A method for preparing hexahydro-β-carboline indole compounds by synergistic catalysis of visible light and cobalt

Abstract

The present invention is a method for preparing hexahydro-β-carboline indole compounds by synergistic catalysis of visible light and cobalt, comprising adding tetrahydro-β-carboline indole alkaloids, hans ester, cobalt bromide, 1,3-bis(diphenylphosphine)propane, and 4CzIPN to a dry tetrahydrofuran solvent to obtain a mixed solution, and irradiating the mixed solution with 450 nanometer LED light at room temperature and in an inert gas atmosphere. The present invention does not require the use of hydrogen, but only uses cheap metals as catalysts and catalytic amounts of photosensitizers, and can achieve gram-level reactions by visible light irradiation at room temperature, with the advantages of high efficiency, conservation and environmental protection, etc. Moreover, the reaction conditions of the present invention are mild, the raw materials are simple and easy to obtain, and it is safe and easy to operate in industrial production, and has huge potential large-scale application value.

Description

Technical Field

[0001] The invention belongs to the technical field of catalytic synthesis, and in particular relates to a method for preparing hexahydro-β-carboline indole compounds by synergistic catalysis of visible light and cobalt. Background Art

[0002] Indole alkaloids containing a tetracyclic skeleton are an important branch of alkaloids. They are a class of natural products that are widely found in nature with a large number of different structures and significant activities. At present, many well-known monoterpenoid indole alkaloids containing hexahydro-β-carboline (HHβC) nuclei, such as strychnine and quebracho, have been used in drugs (such as reserpine, yohimbine, tadalafil, etc.) due to their rich biological activities such as adrenaline blocking, anti-arrhythmic, anti-cancer, and anti-malarial. The unique structure and significant activity of β-carboline indole have attracted the attention of many researchers, especially in the field of asymmetric catalytic synthesis. As an ideal synthetic building block, tryptamine amide can be used to simply and efficiently construct various indole alkaloid nuclei and then synthesize related natural products.

[0003] In 2004, Steven M. Allin et al. used (S)tryptamine as the starting substrate in the asymmetric total synthesis of deplancheine. After condensation with methyl 5-oxopentanoate, ring closure reaction with concentrated hydrochloric acid at room temperature, two consecutive oxidations of the generated hydroxyl group, reaction with tributylbis(diphenylseleno)phosphine to generate selenophenyl ester compounds, and then hydrogen reduction with n-butyltin, a total of six steps were performed to obtain the hexahydro-β-carboline indole skeleton structure. In 2016, PravatMondal and Narshinha P. Argade also used a similar synthetic route in the total synthesis of (−)-desethyleburnamonine, (−)-vindeburnol and (−)-3-epitacamonine. In 2019, Maxime Jarret et al. used D-tryptophan as the starting substrate in the total synthesis of Mavacuran alkaloids, and synthesized the iodoolefin core intermediate in five steps, and then closed the ring through the nickel-catalyzed Heck reaction to obtain the hexahydro-β-carboline indole skeleton structure, a total of 6 steps. In 2021, Benjamin List provided an example of the synthesis of hexahydro-β-carboline indole by the reduction of the double bond of tetrahydro-β-carboline indole catalyzed by chiral phosphoric acid in the study of cluster construction of polycyclic alkaloids, while the racemate was reduced with hydrogen under Pd-C catalysis. In 2024, Wang Yang from the Ocean University of China used 3,4-dihydro-β-carboline oxide as the raw material and developed an asymmetric 1,3-dipolar cycloaddition reaction with olefin ethers under the catalysis of chiral phosphoric acid to obtain three types of tetrahydro-β-carboline indole and isoxazole derivatives.

[0004] At present, most methods for constructing hexahydro-β-carboline indole compounds have problems such as lengthy synthesis steps or the need for hydrogen, which increases the risk of the reaction. There are few reports on methods for constructing hexahydro-β-carboline indole compounds using tetrahydro-β-carboline indole compounds as synthetic intermediates without hydrogen reduction. It is of great practical significance to develop a reaction route with short reaction steps, safety, and greenness. Summary of the invention

[0005] The present invention utilizes visible light cobalt synergistic catalysis, uses Hans ester as a reducing agent, and uses cobalt bromide, a phosphine ligand and a photocatalyst as catalysts to reduce the double bonds in the dilute amide molecule using a photoreaction, thereby solving the problem of lengthy steps in the traditional methodology for constructing hexahydro-β-carboline indole alkaloids.

[0006] A method for preparing hexahydro-β-carboline indole compounds by synergistic catalysis of visible light and cobalt mainly comprises the following steps: adding tetrahydro-β-carboline indole alkaloids, hans ester, cobalt bromide (CoBr2), 1,3-bis(diphenylphosphino)propane (dppp) and photocatalyst 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN) into a solvent to obtain a mixed solution, deoxygenating the mixed solution with an inert gas, and irradiating the mixed solution with visible light at room temperature and in an inert gas atmosphere to obtain hexahydro-β-carboline indole compounds.

[0007] The reaction path of the preparation method of the present invention is as follows: the photocatalyst (hereinafter referred to as 4CzIPN) is photoexcited under the irradiation of 450nm±10nm Blue LEDs to reach the excited state 4CzIPN*, and the photosensitizer obtains an electron in the single electron transfer with the hans ester to generate the reduced state 4CzIPN*-, and then transfers the single electron of the divalent cobalt bromide phosphine complex to return to the ground state 4CzIPN, completing the photocatalytic cycle. After obtaining an electron, the divalent cobalt is reduced to a monovalent cobalt intermediate. The water molecule transfers a proton to the monovalent cobalt to generate a hydroxide ion, and then transfers with the single H atom of the hans ester to generate water, completing the hydrogen source cycle. The β-position C is also reduced, and the cobalt is complexed with the carbon group in the amide. After the single electron transfer, the cobalt leaves to generate a reaction product, completing the cobalt catalytic cycle. Through the deuteration experiment, it is proved that there is a hydrogen atom exchange between the hans ester and water. The divalent cobalt hydrogen is inserted into the double bond, the cobalt is coordinated with the α-C, and the β-C is reduced by hydrogen. After another water cycle, the α-position reduction is completed.

[0008] Furthermore, the structural formula of the tetrahydro-β-carboline indole alkaloid is as follows:

[0009]

[0010] In the formula, R1, R2, R3, R4, R5, and R6 are all H; or one of R2 and R3 is CH3, and the rest are all H; or one of R4 or R2 is OBn, and the rest are all H; or one of R2 and R3 is F, and the rest are all H; or one of R2 and R3 is Cl, and the rest are all H; or one of R1, R2 and R3 is Br, and the rest are all H; or one of R2 and R3 is OMe, and the rest are all H; or R5 and R6 are Me or Cy, and R2 is OMe, and the rest are all H; or R5 and R6 are Me or Cy, and R2 is Br, and the rest are all H.

[0011] Furthermore, the solvent is dry tetrahydrofuran.

[0012] Furthermore, the molar ratio of the cobalt bromide to 1,3-bis(diphenylphosphino)propane is 1:1-1.2; the molar amount of the anhydrous cobalt bromide added is 2%-5% of the tetrahydro-β-carboline indole alkaloid; the molar amount of the 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile added is 2%-5% of the tetrahydro-β-carboline indole alkaloid; the mass ratio of the hans ester to the tetrahydro-β-carboline indole compound is 1:1.5, and the addition ratio of the tetrahydro-β-carboline indole compound to the solvent is 0.05~0.10mmol:1mL.

[0013] Furthermore, the visible light irradiation is performed using Blue LEDs with a wavelength of 450nm±10nm, the irradiation temperature is room temperature, and the irradiation time is 24-48h.

[0014] Furthermore, the structural formula of the hexahydro-β-carboline indole compound is as follows:

[0015]

[0016] In the formula, R1, R2, R3, R4, R5, and R6 are all H; or one of R2 and R3 is CH3, and the rest are all H; or one of R4 or R2 is OBn, and the rest are all H; or one of R2 and R3 is F, and the rest are all H; or one of R2 and R3 is Cl, and the rest are all H; or one of R1, R2 and R3 is Br, and the rest are all H; or one of R2 and R3 is OMe, and the rest are all H; or R5 and R6 are Me or cyclohexyl, and the rest are all H; or R5 and R6 are Me or Cy, and R2 is OMe, and the rest are all H; or R5 and R6 are Me or Cy, and R2 is Br, and the rest are all H; or R1 is Me or Ts or Bn, and the rest are all H; or R5 and R6 are H or Me or Cy, and R8 is CO2Me, and the rest are all H.

[0017] A method for preparing a large amount of hexahydro-β-carboline indole compounds by synergistic catalysis of visible light and cobalt, comprising: firstly adding anhydrous cobalt bromide and 1,3-bis(diphenylphosphino)propane to a dry tetrahydrofuran solution, stirring to form a cobalt phosphine complex; then adding tetrahydro-β-carboline indole alkaloid, hans ester, and 4CzIPN to obtain a mixed solution; deoxygenating the mixed solution with an inert gas, irradiating the mixed solution with visible light at room temperature and in an inert gas atmosphere.

[0018] To prepare large quantities of hexahydro-β-carboline indole compounds, that is, to perform gram-scale reactions, the cobalt and phosphine ligands should be evenly stirred first to fully form a complex, and the reaction effect will be better.

[0019] Compared with the prior art, the present invention constructs hexahydro-β-carboline indole compounds by a simple, efficient, green and safe method, which has the following advantages:

[0020] (1) The reaction system of the present invention is simple and easy to operate. The reaction of the present invention can achieve the reduction of the lactam double bond in the tetrahydro-β-carboline alkaloid skeleton by irradiation with visible light at room temperature and in an inert gas atmosphere. The reaction does not require hydrogen, the reaction conditions are mild, and it is easy to achieve industrial production.

[0021] (2) The reaction system is carried out in a homogeneous solvent, which is conducive to mechanism research.

[0022] (3) The preparation cost of the present invention is low. The cobalt bromide, 1,3-bis(diphenylphosphino)propane and 4CzIPN used in the catalytic system of the present invention are simple, cheap and readily available commercial compounds, the reaction substrates have good universality, and the entire reaction system is economical and efficient.

[0023] (4) The preparation method of the present invention is green and environmentally friendly. The present invention uses cheap metals as catalysts, adds a catalytic amount of photosensitizer, and uses 450nm LEDs to make the reaction occur, which is very green; it can also achieve gram-level reactions and has a good yield. It has the advantages of high efficiency, conservation and environmental protection, and has potential application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The apparatus diagram (a), reaction process diagram (b) and reaction product diagram (c) of the gram-scale reaction of Example 28, wherein 1-fan, 2-water condensation, 3-photoreactor, 4-stirring table;

[0025] Figure 2 is a schematic diagram of the specific operation of the gram-scale reaction of Example 28;

[0026] Figure 3 This is a reaction mechanism diagram of the preparation of hexahydro-β-carboline indole compounds by the synergistic catalysis of visible light and cobalt according to the present invention;

[0027] Figure 4 is the H NMR spectrum of the hexahydro-β-carboline indole compound prepared in Example 1;

[0028] Figure 5 is the carbon spectrum of the hexahydro-β-carboline indole compound prepared in Example 1;

[0029] Figure 6 It is the mass spectrum of the hexahydro-β-carboline indole compound prepared in Example 1. DETAILED DESCRIPTION

[0030] In order to make the objectives, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below with reference to the accompanying drawings.

[0031] Example 1

[0032] Under nitrogen atmosphere, tetrahydro-β-carboline indole alkaloid (47 mg, 0.20 mmol), 102 mg of Hans ester and 2.2 mg of 4CzIPN, 1.2 mg of cobalt bromide and 4.4 mg of 1,3-bis(diphenylphosphine)propane were added to the reaction tube, and 2 mL of anhydrous tetrahydrofuran was added. Stir for 2 minutes until the reaction solution was uniform. Move the reaction tube to 450 nm LED light and react for 24 hours. After the reaction is completed, there is no need for vacuum distillation. The sample is loaded wet and the corresponding product is separated by column chromatography. The hydrogen spectrum, carbon spectrum, and mass spectrum are as follows Figure 4 , Figure 5 and Figure 6 , identified as 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. The yield of the product was 95%.

[0033] 1 H NMR (400 MHz, DMSO- d 6) δ 10.94 (s, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.33(d, J = 8.0 Hz, 1H), 7.11 – 7.02 (m, 1H), 6.97 (t, J = 7.4 Hz, 1H), 4.92 (dd, J =13.0, 4.0 Hz, 1H), 4.78 (d, J = 5.6 Hz, 1H), 2.77 (m, J = 12.0, 4.2 Hz, 1H), 2.72– 2.53 (m, 3H), 2.40 – 2.20 (m, 2H), 1.79 (d, J = 5.1 Hz, 2H), 1.69 – 1.55 (m,1H).

[0034] 13 C NMR (101 MHz, DMSO- d6) δ 168.51, 136.62, 135.18, 126.89, 121.41,119.04, 118.19, 111.58, 107.60, 54.41, 40.00, 32.65, 28.80, 21.24, 19.41.

[0035] HRMS(ESI+) calculated for C 15 H 16 N2O [M+H] + 241.1335, found: 241.1331

[0036] Example 2

[0037] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-2 (R1, R3, R4, R5, R6, R7, R8 are H, and R2 is F). The yield of the product is 82%.

[0038] Example 3

[0039] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-3 (R1, R2, R4, R5, R6, R7, R8 are H, and R3 is F). The yield of the product is 84%.

[0040] Example 4

[0041] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-4 (R1, R3, R4, R5, R6, R7, R8 are H, and R2 is Cl). The yield of the product is 96%.

[0042] Example 5

[0043] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-5 (R1, R2, R4, R5, R6, R7, R8 are H, and R3 is Cl). The yield of the product is 98%.

[0044] Example 6

[0045] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-6 (R1, R3, R4, R5, R6, R7, R8 are H, and R2 is Br). The yield of the product is 94%.

[0046] Example 7

[0047] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-7 (R1, R2, R4, R5, R6, R7, R8 are H, and R3 is Br). The yield of the product is 92%.

[0048] Example 8

[0049] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-8 (R2, R3, R4, R5, R6, R7, R8 are H, R1 is Br). The yield of the product is 87%.

[0050] Example 9

[0051] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-9 (R1, R3, R4, R5, R6, R7, R8 are H, and R2 is Me). The yield of the product is 91%.

[0052] Example 10

[0053] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-10 (R1, R2, R4, R5, R6, R7, R8 are H, and R3 is Me). The yield of the product is 92%.

[0054] Embodiment 11

[0055] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-11 (R1, R3, R4, R5, R6, R7, R8 are H, and R2 is OMe). The yield of the product is 95%.

[0056] Example 12

[0057] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-12 (R1, R2, R4, R5, R6, R7, R8 are H, and R3 is OMe). The yield of the product is 93%.

[0058] Embodiment 13

[0059] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-13 (R1, R3, R4, R5, R6, R7, R8 are H, and R2 is OBn). The yield of the product is 94%.

[0060] Embodiment 14

[0061] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-14 (R1, R2, R3, R5, R6, R7, R8 are H, and R4 is OBn). The yield of the product is 91%.

[0062] Embodiment 15

[0063] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-15 (R1, R2, R3, R4, R5, R6, R8 are H, and R7 is Me). The yield of the product is 87%.

[0064] Example 16

[0065] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-16 (R1, R2, R3, R4, R5, R6, R8 are H, and R7 is Ts). The yield of the product is 85%.

[0066] Embodiment 17

[0067] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-17 (R1, R2, R3, R4, R5, R6, R8 are H, and R7 is Bn). The yield of the product is 90%.

[0068] Embodiment 18

[0069] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-18 (R1, R2, R3, R4, R5, R6, R7 are H, and R8 is CO2Me). The yield of the product is 83%.

[0070] Embodiment 19

[0071] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-19 (R1, R3, R4, R5, R6, R7 are H, R2 is F, and R8 is CO2Me). The yield of the product is 47%

[0072] Embodiment 20

[0073] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-20 (R1, R2, R4, R5, R6, R7 are H, R3 is Br, and R8 is CO2Me). The yield of the product is 89%

[0074] Embodiment 21

[0075] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar to product-21 (R1, R2, R3, R4, R7, R8 are H, R5, R6 are Me). The yield of the product is 96%

[0076] Embodiment 22

[0077] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-22 (R1, R3, R4, R7, R8 are H, R2 is Br, R5, R6 are Me). The yield of the product is 96%

[0078] Embodiment 23

[0079] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-23 (R1, R2, R3, R4, R7 are H, R8 is CO2Me, R5, R6 are Me). The yield of the product is 80%

[0080] Embodiment 24

[0081] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-24 (R1, R3, R4, R7, R8 are H, R2 is Br, R5, R6 are Me). The yield of the product is 91%

[0082] Embodiment 25

[0083] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-25 (R1, R2, R3, R4, R7, R8 are H, R5, R6 are Cy). The yield of the product is 89%

[0084] Embodiment 26

[0085] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-26 (R1, R3, R4, R7, R8 are H, R2 is OMe, R5, R6 are Cy). The yield of the product is 93%

[0086] Embodiment 27

[0087] Same as Example 1, except that the product is 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one. Similar product-26 (R1, R2, R3, R4, R7 are H, R8 is CO2Me, R5, R6 are Cy). The yield of the product is 86%

[0088] Embodiment 28

[0089] Regarding gram-scale reactions, specific operations and Figure 2As shown: 68 mg of cobalt bromide and 240 mg of 1,3-bis(diphenylphosphino)propane were taken under nitrogen atmosphere, dissolved in 100 mL of dry tetrahydrofuran solution, and stirred for 5 minutes to form a cobalt phosphine complex with 1,3-bis(diphenylphosphino)propane. Tetrahydro-β-carboline indole alkaloid (2.71 g, 11.39 mmol), 5.8 g of Hans ester and 125 mg of 4CzIPN were added to the reaction solution under nitrogen atmosphere, and stirred for 5 minutes until the reaction solution was uniform. The Shrek bottle was moved to 450 nm LED light and reacted for 24 hours. After the reaction was completed, the cobalt metal residue was filtered off by vacuum filtration, eluted with dichloromethane, and the solvent was removed by vacuum distillation. Then, the corresponding product was separated by column chromatography to obtain a total of 1.83 g. The product was identified as 2,3,6,7,12,12b-hexahydroindole[2,3-a]quinolazine-4(1H)-one by H-NMR, C-NMR, and mass spectrometry. The yield was 67%.

[0090] Comparative Example 1

[0091] The CoBr2 in Example 1 was replaced by CoCl2, and the other conditions and steps remained unchanged, and the yield of the product was 84%.

[0092] The CoBr2 in Example 1 was replaced by CoI2, and the other conditions and steps remained unchanged, and the yield of the product was 79%.

[0093] The (1,3-bis(diphenylphosphine)propane)DPPP in Example 1 was replaced with (1,3-bis(diphenylphosphine)ethane)DPPE, and other conditions and steps remained unchanged, and the yield of the product was 81%.

[0094] The DPPP in Example 1 was replaced with 1,1′-ferrocenyldiyl-bis(diphenylphosphine) DPPF, and other conditions and steps remained unchanged, and the yield of the product was 63%.

[0095] The tetrahydrofuran (THF) in Example 1 was replaced with dichloromethane (DCM), and other conditions and steps remained unchanged, to obtain a product with a yield of 13%.

[0096] The THF in Example 1 was replaced with acetonitrile MeCN, and the other conditions and steps remained unchanged, trace amount.

[0097] The 4-CzIPN in Example 1 was replaced by Ir(ppy)3, and the other conditions and steps remained unchanged, in trace amounts.

[0098] The 4-CzIPN in Example 1 was replaced with Ru(bpy)3Cl2, and the other conditions and steps remained unchanged, trace amount.

[0099] Replace 4-CzIPN in Example 1 with (Acr-Mes) + (ClO4) ‒, other conditions and steps remain unchanged, and the yield of the product is 54%.

[0100] When the CoBr2 in Example 1 is removed and other conditions and steps remain unchanged, no corresponding product is obtained.

[0101] When 4-CzIPN in Example 1 was removed and other conditions and steps remained unchanged, no corresponding product was obtained.

[0102] Comparative Example 2

[0103] The mass feed ratio of tetrahydro-β-carboline indole alkaloid to hans ester in Example 1 was changed to 1.25:1, and the other conditions and steps remained unchanged, and the yield was 73%.

[0104] The mass feed ratio of tetrahydro-β-carboline indole alkaloid to hans ester in Example 1 was changed to 1:1, and the other conditions and steps remained unchanged, and the yield was 61%.

Claims

1. A method for preparing hexahydro-β-carboline indole compounds by synergistic catalysis of visible light and cobalt, characterized in that: The method comprises adding tetrahydro-β-carboline indole alkaloid, hans ester, anhydrous cobalt bromide, 1,3-bis(diphenylphosphino)propane and 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile into a solvent to obtain a mixed solution, deoxygenating the mixed solution with an inert gas, and irradiating the mixed solution with visible light at room temperature and in an inert gas atmosphere; the solvent is dry tetrahydrofuran; The structural formula of the tetrahydro-β-carboline indole alkaloid is as follows: wherein one of R2 and R3 is CH3, and the others are all H; or one of R4 or R2 is OBn, and the others are all H; or one of R2 and R3 is F, and the others are all H; or one of R2 and R3 is Cl, and the others are all H; or one of R1, R2 and R3 is Br, and the others are all H; or one of R2 and R3 is OMe, and the others are all H; or R5 and R6 are Me, and R2 is OMe, and the others are all H; or R5 and R6 are Me, and R2 is Br, and the others are all H; The structural formula of the hexahydro-β-carboline indole compound is as follows: wherein one of R2 and R3 is CH3, and the others are all H; or one of R4 or R2 is OBn, and the others are all H; or one of R2 and R3 is F, and the others are all H; or one of R2 and R3 is Cl, and the others are all H; or one of R1, R2 and R3 is Br, and the others are all H; or one of R2 and R3 is OMe, and the others are all H; or R5 and R6 are Me, and R2 is OMe, and the others are all H; or R5 and R6 are Me, and R2 is Br, and the others are all H; The structure of the hansester is as follows: 。 2. The method according to claim 1, characterized in that: The molar ratio of the anhydrous cobalt bromide and the 1,3-bis(diphenylphosphino)propane added is 1:1-1.2; the molar amount of the anhydrous cobalt bromide added is 2%-5% of the tetrahydro-β-carboline indole alkaloid; the molar amount of the 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile added is 2%-5% of the tetrahydro-β-carboline indole alkaloid; the mass ratio of the hans ester to the tetrahydro-β-carboline indole alkaloid is 1:0.46; the addition ratio of the tetrahydro-β-carboline indole alkaloid to the solvent is 0.05-0.10 mmol:1 mL.

3. The method according to claim 1, characterized in that: The visible light irradiation is performed using a blue LED light with a wavelength of 450nm±10nm, the irradiation temperature is room temperature, and the irradiation time is 24-48h.

4. A method for preparing a large amount of hexahydro-β-carboline indole compounds by synergistic catalysis of visible light and cobalt, characterized in that: include: First, anhydrous cobalt bromide and 1,3-bis(diphenylphosphino)propane are added to a dry tetrahydrofuran solution and stirred to form a cobalt phosphine complex; then tetrahydro-β-carboline indole alkaloid, hans ester, and 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile are added to obtain a mixed solution; the mixed solution is deoxygenated with an inert gas, and the mixed solution is irradiated with visible light at room temperature and in an inert gas atmosphere; The structural formula of the tetrahydro-β-carboline indole alkaloid is as follows: wherein one of R2 and R3 is CH3, and the others are all H; or one of R4 or R2 is OBn, and the others are all H; or one of R2 and R3 is F, and the others are all H; or one of R2 and R3 is Cl, and the others are all H; or one of R1, R2 and R3 is Br, and the others are all H; or one of R2 and R3 is OMe, and the others are all H; or R5 and R6 are Me, and R2 is OMe, and the others are all H; or R5 and R6 are Me, and R2 is Br, and the others are all H; The structural formula of the hexahydro-β-carboline indole compound is as follows: wherein one of R2 and R3 is CH3, and the others are all H; or one of R4 or R2 is OBn, and the others are all H; or one of R2 and R3 is F, and the others are all H; or one of R2 and R3 is Cl, and the others are all H; or one of R1, R2 and R3 is Br, and the others are all H; or one of R2 and R3 is OMe, and the others are all H; or R5 and R6 are Me, and R2 is OMe, and the others are all H; or R5 and R6 are Me, and R2 is Br, and the others are all H; The structure of the hansester is as follows: 。

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