Synthesis of an α-chiral amidine compound

Abstract

This paper discloses a method for preparing α‑ Chiral amidine method. Through the in situ preparation of chiral allylamine and alkenylimine, the asymmetric N‑ The heterogeneous Claisen rearrangement method was successfully constructed α‑ Chiral amidine. The reaction has the following advantages: (1) The reaction conditions are very mild, the reaction can be carried out at room temperature, and no equivalent strong base is required, which is more environmentally friendly. (2) The one-pot two-step method can eliminate the intermediate processing steps for making chiral substrates, saving manpower and material resources and reducing consumption. (3) It can simultaneously construct the chiral center and the amidine functional group, with atom economy and step economy. (4) The reaction yield is high, and the template product can be obtained with a total yield of 94% in two steps. The chirality of allylamine can also be stereospecifically transferred to the amidine, and the template product has 95% of (5) The substrate universality and functional group tolerance are good, such as cyano, tert-butyl, ester, methoxy, nitro, and trifluoromethyl groups can all react, both ortho- and di-substitutions are active, and heteroaromatic compounds can also obtain the target product.

Description

Technical Field

[0001] The present invention relates to the technical field of medicine and organic chemical synthesis, and specifically relates to a α- A method for synthesizing chiral amidine compounds. Background Art

[0002] Amidines are an important class of nitrogen-containing compounds with widespread applications in various fields. The methods for synthesizing amidines have been well developed over time, using a wide variety of starting materials and diverse methods. Since 2005, the copper-catalyzed cycloaddition of alkynes and azides has become a key method for preparing amidines, enabling the mild and efficient synthesis of various substituted amidines (I. Bae, H. Han, and S. Chang. J. Am. Chem. Soc. 2005, 127 , 2038-2039). Currently, most amidine compounds are racemic (Ref. (a) KD Veeranna, KK Das, and S.Baskaran. (b) HD Xu, ZH Jia, K. Xu, M. Han, SN Jiang, J. Cao, JCWang, and MH Shen. Angew. Chem. Int. Ed.2014, 53, 9284–9288. (c) C.G. Wang, R. Wu, T.P. Li, T. Jia, Y. Li, D.M. Fang, X.Z. Chen, Y.J. Gao, Hai-LiangNi, P. Hu, B.Q. Wang, and P. Cao. Org. Lett. 2020, 22 , 3234−3238.(d)Y. Huang, WY Yi, QH Sun, FP Yi. Adv. Synth. Catal., 2018, 360 , 3074-3082.), there are very few methods for constructing chiral amidines, Cu-catalyzed terminal alkyne-azide cycloaddition (CuAAC) / N- The hetero-Claisen rearrangement tandem reaction can be quickly and efficiently constructed α -chiral homoallyl amidine compounds, but the asymmetric synthesis method has not been reported. Although α-chiral amidine compounds can be achieved through asymmetric substitution reactions (T. Kochi and JA Ellman. J. Am. Chem. Soc. 2004, 126, 15652-15653), but this requires the step-by-step construction of functional groups and chiral centers, and because an equivalent amount of strong base is used, it is neither environmentally friendly nor efficient. The present invention provides a relatively simple and efficient method for synthesizing α-chiral amidines. By preparing chiral allylamines and alkenyl imines on site, using asymmetric N- One-step construction of heterogeneous Claisen rearrangement method α- The chiral center and amidine functional group have better step economy. Summary of the Invention

[0003] The object of the present invention is to provide a synthetic α -Chiral amidine method. By preparing chiral allylamine and alkenylimine in situ, using asymmetric N- One-step construction of heterogeneous Claisen rearrangement method α- Chiral center and amidine functional group.

[0004] The present invention is achieved by the following specific scheme: through a one-pot two-step approach, allyl carbonate, secondary amine, and iridium catalyst are used to react first to generate chiral tertiary allylamine, and then Cu-catalyzed terminal alkyne-azide cycloaddition (CuAAC) reaction to generate alkenyl imine, which is then captured by allylamine to generate asymmetric zwitterion. N- Hetero-Claisen rearrangement generates the corresponding α- Chiral amidine. The reaction process is shown in the following reaction formula (I):

[0005]

[0006] Reaction Formula I

[0007] where R 1 R is a C1-C10 alkyl group, an alkyl group with a functional group at the end, a phenyl group, an aryl group or a heterocyclic group. 2 R is a C1-C10 alkyl group, an alkyl group with a functional group at the end, a phenyl group, an aryl group, or a heterocyclic group. 3 is an alkyl group or an alkyl group with a functional group at the end. 4 The alkyl group or an alkyl group with a terminal functional group is selected from a carbon-carbon double bond, a carbon-carbon triple bond, a hydrocarbon group, a silyl ether group, an ester group, an acyl group, an acyloxy group, an amide group, a sulfonic acid group, a halogen group, a sulfonyl group, a cyano group, a nitro group, a hydrocarbon-substituted amino group, and an acyl-substituted amino group; the aryl group is a phenyl group with an electron-withdrawing or electron-donating substituent at the ortho, meta, or para position; the heterocycle is thiophene, furan, pyridine, or a thiophene, furan, or pyridine group with an electron-donating or electron-withdrawing substituent. The electron-withdrawing substituent includes a halogen group, a nitro group, an ester group, an acyl group, an amide group, a sulfonic acid group, and a cyano group; the electron-donating substituent includes an alkyl group, an alkenyl group, an alkynyl group, a phenyl group, a hydrocarbon group, an aminoacyloxy group, a hydrocarbon-substituted amino group, and an acyl-substituted amino group.

[0008] Preferably, R 1 is phenyl, aryl or heterocyclic. 2 R is a C1-C10 alkyl group, an alkyl group with a functional group at the end, a phenyl group, an aryl group, or a heterocyclic group. 3 is an alkyl group or an alkyl group with a functional group at the end. 4 The alkyl group or an alkyl group with a terminal functional group is selected from a carbon-carbon double bond, a carbon-carbon triple bond, a hydrocarbon group, a silyl ether group, an ester group, an acyl group, an acyloxy group, an amide group, a sulfonic acid group, a halogen group, a sulfonyl group, a cyano group, a nitro group, a hydrocarbon-substituted amino group, and an acyl-substituted amino group; the aryl group is a phenyl group with an electron-withdrawing or electron-donating substituent at the ortho, meta, or para position; the heterocycle is thiophene, furan, pyridine, or a thiophene, furan, or pyridine group with an electron-donating or electron-withdrawing substituent. The electron-withdrawing substituent includes a halogen group, a nitro group, an ester group, an acyl group, an amide group, a sulfonic acid group, and a cyano group; the electron-donating substituent includes an alkyl group, an alkenyl group, an alkynyl group, a phenyl group, a hydrocarbon group, an aminoacyloxy group, a hydrocarbon-substituted amino group, and an acyl-substituted amino group.

[0009] More preferably, R 1 is a phenyl group or an aryl group having an electron-donating group. 2 R is a C1-C10 alkyl group, an alkyl group with a functional group at the end, a phenyl group, an aryl group, or a heterocyclic group. 3 R 4 NH is selected from tetrahydropyrrole, hexahydropyridine, piperazine, and 4-methylpiperidine.

[0010] The specific operations of the present invention are as follows:

[0011] In a glove box, the iridium catalyst, ligand, and solvent A were weighed into a dry reaction tube. Compounds 1 and 2 were then added sequentially. The reaction was stirred at room temperature until the starting materials were completely consumed. The copper catalyst and solvent B were then added to the glove box. TsN3 (p-toluenesulfonyl azide) and 3 were then added sequentially. The reaction was continued at room temperature until the allylamine was completely consumed. After purification, amidine 4 was obtained. The reaction equation is shown in Reaction Equation II:

[0012]

[0013] Reaction Formula II

[0014] The iridium catalyst is [Ir(COD)Cl]2. The molar ratio of [Ir(COD)Cl]2 to 1 is 0.01:1. The ligand is a ligand L to 1 in a molar ratio of 0.02:1.

[0015] The solvent A is 0.5 mL of tetrahydrofuran, and the solvent B is 0.5 mL of acetonitrile.

[0016] The molar ratio of the copper catalyst to 1 is 0.1:1.

[0017] The copper catalyst is selected from cuprous hexafluorophosphate (tetraacetonitrile), cuprous tetrafluoroborate (tetraacetonitrile), cuprous acetate, cuprous trifluoromethanesulfonate toluene complex, cuprous chloride, cuprous bromide, cuprous iodide, and cuprous thiophene-2-carboxylate. Preferably, it is cuprous acetate.

[0018] As a further improvement, the molar ratio of 1 and 2 to p-toluoyl azide and 3 is 1:1.1:1.5:1.5. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 , 2 is the liquid phase spectrum of the product obtained in Example 1; Figure 13 , 14 are the H NMR and C NMR spectra of the product obtained in Example 1;

[0020] Figure 3 , 4 is the liquid phase spectrum of the product obtained in Example 2; Figure 15 , 16 are the H NMR and C NMR spectra of the product obtained in Example 2;

[0021] Figure 5 , 6 is the liquid phase spectrum of the product obtained in Example 3; Figure 17 , 18 is the H NMR spectrum and C NMR spectrum of the product obtained in Example 3;

[0022] Figure 7 , 8 is the liquid phase spectrum of the product obtained in Example 4; Figure 19 , 20 are the H NMR and C NMR spectra of the product obtained in Example 4;

[0023] Figure 9 , 10, is the liquid phase spectrum of the product obtained in Example 5; Figure 21 , 22, 23 are the H NMR spectra, C NMR spectra and F NMR spectra of the product obtained in Example 5;

[0024] Figure 11 , 12 is the liquid phase spectrum of the product obtained in Example 6; Figure 24 ,25 are the H-NMR and C-NMR spectra of the product obtained in Example 6; DETAILED DESCRIPTION

[0025] The present invention will be further described in detail below with reference to specific examples, but the embodiments of the present invention are not limited thereto.

[0026] In a glove box, iridium catalyst [Ir(COD)Cl]2 (1.3 mg, 1 mol%), ligand ( R,R,R)-L (2.2 mg, 2 mol%) and THF (0.5 mL) were added, followed by the sequential addition of allyl carbonate 1a (0.2 mmol) and secondary amine 2a (0.22 mmol). The reaction was stirred at room temperature until the starting material was completely consumed (approximately 10 h). CuOAc (2.5 mg, 10 mol%) and MeCN (0.5 mL) were then added in a glove box. TsN3 (0.3 mmol) and terminal alkyne 3 (0.3 mmol) were then added sequentially, and the reaction was continued for 24 h. The reaction was monitored by TLC. Once the allylamine reaction was complete, the metal was removed by filtration through celite, the solvent was removed by rotary evaporation, and the amidine was obtained by column chromatography.

[0027] Example 1

[0028] The terminal alkyne 3 was phenylacetylene, which was separated and purified by column chromatography to obtain the target product 4a. The column chromatography eluent used was a solvent with a volume ratio (first 100 mL of a 5:1 petroleum ether:ethyl acetate mixture, then a 3:1 petroleum ether:ethyl acetate mixture) with a yield of 94%, 95%. ee The structural characterization data of the product obtained in Example 1 are as follows (the liquid phase spectrum is as follows Figure 1 and Figure 2 (NMR spectrum as shown) Figure 13 (H-spectrum) and Figure 14 (Carbon-ion spectrum) shown):

[0029] the amidine4awas isolated (eluent solvent, EtOAc / petroleum=1 / 5→1 / 3) as the yellow solid (86.4 mg, 0.188 mmol, 94% yield), mp 80 o C.

[0030] 1 H NMR (600 MHz, CDCl3) δ 7.89 (d, J = 8.1 Hz, 2H), 7.32 – 7.27 (m, 8H), 7.26 – 7.19 (m, 4H), 6.43 (d, J = 15.8 Hz, 1H), 6.34 – 6.26 (m, 1H), 5.31 (s,1H), 3.75-3.60 (m, 2H), 3.29 – 3.27(m, 1H), 3.05 – 2.93 (m, 2H), 2.92 – 2.84(m, 1H), 2.38 (s, 3H), 1.81 – 1.60 (m, 4H).

[0031] 13 C NMR(151 MHz, CDCl3) δ 165.7, 142.1, 141.7, 137.6, 137.3,132.1,129.2, 128.9, 128.5, 127.5, 127.3, 127.2, 126.3, 126.3, 50.9, 48.3, 47.8,33.6, 26.1, 23.6, 21.5.

[0032] HRMS (ESI)m / z: C 28 H 30 N2O2S [M+H] + Calcd. For 459.2101; found: 459.2130.HPLC analysis: (Daicel Chiralcel AD-H, eluent,60 / 40 hexane / i -propanol, 1.0mL / min, 25 o C, 254 nm, t major : 35.4 min and t minor : 24.7 min). ee = 95%. [α] D 20 = +94.0 (c =0.2, CHCl3).

[0033] Based on the above data, the structure of the compound is determined as follows

[0034]

[0035] Example 2

[0036] The terminal alkyne 3 is 2-thiophene acetylene, which was separated and purified by column chromatography to obtain the target product 4b. The column chromatography eluent used was dichloromethane, with a yield of 98%, 96%. ee The structural characterization data of the product obtained in Example 2 are as follows (the liquid phase spectrum is as follows Figure 3 and Figure 4 (NMR spectrum as shown) Figure 15 (H-spectrum) and Figure 16 (Carbon-ion spectrum) shown):

[0037] the amidine4bwas isolated (DCM as the eluent solvent) as the redsolid (91 mg, 0.196 mmol, 98% yield), m.p. 153.4 o C

[0038] 1 H NMR(600 MHz, CDCl3) δ 7.85 (d, J = 8.2 Hz, 2H), 7.35 – 7.13 (m, 9H),6.93 – 6.87 (m, 2H), 6.45 (d, J = 15.8 Hz, 1H), 6.29 – 6.20 (m, 1H), 5.48 (br,1H), 3.68 – 3.55 (m, 2H),3.39 – 3.29 (m, 1H), 3.18 – 3.09 (m, 1H), 3.04 –2.94 (m, 1H), 2.94 – 2.87 (m, 1H), 2.33 (s, 3H), 1.81 – 1.60 (m, 4H).

[0039] 13 C NMR(151 MHz, CDCl3) δ 164.7, 141.9, 141.8, 140.7, 137.1,132.7,129.2, 128.5, 127.4, 127.0, 126.4, 126.3, 126.3, 125.3, 124.7, 50.9, 48.3,44.1, 35.3, 26.2, 23.4, 21.5.

[0040] HRMS (ESI) m / z: C 26 H 28 N2O2S2[M+H] + Calcd. For 465.1665; found: 465.1673.HPLC analysis: (Daicel Chiralcel AD-H, 60 / 40 hexane / i -propanol, 0.7 mL / min,25 o C, 254 nm, t major :87.0 min and t minor :56.0 min). ee = 96%. [α]D 20 = -96.5 (c =0.8, CHCl3).

[0041] Based on the above data, the structure of the compound is determined as follows

[0042]

[0043] Example 3

[0044] The terminal alkyne 3 was ethyl propiolate, which was isolated and purified by column chromatography to obtain the target product 4c. The column chromatography eluent used was 100 mL of a 5:1 petroleum ether:ethyl acetate mixture, followed by a 3:1 petroleum ether:ethyl acetate mixture, with a yield of 87%, 89%. ee The structural characterization data of the product obtained in Example 2 are as follows (the liquid phase spectrum is as follows Figure 5 and Figure 6 (NMR spectrum as shown) Figure 17 (H-spectrum) and Figure 18 (Carbon-ion spectrum) shown):

[0045] the amidine4cwas isolated (1:3 EtOAc / petroleum ether as the eluentsolvent) as the colorless oil (79 mg, 0.175 mmol, 87% yield, 89% ee ).

[0046] 1 H NMR(600 MHz, CDCl3) δ 7.84 – 7.79(m, 2H), 7.31 – 7.26 (m, 4H), 7.22– 7.18 (m, 3H), 6.45 (d, J = 15.8 Hz, 1H), 6.26 – 6.20 (m, 1H), 4.90 (s, 1H), 4.22 – 4.16 (m, 2H), 3.65 – 3.59 (m, 1H), 3.56 – 3.49 (m, 2H), 3.34 – 3.28(m, 1H), 3.10 – 3.03(m, 1H), 2.88 – 2.79 (m, 1H), 2.37 (s, 3H), 1.94 – 1.78(m, 4H), 1.23 (t, J = 7.1 Hz, 3H).

[0047] 13C NMR(151 MHz, CDCl3) δ 169.1, 161.2, 141.8, 141.6, 137.1,133.1,129.1, 128.6, 127.5, 126.4, 126.3, 125.7, 61.9, 50.0, 48.2, 48.1, 32.0, 26.2,23.7, 21.5, 14.2.

[0048] HRMS (ESI) m / z: C 25 H 30 N2O4S [M+H] + Calcd. For 455.1999; found: 455.2022.HPLC analysis: (Daicel Chiralcel AD-H, 70 / 30 hexane / i -propanol, 0.8 mL / min,25 o C, 254 nm, t major :27.7 min and t minor :22.1min). ee = 89%. [α] D 20 = +67.4 (c = 0.1, CHCl3).

[0049] Based on the above data, the structure of the compound is determined as follows

[0050]

[0051] Example 4

[0052] Allyl carbonate 1 is 4-methoxycinnamyl carbonate methyl ester, which was separated and purified by column chromatography to obtain the target product. The column chromatography eluent used was a solvent with a volume ratio (first 100 mL of a 5:1 petroleum ether:ethyl acetate mixture, then a 3:1 petroleum ether:ethyl acetate mixture) with a yield of 87%, 89%. ee The structural characterization data of the product obtained in Example 2 are as follows (the liquid phase spectrum is as follows Figure 7 and Figure 8 (NMR spectrum as shown) Figure 19 (H-spectrum) and Figure 20 (Carbon-ion spectrum) shown):

[0053] the amidine4dwas isolated (1:3 EtOAc / petroleum ether as the eluentsolvent) as the white solid (73.3 mg, 0.15 mmol, 75% yield), m.p. 170.0 o C

[0054] 1 H NMR(600 MHz, CDCl3) δ 7.87 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 4.4 Hz,4H), 7.25 – 7.20 (m, 5H), 6.82 (d, J = 8.6 Hz, 2H), 6.36 (d, J = 15.8 Hz, 1H),6.17 – 6.09 (m, 1H), 5.27 (br, 1H), 3.80 (s,3H), 3.74 – 3.60 (m, 1H), 3.30 –3.24 (m, 1H), 3.01 – 2.91 (m, 2H), 2.88 – 2.81 (m, 1H), 2.38 (s, 3H), 1.79 –1.62 (m, 4H).

[0055] 13 C NMR(151 MHz, CDCl3) δ 159.1, 142.2, 141.7, 137.7, 131.5,130.2,129.2, 128.9, 127.6, 127.5, 127.2, 126.4, 125.0, 114.0, 55.4, 50.9, 48.3,48.0, 33.7, 26.2, 23.6, 21.6.

[0056] HRMS (ESI) m / z: C 29 H 33 N2O3S [M+H] + Calcd. For 489.2206; found: 489.2235.HPLC analysis: (Daicel Chiralcel IA, 65 / 35 hexane / i -propanol, 0.7 mL / min,25 o C, 254 nm, tmajor : 39.4 min and t minor :30.6 min). ee = 92% [α] D 20 = +86.2 (c =0.3, CHCl3).

[0057] Based on the above data, the structure of the compound is determined as follows

[0058]

[0059] Example 5

[0060] Allyl carbonate 1 is 3-fluorocinnamyl carbonate methyl ester, which was separated and purified by column chromatography to obtain the target product. The column chromatography eluent used was a solvent with a volume ratio (first 100 mL of a 5:1 petroleum ether: ethyl acetate mixture, then a 3:1 petroleum ether: ethyl acetate mixture) with a yield of 87%, 89%. ee The structural characterization data of the product obtained in Example 2 are as follows (the liquid phase spectrum is as follows Figure 9 and Figure 10 (NMR spectrum as shown) Figure 20 (H-spectrum) and Figure 21 (Carbon-spectrum) and Figure 22 (Fluorine-spectrum) shown):

[0061] the amidine4ewas isolated (1:3 EtOAc / petroleum ether as the eluentsolvent) as the white solid (58.1 mg, 0.122 mmol, 61% yield),

[0062] 1 H NMR (600 MHz, CDCl3) δ 7.87 (d, J = 8.2 Hz, 2H), 7.34 – 7.29 (m, 4H), 7.26 – 7.19 (m, 4H), 7.06 (d, J = 7.7 Hz, 1H), 7.00 – 6.96 (m, 1H), 6.89 (dt, J =8.4, 2.4 Hz, 1H), 6.37 (d, J= 15.9 Hz, 1H), 6.34 – 6.24 (m, 1H), 5.28 (s, 1H), 3.74 – 3.59 (m, 2H), 3.29 – 3.22(m, 1H), 3.04 – 2.92 (m, 2H), 2.90 – 2.82 (m,1H), 2.37 (s, 3H), 1.81 – 1.60 (m, 4H).

[0063] 13 C NMR (151 MHz, CDCl3) δ 165.5, 163.1 (d, J = 244.62 Hz), 142.1, 141.7,139.6, 139.6, 137.4, 131.0, 131.0, 129.9, 129.9, 129.1, 128.9,128.6, 127.4,127.2, 126.3, 122.1, 122.1, 114.1, 113.9, 112.8, 112.7, 50.9, 48.2, 47.7,33.4, 26.1, 23.5, 21.4.

[0064] 19 F NMR (565 MHz, CDCl3) δ -113.65 –-113.70 (m).

[0065] HRMS (ESI) m / z: C 28 H 29 FN2O2S [M+H] + Calcd. For 477.2007; found:477.2045. HPLC analysis: (Daicel Chiralcel OD-H, 80 / 20 hexane / i -propanol, 0.7mL / min, 25 o C, 254 nm, t major :28.7 min and t minor :25.4 min). ee = 95%. [α] D 20 = +87.2(c = 0.9, CHCl3).

[0066] Based on the above data, the structure of the compound is determined as follows

[0067]

[0068] Example 6

[0069] Secondary amine 2 is piperidine, which is separated and purified by column chromatography to obtain the target product. The column chromatography eluent used is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1. The yield is 62%, 96%. ee The structural characterization data of the product obtained in Example 2 are as follows (the liquid phase spectrum is as follows Figure 11 and Figure 12 (NMR spectrum as shown) Figure 24 (H-spectrum) and Figure 25 (Carbon-ion spectrum) shown):

[0070] the amidine4fwas isolated (1:5 EtOAc / petroleum ether as the eluentsolvent) as the yellow oil (60 mg, 0.124 mmol, 62% yield) .mp 134.5 o C

[0071] 1 H NMR (600 MHz, CDCl3) δ 7.84 (d, J = 8.2 Hz, 2H), 7.37 – 7.17 (m, 13H), 6.47 (d, J = 15.9 Hz, 1H), 6.40 – 6.33 (m, 1H), 5.67 (br, 1H), 4.00 – 3.00 (m,5H), 2.86 – 2.76 (m, 1H), 2.36 (s, 3H), 1.59 – 1.15 (m, 5H).

[0072] 13 C NMR(151 MHz, CDCl3) δ 167.0, 141.8, 141.7, 138.2, 137.2,132.2,129.1, 128.9, 128.5, 127.3, 127.2, 126.9, 126.7, 126.3, 126.3, 48.3, 47.5,46.5, 33.7, 25.3, 23.9, 21.5.

[0073] HRMS (ESI) m / z: C 29 H 32 N2O2S [M+H] +Calcd. For 473.2257; found: 473.2269.HPLC analysis: (Daicel Chiralcel IB, 90 / 10 hexane / i -propanol, 0.8 mL / min,25 o C, 254 nm, t major :34.3 min and t minor :31.7 min). ee = 96%. [α] D 20 = +136.3 (c =0.1, CHCl3).

[0074] Based on the above data, the structure of the compound is determined as follows

[0075]

Claims

1. A method for synthesizing α-chiral amidine, characterized in that: By preparing chiral allylamines and alkenyl imines in situ, α-chiral amidines were successfully constructed using the asymmetric N-hetero-Claisen rearrangement method. The reaction equation is: where R 1 is phenyl or fluoro-substituted phenyl; R 2 is phenyl or thienyl; R 3 R 4 NH is a tetrahydropyrrole or hexahydropyridine compound; The specific synthesis method is as follows: in a glove box, iridium catalyst, ligand L and solvent A are weighed into a dry reaction tube, and 1 and 2 are added in sequence. After stirring and reacting until the raw materials are completely consumed, copper catalyst and solvent B are added in the glove box; then TsN3 and 3 are added in sequence, and reacted until allylamine is completely consumed. After treatment and purification, 4 is obtained; The iridium catalyst is [Ir(COD)Cl]2; the molar ratio of [Ir(COD)Cl]2 to 1 is 0.01:1; The ligand L is ; The molar ratio of ligand L to 1 was 0.02:1; The solvent A is 0.5 mL of tetrahydrofuran, and the solvent B is 0.5 mL of acetonitrile; The molar ratio of the copper catalyst to 1 is 0.1:1; The copper catalyst is cuprous acetate.

2. The method according to claim 1, characterized in that It also includes a treatment and purification process, specifically: diatomaceous earth filtration, concentration and then purification by column chromatography; the volume ratio of petroleum ether to ethyl acetate in column chromatography is 5:1 to 1:1.

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