CN118702616A - A method for preparing polycyclic bridged ring compounds by light-promoted dearomatization - Google Patents

Abstract

The invention relates to a method for preparing a polycyclic bridged ring compound by light-promoted dearomatization. Specifically, 4CzIPN catalyzes naphthalene derivative to react with N-aryl glycine under the condition of visible light to obtain a target compound. The invention starts from simple and easy-to-store raw materials, and a series of polycyclic bridged ring compounds are obtained under milder conditions.

Description

A method for preparing polycyclic bridged ring compounds by light-promoted dearomatization

Technical Field

The invention relates to a method for preparing polycyclic bridged ring compounds by light-promoted dearomatization.

Background Art

As a basic chemical transformation method, dearomatization is one of the most effective strategies for converting simple two-dimensional (2D) precursors into complex three-dimensional (3D) systems. With the development of new methods by scientists, the dearomatization toolbox, which is limited to a few reactions, has gradually become richer. Compared with the past, the methods developed in recent years can introduce more functional groups under milder conditions and achieve better control of chemical selectivity, regioselectivity and stereoselectivity. In the past two decades, the main development of dearomatization process is to provide a simpler and more effective method for the total synthesis of complex natural products. It can greatly expand the scope of substrate application with simple aromatic hydrocarbons as basic raw materials, thereby obtaining complex and diverse chemical structural units. Light-promoted organic reactions have the characteristics of friendly reaction environment, mild conditions and simple operation, and have become a major research hotspot in the field of organic synthesis in recent years. Light-promoted dearomatization reaction provides an efficient and simple method for the synthesis of polycyclic fused-ring compounds with diverse structures.

Polycyclic skeletons are important drug active groups in bioactive natural products and pharmaceutical compounds. Among them, two-dimensional (2D) and three-dimensional (3D) fused ring systems are of great significance in medicinal chemistry due to their unique structures and physicochemical properties. Therefore, it is urgent to develop a new and efficient method for constructing fused ring systems containing 2D/3D, which is of great significance to the development of medicinal chemistry. It is worth looking forward to developing a simple and efficient dearomatization method to construct polycyclic bridged ring compounds.

In summary, this paper describes a method for directly synthesizing a high-value-added polycyclic bridged ring compound starting from simple and readily available raw materials by innovatively utilizing visible light-promoted dearomatization reactions.

Summary of the invention

The object of the present invention is to provide a method for preparing polycyclic bridged ring compounds by light-promoted dearomatization.

Reaction equation 1: Synthesis of polycyclic bridged ring compounds

The specific operation steps are as follows (reaction equation 1):

Under _N2 protection, naphthalene derivative 1, amino acid derivative 2, and photocatalyst preferably 4CzIPN are added to a reaction bottle in an amount of 0.01-0.05 molar equivalents, preferably 0.04 molar equivalents, and the first base and the first solvent are added. The reaction is carried out at room temperature and under visible light (380-480nm) irradiation for 24 hours, preferably blue light with a wavelength of 450-455nm. After the reaction is completed, the second base is added to the reaction solution, and the reaction is carried out at room temperature for 24 hours to separate compound 3. Under an inert atmosphere, compound 3, a second photocatalyst, and a second solvent are added to a photoreaction tube or a reaction bottle, and the reaction is carried out at room temperature and under visible light (380-480nm) irradiation for 24 hours to separate compound 4.

The molar ratio of the naphthalene derivative 1 to the amino acid derivative 2 is 1:2.

The photocatalyst used in the first step may be one or more of 4CzIPN, [Ir(ppy) ₂ (dtbbpy)]PF ₆ , Ir(ppy) ₃ and [Ir(dF(CF ₃ )ppy) ₂ (dtbbpy)]PF ₆ , preferably 4CzIPN is the catalyst for the reaction, and the amount used is 0.01-0.05 molar equivalent (relative to the raw material naphthalene derivative 1). The photocatalyst used in the second step may be one or more of 4CzIPN, [Ir(ppy) ₂ (dtbbpy)]PF ₆ , Ir(ppy) ₃ and [Ir(dF(CF ₃ )ppy) ₂ (dtbbpy)]PF ₆ , preferably 4CzIPN is the catalyst for the reaction, and the amount used is 0.01-0.05 molar equivalent (relative to compound 3).

The first base is one or more of NaHCO ₃ , Na ₂ CO ₃ , K ₂ CO ₃ and K ₃ PO ₄ , preferably Na ₂ CO ₃ ; the amount of the base used is 0.10-0.50 molar equivalent of the amount of the naphthalene derivative 1 , preferably 0.40 molar equivalent.

The wavelength of the light used is 380-480 nm, which is within the visible light wavelength range. The first step and the second step both preferably use blue light with a wavelength of 450-455 nm.

The first solvent is one or more of dichloromethane, methanol, toluene, tetrahydrofuran, and dimethyl sulfoxide, preferably tetrahydrofuran; the amount of the solvent is 5-10 mL, preferably 7 mL, per mmol of the naphthalene derivative.

The second base is one or more of NaO ^t Bu, KO ^t Bu, Cs ₂ CO ₃ and DBU, preferably DBU; the amount of the base is 0.10-0.50 molar equivalent of the amount of the amino acid derivative 2, preferably 0.25 molar equivalent.

The second solvent is one or more of methanol, acetone, N,N-dimethylformamide and 1,2-dichloroethane, preferably methanol; the amount of the solvent is 5-10 mL, preferably 10 mL, per mmol of compound 3.

The invention starts from simple and easy-to-store raw materials and obtains a series of polycyclic bridged ring compounds under relatively mild conditions.

The present invention has the following advantages:

First, the raw materials of the reaction, naphthalene derivatives, are easy to synthesize and store, amino acid derivatives are commercial products, cheap and easy to obtain, and the reaction conditions are simple and mild. Secondly, by using visible light to promote the reaction, the use of a large amount of condensing agents, strong acids, and strong bases is avoided, making the reaction greener. Finally, the resulting product, the polycyclic bridged ring compound, has a high added value and has a broad application prospect in drug research and development.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a calibration curve of cytokine content.

DETAILED DESCRIPTION

In order to better understand the present invention, the following examples are provided for illustration. The reaction materials and results of Examples 1-12 are shown in Table 1.

Table 1 Reaction results of different substituted substrates

Example 1

Step 1: Under N ₂ protection, 4CzIPN (0.012 mmol, 4 mol%), Na ₂ CO ₃ (0.12 mmol, 0.40 equiv.), N-phenylglycine 2a (0.60 mmol, 2.0 equiv.), 1-naphthoic acid methyl ester 1a (0.30 mmol, 1.0 equiv.), and tetrahydrofuran (2.0 mL) were added to a photoreaction tube in sequence and reacted at room temperature (25°C) and 450 nm light for 24 hours. DBU (0.15 mmol, 0.50 equiv.) was added to the reaction bottle and reacted at room temperature (25°C) for 24 hours. After the reaction, compound 3aa was obtained by column chromatography.

Step 2: Under an inert atmosphere _{of N2} , compound 3aa (0.20 mmol, 1.0 equiv.), 4CzIPN (0.004 mmol, 2 mol%) and MeOH (2.0 mL) were added to a photoreaction tube or reaction bottle, and the mixture was reacted at room temperature (25°C) and under visible light (450 nm) for 24 hours to obtain compound 4aa in a yield of 93%. The structure was identified by NMR (hydrogen spectrum and carbon spectrum).

Compound 4aa has a good inhibitory activity on the necrosis pathway of L929 cells, with an IC ₅₀ value of 30 nM.

The specific steps of the assay are as follows: first, mouse fibroblast L929 (Shanghai Yongsheng Biotechnology Co., Ltd.) is added to a 96-well cell culture plate, and 0.1 mL of culture medium containing 2×104 L929 cells (RPMI-1640 culture medium containing 10% fetal bovine serum) is added to each well, and then the test compound 4aa is added at a final concentration of 10uM for pretreatment for one hour, and then the cells are treated with tumor necrosis factor TNF-a (final concentration 40ng/mL, Shanghai Saida Biotechnology Co., Ltd.) and z-VAD (caspase inhibitor, final concentration 20uM, Shanghai Saida Biotechnology Co., Ltd. (concentration 10mM)) for 48 hours. The cell survival rate is determined by detecting the level of adenosine triphosphate (ATP), and the specific method is as follows: 0.1 mL of ATP release factor (concentration 1mg/mL, Shanghai Yongsheng Biotechnology Co., Ltd.) is added to each well of the 96-well plate that has been tested, and reacted at room temperature for 5 minutes, and then 0.1 mL of cell lysate is respectively pipetted into the corresponding empty wells of the second new plate. At a temperature below 25°C (maintained at about 20°C), place the second plate in an automatic multi-well fluorescence detector and immediately detect the fluorescence intensity. Use RLU (relative light unit) as the Y axis and the dilution of the cytokine standard (the standard is the above-mentioned untreated culture medium containing 2×10 ⁴ L929 cells per 0.1 mL, and the cytokine standard is diluted 2 to 10 times with RPMI-1640 culture medium, respectively, and diluted 2, 4, 6, 8 and 10 times, respectively. When testing, add 0.1 mL of the diluted standard to each well, and make 5 sets of data) as the X axis to draw a standard curve, and calculate the content of cytokines in the sample to be tested according to the standard curve.

The negative control group was a DMSO pretreatment group, except that the three or two inhibitors were not added, and DMSO was added at a final volume concentration of 5% (the process and conditions were the same as the above-mentioned specific steps of the determination, and the difference from the above-mentioned treatment process was that 5% DMSO was used instead of 4aa for one hour, and TNF-a and z-VAD were not added);

Nec-1 (cell necroptosis inhibitor, final concentration 30 μM, Shanghai Yongsheng Biotechnology Co., Ltd. (concentration 10 mM)) was used instead of 4aa and the three inhibitors as the pretreatment group as the positive control (the process and conditions were the same as the above-mentioned specific steps of the determination, and the difference from the above-mentioned treatment process was that Nec-1 was used instead of 4aa).

Finally, the _IC50 value was obtained by fitting the calibration curve (the vertical axis is the inhibition percentage, and the horizontal axis is the concentration of compound 4aa). As shown in Figure 1;

The test data are as follows:

4aa: Colorless oil, 54.5mg, 93% yield (83:17dr). R _f = 0.56 (PE/EA = 20/1). ¹ HNMR (700MHz, CDCl ₃ )δ7.24–7.15(m,5H),7.11–7.06(m,1H),6.63(t,J＝7.2Hz,1H),6.60(d,J＝8.1Hz,2H),4.86(dd,J ＝6.0,3.1Hz,1H),4.19(d,J＝3.1Hz,1H),3.55–3.48(m,2H),3.48(s,3H),3.44(t,J＝4.3Hz,1H),2.20 (ddd, J＝11.0, 5.9, 4.0Hz, 1H), 2.07 (d, J＝10.9Hz, 1H). ¹³ C NMR (175MHz, CDCl ₃ )δ173.82,147.18,142.74,131.51,130.57,129.19,127.11,127.03,116.02,111.35,57.84,57.24,53.50,52.23,40.13,36.09.One aromaticsignal is missing, most likely due to overlap.

Embodiment 2:

The operation process and conditions are the same as those in Example 1, except that the raw material 1 and/or raw material 2 (see Table 1 for details) are used, and the product 4ba has a yield of 86%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

The test data are as follows:

4ba: Colorless oil, 52.9mg, 86% yield (81:19dr). R _f = 0.58 (PE/EA = 20/1). ¹ HNMR (400MHz, CDCl ₃ )δ7.27–7.13(m,5H),7.13–7.06(m,1H),6.68–6.59(m,3H),4.88(dd,J＝5.9,3.1Hz,1H),4.17(d,J＝ 3.0Hz,1H),4.03–3.85(m,2H),3.57–3.45(m,2H),3.44(t,J＝4.2Hz,1H),2.19(ddd,J＝11.0,5.9,4.0Hz,1H ), 2.07 (d, J = 11.0Hz, 1H), 1.06 (t, J = 7.1Hz, 3H). ¹³ C NMR (100MHz, CDCl ₃ )δ173.34,147.35,142.77,131.70,130.57,129.10,127.03,126.96,126.94,115.95,111.39,61.23,57.89,57.10,53.71,40.17,36.08,13.80.

Embodiment 3:

The operation process and conditions are the same as those in Example 1, except that raw material 1 and/or raw material 2 (see Table 1 for details) are used, and the product 4ca has a yield of 81%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

The test data are as follows:

4ca: Colorless oil, 52.3mg, 81% yield (79:21dr). R _f = 0.59 (PE/EA = 20/1). ¹ HNMR (400MHz, CDCl ₃ )δ7.23–7.10(m,5H),7.09–7.00(m,1H),6.65–6.56(m,3H),4.84(dd,J＝5.9,3.1Hz,1H),4.77(sep,J＝ 6.3Hz,1H),3.49(d,J＝2.6Hz,2H),3.41(q,J＝3.1Hz,1H),2.18(ddd,J＝10.9,5.9,4.0Hz,1H),2.05(d, J＝10.9Hz, 1H), 1.17 (d, J＝6.3Hz, 3H), 0.72 (d, J＝6.3Hz, 3H). ¹³ C NMR (100MHz, CDCl ₃ )δ173.10,147.49,142.73,132.04,130.49,129.11,126.96,126.91,126.85,115.90,111.43,68.88,57.92,57.02,54.22,40.23,36.13,21.62,2 1.11.

Embodiment 4:

The operation process and conditions are the same as those in Example 1, except that raw material 1 and/or raw material 2 (see Table 1 for details) are used, and the product 4da has a yield of 60%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

The test data are as follows:

4da: White solid, mp 79.6–80.9°C, 40.2mg, 60% yield (74:26dr). R _f = 0.58 (PE/EA = 20/1). ¹ H NMR (400MHz, CDCl ₃ )δ7.25–7.13(m,5H),7.13–7.05(m,1H),6.73–6.65(m,2H),6.65–6.59(m,1H),4.89(dd,J＝5.8,3.3Hz, 1H),4.05(d,J＝3.6Hz,1H),3.54–3.43(m,2H),3.40(t,J＝4.3Hz,1H),2.12(ddd,J＝10.9,5.8,4.1Hz,1H ), 2.00 (d, J = 10.9Hz, 1H), 1.21 (s, 9H). ¹³ C NMR (100MHz, CDCl ₃ )δ172.29,147.90,142.92,132.45,130.57,129.05,126.80,126.75,126.65,116.01,112.10,81.34,58.34,56.66,55.02,40.30,35.97,27.87.

Embodiment 5:

The operation process and conditions are the same as those in Example 1, except that raw material 1 and/or raw material 2 (see Table 1 for details) are used, and the product 4ea has a yield of 88%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

Embodiment 6:

The operation process and conditions are the same as those in Example 1, except that raw material 1 and/or raw material 2 (see Table 1 for details) are used, and the product 4fa has a yield of 93%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

Embodiment 7:

The operation process and conditions are the same as those in Example 1, except that raw material 1 and/or raw material 2 (see Table 1 for details) are used, and the product 4ga has a yield of 88%. The structure of the compound is identified by nuclear magnetic resonance (H spectrum and C spectrum).

Embodiment 8:

The operation process and conditions are the same as those in Example 1, except that the raw material 1 and/or raw material 2 (see Table 1 for details) are used, and the product 4ab has a yield of 90%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

Embodiment 9:

The operation process and conditions are the same as those of Example 1, except that starting material 1 and/or starting material 2 (see Table 1 for details) are used. The yield of product 4ac is 70%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

The test data are as follows:

4ac: Colorless oil, 52.2mg, 70% yield (63:37dr). R _f = 0.58 (PE/EA = 20/1). ¹ HNMR (400MHz, CDCl ₃ ) δ7.24–7.16 (m, 6H), 6.45(d,J＝9.1Hz,2H),4.78(dd,J＝5.7,3.1Hz,1H),4.16(d,J＝2.9Hz,1H),3.48(s,3H),3.46–3.40(m ,3H),2.22–2.16(m,1H),2.06(d,J＝11.2Hz,1H). ¹³ C NMR (100MHz, CDCl ₃ )δ173.65,144.43,142.49,131.81,131.27,130.60,127.26,127.25,127.05,113.04,107.76,57.97,57.48,52.35,48.15,40.12,32.64.

Embodiment 10:

The operation process and conditions are the same as those in Example 1, except that starting material 1 and/or starting material 2 (see Table 1 for details) are used. The yield of product 4ad is 86%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

The test data are as follows:

4ad: Colorless oil, 52.8mg, 86% yield (>95:5dr). R _f = 0.54 (PE/EA = 20/1). ¹ HNMR (400MHz, CDCl ₃ )δ7.26(d,J＝1.6Hz,1H),7.24–7.19(m,2H),7.16–7.07(m,4H),6.89(ddd,J＝7.6,6.4,2.1Hz,1H),4.92 (t,J＝4.7Hz,1H),4.02(d,J＝3.9Hz,1H),3.67(d,J＝8.5Hz,1H),3.41(t,J＝4.6Hz,1H),3.32(s ,3H),3.01(dd,J＝8.5,5.0Hz,1H),2.39–2.29(m,1H),2.12(s,3H),2.03(d,J＝10.9Hz,1H). ¹³ C NMR ( 100MHz,CDCl ₃ )δ172.97,150.36,144.02,133.05,131.65,131.12,131.08,126.83,126.76,126.58,122.34,120.33,62.56,61.28,53.99,51.39,42.41,35.40, 19.21.One aromatic signal is missing,most likely due to overlap.

Embodiment 11:

The operation process and conditions are the same as those in Example 1, except that raw material 1 and/or raw material 2 (see Table 1 for details) are used, and the product 4ae has a yield of 76%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

The test data are as follows:

4ae: Colorless oil, 56.5mg, 76% yield (>95:5dr). R _f = 0.53 (PE/EA = 20/1). ¹ HNMR (700MHz, CDCl ₃ )δ7.48(d,J＝7.9Hz,1H),7.26–7.22(m,2H),7.22–7.17(m,2H),7.15–7.09(m,2H),6.81(t,J＝7.6Hz ,1H),5.04(t,J＝4.9Hz,1H),4.01(d,J＝4.0Hz,1H),3.98(d,J＝8.7Hz,1H),3.39(t,J＝4.8Hz,1H ),3.35(s,3H),3.13(dd,J＝8.7,5.1Hz,1H),2.38–2.33(m,1H),2.02(d,J＝10.9Hz,1H). ¹³ C NMR(175MHz, CDCl ₃ )δ172.65,149.37,143.95,133.99,131.66,130.91,128.07,126.85,126.82,126.56,123.72,123.60,119.40,61.91,60.60,53.59,51.69,41.88 ,35.55.

Embodiment 12:

The operation process and conditions are the same as those in Example 1, except that raw material 1 and/or raw material 2 (see Table 1 for details) are used. The yield of product 4bd is 84%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

The test data are as follows:

4bd: Colorless oil, 53.9mg, 84% yield (>95:5dr). R _f = 0.52 (PE/EA = 20/1). ¹ HNMR (400MHz, CDCl ₃ )δ7.31–7.20(m,2H),7.24–7.16(m,1H),7.16–7.02(m,4H),6.92–6.81(m,1H),4.94(t,J＝4.9Hz,1H) ,3.97(d,J＝3.9Hz,1H),3.84–3.72(m,2H),3.64(d,J＝8.4Hz,1H),3.40(t,J＝4.6Hz,1H),2.96(dd, J＝8.5,5.0Hz,1H),2.36–2.26(m,1H),2.09(s,3H),2.01(d,J＝10.9Hz,1H),0.73(t,J＝7.1Hz,3H). ¹³ C NMR (100MHz, CDCl ₃ )δ172.33,150.79,143.98,133.20,131.75,131.07,126.80,126.69,126.53,126.52,122.33,120.13,62.65,61.18,60.49,54.04,42.54,35.25, 19.27,13.53.One aromatic signal is missing, most likely due to overlap.

Embodiment 13:

The operation process and conditions are the same as those in Example 1, except that an equal amount of photocatalyst [Ir(ppy) ₂ (dtbbpy)]PF ₆ (PC-1) is used in the reaction to replace 4CzIPN used in the second step. The product is 4aa with a yield of 92%. The structure of the compound is identified by NMR (hydrogen spectrum and carbon spectrum).

Embodiment 14:

The operation process and conditions were the same as those in Example 1, except that an equal amount of photocatalyst Ir(ppy) ₃ (PC-2) was used in the reaction instead of 4CzIPN used in the second step. The product was 4aa with a yield of 59%. The structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum).

Embodiment 15:

The operation process and conditions were the same as those in Example 1, except that tetrahydrofuran was used instead of MeOH in the second step of the reaction. The product was 4aa with a yield of 73%. The structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum).

Embodiment 16:

The operation process and conditions were the same as those in Example 1, except that acetone was used instead of MeOH in the second step of the reaction. The product was 4aa with a yield of 75%. The structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum).

Embodiment 17:

The operation process and conditions were the same as those in Example 1, except that 1,2-dichloroethane was used as the solvent instead of MeOH. The product was 4aa with a yield of 90%. The structure of the compound was identified by NMR (hydrogen spectrum and carbon spectrum).

Embodiment 18:

The operation process and conditions were the same as those in Example 1, except that the reaction was carried out under light-proof conditions, and the target compound 4aa could not be obtained.

Embodiment 19:

The operation process and conditions were the same as those in Example 1, except that no photocatalyst was added during the reaction and the target compound 4aa was not obtained.

Claims (5)

1. A method for preparing a polycyclic bridged ring compound by light-promoted dearomatization, which is characterized by comprising the following steps of:

the reaction formula is as follows:

Wherein R ¹ can be one or more than two of hydrogen, bromine, chlorine, hydroxyl, methoxy, ethoxy, isopropoxy, tert-butoxy, phenoxy, methyl, phenyl, benzyl or trimethylsilylmethyl, and the number of the radicals is 1-4;

R ² can be one OR more than two of tertiary amine positive ions (-NR ₃ ⁺), nitro (-NO ₂), cyano (-CN), sulfonic acid (-SO ₃ H), formyl (-CHO), acyl (-COR), carboxyl (-CO ₂ H), ester (-CO ₂ R), benzenesulfonyl (-SO ₂ Ph), amido (-CONHR and-CONR ₂), trifluoromethyl (CF ₃) and phosphate (-PO (OR) ₂); wherein R is one or more than two of methyl, ethyl, isopropyl, tertiary butyl and benzyl;

r ³ can be the following group: one or more of methyl, ethyl, benzyl, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 3-chlorophenyl, 3-bromophenyl, 4-methylphenyl and 1-naphthyl.

2. The synthesis method according to claim 1, wherein:

The specific operation steps are as follows:

The first step: under the protection of inert atmosphere (such as N ₂), firstly adding naphthalene derivative (formula 1) and amino acid derivative (formula 2) into a photoreaction tube or a photoreaction bottle or a photoreaction reactor, then adding a first photocatalyst, a first solvent and a first alkali, and reacting for 24-48 hours at room temperature (20-30 ℃) under the irradiation of visible light; after the reaction is finished, adding a second base into the reaction solution, and reacting for 24-48 hours at room temperature to obtain a compound (formula 3);

The first base is one or more than two of NaHCO ₃、Na₂CO₃、K₂CO₃ and K ₃PO₄, preferably Na ₂CO₃; the amount of the base is 0.10 to 0.50 molar equivalent, preferably 0.02 to 0.40 molar equivalent to the amount of the naphthalene derivative 1;

The first solvent is one or more of dichloromethane, toluene, tetrahydrofuran and dimethyl sulfoxide, preferably tetrahydrofuran; the solvent is used in an amount of 5 to 10mL, preferably 6 to 8mL, per millimole of naphthalene derivative 1;

The second base is one or more than two of NaO ^tBu、KO^tBu、Cs₂CO₃ and DBU, preferably DBU; the amount of the base is 0.10 to 0.50 molar equivalent, preferably 0.20 to 0.25 molar equivalent to the amount of the amino acid derivative 2;

And a second step of: under the protection of inert atmosphere (such as N ₂), adding the compound 3, a second photocatalyst and a second solvent into a photoreaction tube or a reaction bottle, and reacting for 12-24 hours at room temperature (20-30 ℃) under the illumination of visible light (380-480 nm) to obtain a compound (formula 4);

The second solvent is one or more of methanol, acetone, N-dimethylformamide and 1, 2-dichloroethane, preferably methanol; the amount of the solvent used is 5 to 10mL, preferably 8 to 10mL, per millimole of compound 3.

3. A method according to claim 1 or 2, characterized in that:

The molar ratio of naphthalene derivative 1 to amino acid derivative 2 is 1:1-2, preferably in a ratio of 1:1.5-1:2.

4. A method according to claim 1 or 2, characterized in that:

The photocatalyst used in the first step may be 4CzIPN, [ Ir (ppy) ₂(dtbbpy)]PF₆、Ir(ppy)₃, and [ Ir (dF (one or more of CF ₃)ppy)₂(dtbbpy)]PF₆, preferably 4 CzIPN) as a catalyst for the reaction, in an amount of 0.01 to 0.05 molar equivalents (relative to the starting naphthalene derivative 1), preferably 0.02 to 0.04 molar equivalents;

The photocatalyst used in the second step may be 4CzIPN, [ Ir (ppy) ₂(dtbbpy)]PF₆、Ir(ppy)₃, and [ Ir (dF (one or more of CF ₃)ppy)₂(dtbbpy)]PF₆, preferably 4 CzIPN) as a catalyst for the reaction, in an amount of 0.01 to 0.05 molar equivalents (relative to compound 3), preferably 0.01 to 0.02 molar equivalents;

5. A method according to claim 1 or 2, characterized in that:

the illumination wavelength used in the first step is 380-480nm in the visible wavelength range, preferably blue illumination with a wavelength of 450-455 nm;

The illumination wavelength used in the second step is 380-480nm in the visible wavelength range, preferably blue illumination with a wavelength of 450-455 nm.