 2.53(tt, J = 11.7, 3.4Hz, 1H), 2.03–1.97(m, 2H), 1.82–1.76(m, 2H), 1.62(s, 1H), 1.46–1.35(m, 2H), 1.28–1.18(m, 2H); 13C NMR(100MHz, CDCl3)δ143.99, 136.14, 133.19, 132.00, 125.77, 117.87, 110.24, 108.28, 70.62, 57.59, 53.88, 52.84, 34.77, 25.75. HRMS(ESI) m / z: [M+H]+ Calcd for C16H23Br2N2O 417.0172; found 417.0173.

[0146] Compound I-29

[0147]

[0148] (allylamino)-N-(pyrimidin-2-yl)benzenesulfonamide (65mg, Yield=43%, Rf=0.80 (DCM / MeOH=10:1)) was isolated as a white solid; mp 151–152℃.1H NMR (500MHz, DMSO-d6) δ11.28(s,1H),8.48(d,J=4.8Hz,2H),7.66(d,J=8.8Hz,2H),7.01(t,J=4.8Hz,1H),6.79(t,J=5.8Hz,1H), 13C NMR(125MHz,DMSO-d6)δ158.32,157.24,152.24,135.10,129.65,125.05,115.80,115.60,110.68,44.59.HRMS(ESI)m / z:[M+H]+Calcd for C13H15N4O2S291.0910; found 291.0910.

[0149] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be considered exemplary and non-restrictive in all respects, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims be included in the present invention.

[0150] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A method for synthesizing an N-monoallylamine derivative, wherein the structural formula of the N-monoallylamine derivative is shown in I in: R is any one of a C1-C6 alkyl group, a C1-C6 perfluoroalkyl group, a C6-C12 aryl group, a benzyl group, and a C2-C10 heterocyclic group; R' is any one of hydrogen, C1-C6 alkyl, C1-C6 perfluoroalkyl, C6-C12 aryl, benzyl, and C2-C10 heterocyclic group; It is characterized in that the synthesis method is shown in the following formula: In the formula, the preparation steps of compound I are: S1, placing a palladium metal precursor and a ligand in an organic solvent and stirring them in a closed magnetic manner; S2, continue to stir in a closed manner after adding additives; S3, continue to add compound II and stir in a sealed manner; S4, after adding compound III, the reaction system is replaced with nitrogen and the temperature is raised and stirred until compound II is completely consumed; S5. Concentrate the reaction solution and then use silica gel column chromatography to obtain compound I.

2. The method for synthesizing an N-monoallylamine derivative according to claim 1, characterized in that: The molar ratio of the compound II to the compound III is II:III=1.0:0.6-3.

0.

3. The method for synthesizing an N-monoallylamine derivative according to claim 1, characterized in that: In the compound III, R" is any one of hydrogen, allyl, methyl, and trimethylsilyl.

4. The method for synthesizing an N-monoallylamine derivative according to claim 1, characterized in that: The palladium metal precursor is any one of palladium halide, palladium sulfate, palladium nitrate, palladium perchlorate, palladium acetate, palladium trifluoroacetate, palladium trifluoromethanesulfonate, palladium tetrafluoroborate, palladium hexafluorophosphate, palladium hexafluoroantimonate, a complex of palladium metal salt and acetonitrile, a complex of palladium metal salt and 1,10-phenanthroline compound or a zero-valent palladium complex.

5. The method for synthesizing an N-monoallylamine derivative according to claim 1, characterized in that: The ligands include 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, 4,4'-di-tert-butyl-2,2'-bipyridine, 1,1'-bis(diphenylphosphino)ferrocene, 4,5-bisdiphenylphosphino-9,9-dimethylxanthene, bis(2-diphenylphosphinophenyl)ether, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane , bis(diphenylphosphinobutane), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl, 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl, 1,1'-bis(dicyclohexylphosphino)-ferrocene, triphenylphosphine, 1,1'-bis(di-tert-butylphosphino)-ferrocene, one or more of them are selected and mixed for use as ligands.

6. The method for synthesizing an N-monoallylamine derivative according to claim 1, characterized in that: The additive is any one of copper trifluoromethanesulfonate, cuprous trifluoromethanesulfonate, silver trifluoromethanesulfonate, scandium trifluoromethanesulfonate, indium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, bismuth trifluoromethanesulfonate, iron trifluoromethanesulfonate, magnesium trifluoromethanesulfonate, and calcium trifluoromethanesulfonate.

7. The method for synthesizing an N-monoallylamine derivative according to claim 1, characterized in that: The ratio of the amount of the palladium metal precursor, the ligand, and the additive to the amount of the compound represented by formula I-1 is 0.0005:1-0.1:

1.

8. The method for synthesizing an N-monoallylamine derivative according to claim 1, characterized in that: The organic solvent includes any one or more combinations of benzene, xylene, chlorobenzene, carbon tetrachloride, ethylene glycol dimethyl ether, ethyl acetate, acetonitrile, ethyl chloride, ethylene dichloride, 1,4-dioxane, 1,2-dichloropropane, N-methylpyrrolidone, N N-dimethylpropylene urea, dimethylformamide or dimethylacetamide.

9. The method for synthesizing an N-monoallylamine derivative according to claim 1, characterized in that: The eluent used in the column chromatography is a mixture of petroleum ether and ethyl acetate, and the volume ratio V petroleum ether:V ethyl acetate=100:1-1:2.

Images