Synthesis method of allyl tertiary amine compound

Abstract

The invention relates to a synthesis method of an allyl tertiary amine compound, which comprises the following steps: under the protection of nitrogen, taking alkyne with different substitutions and alkylamine with different substitutions as raw materials, taking metal cobalt salt and organic ligand as catalysts, taking Hanus ester as a reducing agent, taking zinc trifluoromethanesulfonate as an additive, and reacting at the temperature of 60-80 DEG C to obtain the allyl tertiary amine compound. In the presence of an organic solvent and a photosensitizer, the allyl tertiary amine compound is prepared through illumination reaction. According to the method, reaction raw materials and reagents are simple and easy to obtain, conditions are mild and easy to control, atom economy is high, precious metal catalysis is not needed, the substrate application range is wide, regioselectivity is high, and wide application prospects are achieved.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis methods, and in particular to a method for synthesizing tertiary allyl amine compounds. Background Art

[0002] Tertiary amines are important motifs in alkaloid natural products and drug compounds (Blakemore, DC; Castro, L.; Churcher, I.; Rees, DC; Thomas, AW; Wilson, DM; Wood, A. Nat. Chem. 2018, 10, 383-394.). Among them, allyl tertiary amines, an important type of structure, are usually found in natural products, medicines and other synthetic materials. For example, naftifine, terbinafine, cinnarizine and other commercially available drugs all contain obvious allyl tertiary amine skeletons (Johannsen, M.; KA Chem. Rev. 1998, 98, 1689.). Therefore, new methods for synthesizing allyl tertiary amine skeletons have always attracted people's attention.

[0003] The synthesis of tertiary allyl amine skeletons has been reported in the literature before. For example, the early palladium-catalyzed vinylation of amines with simple olefins and the titanium-catalyzed hydromethylamination of alkynes with amines (Xie, Y.; Hu, J.; Wang, Y.; Xia, C-Gu.; Huang, HM. J. Am. Chem. Soc. 2012, 134, 20613-20616. (2) Kaper, T.; Geik, D.; Fornfeist, F.; Schmidtmann, M.; Doye, S. Chem. Eur. J. 2022, 28, e202103931.). Alternatively, hydroaminoalkylation of non-activated alkynes with iminium salts or tetramethylmethanediamine (Ofial, AR; Mayr, H. Angew. Chem. Int. Ed. 1997, 36, 143–145. Rehn, S.; Ofial, AR; Mayr, H. Synthesis 2003, 12, 1790–1796. Kaiser, D.; Tona, V.; Gonlves, CR; Shaaban, S.; Oppedisano, A.; Maulide, N. Angew. Chem. Int. Ed. 2019, 58, 14639–14643. Hsu, CS.; Gonlves, CR; Tona, V.; Pons, A.; Kaiser, M.; Maulide, N. Angew. Chem. Int. Ed. 2022, 61, e202115435.). In recent years, there have also been photocatalytic strategies for the nickel-catalyzed hydrogenation of non-activated alkynes and proline (Till, NA; Smith, RT; MacMillan, David WCJAm. Chem. Soc. 2018, 140, 5701-5705.). For the above reaction types, under the conditions of metal catalysts, usually aryl-substituted alkenes or alkynes can react, but under light conditions, only alkyl-substituted alkynes can react. In addition, for non-metal-catalyzed reaction conditions, a large excess of acid-catalyzed reactions is required. Therefore, it is particularly important to develop a new synthesis method that is suitable for both aryl- and alkyl-substituted alkynes and can quickly and highly regioselectively synthesize allylamine compounds.

[0004] Methylenediamine compounds are good aminoalkylation agents that can react directly with simple alkynes to conveniently synthesize allyl tertiary amine skeleton compounds, which have the advantages of simplicity, high efficiency, high atom economy, and convenient substrate sources. However, this reaction has not been reported yet. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a method for synthesizing allyl tertiary amine compounds with low cost, mild reaction conditions and easy controllability.

[0006] To solve the above problems, the present invention discloses a method for synthesizing an allyl tertiary amine compound, characterized in that: the method is to prepare an allyl tertiary amine compound as shown in the general formula III by light irradiation reaction under nitrogen protection, using alkynes as shown in the general formula I and amines as shown in the general formula II as raw materials, metal cobalt salts and organic ligands as catalysts, Hans ester as a reducing agent, zinc trifluoromethanesulfonate as an additive, in the presence of an organic solvent and a photosensitizer;

[0007] The general formula I:

[0008] The general formula II:

[0009] The general formula III:

[0010] Where: R 1 , R 2 are each independently selected from substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 The aromatic group, and R 1 , R 2 Same or different; R 3 , R 4 is independently selected from substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C4-C 10 arylalkyl, and R 3 , R 4 Same or different.

[0011] The reaction formula is as follows:

[0012]

[0013] The R 1 , R 2 Each of them is independently selected from a halogen atom, a hydroxyl group, an ester group, an alkoxy group, an aryloxy group, and a silicon group.

[0014] The metal cobalt salt is one of Co(acac)2, CoBr2, CoI2, CoF2, Co(NO3)2·6H2O, Co(OTf)2, Co(OAc)2, Co(CO3)2, and Co3(PO4)2, and its usage is 5% of the molar amount of the alkyne substrate.

[0015] The organic ligand is selected from one of monophosphine ligand, diphosphine ligand, monodentate nitrogen ligand, bidentate nitrogen ligand and bidentate nitrogen phosphine ligand, and its usage is 10% of the molar amount of the alkyne substrate.

[0016] The usage amount of the hans ester is 1 times the chemical equivalent of the alkyne substrate.

[0017] The organic solvent is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, diethylene glycol dimethyl ether, diethyl ether, methanol, ethanol or isopropanol.

[0018] The photosensitizer is 2,4,5,6-tetrakis(9H-carbazole-9-yl)isophthalonitrile (4CzIPN), 2,4,5,6-tetrakis(3,6-diphenyl-9H-carbazole-9-yl)isophthalonitrile (4CzIPN-Ph), 3,4,5,6-tetrakis(3,6-di-tert-butyl-9H-carbazole-9-yl)ophthalonitrile (4CzPN- t Bu), 3,4,5,6-tetrakis(3,6-diphenyl-9H-carbazole-9-yl)phthalonitrile (4CzPN-Ph), 3,4,5,6-tetrakis(3,6-dibromo-9H-carbazole-9-yl)phthalonitrile (4CzPN-Br), 2,3,5,6-tetrakis(9H-carbazole-9-yl)terephthalonitrile (4CzTPN), 2,3,5,6-tetrakis(3,6-diphenyl-9-carbazole-9-yl)terephthalonitrile (4CzTPN-Ph), 2,3,5,6-tetrakis(3,6-tert-butyl-9-carbazole-9-yl)terephthalonitrile (4CzTPN- t Bu), and its amount is 1% of the molar amount of the alkyne substrate.

[0019] The light irradiation reaction refers to irradiation with a 5-watt blue LED lamp and stirring the reaction at room temperature for 16 hours.

[0020] The mass ratio of the alkyne to the amine is 1:100 to 100:1.

[0021] Compared with the prior art, the present invention has the following advantages:

[0022] 1. The present invention uses cheap cobalt salt as a catalyst, assisted by an organic ligand, alkynes and amines as raw materials, hans ester as a reducing agent, zinc trifluoromethanesulfonate as an additive, and in the presence of an organic solvent and a photosensitizer, to prepare allyl tertiary amine compounds through light reaction. Not only are the raw materials cheap and easy to obtain, the cost is low, the reaction conditions are mild and easy to control, and the reaction has excellent regioselectivity, it is currently the most competitive method for synthesizing allyl tertiary amine compounds.

[0023] 2. The reaction of the present invention has high atom economy, does not require precious metal catalysis, has a wide range of substrate applicability, and has high regional selectivity, and has broad application prospects. DETAILED DESCRIPTION

[0024] A method for synthesizing an allyl tertiary amine compound, the method comprising: using an alkyne represented by general formula I and an amine represented by general formula II as raw materials, using a metal cobalt salt and an organic ligand as catalysts, using Hans ester as a reducing agent, using zinc trifluoromethanesulfonate as an additive, irradiating with a 5-watt blue light LED lamp in the presence of an organic solvent and a photosensitizer, and reacting at room temperature for 16 hours under nitrogen protection to obtain an allyl tertiary amine compound represented by general formula III;

[0025] The general formula I:

[0026] The general formula II:

[0027] The general formula III:

[0028] Where: R 1 , R 2 are each independently selected from substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 The aromatic group, and R 1 , R 2 Same or different; R 3 , R 4 is independently selected from substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C4-C 10 arylalkyl, and R 3 , R 4 Same or different.

[0029] Where: R 1 , R 2 Each of them is independently selected from a halogen atom, a hydroxyl group, an ester group, an alkoxy group, an aryloxy group, and a silicon group.

[0030] The metal cobalt salt is one of Co(acac)2, CoBr2, CoI2, CoF2, Co(NO3)2·6H2O, Co(OTf)2, Co(OAc)2, Co(CO3)2, Co3(PO4)2, and its amount is 5% of the molar amount of the alkyne substrate.

[0031] The organic ligand is selected from one of monophosphine ligand, diphosphine ligand, monodentate nitrogen ligand, bidentate nitrogen ligand and bidentate nitrogen phosphine ligand, and its usage is 10% of the molar amount of the alkyne substrate.

[0032] The amount of the hans ester used was 1 chemical equivalent of the alkyne substrate.

[0033] The organic solvent is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, diethylene glycol dimethyl ether, ethyl ether, methanol, ethanol or isopropanol, and the amount used is 1 ml.

[0034] The photosensitizers are 2,4,5,6-tetrakis(9H-carbazole-9-yl)isophthalonitrile (4CzIPN), 2,4,5,6-tetrakis(3,6-diphenyl-9H-carbazole-9-yl)isophthalonitrile (4CzIPN-Ph), 3,4,5,6-tetrakis(3,6-di-tert-butyl-9H-carbazole-9-yl)ophthalonitrile (4CzPN- t Bu), 3,4,5,6-tetrakis(3,6-diphenyl-9H-carbazole-9-yl)phthalonitrile (4CzPN-Ph), 3,4,5,6-tetrakis(3,6-dibromo-9H-carbazole-9-yl)phthalonitrile (4CzPN-Br), 2,3,5,6-tetrakis(9H-carbazole-9-yl)terephthalonitrile (4CzTPN), 2,3,5,6-tetrakis(3,6-diphenyl-9-carbazole-9-yl)terephthalonitrile (4CzTPN-Ph), 2,3,5,6-tetrakis(3,6-tert-butyl-9-carbazole-9-yl)terephthalonitrile (4CzTPN- t Bu), and its amount is 1% of the molar amount of the alkyne substrate.

[0035] The mass ratio (g / g) of alkynes to amines is 1:100 to 100:1.

[0036] Example 1

[0037] 1-Phenyl-1-propyne and tetramethylmethanediamine react under the catalysis of different metal cobalt salts to prepare (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine:

[0038]

[0039] Under nitrogen protection, a 25 mL reaction tube was added with cobalt catalyst (0.02 mmol), tri(3,5-dimethylphenyl)phosphine (L1, 0.04 mmol), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (photosensitizer 4CzIPN, 0.004 mmol), diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (Hans ester, HE, 0.2 mmol) and tetrahydrofuran (2 mL), 1-phenyl-1-propyne (0.2 mmol) and tetramethylmethanediamine (0.4 mmol). The test tube was sealed and stirred at room temperature for 16 hours under 5 watt blue LED light. After the solvent was removed under reduced pressure, the residue was directly separated by column chromatography to obtain the product (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine.

[0040] After the reaction was completed, dodecane was added as an internal standard, and the yield of the reaction was determined by nuclear magnetic resonance. The results are shown in Table 1.

[0041] Table 1 Yield and selectivity of different cobalt catalysts

[0042] Serial number Co catalyst Yield (%) Serial number Co catalyst Yield (%) 1 <![CDATA[CoI2]]> 36 7 <![CDATA[Co(NO3)2·6H2O]]> NR 2 <![CDATA[CoBr2]]> 25 8 <![CDATA[Co(OTf)2]]> trace 3 <![CDATA[CoCl2]]> 18 9 <![CDATA[Co(CO3)2]]> NR 4 <![CDATA[CoF2]]> trace 10 <![CDATA[Co3(PO4)2]]> NR 5 <![CDATA[Co(acac)2]]> NR 11 <![CDATA[CoI2·MeCN]]> 10 6 <![CDATA[Co(OAc)2]]> NR 12 No Co Catalyst NR

[0043] It can be seen from Table 1 that when CoCl2, CoBr2, CoCl2 or CoI2·MeCN are used as catalysts, 1-phenyl-1-propyne and tetramethylmethanediamine can be coupled to obtain (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine in a relatively low yield.

[0044] Example 2

[0045] Preparation of (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine from 1-phenyl-1-propyne and tetramethylmethanediamine using different additives under cobalt catalysis:

[0046]

[0047] Under nitrogen protection, cobalt iodide (0.02mmol), tri(3,5-dimethylphenyl)phosphine (L1, 0.04mmol), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (photosensitizer 4CzIPN, 0.004mmol), diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (Hans ester, HE, 0.2mmol), additive (0.2mmol) and tetrahydrofuran (2mL), 1-phenyl-1-propyne (0.2mmol) and tetramethylmethanediamine (0.4mmol) were added to a 25mL reaction tube. The test tube was sealed and stirred at room temperature for 16 hours under 5W blue LED light. After the solvent was removed under reduced pressure, the residue was directly separated by column chromatography to obtain the product (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine.

[0048] After the reaction was completed, dodecane was added as an internal standard, and the yield of the reaction was determined by nuclear magnetic resonance. The results are shown in Table 2.

[0049] Table 2 Yield of different additives

[0050] Serial number additive Yield (%) Serial number additive Yield (%) 1 none 36 10 <![CDATA[ZnCl2]]> 54 2 <![CDATA[NaBF4]]> 26 11 <![CDATA[ZnBr2]]> 60 3 KBARF 26 12 <![CDATA[ZnI2]]> 64 4 NaBARF 24 13 <![CDATA[Zn(OTf)2]]> 68 5 <![CDATA[KBPhF3]]> 16 14 <![CDATA[Zn(OTf)2 a ]]> 50 6 <![CDATA[NaHCO3]]> 20 15 <![CDATA[Zn(CN)2]]> 15 7 Cf 10 16 <![CDATA[Zn(OAc)2]]> 20 8 LiCl 15 17 Zinc pivalate 10 9 LqCy 18 18 Zinc propionate 15

[0051] a Zn(OTf)2(0.5eq.)

[0052] As can be seen from Table 2, when zinc trifluoromethanesulfonate is used, the reaction can obtain the product (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine with excellent regioselectivity and moderate yield.

[0053] Example 3

[0054] 1-Phenyl-1-propyne and tetramethylmethanediamine were used to prepare (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine in the presence of cobalt catalysts using different photosensitizers:

[0055]

[0056] Under nitrogen protection, cobalt iodide (0.02mmol), tri(3,5-dimethylphenyl)phosphine (L1, 0.04mmol), photosensitizer (0.004mmol), diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (Hans ester, HE, 0.2mmol) and tetrahydrofuran (2mL), 1-phenyl-1-propyne (0.2mmol) and tetramethylmethanediamine (0.5mmol) were added to a 25mL reaction tube. The test tube was sealed and stirred at room temperature for 16 hours under 5W blue LED light. After the solvent was removed under reduced pressure, the residue was directly separated by column chromatography to obtain the product (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine.

[0057] After the reaction was completed, dodecane was added as an internal standard, and the yield of the reaction was determined by nuclear magnetic resonance. The results are shown in Table 3.

[0058] Table 3 Yield of different photosensitizers

[0059]

[0060] As can be seen from Table 3, when 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN) is used, the reaction can obtain the product (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine in excellent yield.

[0061] Example 4

[0062] 1-Phenyl-1-propyne and tetramethylmethanediamine were used to prepare (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine in different solvents under cobalt catalysis:

[0063]

[0064] Under nitrogen protection, cobalt iodide (0.02mmol), tri(3,5-dimethylphenyl)phosphine (L1, 0.04mmol), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN, 0.004mmol), diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (Hans ester, HE, 0.2mmol) and tetrahydrofuran (2mL), 1-phenyl-1-propyne (0.2mmol) and tetramethylmethanediamine (0.4mmol) were added to a 25mL reaction tube. The test tube was sealed and stirred at room temperature for 16 hours under 5W blue LED light. After the solvent was removed under reduced pressure, the residue was directly separated by column chromatography to obtain the product (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine.

[0065] After the reaction was completed, dodecane was added as an internal standard, and the yield of the reaction was determined by nuclear magnetic resonance. The results are shown in Table 4.

[0066] Table 4 Yields of different solvents

[0067] Serial number Solvents Yield (%) 1 THF 68 2 1.4-dioxane 66 3 MeCN 10 4 DME 68 5 DCE 46 6 2-MeTHF 60

[0068] It can be seen from Table 4 that when tetrahydrofuran is used as the solvent, the product (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine can be obtained in good yield.

[0069] Example 5

[0070] 1-Phenyl-1-propyne and tetramethylmethanediamine were used in the presence of cobalt to prepare (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine using different amounts of photosensitizer, catalyst, ligand, amine and solvent:

[0071]

[0072] Under nitrogen protection, cobalt iodide (x mol%), tri(3,5-dimethylphenyl)phosphine (L1, x mol%), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (photosensitizer 4CzIPN, x mol%), diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (Hans ester, HE, 0.2 mmol) and tetrahydrofuran (x mL), 1-phenyl-1-propyne (0.2 mmol) and tetramethylmethanediamine (x mmol) were added to a 25 mL reaction tube. The test tube was sealed and stirred at room temperature for 16 hours under 5 W blue LED light. After the solvent was removed under reduced pressure, the residue was directly separated by column chromatography to obtain the product (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine.

[0073] After the reaction was completed, dodecane was added as an internal standard, and the yield of the reaction was determined by nuclear magnetic resonance. The results are shown in Table 5.

[0074] Table 5 Yields of different amounts of photosensitizer, catalyst, ligand, amine and solvent

[0075]

[0076] a Separation yield

[0077] As can be seen from Table 5, when cobalt iodide (0.01 mmol) and tri(3,5-dimethylphenyl)phosphine (L1, 0.02 mmol), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (photosensitizer 4CzIPN, 0.001 mmol), tetramethylmethanediamine (0.5 mmol), and tetrahydrofuran (1 mL) were used, the product (E)-N,N,2-trimethyl-3-phenylpropyl-2-en-1-amine was obtained in excellent yield.

[0078] Example 6

[0079] Preparation of allyl tertiary amines from different alkynes and tetramethylmethanediamine under cobalt catalysis:

[0080]

[0081] Under nitrogen protection, cobalt iodide (0.01mmol), tri(3,5-dimethylphenyl)phosphine (L1, 0.02mmol), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (photosensitizer 4CzIPN, 0.01mmol), diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (Hans ester, HE, 0.2mmol) and tetrahydrofuran (1mL), alkyne (0.2mmol), tetramethylmethanediamine or 1,1-dipiperidinylmethane (0.5mmol) were added to a 25mL reaction tube. The test tube was sealed and stirred at room temperature for 16 hours under 5W blue LED light. After the solvent was removed under reduced pressure, the residue was directly separated by column chromatography to obtain the product. The obtained product can be separated by thin layer chromatography or column chromatography. The developing solvent used in the thin layer chromatography and column chromatography method is a mixed solvent of a polar solvent and a non-polar solvent. Preferably, the solvent may be a mixed solvent such as ethyl acetate-petroleum ether, dichloromethane-methanol, etc., and the volume ratio (ml / ml) thereof may be respectively: polar solvent: non-polar solvent = 1:2-30. For example: ethyl acetate:petroleum ether = 1:2-4, dichloromethane-methanol = 1:10-30.

[0082] The regioselectivity and cis-trans selectivity of the obtained products were determined by NMR, and the results are shown in Table 6.

[0083] Table 6 Yield and selectivity of different products

[0084]

[0085]

[0086]

[0087] As can be seen from Table 6, various alkynes can react with tetramethylmethanediamine or 1,1-dipiperidinylmethane, and the reaction can obtain the product in medium to excellent yields with excellent regioselectivity and E-type stereoselectivity.

[0088] Example 7

[0089] Preparation of allyl tertiary amines from 1-phenyl-1-propyne and different diamines under cobalt catalysis:

[0090]

[0091] Under nitrogen protection, cobalt iodide (0.01mmol), tri(3,5-dimethylphenyl)phosphine (L1, 0.02mmol), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (photosensitizer 4CzIPN, 0.01mmol), diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (Hans ester, HE, 0.2mmol) and tetrahydrofuran (1mL), 1-phenyl-1-propyne (0.2mmol) and different amine compounds (0.5mmol) were added to a 25mL reaction tube. The test tube was sealed and stirred at room temperature for 16 hours under 5W blue LED light. After the solvent was removed under reduced pressure, the residue was directly separated by column chromatography to obtain the product. The obtained product can be separated by thin layer chromatography or column chromatography. The developing solvent used in the thin layer chromatography and column chromatography method is a mixed solvent of a polar solvent and a non-polar solvent. Preferably, the solvent may be a mixed solvent such as ethyl acetate-petroleum ether, dichloromethane-methanol, etc., and the volume ratio (ml / ml) thereof may be respectively: polar solvent: non-polar solvent = 1:2-30. For example: ethyl acetate:petroleum ether = 1:2-4, dichloromethane-methanol = 1:10-30.

[0092] The regioselectivity and cis-trans selectivity of the obtained products were determined by NMR, and the results are shown in Table 7.

[0093] Table 7 Yield and selectivity of different products

[0094]

[0095]

[0096] As can be seen from Table 6, various alkylamines can react with 1-phenyl-1-propyne, and the reaction can obtain the product with excellent regioselectivity and E-stereoselectivity in moderate to excellent yields.

[0097] It should be pointed out that the above preferred embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing an allyl tertiary amine compound, characterized in that: The synthesis method is to prepare the allyl tertiary amine compound as shown in the general formula III by light irradiation reaction under nitrogen protection, using the alkyne as shown in the general formula I and the amine as shown in the general formula II as raw materials, using metal cobalt salt and organic ligand as catalysts, using Hans ester as a reducing agent, using zinc trifluoromethanesulfonate as an additive, and in the presence of an organic solvent and a photosensitizer; The general formula I: The general formula II: The general formula III: Where: R 1 , R 2 are each independently selected from substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C6-C 10 The aromatic group, and R 1 , R 2 Same or different; R 3 , R 4 is independently selected from substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C4-C 10 arylalkyl, and R 3 , R 4 Same or different.

2. The method for synthesizing an allyl tertiary amine compound according to claim 1, characterized in that: The R 1 , R 2 Each of them is independently selected from a halogen atom, a hydroxyl group, an ester group, an alkoxy group, an aryloxy group, and a silicon group.

3. The method for synthesizing an allyl tertiary amine compound according to claim 1, characterized in that: The metal cobalt salt is one of Co(acac)2, CoBr2, CoI2, CoF2, Co(NO3)2·6H2O, Co(OTf)2, Co(OAc)2, Co(CO3)2, and Co3(PO4)2, and its usage is 5% of the molar amount of the alkyne substrate.

4. The method for synthesizing an allyl tertiary amine compound according to claim 1, characterized in that: The organic ligand is selected from one of monophosphine ligand, diphosphine ligand, monodentate nitrogen ligand, bidentate nitrogen ligand and bidentate nitrogen phosphine ligand, and its usage is 10% of the molar amount of the alkyne substrate.

5. The method for synthesizing an allyl tertiary amine compound according to claim 1, characterized in that: The usage amount of the hans ester is 1 times the chemical equivalent of the alkyne substrate.

6. The method for synthesizing an allyl tertiary amine compound according to claim 1, characterized in that: The organic solvent is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, diethylene glycol dimethyl ether, diethyl ether, methanol, ethanol or isopropanol.

7. The method for synthesizing an allyl tertiary amine compound according to claim 1, characterized in that: The photosensitizer is 2,4,5,6-tetrakis(9H-carbazole-9-yl)isophthalonitrile, 2,4,5,6-tetrakis(3,6-diphenyl-9H-carbazole-9-yl)isophthalonitrile, 3,4,5,6-tetrakis(3,6-di-tert-butyl-9H-carbazole-9-yl)phthalonitrile, 3,4,5,6-tetrakis(3,6-diphenyl-9H-carbazole-9-yl)phthalonitrile, , 4,5,6-tetrakis(3,6-dibromo-9H-carbazole-9-yl)phthalonitrile, 2,3,5,6-tetrakis(9H-carbazole-9-yl)terephthalonitrile, 2,3,5,6-tetrakis(3,6-diphenyl-9-carbazole-yl)-terephthalonitrile, 2,3,5,6-tetrakis(3,6-tert-butyl-9-carbazole-yl)-terephthalonitrile, and the amount used is 1% of the molar amount of the alkyne substrate.

8. The method for synthesizing an allyl tertiary amine compound according to claim 1, characterized in that: The light irradiation reaction refers to irradiation with a 5-watt blue LED lamp and stirring the reaction at room temperature for 16 hours.

9. The method for synthesizing an allyl tertiary amine compound according to claim 1, characterized in that: The mass ratio of the alkyne to the amine is 1:100 to 100:1.

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